| ID Source | ID |
|---|---|
| PubMed CID | 104778 |
| SCHEMBL ID | 2049245 |
| MeSH ID | M0539798 |
| Synonym |
|---|
| carbidopa and levodopa |
| sinemet cr |
| 57308-51-7 |
| nacom |
| chf 1512 |
| nakom |
| carbidopa-levodopa (1:10) |
| l-tyrosine, 3-hydroxy-, mixt. with (s)-alpha-hydrazino-3,4-dihydroxy-alpha-methylbenzenepropanoic acid (10:1) |
| levodopa-carbidopa (10:1) |
| isicom |
| dopabain |
| l-tyrosine, 3-hydroxy-, mixt. with (s)-alpha-hydrazino-3,4-dihydroxy-alpha-methylbenzenepropanoic acid |
| co-careldopa |
| carbilev |
| carbidopa, levodopa drug combination |
| ipx066 |
| rytary |
| carbidopa-levodopa er |
| duopa |
| ipx 066 |
| carbidopa-l-dopa mixt. |
| levodopa / carbidopa |
| carbidopa-levodopa extended release |
| dm-1992 |
| nd 0612 |
| nd0612 |
| carbidopa-levodopa mixt. |
| carbidopa / levodopa |
| carbidopa levodopa |
| IVTMXOXVAHXCHI-YXLMWLKOSA-N |
| levodopa carbidopa |
| SCHEMBL2049245 |
| carbidopa/levodopa |
| Q5037862 |
| levodopa and carbidopa |
| Excerpt | Relevance | Reference |
|---|---|---|
| " Actual total daily levodopa dosage in patients treated with Sinemet CR was increased by 33%; however, the plasma level of this dosage is calculated to be similar to that of the previous dosage of Sinemet-STD (bio-availability of Sinemet CR is 71%)." | ( Clinical efficacy of Sinemet CR 50/200 versus Sinemet 25/100 in patients with fluctuating Parkinson's disease. An open, and a double-blind, double-dummy, multicenter treatment evaluation. The Dutch Sinemet CR Study Group. Horstink, MW; Jansen, EN; Roos, RA; Wolters, EC, 1992) | 0.28 |
| " dosage schedule." | ( Comparative multiple-dose pharmacokinetics of controlled-release levodopa products. Collin, C; Eckernäs, SA; Grahnén, A; Ling-Andersson, A; Nilsson, M; Tiger, G, 1992) | 0.28 |
| " Bioavailability of Sinemet CR levodopa is less than that of standard Sinemet, so a slightly higher total daily levodopa dose is required to achieve a comparable effect; but because Sinemet CR is absorbed much more slowly than is the standard preparation, dosing frequency can be reduced by up to half." | ( The use of Sinemet CR in the management of mild to moderate Parkinson's disease. Rodnitzky, RL, 1992) | 0.28 |
| " The average daily levodopa dosing frequency did not change significantly during long-term treatment." | ( Long-term evaluation of Sinemet CR in parkinsonian patients with motor fluctuations. Hutton, JT; Morris, JL, 1991) | 0.28 |
| "Almost all patients with idiopathic Parkinson's disease respond to levodopa and progress steadily, requiring an increased overall dosage with time." | ( Sinemet (CR4): an open-label study in moderately severe Parkinson's disease. Fritz, VU; Ming, A; Temlett, JA, 1991) | 0.28 |
| " The IR dosage forms were found to disperse soon after administration and to empty rapidly from both fasted and fed stomachs." | ( Characterisation of the in vivo behaviour of a controlled-release formulation of levodopa (Sinemet CR). Davis, SS; Evans, DF; Hardy, JG; Melia, CD; Short, AH; Sparrow, RA; Wilding, IR; Yeh, KC, 1991) | 0.28 |
| " Overall 'Sinemet CR4' allowed a longer dosage interval and provided more stable control of disease manifestations than conventional 'Sinemet'." | ( Controlled release levodopa/carbidopa (Sinemet CR4) in Parkinson's disease--an open evaluation of efficacy and safety. Bulling, MT; Burns, RJ; Wing, LM, 1991) | 0.28 |
| " The dosage of agonist was gradually increased over 12 weeks to a maximum tolerated level of up to 60 mg/day, and that of Sinemet was reduced concurrently." | ( Sustained-release (+)-PHNO [MK-458 (HPMC)] in the treatment of Parkinson's disease: evidence for tolerance to a selective D2-receptor agonist administered as a long-acting formulation. Cedarbaum, JM; Clark, M; Green-Parsons, A; Toy, LH, 1990) | 0.28 |
| " However significantly less frequent dosing was necessary with Sinemet CR." | ( Sinemet CR in Parkinson's disease. Glaeske, CS; Hofman, R; Pfeiffer, RF; Wilken, KE, 1991) | 0.28 |
| " We carried out an oral levodopa dose-response study in two rhesus monkeys whose left hemiparkinsonism was induced by intracarotid administration of MPTP." | ( Oral levodopa dose-response study in MPTP-induced hemiparkinsonian monkeys: assessment with a new rating scale for monkey parkinsonism. Gash, DM; Kim, MH; Kurlan, R, 1991) | 0.28 |
| " Its administration with levodopa, as initial therapy, allows for use of lower dosage and less side-effects of the latter agent." | ( Selegiline in the treatment of Parkinson's disease--long term experience. Elizan, TS; Moros, D; Yahr, MD, 1989) | 0.28 |
| " We performed a dosage ranging and placebo crossover study in six patients to evaluate the efficacy and tolerance of CV when used as an adjunct to Sinemet in patients with Parkinson's disease." | ( CV 205-502: safety, tolerance to, and efficacy of increasing doses in patients with Parkinson's disease in a double-blind, placebo crossover study. Gauger, LL; Olanow, CW; Werner, EG, 1989) | 0.28 |
| " Twelve patients in each treatment group were pair-matched for age, PD duration, duration of levodopa therapy, dosage of Sinemet, PD disability, and side-effect prevalence at study entry." | ( Development and progression of motor fluctuations and side effects in Parkinson's disease: comparison of Sinemet CR versus carbidopa/levodopa. Gilley, DW; Goetz, CG; Klawans, HL; Tanner, CM, 1989) | 0.28 |
| " The daily dosage after 1 year, 766 mg +/- 250 mg, was increased by 23% compared with standard Sinemet dosage, without additional secondary effects." | ( Effect of controlled-release carbidopa/levodopa on motor performance in advanced Parkinson's disease. Aymard, N; Rondot, P; Teinturier, A; Ziegler, M, 1989) | 0.28 |
| " The optimal therapeutic dosage of Sinemet CR was equal to that of Madopar HBS but 12% higher than that of standard Madopar." | ( Treatment of early Parkinson's disease with controlled-release levodopa preparations. Rinne, JO; Rinne, UK, 1989) | 0.28 |
| " The mean daily dosage of levodopa was 662." | ( Sinemet CR in the treatment of patients with Parkinson's disease already on long-term treatment with levodopa. Aarli, JA; Gilhus, NE, 1989) | 0.28 |
| " For optimal results, a higher dosage is needed (mean = 33%), but the number of doses per day can be reduced (mean = 30%)." | ( Experiences with Sinemet CR in the Paracelsus-Elena-Klinik. Gerdes, U; Haagen, K; Ulm, G, 1989) | 0.28 |
| " Daily "on" time, dyskinesia time, disability score, levodopa dosage requirement, and dosing frequency on Sinemet CR were compared with baseline values on standard Sinemet therapy." | ( Long-term clinical efficacy of Sinemet CR in patients with Parkinson's disease. Dickins, QS; Dobson, J; Rodnitzky, RL, 1989) | 0.28 |
| " Although the total number of tablets and doses per day of CR-4 was reduced during the C/S period, total levodopa dosage per day was not significantly changed from either of the previous periods." | ( Controlled-release carbidopa-levodopa (Sinemet) in combination with standard Sinemet in advanced Parkinson's disease. Mark, MH; Sage, JI, ) | 0.13 |
| "Many different formulation techniques are available for designing controlled-release dosage forms." | ( Pharmaceutical design and development of a Sinemet controlled-release formulation. Dempski, RE; Oberholtzer, ER; Scholtz, EC; Yeh, KC, 1989) | 0.28 |
| " These patients required a higher total daily dosage of Sinemet CR than of Sinemet for control of parkinsonian symptoms, but less frequent dosing was required during chronic therapy." | ( Pharmacokinetics and bioavailability of Sinemet CR: a summary of human studies. August, TF; Bush, DF; Lasseter, KC; Musson, DG; Schwartz, S; Smith, ME; Titus, DC; Yeh, KC, 1989) | 0.28 |
| " In 19 parkinsonians with prominent dose-by-dose fluctuations, double-blind crossover trials comparing 8-week regimens of standard carbidopa/levodopa (25/100) to Sinemet CR (50/200) showed comparable clinical outcomes, with mean daily dosing for optimal control reduced from 10." | ( Controlled-release carbidopa/levodopa (Sinemet 50/200 CR4): clinical and pharmacokinetic studies. Berchou, RC; Galloway, MP; Kareti, D; Kesaree, N; LeWitt, PA; Nelson, MV; Schlick, P, 1989) | 0.28 |
| " The standard dosage forms were found to disperse soon after administration and to empty rapidly from both the fasting and the "fed" stomach." | ( Gastrointestinal transit of Sinemet CR in healthy volunteers. Davis, SS; Evans, DF; Hardy, JG; Melia, CD; Short, AH; Sparrow, RA; Wilding, IR, 1989) | 0.28 |
| " Daily dosing frequency was 33% less with Sinemet CR, while daily intake of levodopa required was increased by 25%." | ( Multicenter controlled study of Sinemet CR vs Sinemet (25/100) in advanced Parkinson's disease. Bush, DF; Hutton, JT; Liss, CL; Morris, JL; Reines, S; Smith, ME, 1989) | 0.28 |
| " With continuous levodopa treatment, however, the threshold for dyskinesias begins to rise and the dose-response relation shifts to the right; clinically, the severity of both dyskinesias and on-off fluctuations tends to diminish." | ( Rationale for continuous dopaminomimetic therapy of Parkinson's disease. Baronti, F; Chase, TN; Fabbrini, G; Heuser, IJ; Juncos, JL; Mouradian, MM, 1989) | 0.28 |
| " Memory scores were correlated with age, sex, education, marital status, length of illness, age at onset of illness, dosage and time on medication, functional status, and the major symptoms of parkinsonism." | ( Correlates of memory in Parkinson's disease. Reynolds, CM; Riklan, M; Stellar, S, 1989) | 0.28 |
| " The total daily dose of L-DOPA was not significantly changed, but dosing frequency was almost halved." | ( An open trial of controlled release carbidopa/L-dopa (sinemet CR) for the treatment of mild-to-moderate Parkinson's disease. Friedman, JH; Lannon, MC, 1989) | 0.28 |
| " Reduced dosage frequency and significant motor improvement with reduced fluctuation occurred and were maintained with CR4-Sinemet compared with baseline on Sinemet." | ( Controlled-release carbidopa/levodopa (CR4-Sinemet) in Parkinson's disease patients with and without motor fluctuations. Carroll, VS; Carvey, PM; Gilley, D; Goetz, CG; Klawans, HL; Shannon, KM; Tanner, CM, 1988) | 0.27 |
| " Daily dosage frequency was significantly reduced with SINEMET CR compared with SINEMET 25/100, while the daily amount of levodopa required with SINEMET CR was significantly greater." | ( Treatment of chronic Parkinson's disease with controlled-release carbidopa/levodopa. Elias, JW; Hutton, JT; Imke, SC; Morris, JL; Román, GC, 1988) | 0.27 |
| "In five patients with parkinsonism, the optimal dosage of a controlled-release levodopa/carbidopa preparation (CR-3) was three times higher than the dosage of Sinemet and produced higher plasma levodopa concentrations, but did not reduce the fluctuations in plasma levodopa or clinical response." | ( Clinical and biochemical studies with controlled-release levodopa/carbidopa. Carter, JH; Nutt, JG; Woodward, WR, 1986) | 0.27 |
| " In the sixth year, it appeared necessary to increase the dosage in the first three groups." | ( Low-dosage treatment in de novo patients with Parkinson's disease: a prospective study. van der Drift, JH, 1987) | 0.27 |
| " We describe five patients in whom an apparent psychologic effect from levodopa prompted dosage escalation to the point of toxicity." | ( Sinemet "abusers". Nausieda, PA, 1985) | 0.27 |
| " In some subjects it is difficult to establish a clear relation between levodopa dosage and timing and the resultant clinical effects." | ( Complicated response fluctuations in Parkinson's disease: response to intravenous infusion of levodopa. Marsden, CD; Parkes, JD; Quinn, N, 1982) | 0.26 |
| " The relation of complications to dosage is now better understood, and the ratio of dopa-decarboxylase inhibitor to levodopa inhibitor to levodopa of 1:4 is better than the previous 1:10." | ( Sinemet and the treatment of Parkinsonism. Boshes, B, 1981) | 0.26 |
| " PRL increase after benserazide was compared with PRL response after carbidopa at the same dosage in untreated parkinsonian patients." | ( Prolactin response to acute administration of different L-dopa plus decarboxylase inhibitors in Parkinson's disease. Agnoli, A; Baldassarre, M; D'Urso, R; De Giorgio, G; Falaschi, P; Rocco, A; Ruggieri, S, 1982) | 0.26 |
| " Patients were maintained on a stable, therapeutically optimal dosage and schedule of levadopa-carbidopa (Sinemet) throughout the study." | ( Parkinson's disease: Cogentin with Sinemet, a better response. Gilden, ER; Hansch, EC; Hirsch, SB; Potvin, AR; Potvin, JH; Syndulko, K; Tourtellotte, WW, 1982) | 0.26 |
| "We characterized the clinical dose-response curves for relief of parkinsonism and production of dyskinesias as a function of plasma levodopa and 3-O-methyldopa levels in six patients with advanced Parkinson's disease (PD) and fluctuating responses to oral levodopa/carbidopa." | ( Suppression of dyskinesias in advanced Parkinson's disease. I. Continuous intravenous levodopa shifts dose response for production of dyskinesias but not for relief of parkinsonism in patients with advanced Parkinson's disease. Bennett, JP; Schuh, LA, 1993) | 0.29 |
| " Dosage titration occurred over the 5 years of evaluations to maintain an optimal response." | ( Comparison of immediate-release and controlled release carbidopa/levodopa in Parkinson's disease. A multicenter 5-year study. The CR First Study Group. Block, G; Irr, J; Liss, C; Nibbelink, D; Reines, S, 1997) | 0.3 |
| " As a consequence, levodopa dosage might be increased and the interdose interval progressively shortened." | ( Clinical implications of sustained dopaminergic stimulation. Barbato, L; Berardelli, A; Bonamartini, A; Manfredi, M; Patsalos, PN; Ruggieri, S; Stocchi, F, 1994) | 0.29 |
| " Daily levodopa dosage requirements decreased significantly." | ( Highlights of the North American and European experiences. Goetz, CG, 1998) | 0.3 |
| "Thirteen older amblyopic children were randomly assigned to receive or not receive part-time occlusion (3 h/day) combined with 7 weeks of oral dosing with levodopa-carbidopa (1." | ( Occlusion and levodopa-carbidopa treatment for childhood amblyopia. Bremer, DL; Leguire, LE; McGregor, ML; Rogers, GL; Walson, PD, 1998) | 0.3 |
| " In the 19 patients studied, there were negative correlations between dosage or absorption and extent of O-methylation and of sulfation of L-DOPA or its metabolites." | ( L-DOPA biotransformation: correlations of dosage, erythrocyte catechol O-methyltransferase and platelet SULT1A3 activities with metabolic pathways in Parkinsonian patients. Decker, PA; Dousa, MK; Muenter, MD; Offord, KP; Tyce, GM; Weinshilboum, RM, 2003) | 0.32 |
| " Twenty-one treated PD patients received LD/CD and then the identical oral LD dosage of LCE within a standardized setting on 2 consecutive days." | ( Inhibition of catechol-O-methyltransferase contributes to more stable levodopa plasma levels. Bremen, D; Erdmann, C; Muhlack, S; Müller, T; Przuntek, H; Woitalla, D, 2006) | 0.33 |
| " The present study was directed toward examining reach-to-eat movements in early PD patients untreated with medication, along with a follow-up examination of a PD patient sub-group who were treated with a symptomatically stable dosage of dopamine replacement." | ( Bilateral impairments of skilled reach-to-eat in early Parkinson's disease patients presenting with unilateral or asymmetrical symptoms. Doan, JB; Melvin, KG; Suchowersky, O; Whishaw, IQ, 2008) | 0.35 |
| "In this open-label naturalistic study, 75 PD patients (group A) completely switched standard LD (Sinemet or Madopar) with Sirio at an equivalent dosage (800-1000 mg/d)." | ( Clinical experiences with levodopa methylester (melevodopa) in patients with Parkinson disease experiencing motor fluctuations: an open-label observational study. Antonini, A; Guidi, M; Mancini, F; Martignoni, E; Pacchetti, C; Sciarretta, M; Stocchi, F; Zangaglia, R, ) | 0.13 |
| " This study demonstrates that gastric-retentive ER dosage forms may reduce dose frequency while minimizing the plasma peak-to-trough fluctuation and consequently reduce motor fluctuation in patients with Parkinson's disease." | ( Pharmacokinetics of levodopa/carbidopa delivered from gastric-retentive extended-release formulations in patients with Parkinson's disease. Chen, C; Cowles, VE; Illarioshkin, SN; Stolyarov, ID; Sweeney, M, 2012) | 0.38 |
| " This case report serves as a reminder of the importance that patients receive their anti-Parkinsonian medications perioperatively, and highlights the potential benefits of inserting a gastric tube to continue anti-Parkinson's medication dosing during prolonged surgery." | ( Nasogastric medication for perioperative Parkinson's rigidity during anaesthesia emergence. Grice, T; Stagg, P, 2011) | 0.37 |
| " Dosage of the drug was stable over time." | ( Levodopa/carbidopa intestinal gel infusion long-term therapy in advanced Parkinson's disease. Johansson, A; Klangemo, K; Nyholm, D, 2012) | 0.38 |
| " The microtablets are intended for individualized dosing of levodopa/carbidopa in Parkinson disease by means of an electronic dose dispenser with a built-in diary for symptom registration." | ( Pharmacokinetics of levodopa/carbidopa microtablets versus levodopa/benserazide and levodopa/carbidopa in healthy volunteers. Aquilonius, SM; Bäckström, T; Ehrnebo, M; Gomes-Trolin, C; Lewander, T; Nyholm, D; Nyström, C; Panagiotidis, G, ) | 0.13 |
| "For best symptom management, careful consideration should be given to scheduling surgery at the earliest possible time, administering medications as close to the patient's usual dosing schedule as possible, and providing nursing education about optimal medication management for this patient population." | ( Perioperative medication withholding in patients with Parkinson's disease: a retrospective electronic health records review. Anderson, LC; Fagerlund, K; Gurvich, O, 2013) | 0.39 |
| " Effects of escalating ropinirole dosage on plasma AVP levels were evaluated using a one-way analysis of variance for repeated measures, an a priori Dunnett multiple comparison test, and a regression analysis." | ( Ropinirole does not affect plasma arginine vasopressin levels in patients with advanced Parkinson's disease. Arai, M, 2012) | 0.38 |
| " There was no statistically significant dose-response relationship between the ropinirole dosage and plasma AVP levels." | ( Ropinirole does not affect plasma arginine vasopressin levels in patients with advanced Parkinson's disease. Arai, M, 2012) | 0.38 |
| "A minimal therapeutic dosage of ropinirole did not affect plasma AVP levels in patients with PD taking levodopa." | ( Ropinirole does not affect plasma arginine vasopressin levels in patients with advanced Parkinson's disease. Arai, M, 2012) | 0.38 |
| "Extended-release carbidopa-levodopa might be a useful treatment for patients with Parkinson's disease who have motor fluctuations, with potential benefits including decreased off-time and reduced levodopa dosing frequency." | ( Extended-release carbidopa-levodopa (IPX066) compared with immediate-release carbidopa-levodopa in patients with Parkinson's disease and motor fluctuations: a phase 3 randomised, double-blind trial. Espay, AJ; Gupta, S; Hauser, RA; Hsu, A; Kell, S; O'Connell, M; Ondo, W; Sethi, K; Stacy, M, 2013) | 0.39 |
| " Staff familiarity with Parkinson disease, and especially carbidopa-levodopa dosing and dynamics, may prevent such problems and streamline hospital and nursing home care." | ( Parkinson disease treatment in hospitals and nursing facilities: avoiding pitfalls. Ahlskog, JE, 2014) | 0.4 |
| " Their median daily LD dosage was 1495 mg from IPX066 and 600 mg from CL + E, corresponding, after correction for bioavailability, to an approximately 22% higher LD exposure on IPX066." | ( Comparison of IPX066 with carbidopa-levodopa plus entacapone in advanced PD patients. Dillmann, U; Ellenbogen, A; Gupta, S; Hsu, A; Kell, S; Khanna, S; Liang, G; Mahler, A; Rubens, R; Stocchi, F, 2014) | 0.4 |
| " Both patients exhibited the clinical features of serotonin syndrome, coinciding with an increase in dosage of each drug." | ( Serotonin syndrome in stroke patients. Chang, MC; Jang, SH; Kwon, YM, 2015) | 0.42 |
| "Thirty-four patients were enrolled; mean baseline L-dopa dosage was 968 mg/d." | ( Gastroretentive carbidopa/levodopa, DM-1992, for the treatment of advanced Parkinson's disease. Chen, C; Cowles, VE; Stover, N; Sweeney, M; Verhagen Metman, L, 2015) | 0.42 |
| "DM-1992 was associated with a reduction in %OFF time compared with CD/L-dopa IR despite a reduced dosing frequency." | ( Gastroretentive carbidopa/levodopa, DM-1992, for the treatment of advanced Parkinson's disease. Chen, C; Cowles, VE; Stover, N; Sweeney, M; Verhagen Metman, L, 2015) | 0.42 |
| " Early PD patients were titrated to an appropriate dosing regimen while advanced patients started with regimens established in the antecedent studies." | ( Long-Term Treatment with Extended-Release Carbidopa-Levodopa (IPX066) in Early and Advanced Parkinson's Disease: A 9-Month Open-Label Extension Trial. Dzyak, L; Gupta, S; Hsu, A; Kell, S; Khanna, S; Nausieda, P; Rudzinska, M; Silver, DE; Spiegel, J; Tsurkalenko, ES; Waters, CH, 2015) | 0.42 |
| " IPX066 was designed to rapidly attain therapeutic LD concentrations and maintain them to allow a dosing interval of ∼6 hours." | ( Conversion to IPX066 from Standard Levodopa Formulations in Advanced Parkinson's Disease: Experience in Clinical Trials. Elmer, L; Gil, RA; Gupta, S; Hsu, A; Kell, S; Khanna, S; Modi, NB; Nausieda, PA; Rubens, R; Singer, C; Spiegel, J, 2015) | 0.42 |
| "To extensively analyze the dosing data collected in IPX066 studies during open-label conversions from IR CD-LD alone or with entacapone (CLE) and identify patterns relevant for managing conversion in the clinical setting." | ( Conversion to IPX066 from Standard Levodopa Formulations in Advanced Parkinson's Disease: Experience in Clinical Trials. Elmer, L; Gil, RA; Gupta, S; Hsu, A; Kell, S; Khanna, S; Modi, NB; Nausieda, PA; Rubens, R; Singer, C; Spiegel, J, 2015) | 0.42 |
| " Suggested initial dosing conversion tables based on prior LD daily dosage were provided." | ( Conversion to IPX066 from Standard Levodopa Formulations in Advanced Parkinson's Disease: Experience in Clinical Trials. Elmer, L; Gil, RA; Gupta, S; Hsu, A; Kell, S; Khanna, S; Modi, NB; Nausieda, PA; Rubens, R; Singer, C; Spiegel, J, 2015) | 0.42 |
| " A dose-response relationship is established for carbidopa-levodopa extended-release capsules (IPX066) in levodopa-naive Parkinson disease patients using a disease progression model." | ( Dose-Response Analysis of the Effect of Carbidopa-Levodopa Extended-Release Capsules (IPX066) in Levodopa-Naive Patients With Parkinson Disease. Mao, ZL; Modi, NB, 2016) | 0.43 |
| " It is critical to understand the appropriate conversion of the carbidopa/levodopa daily dosages to the CLES dosage and how to program the pump and titrate CLES to achieve the most effective dose." | ( Outpatient titration of carbidopa/levodopa enteral suspension (Duopa). Lyons, KE; Pahwa, R, 2017) | 0.46 |
| " Examples and a case study to illustrate how pharmacokinetics and pharmacodynamics contributed to the selection of dosing regimens, demonstration of an improved therapeutic effect, or regulatory approval of an improved product label are presented." | ( Application of Pharmacokinetics and Pharmacodynamics in Product Life Cycle Management. A Case Study with a Carbidopa-Levodopa Extended-Release Formulation. Modi, NB, 2017) | 0.46 |
| "IPX066 (Rytary®; carbidopa and levodopa [CD-LD] extended-release capsules) was designed to achieve therapeutic LD plasma concentrations within 1h of dosing and maintain LD concentrations for a prolonged duration in early or advanced Parkinson's disease (PD)." | ( Conversion to carbidopa and levodopa extended-release (IPX066) followed by its extended use in patients previously taking controlled-release carbidopa-levodopa for advanced Parkinson's disease. Duker, AP; Ellenbogen, A; Farbman, ES; Gupta, S; Hauser, RA; Hsu, A; Kell, S; Khanna, S; Kreitzman, D; Liang, GS; Nausieda, P; Nieves, A; Rubens, R; Tetrud, J, 2017) | 0.46 |
| "To evaluate individualized levodopa/carbidopa dosing using microtablets dispensed with a dose dispenser, with respect to efficacy and usability as perceived by patients." | ( First clinical experience with levodopa/carbidopa microtablets in Parkinson's disease. Albo, J; Hellström, M; Nyholm, D; Senek, M; Svenningsson, P, 2017) | 0.46 |
| "A new extended release levodopa capsule (C/L ERC), Rytary®, has demonstrated improved "on" time in fluctuating Parkinson's disease patients, compared to optimally dosed immediate release levodopa." | ( Conversion of L-dopa to Extended Release L-dopa (Rytary®) in Patients with Fluctuating Parkinson's Disease: Predictors of Dose. Christie, M; Coss, P; Ondo, W; Pascual, B, 2019) | 0.51 |
| " This study proposes a dosing algorithm for oral administration of levodopa and evaluates its integration into a sensor-based dosing system (SBDS)." | ( Sensor-based algorithmic dosing suggestions for oral administration of levodopa/carbidopa microtablets for Parkinson's disease: a first experience. Alam, M; Bergquist, F; Johansson, D; Memedi, M; Nyholm, D; Thomas, I; Westin, J, 2019) | 0.51 |
| " The SBDS uses data from wearable sensors to fit individual patient models, which are then used as input to the dosing algorithm." | ( Sensor-based algorithmic dosing suggestions for oral administration of levodopa/carbidopa microtablets for Parkinson's disease: a first experience. Alam, M; Bergquist, F; Johansson, D; Memedi, M; Nyholm, D; Thomas, I; Westin, J, 2019) | 0.51 |
| "This study shows that it is possible to use algorithmic sensor-based dosing adjustments to optimize treatment with oral medication for PD patients." | ( Sensor-based algorithmic dosing suggestions for oral administration of levodopa/carbidopa microtablets for Parkinson's disease: a first experience. Alam, M; Bergquist, F; Johansson, D; Memedi, M; Nyholm, D; Thomas, I; Westin, J, 2019) | 0.51 |
| " Using a randomized, double-blind, 2-way crossover design, eligible patients in the morning OFF state (having not received PD medication overnight) received a single dose of CVT-301 84 mg or placebo on 2 dosing days, immediately after their first morning oral carbidopa/levodopa dose." | ( Orally inhaled levodopa (CVT-301) for early morning OFF periods in Parkinson's disease. Ellenbogen, A; Hauser, RA; Isaacson, SH; Kegler-Ebo, DM; Komjathy, SF; Oh, C; Safirstein, BE; Truong, DD; Zhao, P, 2019) | 0.51 |
| "ND0612 is a continuous, subcutaneous levodopa/carbidopa delivery system in development for patients with Parkinson's disease (PD) experiencing motor fluctuationsObjective:Evaluate the efficacy and safety of two ND0612 dosing regimens in patients with PD." | ( Continuous Subcutaneous Levodopa Delivery for Parkinson's Disease: A Randomized Study. Adar, L; Case, RJ; Ellenbogen, AL; Espay, AJ; Leinonen, M; Olanow, CW; Oren, S; Orenbach, SF; Poewe, W; Stocchi, F; Yardeni, T, 2021) | 0.62 |
| Timeframe | Studies, This Drug (%) | All Drugs % |
|---|---|---|
| pre-1990 | 135 (19.77) | 18.7374 |
| 1990's | 147 (21.52) | 18.2507 |
| 2000's | 47 (6.88) | 29.6817 |
| 2010's | 298 (43.63) | 24.3611 |
| 2020's | 56 (8.20) | 2.80 |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be strong demand-to-supply ratio for research on this compound.
| This Compound (43.54) All Compounds (24.57) |
| Publication Type | This drug (%) | All Drugs (%) |
|---|---|---|
| Trials | 153 (20.79%) | 5.53% |
| Reviews | 74 (10.05%) | 6.00% |
| Case Studies | 186 (25.27%) | 4.05% |
| Observational | 20 (2.72%) | 0.25% |
| Other | 303 (41.17%) | 84.16% |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
| Trial | Phase | Enrollment | Study Type | Start Date | Status | ||
|---|---|---|---|---|---|---|---|
| An Open-Label, 12-Month Safety and Efficacy Study of Levodopa - Carbidopa Intestinal Gel in Levodopa-Responsive Subjects With Advanced Parkinson's Disease and Severe Motor Fluctuations Despite Optimized Treatment With Available Parkinson's Disease Medicat [NCT00335153] | Phase 3 | 354 participants (Actual) | Interventional | 2008-01-31 | Completed | ||
| A Phase 1 Single-Dose, Open-label, Sequential, Three-Period Crossover Study to Evaluate the Pharmacokinetics of WD-1603 Tablets in Healthy Subjects [NCT03761004] | Phase 1 | 8 participants (Actual) | Interventional | 2019-01-14 | Completed | ||
| A Randomized, Multiple Dose Study to Assess the Pharmacokinetics and Pharmacodynamics of IPX203 in Subjects With Advanced Parkinson's Disease [NCT03007888] | Phase 2 | 28 participants (Actual) | Interventional | 2016-11-14 | Completed | ||
| Clinical Study to Compare the Possible Safety and Efficacy of Pentoxifylline in Patients With Parkinson's Disease Treated With Conventional Treatment [NCT05962957] | Phase 2 | 50 participants (Anticipated) | Interventional | 2023-08-07 | Recruiting | ||
| A Phase Ib Safety, Tolerability, and Efficacy Study of Two Days of Oral Split Dose (25/20 mg) Administration of PF 06412562 in Subjects With Advanced Stage Parkinson's Disease [NCT03665454] | Phase 1 | 8 participants (Actual) | Interventional | 2018-09-24 | Completed | ||
| An Open Label Phase 2 Study to Assess the Pharmacokinetics of the Accordion Pill Carbidopa-Levodopa Compared to Immediate Release Carbidopa-Levodopa in Patients With Parkinson's Disease [NCT03576638] | Phase 2 | 12 participants (Anticipated) | Interventional | 2018-07-31 | Not yet recruiting | ||
| An Open-label, Randomized 26-Week Study Comparing Levodopa-Carbidopa INteStInal Gel (LCIG) THerapy to Optimized Medical Treatment (OMT) on Non-Motor Symptoms (NMS) in Subjects With Advanced Parkinson's Disease - INSIGHTS Study [NCT02549092] | Phase 3 | 89 participants (Actual) | Interventional | 2015-10-26 | Completed | ||
| Study of the Efficacy of Co-administration of an NSAID With a Dopamine Agonist in the Alleviation of Acute Cutaneous Inflammatory Pain in Healthy Subjects [NCT02116790] | Phase 2 | 0 participants (Actual) | Interventional | 2014-05-31 | Withdrawn | ||
| Randomized, Multi-center, Open-label, Crossover Pharmacokinetic Study of CVT-301 (Levodopa Inhalation Powder) and an Oral Dose of Carbidopa/Levodopa CD/LD Under Fed Conditions in Patients With Parkinson's Disease [NCT03887884] | Phase 1 | 23 participants (Actual) | Interventional | 2019-03-05 | Completed | ||
| A Long-term Health Economics Study of Intraduodenal Levodopa (Duodopa®) in Routine Care for Patients With Advanced Idiopathic Parkinson's Disease With Severe Motor Fluctuations and Hyper-/Dyskinesia [NCT00141518] | Phase 4 | 77 participants (Actual) | Interventional | 2006-03-31 | Completed | ||
| 1/2-Dopaminergic Dysfunction in Late-Life Depression (The D3 Study) [NCT04493320] | Phase 4 | 5 participants (Actual) | Interventional | 2021-02-10 | Terminated(stopped due to Study terminated by sponsor (NIMH)) | ||
| Targeting Dopaminergic Mechanisms of Slowing to Improve Late Life Depression [NCT03761030] | Phase 4 | 51 participants (Actual) | Interventional | 2019-01-09 | Terminated(stopped due to The project end date was reached prior to the full sample enrollment) | ||
| A Single Period Investigation to Assess the Tolerability of Healthy Subjects to Oral Sinemet® (Levodopa/Carbidopa) Doses Administered Using a Divided Dose Approach [NCT02486432] | Phase 1 | 6 participants (Actual) | Interventional | 2015-04-30 | Completed | ||
| Gait Pattern Analysis in Neurological Disease [NCT02994719] | 120 participants (Anticipated) | Observational | 2016-03-01 | Active, not recruiting | |||
| Research on Translational Outcomes of Alcohol (Project RETRO) [NCT04742348] | Phase 4 | 0 participants (Actual) | Interventional | 2023-02-28 | Withdrawn(stopped due to COVID-19 and expiration of funding) | ||
| An Open-label, Randomized 12 Week Study Comparing Efficacy of Levodopa-Carbidopa Intestinal Gel/Carbidopa-Levodopa Enteral Suspension and Optimized Medical Treatment on Dyskinesia in Subjects With Advanced Parkinson's Disease DYSCOVER (DYSkinesia COmparat [NCT02799381] | Phase 3 | 63 participants (Actual) | Interventional | 2017-02-09 | Completed | ||
| An Exploratory Pharmacokinetic, Pharmacodynamic and Safety Study of XP21279 (With Lodosyn®) and Sinemet® in Parkinson's Disease Subjects With Motor Fluctuations [NCT00914602] | Phase 1/Phase 2 | 14 participants (Actual) | Interventional | 2009-05-31 | Completed | ||
| A Phase 1, Open-Label Study to Assess the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Repeated Doses of Opicapone, and Effect on Levodopa Pharmacokinetics in Subjects With Parkinson's Disease [NCT03496870] | Phase 1 | 16 participants (Actual) | Interventional | 2018-02-08 | Completed | ||
| [NCT01291537] | Phase 2 | 56 participants (Actual) | Interventional | 2011-11-30 | Completed | ||
| Levodopa Pharmacokinetics in Patients With Parkinson's Disease and Symptom Fluctuation: A Phase I, Open-label, Randomized, Multicentre, Crossover Study Comparing Intravenous and Subcutaneous Infudopa With Intestinal Duodopa [NCT03419806] | Phase 1 | 25 participants (Actual) | Interventional | 2018-02-16 | Completed | ||
| Treating Early Stage Diabetic Retinopathy [NCT05132660] | Early Phase 1 | 244 participants (Anticipated) | Interventional | 2022-07-01 | Enrolling by invitation | ||
| A Randomized, Double-Blind, Double-Dummy, Efficacy, Safety and Tolerability Study of Levodopa - Carbidopa Intestinal Gel in Levodopa-Responsive Parkinson's Subjects Receiving Optimized Treatments With Parkinson Medicinal Products Who Continue to Experienc [NCT00357994] | Phase 3 | 36 participants (Actual) | Interventional | 2009-01-31 | Completed | ||
| An Open Label Extension Study of the Safety and Clinical Utility of IPX066 in Subjects With Parkinson's Disease [NCT01096186] | Phase 3 | 617 participants (Actual) | Interventional | 2010-03-31 | Completed | ||
| Pilot Study of L-DOPA Safety and Tolerability in Patients With AMD, and Proof of Concept That L-DOPA Improves Surrogate Biomarkers in Patients With Moderate to Advanced AMD [NCT02873351] | Phase 2 | 0 participants (Actual) | Interventional | 2019-09-30 | Withdrawn(stopped due to Decided to do studies in patients with AMD) | ||
| Common Noradrenergic Mechanisms in Parkinson´s Disease and L-DOPA Induced Dyskinesia and Healthy Age Matched Controls; [11C]Yohimbine and [11C]MeNER PET [NCT02578849] | 45 participants (Anticipated) | Observational | 2012-01-31 | Recruiting | |||
| The Effect of L-Dopa on the Progression of Retinitis Pigmentosa [NCT02837640] | Phase 2 | 50 participants (Anticipated) | Interventional | 2016-06-30 | Recruiting | ||
| Open-label, Two-treatment, 4-period Replicated Crossover Study in Healthy Subjects to Investigate the Plasma Pharmacokinetics of Levodopa and Carbidopa After Oral Administration of Single Doses of Two Fixed-dose Combination Products [NCT02116465] | Phase 1 | 12 participants (Actual) | Interventional | 2014-03-31 | Completed | ||
| A Double-blind, Randomised, Placebo-controlled Study in Healthy Volunteers to Investigate the Tolerability and Pharmacokinetics of Rising Single-doses of BIA 6-512 and Their Effect on the Levodopa Pharmacokinetics When Administered in Combination With a S [NCT03091868] | Phase 1 | 80 participants (Actual) | Interventional | 2004-11-03 | Completed | ||
| Extension of Protocol 002, Carbidopa-levodopa in Neovascular Extension of Protocol 002, Carbidopa-levodopa in Neovascular AMD [NCT03197493] | Phase 2 | 32 participants (Actual) | Interventional | 2017-08-01 | Completed | ||
| Dopaminergic Therapy for Inflammation-Related Anhedonia in Depression [NCT04723147] | Phase 4 | 20 participants (Actual) | Interventional | 2021-01-29 | Completed | ||
| Open-Label, 12-Month Safety and Efficacy Study of Levodopa - Carbidopa Intestinal Gel in Levodopa-Responsive Parkinson's Disease Subjects [NCT00360568] | Phase 3 | 62 participants (Actual) | Interventional | 2009-06-30 | Completed | ||
| A Phase 1 Single Dose Pharmacokinetic Bridging Study to Compare Two Dose Strengths of CVT-301 (Levodopa Inhalation Powder) With an Oral Dose of Sinemet® (Carbidopa-levodopa) Tablets [NCT02812394] | Phase 1 | 24 participants (Actual) | Interventional | 2016-06-30 | Completed | ||
| Observational, Cross-sectional Clinical Study in Parkinson's Disease (PD) Patients and Healthy Controls (HC) to Identify PD Specific Microbial and Metabolic Fingerprints in Small Intestinal (SI) Fluid and Blood [NCT06003608] | 100 participants (Anticipated) | Observational | 2023-10-31 | Not yet recruiting | |||
| Pharmacokinetic-pharmacodynamic Interaction Between Three Different Single Doses of BIA 3-202 and a Single Dose of Controlled-release 200/50 mg Levodopa/Carbidopa (Sinemet® cr 200/50): a Double-blind, Randomised, Four-way Crossover, Placebo-controlled Stu [NCT02774564] | Phase 1 | 16 participants (Actual) | Interventional | 2005-09-30 | Completed | ||
| A Double-blind, Randomised, Placebo- and Active-controlled, Cross-over Study to Investigate the Effect of Two Multiple-dose Regimens of BIA 3-202 on the Pharmacokinetics and Motor Response of Levodopa, and on the Erythrocyte Comt Activity in Parkinson's D [NCT02834507] | Phase 2 | 19 participants (Actual) | Interventional | 2005-03-31 | Completed | ||
| A Placebo-Controlled Study To Evaluate The Safety And Efficacy Of IPX066 In Subjects With Parkinson's Disease [NCT00880620] | Phase 3 | 381 participants (Actual) | Interventional | 2009-04-30 | Completed | ||
| Pharmacokinetic-Pharmacodynamic Interaction Between Four Different Single Doses of BIA 3-202 and a Single Dose of Levodopa/Carbidopa (100/25 mg): a Double-blind, Randomised, Crossover, Placebo Controlled Study in Healthy Volunteers [NCT02763839] | Phase 1 | 19 participants (Actual) | Interventional | 2001-04-30 | Completed | ||
| Dual Release Gastric Retentive AP09004, Vs. Active Control; a Pharmacokinetic/Pharmacodynamic, Comparative, Safety Evaluation in Parkinson's Patients [NCT00918177] | Phase 2 | 72 participants (Anticipated) | Interventional | 2009-07-31 | Completed | ||
| 1) To Identify the Concentration of CD That Provides Optimal Bioavailability of a Concomitant Fixed Concentration of LD Infused SC Continuously; 2) To Compare the Bioavailability of the Optimal LD/CD Solution to That of LD/CD Intestinal Gel [NCT02604914] | Phase 1 | 36 participants (Actual) | Interventional | 2015-05-31 | Completed | ||
| An Open-Label,Multi-Center, Follow-Up Study Designed to Evaluate the Long-Term Effects of AP-CD/LD in Fluctuating Parkinson's Disease Subjects Who Completed Study IN 11 004 [NCT02615873] | Phase 3 | 460 participants (Anticipated) | Interventional | 2016-07-31 | Recruiting | ||
| Phase 3 Multicenter Randomized Double-Blind, Double-dummy, Active-Controlled Study Comparing Efficacy/Safety of Gastric-retentive, Controlled-release Accordion Pill Carbidopa/Levodopa to Immediate Release in Fluctuating Parkinson's Patients [NCT02605434] | Phase 3 | 420 participants (Anticipated) | Interventional | 2016-03-31 | Active, not recruiting | ||
| Neurobiological Principles Applied to the Rehabilitation of Stroke Patients [NCT00715520] | 33 participants (Actual) | Interventional | 2007-04-30 | Completed | |||
| A Randomized, Double-Blind, Double-Dummy, Efficacy, Safety and Tolerability Study of Levodopa - Carbidopa Intestinal Gel in Levodopa-Responsive Parkinson's Subjects Receiving Optimized Treatments With Parkinson Medicinal Products Who Continue to Experienc [NCT00660387] | Phase 3 | 35 participants (Actual) | Interventional | 2009-12-31 | Completed | ||
| Dopaminergic Dysfunction in Late-Life Depression [NCT04469959] | Phase 2 | 80 participants (Anticipated) | Interventional | 2021-02-15 | Recruiting | ||
| Treatment in Advanced Parkinson's Disease: Continuous Intrajejunal Levodopa INfusion VErsus Deep Brain STimulation [NCT02480803] | Phase 4 | 66 participants (Anticipated) | Interventional | 2014-12-19 | Active, not recruiting | ||
| An 8-week, Prospective, Randomized, Double-blind, Double-dummy, Active-controlled, Multi-center Comparison Study of the Effects of Carbidopa/Levodopa/Entacapone Versus Immediate Release Carbidopa/Levodopa on Non-motor Symptoms in Patients With Idiopathic [NCT00642356] | Phase 4 | 14 participants (Actual) | Interventional | 2008-03-31 | Terminated(stopped due to slow enrollment) | ||
| A Long Term, Double-blind, Randomized, Parallel-group, Carbidopa/Levodopa Controlled, Multi-center Study to Evaluate the Effect of Carbidopa/Levodopa/Entacapone in Patients With Parkinson's Disease Requiring Initiation of Levodopa Therapy [NCT00099268] | Phase 3 | 747 participants (Actual) | Interventional | 2004-09-30 | Completed | ||
| Levodopa Concentration Profile After Repeated Doses of Different Stalevo® Strengths With 3.5 Hours Dosing Frequency; an Open, Randomised, Crossover, Levodopa/Carbidopa Controlled Single Centre Study in Healthy Subjects, Two Parallel Groups [NCT01070628] | Phase 1 | 20 participants (Anticipated) | Interventional | 2009-12-31 | Completed | ||
| Effects of Single Doses of Stalevo 200 and Levodopa/Carbidopa 200/50mg on Striatal 11C-Raclopride Binding Potential in Parkinson's Disease Patients With Wearing-Off Symptoms;an Open, Randomised, Active-Controlled,Two-Period Crossover Study. [NCT00562198] | Phase 2 | 16 participants (Anticipated) | Interventional | 2008-01-31 | Terminated(stopped due to Illogistical results found in interim evaluation.) | ||
| Evaluation and Treatment of Autonomic Failure. [NCT00223691] | Phase 1 | 389 participants (Actual) | Interventional | 2002-03-31 | Completed | ||
| The Role of Dopamine in the Central Neural Signature of Chronic Pain [NCT05285683] | Phase 2 | 10 participants (Anticipated) | Interventional | 2023-01-01 | Recruiting | ||
| The Effects of Mood Symptoms Treatment on Quality of Life and Motor Function in de Novo Parkinson's Disease Patients [NCT04590612] | 30 participants (Anticipated) | Interventional | 2021-01-31 | Not yet recruiting | |||
| An Open Label, Balanced, Randomised, Four-treatment, Four-period, Four-sequence, Single Oral Dose, Crossover PK Study of WD-1603 in Normal, Healthy, Adult Human Subjects Under Fed Conditions [NCT04591535] | Phase 1 | 8 participants (Anticipated) | Interventional | 2020-09-28 | Recruiting | ||
| Carbidopa-Levodopa in Dry Age Related Macular Degeneration With Geographic Atrophy [NCT03451500] | Phase 2 | 7 participants (Actual) | Interventional | 2018-07-01 | Active, not recruiting | ||
| A Study to Assess the Pharmacokinetics and Pharmacodynamics of a Single Dose of IPX203 in Patients With Advanced Parkinson's Disease [NCT02271503] | Phase 2 | 26 participants (Actual) | Interventional | 2015-11-30 | Completed | ||
| Transition From Acute to Chronic Back Pain : Effect of L-dopa,Gender,and Associated Brain Plasticity [NCT04082715] | Phase 2 | 0 participants (Actual) | Interventional | 2019-10-31 | Withdrawn(stopped due to we don't have enough research funding.) | ||
| The Effect of Dopamine on Diabetic Retinopathy [NCT02706977] | Phase 1 | 60 participants (Actual) | Interventional | 2016-01-31 | Completed | ||
| A Study To Evaluate The Safety And Efficacy Of IPX066 In Advanced Parkinson's Disease [NCT00974974] | Phase 3 | 471 participants (Actual) | Interventional | 2009-09-30 | Completed | ||
| Comparison of Orally Dissolving Carbidopa/Levodopa (Parcopa) to Conventional Oral Carbidopa/Levodopa: A Single-Dose, Double-Blind, Double-Dummy, Placebo-Controlled, Crossover Trial [NCT00590122] | Phase 4 | 20 participants (Actual) | Interventional | 2006-10-31 | Completed | ||
| Pharmacokinetic-pharmacodynamic Interaction Between Each of Three Different Single Doses of BIA 9-1067 and a Single-dose of Controlled-release 100/25 mg Levodopa/Carbidopa: a Double-blind, Randomized, Four-way Crossover, Placebo-controlled Study in Health [NCT02169453] | Phase 1 | 12 participants (Actual) | Interventional | 2008-10-31 | Completed | ||
| A 12-Week, Multi-center, Randomized, Prospective, Open-Label, Blinded Rater, Crossover Study of the Effects of Immediate-Release Carbidopa/Levodopa Versus Carbidopa/Levodopa/Entacapone on Markers of Event-Related Potentials (ERPs) in Patients With Idiopat [NCT00601978] | Phase 4 | 0 participants (Actual) | Interventional | 2008-08-31 | Withdrawn(stopped due to Business decision brand strategy; no patients enrolled) | ||
| A Pharmacokinetic Study of Levodopa and Carbidopa Intestinal Gel in Subjects With Advanced Parkinson's Disease [NCT01484990] | Phase 1 | 19 participants (Actual) | Interventional | 2010-04-30 | Completed | ||
| A Randomized, Two-Way Crossover Study to Investigate the Bioavailability of a Single Oral Dose of 12.5 mg Carbidopa, 50 mg Levodopa and 200 mg Entacapone Compared to a Single Oral Combined Dose of Both 12.5 mg Carbidopa and 50 mg Levodopa and 200 mg Entac [NCT00415831] | Phase 1 | 42 participants | Interventional | 2006-06-30 | Completed | ||
| An Open Label, Multiple-Dose Study ot Determine the Plasma Levodopa Profiles of Sinemet® CR (Carbidopa/Levodopa) at 4 Daily Dose Levels in Healthy Subjects [NCT00460954] | 20 participants (Anticipated) | Observational | 2007-06-30 | Completed | |||
| A Single Center, Randomized, Double-blind, Crossover Pilot Trial Comparing the Onset of Action of Parcopa™ With Sinemet® in Subjects With Stable Parkinson's Disease [NCT00139880] | Phase 3 | 0 participants | Interventional | 2005-06-30 | Completed | ||
| An Efficacy, Safety, and Pharmacokinetics/Pharmacodynamic Relationship Study of L-Dopa/Carbidopa in a Novel Release Formulation in Parkinson's Disease Patients [NCT00558337] | Phase 2 | 78 participants (Actual) | Interventional | 2007-11-30 | Completed | ||
| A Study to Compare IPX066 and Carbidopa/Levodopa/Entacapone (CLE) Followed by an Open-Label Safety Study of IPX066 in Advanced Parkinson's Disease [NCT01130493] | Phase 3 | 110 participants (Actual) | Interventional | 2010-05-31 | Completed | ||
| A Single-blinded Assessment of the Short-term Effects of Cabergoline vs. Carbidopa/Levodopa on SPECT Dopamine Transporter Density in Out-patient Subjects With Parkinson's Disease [NCT00129181] | 30 participants (Actual) | Interventional | 2005-01-31 | Completed | |||
| A Multicenter, Open-label Trial to Assess Subject Preference of PARCOPA, Carbidopa/Levodopa Orally Disintegrating Tablets, Compared to Conventional Carbidopa/Levodopa Tablets in Subjects With Stable Parkinson's Disease [NCT00139867] | Phase 3 | 0 participants | Interventional | 2004-01-31 | Completed | ||
| A Prospective, Multi-center, Randomized, Open-label Study With Blinded Raters to Evaluate the Effects of Immediate Versus Delayed Switch to Carbidopa/Levodopa/Entacapone on Motor Function and Quality of Life in Patients With Parkinson's Disease With End-o [NCT00219284] | Phase 4 | 359 participants (Actual) | Interventional | 2005-01-31 | Completed | ||
| Acute Effects of Pharmacological Neuromodulation on Leg Motor Activity in Patients With Spinal Cord Injury Treated With Epidural Electrical Stimulation [NCT04052776] | Phase 1 | 3 participants (Actual) | Interventional | 2020-09-11 | Completed | ||
| A Study to Compare Pharmacokinetics and Pharmacodynamics of IPX066 to Standard Carbidopa-Levodopa [NCT00869791] | Phase 2 | 27 participants (Actual) | Interventional | 2008-11-30 | Completed | ||
| Sinemet in ALS and PLS [NCT03929068] | Phase 1 | 15 participants (Actual) | Interventional | 2019-05-13 | Completed | ||
| A Randomized, Two-Way Crossover Study to Investigate the Bioavailability of a Single Oral Dose of 12.5 mg Carbidopa, 50 mg Levodopa and 200 mg Entacapone Compared to a Single Oral Combined Dose of Both 12.5 mg Carbidopa and 50 mg Levodopa and 200 mg Entac [NCT00415740] | Phase 1 | 42 participants | Interventional | 2006-05-31 | Completed | ||
| A Randomized, Double-Blind, Placebo-Controlled, Crossover Study to Compare IPX054 200 mg and 250 mg to CD-LD IR 200 (2x100) mg Tablets and CD-LD CR 200 mg Tablet in Subjects With Parkinson's Disease [NCT00279825] | Phase 2 | 16 participants (Actual) | Interventional | 2006-01-31 | Completed | ||
| A Randomized, Two-Way Crossover Study to Investigate the Bioavailability of a Single Oral Dose of 25 mg Carbidopa, 100 mg Levodopa and 200 mg Entacapone Compared to a Single Oral Combined Dose of Both 25 mg Carbidopa and 100 mg Levodopa and 200 mg Entacap [NCT00415844] | Phase 1 | 42 participants | Interventional | 2006-06-30 | Completed | ||
| A Randomized, Two-Way Crossover Study to Investigate the Bioavailability of a Single Oral Dose of 37.5 mg Carbidopa, 150 mg Levodopa and 200 mg Entacapone Compared to a Single Oral Combined Dose of Both 37.5 mg Carbidopa and 150 mg Levodopa and 200 mg Ent [NCT00415922] | Phase 1 | 42 participants | Interventional | 2006-07-31 | Completed | ||
| Augmentation of Antipsychotics With L-Dopa (Sinemet) [NCT01636037] | Phase 2 | 13 participants (Actual) | Interventional | 2012-09-30 | Completed | ||
| A Phase 2, Randomized, Open-Label, Crossover Study to Compare DM-1992, a Novel Gastric-Retentive Extended-Release Formulation of Levodopa/Carbidopa, to an Immediate-Release Carbidopa Tablet in Patients With Advanced Parkinson's Disease With Motor Fluctuat [NCT01515410] | Phase 2 | 34 participants (Actual) | Interventional | 2012-01-31 | Completed | ||
| A Pilot Study of the Drug Effects on Brain Connectivity of Parkinson's Disease [NCT01528592] | 18 participants (Actual) | Interventional | 2011-06-30 | Completed | |||
| Clinical Study to Evaluate the Possible Efficacy of Metformin in Patients With Parkinson's Disease [NCT05781711] | Phase 2 | 60 participants (Anticipated) | Interventional | 2023-01-06 | Recruiting | ||
| Proof of Concept and Dose Ranging Study of Carbidopa-levodopa in Neovascular AMD [NCT03023059] | Phase 2 | 35 participants (Actual) | Interventional | 2017-05-02 | Completed | ||
| A Randomized Controlled Study to Compare the Safety and Efficacy of IPX203 With Immediate-Release Carbidopa-Levodopa in Parkinson's Disease Patients With Motor Fluctuations [NCT03670953] | Phase 3 | 630 participants (Actual) | Interventional | 2018-11-06 | Completed | ||
| A Phase 2 Efficacy, Safety and Pharmacokinetic Study of XP21279 BL2 and Sinemet® in Parkinson's Disease Subjects With Motor Fluctuations [NCT01171313] | Phase 2 | 35 participants (Actual) | Interventional | 2010-07-31 | Completed | ||
| Pharmacokinetic-pharmacodynamic Interaction Between Each of Three Diferente Single Doses of BIA 9-1067 and a Single-dose of Immediate-release 100/25 mg Levodopa/Carbidopa: a Doubleblind, Randomized, Four-way Crossover, Placebo-controlled Study in Healthy [NCT02169479] | Phase 1 | 16 participants (Actual) | Interventional | 2008-09-30 | Completed | ||
| Effect of Long-acting Levodopa on Obstructive Sleep Apnea in Parkinson's Disease [NCT03111485] | Phase 4 | 42 participants (Anticipated) | Interventional | 2017-05-24 | Recruiting | ||
| Project 1 Aim 2, Adaptations of the Brain in Chronic Pain With Opioid Exposure [NCT05463367] | Phase 2 | 80 participants (Anticipated) | Interventional | 2021-01-01 | Recruiting | ||
| An Open Label Conversion Study of Carbidopa-Levodopa (CD-LD) Extended-Release Taken Alone or in Combination With CD-LD Immediate Release to IPX066 Followed by an Open-Label Extension Safety Study of IPX066 in Advanced PD [NCT01411137] | Phase 3 | 43 participants (Actual) | Interventional | 2011-08-31 | Completed | ||
| A Phase IIa Study to Assess the Safety, Tolerability, Plasma Pharmacokinetics and Efficacy of Intermittent Oral Administration of Standard Levodopa/Carbidopa vs. Semi-continuous Intra-oral Administration of Levodopa/Carbidopa in Patients With Advanced Par [NCT02763137] | Phase 2 | 18 participants (Actual) | Interventional | 2014-07-30 | Completed | ||
| Open-Label Continuation Treatment Study With Levodopa - Carbidopa Intestinal Gel In Subjects With Advanced Parkinson's Disease And Severe Motor-Fluctuations Who Have Exhibited A Persistent And Positive Effect To Treatment In Previous Studies [NCT00660673] | Phase 3 | 262 participants (Actual) | Interventional | 2009-11-13 | Completed | ||
| "A Randomized, Placebo-Controlled, Phase 2 Study of the Safety, Pharmacokinetics and Pharmacodynamics of CVT-310 (Levodopa Inhalation Powder) in Patients With Parkinson's Disease and Motor Response Fluctuations (Off Episodes)" [NCT01617135] | Phase 2 | 25 participants (Actual) | Interventional | 2012-05-31 | Completed | ||
| Effect of Levodopa-Carbidopa on Visual Function in Patients With Recent-Onset Nonarteritic Anterior Ischemic Optic Neuropathy [NCT00432393] | Phase 4 | 0 participants | Interventional | 2002-06-30 | Completed | ||
| An Open-Label, Single-Arm, Baseline-Controlled, Multicenter Study to Evaluate the Efficacy, Safety and Tolerability of ABT-SLV187 Monotherapy in Subjects With Advanced Parkinson's Disease and Persistent Motor-Complications Despite Optimized Treatment With [NCT01960842] | Phase 3 | 31 participants (Actual) | Interventional | 2013-10-31 | Completed | ||
| A Phase 4, Open-Label, Efficacy and Safety Study of Apokyn® for Rapid and Reliable Improvement of Motor Symptoms in Parkinson Disease Subjects With Delayed Onset of L-Dopa Action [NCT01770145] | Phase 4 | 127 participants (Actual) | Interventional | 2012-12-31 | Completed | ||
| A Single Centre, Two-period, Open Label, Randomised, Cross-over Study to Assess Plasma Levodopa, Carbidopa and Entacapone Concentrations After Continuous Infusion of TRIGEL or Duodopa in Patients With Advanced Parkinson´s Disease [NCT02448914] | Phase 1 | 11 participants (Actual) | Interventional | 2015-05-31 | Completed | ||
| Combination Treatment With L-DOPA and Exercise for Mood and Mobility Problems in Late-Life [NCT04650217] | Phase 4 | 1 participants (Actual) | Interventional | 2021-10-07 | Terminated(stopped due to Study terminated by sponsor (NIMH)) | ||
| Effect of Serotonin and Levodopa Functional Recovery in Patients With Cerebral Infarction [NCT02386475] | Phase 4 | 39 participants (Actual) | Interventional | 2015-01-31 | Completed | ||
| An Open-label, Balanced, Randomized, Five-treatment, Five-period, Five-sequence, Multiple Oral Dose, Crossover Comparative Bioavailability Study of Different Strengths of Carbidopa/Levodopa Extended-release Tablets With Carbidopa and Levodopa Tablets in N [NCT05128175] | Phase 1 | 15 participants (Anticipated) | Interventional | 2021-10-29 | Recruiting | ||
| Pharmacokinetic Interaction Between BIA 9-1067 and Standard-release Levodopa/Carbidopa in Healthy Subjects [NCT01533077] | Phase 1 | 18 participants (Actual) | Interventional | 2009-03-31 | Completed | ||
| Short Term Effects of Carbidopa-levodopa in Neovascular AMD [NCT03022318] | Phase 2 | 21 participants (Actual) | Interventional | 2017-05-02 | Completed | ||
| Clinical Study to Investigate the Possible Efficacy and Safety of Montleukast in Parkinson Disease [NCT06113640] | Phase 2/Phase 3 | 60 participants (Anticipated) | Interventional | 2023-11-05 | Recruiting | ||
| A Phase II Randomized, Parallel, Double-blind, Placebo-controlled, Multi-center Clinical Trial of the Efficacy and Safety of WD-1603 Carbidopa-Levodopa Extended-Release Tablets in Patients With Parkinson's Disease [NCT05036473] | Phase 2 | 40 participants (Anticipated) | Interventional | 2021-10-12 | Recruiting | ||
| a Pilot Follow-up Study of Investigating the Effect of Pramipexole on Metabolic Network Activity Compared With Levodopa in Chinese Patients With Early Parkinson's Disease [NCT01470859] | 30 participants (Actual) | Interventional | 2011-12-31 | Completed | |||
| Corticostriatal Plasticity in the Transition to Chronic Pain: Effect of L-dopa [NCT01951105] | Phase 4 | 72 participants (Actual) | Interventional | 2015-02-24 | Completed | ||
| Imaging the Neurobiology of Behavioral and Medication Treatment for Cocaine Dependence [NCT01468012] | Phase 2/Phase 3 | 23 participants (Actual) | Interventional | 2014-07-31 | Completed | ||
| Vigor and the LDR in Parkinson Disease [NCT04821830] | 40 participants (Anticipated) | Observational | 2020-02-12 | Recruiting | |||
| Dopaminergic Enhancement of Rehabilitation Therapy Early After Stroke [NCT05369533] | Phase 1/Phase 2 | 72 participants (Anticipated) | Interventional | 2022-08-01 | Active, not recruiting | ||
| Dopaminergic Therapy for Inflammation-Related Anhedonia in Depression - 2 [NCT06075771] | Phase 4 | 70 participants (Anticipated) | Interventional | 2023-11-30 | Not yet recruiting | ||
| Novel Non-opioid Post-surgical Pain Treatment in Females [NCT05087914] | Phase 2 | 60 participants (Anticipated) | Interventional | 2021-11-01 | Recruiting | ||
| An Open-Label, Two Part, Multicenter Study to Assess the Safety and Efficacy of Levodopa-Carbidopa Intestinal Gel (LCIG) for the Treatment of Non-Motor Symptoms in Subjects With Advanced Parkinson's Disease [NCT01736176] | Phase 3 | 39 participants (Actual) | Interventional | 2013-03-31 | Completed | ||
| [information is prepared from clinicaltrials.gov, extracted Sep-2024] | |||||||
The PDQ-39 instrument is used to assess quality of life in individuals with Parkinson's disease. The questionnaire provides scores on eight scales: Mobility, activities of daily living, emotions, stigma, social support, cognition, communication, and bodily discomfort. Questions are scored on a 5-point Likert scale ranging from 1 (never) to 3 (sometimes) to 5 (always). The total score can range from 39 to 190. A lower score indicates better quality of life. A negative change score indicates an improvement. (NCT00099268)
Timeframe: Baseline to Week 156
| Intervention | Units on a scale (Mean) |
|---|---|
| Carbidopa/Levodopa/Entacapone | 4.1 |
| Carbidopa/Levodopa | 1.8 |
Wearing off is defined as a perception of loss of mobility or dexterity, usually taking place gradually over minutes (up to an hour) and usually bearing a close temporal relationship to the timing of anti-parkinsonian medications; it does not include early-morning akinesia. To ascertain its occurrence, a blinded rater questioned the patient whether he/she had noticed that the benefits of the study drug wear-off. A motor complications and patient questionnaire card were provided to assist the blinded rater in determining whether a patient had experienced wearing-off. (NCT00099268)
Timeframe: Baseline to end of study (134-208 weeks of treatment)
| Intervention | Weeks (Mean) |
|---|---|
| Carbidopa/Levodopa/Entacapone | 131.7 |
| Carbidopa/Levodopa | 129.5 |
The UPDRS is a standardized assessment scale used to measure the patient's disease state. It was to be completed by a blinded rater. There are 6 parts to the UPDRS. Part II (items 5-17; total score 0-52 units on the scale) measures the patient's activities of daily living and part III (items 18-31; total score 0-56 units on the scale) measures the motor function of the patient. The total score ranges from 0 to 108 units on the scale. A higher score indicates greater disability. A negative change score indicates improvement. (NCT00099268)
Timeframe: Baseline, Week 6 and Week 130
| Intervention | Units on a scale (Mean) | |
|---|---|---|
| Change from baseline to Week 6 | Change from baseline to Week 130 | |
| Carbidopa/Levodopa | 21.8 | 22.8 |
| Carbidopa/Levodopa/Entacapone | 21.9 | 23.2 |
"Dyskinesia was assessed by a blinded rater at each visit. Time to dyskinesia was defined as the visit at which the rater first answered yes to the following question: In your opinion, does this patient have dyskinesia? Time to dyskinesia was estimated by Kaplan-Meier product limit estimate that takes into consideration patients who did not experience dyskinesia by censoring them at the end of the study." (NCT00099268)
Timeframe: Treatment duration for an individual patient varied between a minimum of 134 weeks for those patients recruited last and a maximum of 208 weeks for those patients recruited first
| Intervention | weeks (Number) |
|---|---|
| Carbidopa/Levodopa/Entacapone | 90.7 |
| Carbidopa/Levodopa | 117.1 |
Wearing-off is defined as a perception of loss of mobility or dexterity, usually taking place gradually over minutes (up to an hour) and usually bearing a close temporal relationship to the timing of anti-parkinsonian medications; it does not include early-morning akinesia. To ascertain its occurrence, a blinded rater questioned the patient as to whether he/she had noticed that the benefits of the study drug were wearing-off. (NCT00099268)
Timeframe: Baseline to Week 134
| Intervention | Participants (Number) |
|---|---|
| Carbidopa/Levodopa/Entacapone | 139 |
| Carbidopa/Levodopa | 161 |
"Dyskinesia was assessed by a blinded rater at each visit. Time to dyskinesia was defined as the visit at which the rater first answered yes to the following question: In your opinion, does this patient have dyskinesia?" (NCT00099268)
Timeframe: Baseline to Week 208
| Intervention | Participants (Number) |
|---|---|
| Carbidopa/Levodopa/Entacapone | 128 |
| Carbidopa/Levodopa | 103 |
The MMSE is used to assess orientation, attention, immediate and short term recall, language, and ability to follow simple verbal and written commands. The Attention and Calculation subscale results in a total possible score of 0 to 5, with higher scores indicating better function. (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | units on a scale (Mean) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline (Month -3); n=26, 0, 0 | Month 0; n=27, 22, 18 | Month 3; n=24, 22, 18 | Month 6; n=25, 21, 18 | Month 9; n=25, 20, 17 | Month 12; n=25, 20, 17 | Month 18; n=24, 19, 16 | Month 24; n=23, 18, 15 | Month 30; n=23, 17, 13 | Month 36; n=21, 16, 12 | Endpoint; n=27, 22, 17 | |
| Duodopa Naïve | 4.9 | 4.6 | 4.6 | 4.6 | 4.7 | 4.7 | 4.5 | 4.6 | 4.6 | 4.2 | 4.2 |
| Duodopa Non-naïve < 2 Years | NA | 4.4 | 4.3 | 4.5 | 4.3 | 4.7 | 4.7 | 4.6 | 4.1 | 3.7 | 4.0 |
| Duodopa Non-naïve ≥ 2 Years | NA | 4.6 | 4.7 | 4.7 | 4.8 | 4.6 | 4.5 | 4.3 | 4.8 | 4.8 | 4.4 |
The Electronic Diary consisted of 15 items addressing motor performance, complication of therapy, self-assessment, and various types of tapping. Six conceptual dimensions were defined; four subjectively-reported: 'walking', 'satisfied', 'dyskinesia', and 'off' and two objectively-measured: 'tapping' and 'spiral'. Each of the items was assessed in the morning and during the day. 'Tapping at increased speed - accuracy' is the percentage of accurate taps per all taps on computer-generated fields. (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | percentage of accurate taps (Mean) | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Morning, Baseline (Month -3); n=20, 0, 0 | Day, Baseline (Month -3); n=20, 0, 0 | Morning, Month 0; n=19, 20, 15 | Day, Month 0; n=19, 20, 15 | Morning, Month 3; n=19, 18, 13 | Day, Month 3; n=19, 19, 13 | Morning, Month 6; n=16, 19, 11 | Day, Month 6; n=16, 19, 11 | Morning, Month 9; n=16, 17, 9 | Day, Month 9; n=16, 17, 9 | Morning, Month 12; n=16, 16, 9 | Day, Month 12; n=16, 16, 9 | Morning, Month 18; n=15, 14, 10 | Day, Month 18; n=15, 14, 10 | Morning, Month 24; n=13, 13, 7 | Day, Month 24; n=13, 13, 7 | Morning, Month 30; n=9, 9, 5 | Day, Month 30; n=9, 9, 5 | Morning, Month 36; n=6, 11, 5 | Day, Month 36; n=5, 11, 5 | Morning, Endpoint; n=23, 20, 16 | Day, Endpoint; n=23, 20, 16 | |
| Duodopa Naïve | 74.6 | 73.7 | 83.7 | 80.4 | 83.1 | 81.3 | 87.1 | 87.8 | 86.4 | 86.0 | 87.0 | 81.8 | 81.3 | 82.1 | 85.7 | 85.3 | 87.3 | 88.6 | 77.9 | 70.7 | 79.5 | 74.6 |
| Duodopa Non-naïve < 2 Years | NA | NA | 71.0 | 73.9 | 73.5 | 74.7 | 74.2 | 73.6 | 78.2 | 78.8 | 80.1 | 77.5 | 77.9 | 78.7 | 79.4 | 82.0 | 73.5 | 74.5 | 71.7 | 72.8 | 70.4 | 72.0 |
| Duodopa Non-naïve ≥ 2 Years | NA | NA | 73.2 | 73.2 | 68.8 | 69.3 | 73.3 | 73.0 | 77.1 | 75.6 | 74.6 | 72.4 | 71.4 | 72.1 | 69.0 | 70.0 | 79.8 | 80.6 | 81.0 | 77.9 | 68.0 | 67.5 |
"The Electronic Diary consisted of 15 items addressing motor performance, complication of therapy, self-assessment, and various types of tapping. Six conceptual dimensions were defined; four subjectively-reported: 'walking', 'satisfied', 'dyskinesia', and 'off' and two objectively-measured: 'tapping' and 'spiral'. Each of the items was assessed in the morning and during the day. 'Self-assessment' scores were -3 (Off) to +3 (dyskinetic). 'Off' time is when PD symptoms are not adequately controlled by the drug. 'Dyskinetic' time is time with involuntary muscle movement. 0 is defined as the normal ON state without dyskinesia (the desired motor state). Everything closer to 0 means improvement, everything more away from 0 means either less mobility (in the negative score) or involuntary movements (dyskinesia, in the positive score)." (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | units on a scale (Mean) | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Morning, Baseline (Month -3); n=20, 0, 0 | Day, Baseline (Month -3); n=20, 0, 0 | Morning, Month 0; n=19, 20, 15 | Day, Month 0; n=19, 20, 15 | Morning, Month 3; n=19, 18, 13 | Day, Month 3; n=19, 19, 13 | Morning, Month 6; n=16, 19, 11 | Day, Month 6; n=16, 19, 11 | Morning, Month 9; n=16, 17, 9 | Day, Month 9; n=16, 17, 9 | Morning, Month 12; n=16, 16, 9 | Day, Month 12; n=16, 16, 9 | Morning, Month 18; n=15, 14, 10 | Day, Month 18; n=15, 14, 10 | Morning, Month 24; n=13, 13, 7 | Day, Month 24; n=13, 13, 7 | Morning, Month 30; n=9, 9, 5 | Day, Month 30; n=9, 9, 5 | Morning, Month 36; n=6, 11, 5 | Day, Month 36; n=5, 11, 5 | Morning, Endpoint; n=23, 20, 16 | Day, Endpoint; n=23, 20, 16 | |
| Duodopa Naïve | -0.9 | -0.3 | -0.4 | -0.2 | -0.2 | -0.3 | -0.4 | -0.2 | -0.2 | 0.2 | -0.3 | -0.3 | -0.3 | -0.2 | -0.5 | -0.2 | -0.4 | -0.3 | -0.9 | -0.2 | -0.6 | -0.3 |
| Duodopa Non-naïve < 2 Years | NA | NA | -0.1 | -0.1 | -0.6 | -0.1 | -0.2 | 0.0 | -0.4 | -0.0 | -0.2 | 0.1 | 0.1 | -0.2 | -0.0 | -0.1 | -0.2 | -0.3 | -0.0 | 0.2 | -0.2 | -0.0 |
| Duodopa Non-naïve ≥ 2 Years | NA | NA | 0.2 | 0.1 | 0.0 | 0.3 | 0.3 | 0.3 | 0.4 | -0.1 | 0.4 | 0.1 | -0.0 | 0.1 | 0.1 | -0.0 | 0.2 | -0.3 | 0.3 | -0.2 | 0.2 | 0.2 |
The Electronic Diary consisted of 15 items addressing motor performance, complication of therapy, self-assessment, and various types of tapping. Six conceptual dimensions were defined; four subjectively-reported: 'walking', 'satisfied', 'dyskinesia', and 'off' and two objectively-measured: 'tapping' and 'spiral'. Each of the items was assessed in the morning and during the day. 'Satisfied with function' scores were 1 (worst) to 5 (best). (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | units on a scale (Mean) | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Morning, Baseline (Month -3); n=20, 0, 0 | Day, Baseline (Month -3); n=20, 0, 0 | Morning, Month 0; n=19, 20, 15 | Day, Month 0; n=19, 20, 15 | Morning, Month 3; n=19, 18, 13 | Day, Month 3; n=19, 19, 13 | Morning, Month 6; n=16, 19, 11 | Day, Month 6; n=16, 19, 11 | Morning, Month 9; n=16, 17, 9 | Day, Month 9; n=16, 17, 9 | Morning, Month 12; n=16, 16, 9 | Day, Month 12; n=16, 16, 9 | Morning, Month 18; n=15, 14, 10 | Day, Month 18; n=15, 14, 10 | Morning, Month 24; n=13, 13, 7 | Day, Month 24; n=13, 13, 7 | Morning, Month 30; n=9, 9, 5 | Day, Month 30; n=9, 9, 5 | Morning, Month 36; n=6, 11, 5 | Day, Month 36; n=5, 11, 5 | Morning, Endpoint; n=23, 20, 16 | Day, Endpoint; n=23, 20, 16 | |
| Duodopa Naïve | 2.5 | 2.6 | 3.3 | 3.4 | 3.4 | 3.5 | 3.5 | 3.6 | 3.4 | 3.5 | 3.6 | 3.5 | 3.4 | 3.5 | 3.4 | 3.6 | 3.6 | 3.5 | 3.4 | 3.5 | 3.2 | 3.4 |
| Duodopa Non-naïve < 2 Years | NA | NA | 3.2 | 3.4 | 3.0 | 3.4 | 3.3 | 3.4 | 3.3 | 3.4 | 3.4 | 3.6 | 3.4 | 3.6 | 3.6 | 3.5 | 3.4 | 3.6 | 3.3 | 3.5 | 3.3 | 3.4 |
| Duodopa Non-naïve ≥ 2 Years | NA | NA | 3.8 | 3.3 | 3.4 | 3.3 | 3.7 | 3.5 | 3.6 | 3.4 | 3.5 | 3.6 | 3.3 | 3.4 | 3.1 | 3.3 | 3.6 | 3.6 | 3.5 | 3.5 | 3.4 | 3.1 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. These include: mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness. (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | units on a scale (Mean) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline (Month -3); n=27, 0, 0 | Month 0; n=27, 22, 18 | Month 3; n=23, 22, 18 | Month 6; n=25, 20, 18 | Month 9; n=25, 20, 17 | Month 12; n=25, 20, 17 | Month 18; n=24, 20, 16 | Month 24; n=21, 17, 15 | Month 30; n=22, 16, 12 | Month 36; n=21, 15, 11 | Endpoint; n=26, 22, 17 | |
| Duodopa Naïve | 35.3 | 30.9 | 24.8 | 31.3 | 33.0 | 29.0 | 32.1 | 31.9 | 33.9 | 39.7 | 39.4 |
| Duodopa Non-naïve < 2 Years | NA | 27.1 | 27.5 | 33.3 | 32.1 | 34.8 | 30.2 | 37.7 | 33.3 | 30.0 | 31.1 |
| Duodopa Non-naïve ≥ 2 Years | NA | 37.7 | 35.4 | 35.9 | 34.8 | 38.0 | 32.6 | 33.1 | 31.3 | 38.6 | 39.7 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. These include: mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness. (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | units on a scale (Mean) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline (Month -3); n=27, 0, 0 | Month 0; n=27, 22, 18 | Month 3; n=23, 20, 18 | Month 6; n=25, 21, 18 | Month 9; n=24, 20, 17 | Month 12; n=25, 20, 17 | Month 18; n=24, 18, 16 | Month 24; n=21, 17, 15 | Month 30; n=22, 17, 12 | Month 36; n=21, 15, 11 | Endpoint; n=26, 21, 17 | |
| Duodopa Naïve | 55.7 | 38.8 | 36.0 | 39.5 | 40.2 | 41.0 | 40.9 | 46.0 | 50.9 | 57.3 | 55.6 |
| Duodopa Non-naïve < 2 Years | NA | 43.9 | 40.6 | 43.5 | 41.9 | 45.3 | 41.1 | 47.1 | 42.1 | 43.0 | 50.2 |
| Duodopa Non-naïve ≥ 2 Years | NA | 53.3 | 50.6 | 54.7 | 52.8 | 54.4 | 54.7 | 49.5 | 53.3 | 61.1 | 61.6 |
Drug costs include Duodopa cost and cost of concomitant anti-PD medication. Drug costs are a direct medical cost. The average rate for US Dollar (USD) to SEK on 31 December 2010 was 1 USD = 6.734 SEK. (NCT00141518)
Timeframe: Baseline (month -3) for Duodopa-naïve participants, then at Month 0, and monthly thereafter until study completion (up to 48 months) for all participants
| Intervention | SEK 2010 (Mean) |
|---|---|
| Duodopa Naïve | 39382 |
| Duodopa Non-naïve < 2 Years | 34417 |
| Duodopa Non-naïve ≥ 2 Years | 37679 |
| Total | 37339 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. These include: mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness. (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | units on a scale (Mean) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline (Month -3); n=27, 0, 0 | Month 0; n=27, 22, 18 | Month 3; n=24, 22, 18 | Month 6; n=25, 21, 18 | Month 9; n=25, 20, 17 | Month 12; n=25, 19, 17 | Month 18; n=24, 20, 16 | Month 24; n=21, 17, 15 | Month 30; n=21, 17, 12 | Month 36; n=21, 15, 11 | Endpoint; n=26, 22, 17 | |
| Duodopa Naïve | 24.8 | 16.2 | 16.1 | 20.8 | 15.5 | 17.8 | 15.6 | 15.8 | 16.4 | 20.5 | 19.5 |
| Duodopa Non-naïve < 2 Years | NA | 16.5 | 18.8 | 19.0 | 12.8 | 19.4 | 13.8 | 23.5 | 14.0 | 12.9 | 15.6 |
| Duodopa Non-naïve ≥ 2 Years | NA | 22.9 | 19.8 | 23.6 | 24.6 | 25.4 | 18.8 | 15.4 | 18.2 | 24.4 | 25.0 |
The UPDRS is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. For Parts I-III and Total Score, each question is measured on a 5-point scale of 0 (normal or no disease effect) to 4 (maximum negative effect); for Part IV, questions are measured on a 5- or 2-point scale (0 or 1). Part I score is the sum of answers to 'Mentation, Behavior and Mood' questions, with a score range from 0-16. Part II score is the sum of answers to 'Activities of Daily Living' questions, with a score range from 0-52. Part III score is the sum of answers to 'Motor Examination' questions, with a score range from 0-108. Part IV score is the sum of answers to 'Complications of Therapy' questions, with a score range from 0-23. Total Score is the sum of the responses to the 31 questions (44 answers) that comprise Parts I-III of the scale, with a score range from 0-176. Higher scores are associated with more disability. (NCT00141518)
Timeframe: Baseline (Month -3), Month 12
| Intervention | units on a scale (Mean) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Total Score, Baseline (Month -3); n=27, 0, 0 | Total Score, Month 12; n=25, 20, 17 | Part I, Baseline (Month -3); n=27, 0, 0 | Part I, Month 12; n=25, 20, 17 | Part II, Baseline (Month -3); n=27, 0, 0 | Part II, Month 12; n=25, 20, 17 | Part III, Baseline (Month -3); n=27, 0, 0 | Part III, Month 12; n=25, 20, 17 | Part IV, Baseline (Month -3); n=27, 0, 0 | Part IV, Month 12; n=25, 20, 17 | |
| Duodopa Naïve | 52.1 | 42.5 | 2.9 | 3.1 | 15.4 | 12.2 | 24.4 | 21.5 | 9.4 | 5.7 |
| Duodopa Non-naïve < 2 Years | NA | 44.0 | NA | 2.6 | NA | 13.4 | NA | 21.2 | NA | 7.0 |
| Duodopa Non-naïve ≥ 2 Years | NA | 48.2 | NA | 3.2 | NA | 14.3 | NA | 23.5 | NA | 7.2 |
The UPDRS is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. For Parts I-III and Total Score, each question is measured on a 5-point scale of 0 (normal or no disease effect) to 4 (maximum negative effect). Part I score is the sum of answers to 'Mentation, Behavior and Mood' questions, with a score range from 0-16. Higher scores are associated with more disability. (NCT00141518)
Timeframe: Months 0, 3, 6, 9, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | units on a scale (Mean) | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Month 0; n=27, 22, 18 | Month 3; n=24, 22, 18 | Month 6; n=25, 22, 18 | Month 9; n=25, 20, 17 | Month 18; n=24, 20, 17 | Month 24; n=23, 18, 15 | Month 30; n=23, 17, 13 | Month 36; n=21, 16, 12 | Endpoint visit; n=27, 22, 18 | |
| Duodopa Naïve | 2.4 | 2.5 | 2.9 | 3.0 | 4.1 | 3.9 | 4.1 | 3.9 | 3.9 |
| Duodopa Non-naïve < 2 Years | 2.0 | 2.0 | 2.3 | 2.9 | 2.7 | 3.0 | 3.5 | 3.9 | 3.5 |
| Duodopa Non-naïve ≥ 2 Years | 2.7 | 3.2 | 2.9 | 3.3 | 3.3 | 3.5 | 2.8 | 3.8 | 4.0 |
The UPDRS is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. For Parts I-III and Total Score, each question is measured on a 5-point scale of 0 (normal or no disease effect) to 4 (maximum negative effect). Part II score is the sum of answers to 'Activities of Daily Living' questions, with a score range from 0-52. Higher scores are associated with more disability. (NCT00141518)
Timeframe: Months 0, 3, 6, 9, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | units on a scale (Mean) | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Month 0; n=27, 22, 18 | Month 3; n=24, 22, 18 | Month 6; n=25, 22, 18 | Month 9; n=25, 20, 17 | Month 18; n=24, 20, 17 | Month 24; n=23, 18, 15 | Month 30; n=23, 17, 13 | Month 36; n=21, 16, 12 | Endpoint visit; n=27, 22, 18 | |
| Duodopa Naïve | 12.3 | 12.0 | 12.4 | 11.8 | 13.3 | 12.9 | 14.0 | 13.9 | 14.6 |
| Duodopa Non-naïve < 2 Years | 13.7 | 12.8 | 13.4 | 13.0 | 12.9 | 12.2 | 14.6 | 14.6 | 15.7 |
| Duodopa Non-naïve ≥ 2 Years | 15.4 | 15.0 | 14.3 | 14.4 | 15.6 | 17.2 | 16.9 | 16.8 | 17.3 |
The UPDRS is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. For Parts I-III and Total Score, each question is measured on a 5-point scale of 0 (normal or no disease effect) to 4 (maximum negative effect). Part III score is the sum of answers to 'Motor Examination' questions, with a score range from 0-108. Higher scores are associated with more disability. (NCT00141518)
Timeframe: Months 0, 3, 6, 9, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | units on a scale (Mean) | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Month 0; n=27, 22, 18 | Month 3; n=24, 22, 18 | Month 6; n=25, 20, 18 | Month 9; n=25, 20, 17 | Month 18; n=24, 20, 16 | Month 24; n=23, 18, 15 | Month 30; n=23, 17, 13 | Month 36; n=21, 16, 12 | Endpoint visit; n=27, 22, 17 | |
| Duodopa Naïve | 22.0 | 21.6 | 21.5 | 19.9 | 21.3 | 21.4 | 23.1 | 22.0 | 23.1 |
| Duodopa Non-naïve < 2 Years | 23.4 | 22.9 | 22.8 | 21.9 | 21.7 | 18.2 | 22.6 | 22.2 | 24.1 |
| Duodopa Non-naïve ≥ 2 Years | 22.4 | 21.9 | 22.6 | 22.9 | 23.3 | 25.4 | 24.0 | 28.0 | 28.6 |
The UPDRS is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. For Part IV, questions are measured on a 5-point scale of 0 (normal or no disease effect) to 4 (maximum negative effect) or 2-point scale (0 or 1). Part IV score is the sum of answers to 'Complications of Therapy' questions, with a score range from 0-23. Higher scores are associated with more disability. (NCT00141518)
Timeframe: Months 0, 3, 6, 9, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | units on a scale (Mean) | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Month 0; n=27, 22, 18 | Month 3; n=24, 22, 18 | Month 6; n=25, 22, 18 | Month 9; n=25, 20, 17 | Month 18; n=24, 20, 17 | Month 24; n=23, 18, 15 | Month 30; n=22, 17, 13 | Month 36; n=21, 16, 12 | Endpoint visit; n=26, 22, 18 | |
| Duodopa Naïve | 6.5 | 6.3 | 6.5 | 6.1 | 6.5 | 6.3 | 6.2 | 6.4 | 6.5 |
| Duodopa Non-naïve < 2 Years | 7.1 | 7.8 | 7.1 | 7.3 | 7.0 | 6.8 | 6.6 | 6.4 | 7.5 |
| Duodopa Non-naïve ≥ 2 Years | 7.2 | 6.7 | 7.7 | 7.5 | 7.6 | 6.6 | 6.5 | 5.5 | 6.7 |
The Electronic Diary consisted of 15 items addressing motor performance, complication of therapy, self-assessment, and various types of tapping. Six conceptual dimensions were defined; four subjectively-reported: 'walking', 'satisfied', 'dyskinesia', and 'off' and two objectively-measured: 'tapping' and 'spiral'. Each of the items was assessed in the morning and during the day. Tapping: Random chase speed' is defined as the number of correct taps of fields randomly selected by the computer per 20 seconds. (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | taps/20 seconds (Mean) | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Morning, Baseline (Month -3); n=20, 0, 0 | Day, Baseline (Month -3); n=20, 0, 0 | Morning, Month 0; n=19, 20, 15 | Day, Month 0; n=19, 20, 15 | Morning, Month 3; n=19, 18, 13 | Day, Month 3; n=19, 19, 13 | Morning, Month 6; n=16, 19, 11 | Day, Month 6; n=16, 19, 11 | Morning, Month 9; n=16, 17, 9 | Day, Month 9; n=16, 17, 9 | Morning, Month 12; n=16, 16, 9 | Day, Month 12; n=16, 16, 9 | Morning, Month 18; n=15, 14, 10 | Day, Month 18; n=15, 14, 10 | Morning, Month 24; n=13, 13, 7 | Day, Month 24; n=13, 13, 7 | Morning, Month 30; n=9, 9, 5 | Day, Month 30; n=9, 9, 5 | Morning, Month 36; n=6, 11, 5 | Day, Month 36; n=5, 11, 5 | Morning, Endpoint; n=23, 20, 16 | Day, Endpoint; 23, 20, 16 | |
| Duodopa Naïve | 24.5 | 24.2 | 26.3 | 26.3 | 27.2 | 27.2 | 28.3 | 28.2 | 27.2 | 27.0 | 27.2 | 26.3 | 26.2 | 26.3 | 27.0 | 26.7 | 27.4 | 27.9 | 26.5 | 25.2 | 25.1 | 25.1 |
| Duodopa Non-naïve < 2 Years | NA | NA | 22.6 | 23.4 | 23.8 | 24.4 | 24.2 | 24.4 | 24.4 | 25.6 | 25.5 | 26.4 | 24.9 | 25.9 | 24.8 | 26.5 | 24.4 | 25.1 | 23.1 | 23.9 | 22.7 | 23.6 |
| Duodopa Non-naïve ≥ 2 Years | NA | NA | 22.7 | 22.0 | 24.3 | 24.0 | 24.4 | 25.3 | 25.0 | 25.6 | 23.8 | 24.7 | 24.8 | 25.0 | 22.7 | 23.8 | 25.1 | 27.0 | 25.1 | 26.3 | 22.8 | 23.0 |
The UPDRS is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. For Parts I-III and Total Score, each question is measured on a 5-point scale of 0 (normal or no disease effect) to 4 (maximum negative effect). Part I score is the sum of answers to 'Mentation, Behavior and Mood' questions, with a score range from 0-16. Part II score is the sum of answers to 'Activities of Daily Living' questions, with a score range from 0-52. Part III score is the sum of answers to 'Motor Examination' questions, with a score range from 0-108. Total Score is the sum of the responses to the 31 questions (44 answers) that comprise Parts I-III of the scale, with a score range from 0-176. Higher scores are associated with more disability. (NCT00141518)
Timeframe: Months 0, 3, 6, 9, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | units on a scale (Mean) | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Month 0; n=27, 22, 18 | Month 3; n=24, 22, 18 | Month 6; n=25, 22, 18 | Month 9; 5, 20, 17 | Month 18; n=24, 20, 17 | Month 24; n=23, 18, 15 | Month 30; n=23, 17, 13 | Month 36; n=21, 16, 12 | Endpoint visit; n=27, 22, 18 | |
| Duodopa Naïve | 43.1 | 42.4 | 43.3 | 40.8 | 45.2 | 44.5 | 47.1 | 46.2 | 47.9 |
| Duodopa Non-naïve < 2 Years | 46.2 | 45.5 | 43.5 | 45.1 | 44.2 | 40.2 | 47.4 | 47.1 | 50.8 |
| Duodopa Non-naïve ≥ 2 Years | 47.8 | 46.8 | 47.4 | 48.1 | 48.5 | 52.7 | 50.2 | 54.0 | 55.0 |
"The Electronic Diary consisted of 15 items addressing motor performance, complication of therapy, self-assessment, and various types of tapping. Six conceptual dimensions were defined; four subjectively-reported: 'walking', 'satisfied', 'dyskinesia', and 'off' and two objectively-measured: 'tapping' and 'spiral'. Each of the items was assessed in the morning and during the day. On time is when PD symptoms are well controlled by the drug, and is represented as a percentage of total time of the last __ hours." (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | percentage of 'on' time (Mean) | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Morning, Baseline (Month -3); n=20, 0, 0 | Day, Baseline (Month -3); n=20, 0, 0 | Morning, Month 0; n=19, 20, 15 | Day, Month 0; n=19, 20, 15 | Morning, Month 3; n=19, 18, 13 | Day, Month 3; n=19, 19, 13 | Morning, Month 6; n=16, 19, 11 | Day, Month 6; n=16, 19, 11 | Morning, Month 9; n=16, 17, 9 | Day, Month 9; n=16, 17, 9 | Morning, Month 12; n=16, 16, 9 | Day, Month 12; n=16, 16, 9 | Morning, Month 18; n=15, 14, 10 | Day, Month 18; n=15, 14, 10 | Morning, Month 24; n=13, 13, 7 | Day, Month 24; n=13, 13, 7 | Morning, Month 30; n=9, 9, 5 | Day, Month 30; n=9, 9, 5 | Morning, Month 36; n=6, 11, 5 | Day, Month 36; n=5, 11, 5 | Morning, Endpoint; n=23, 20, 16 | Day, Endpoint; n=23, 20, 16 | |
| Duodopa Naïve | 40.2 | 40.3 | 58.4 | 61.8 | 61.6 | 62.6 | 57.7 | 62.2 | 60.5 | 59.7 | 61.1 | 59.5 | 61.9 | 61.5 | 61.3 | 62.3 | 64.8 | 62.4 | 54.5 | 59.1 | 52.9 | 56.0 |
| Duodopa Non-naïve < 2 Years | NA | NA | 49.8 | 60.2 | 52.0 | 58.3 | 55.5 | 57.3 | 52.3 | 59.5 | 57.5 | 63.0 | 55.2 | 57.6 | 59.5 | 57.4 | 49.3 | 56.9 | 55.3 | 61.8 | 54.6 | 56.5 |
| Duodopa Non-naïve ≥ 2 Years | NA | NA | 55.2 | 46.5 | 49.8 | 55.0 | 55.8 | 53.2 | 47.9 | 50.8 | 49.0 | 51.4 | 51.1 | 52.5 | 41.3 | 42.7 | 58.6 | 58.8 | 51.9 | 55.1 | 49.9 | 46.2 |
"The Electronic Diary consisted of 15 items addressing motor performance, complication of therapy, self-assessment, and various types of tapping. Six conceptual dimensions were defined; four subjectively-reported: 'walking', 'satisfied', 'dyskinesia', and 'off' and two objectively-measured: 'tapping' and 'spiral'. Each of the items was assessed in the morning and during the day. Off time is when PD symptoms are not adequately controlled by the drug, and is represented as a percentage of total time awake per day." (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | percentage of 'off' time (Mean) | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Morning, Baseline (Month -3); n=20, 0, 0 | Day, Baseline (Month -3); n=20, 0, 0 | Morning, Month 0; n=19, 20, 15 | Day, Month 0; n=19, 20, 15 | Morning, Month 3; n=19, 18, 13 | Day, Month 3; n=19, 19, 13 | Morning, Month 6; n=16, 19, 11 | Day, Month 6; n=16, 19, 11 | Morning, Month 9; n=16, 17, 9 | Day, Month 9; n=16, 17, 9 | Morning, Month 12; n=16, 16, 9 | Day, Month 12; n=16, 16, 9 | Morning, Month 18; n=15, 14, 10 | Day, Month 18; n=15, 14, 10 | Morning, Month 24; n=13, 13, 7 | Day, Month 24; n=13, 13, 7 | Morning, Month 30; n=9, 9, 5 | Day, Month 30; n=9, 9, 5 | Morning, Month 36; n=6, 11, 5 | Day, Month 36; n=5, 11, 5 | Morning, Endpoint; n=23, 20, 16 | Day, Endpoint; n=23, 20, 16 | |
| Duodopa Naïve | 41.2 | 35.4 | 23.4 | 20.8 | 26.4 | 23.0 | 25.6 | 21.9 | 23.9 | 19.5 | 25.3 | 24.0 | 21.1 | 17.9 | 29.1 | 22.0 | 23.4 | 21.6 | 35.1 | 24.7 | 30.7 | 24.8 |
| Duodopa Non-naïve < 2 Years | NA | NA | 30.6 | 21.4 | 34.3 | 22.7 | 30.1 | 21.8 | 32.3 | 21.5 | 28.0 | 19.5 | 28.9 | 21.6 | 25.4 | 21.3 | 29.4 | 24.0 | 29.4 | 18.8 | 28.5 | 22.3 |
| Duodopa Non-naïve ≥ 2 Years | NA | NA | 25.1 | 25.7 | 25.7 | 20.2 | 18.6 | 20.9 | 23.6 | 22.8 | 23.8 | 23.5 | 24.9 | 20.1 | 30.4 | 24.9 | 28.0 | 23.0 | 31.5 | 23.6 | 27.1 | 25.9 |
The Electronic Diary consisted of 15 items addressing motor performance, complication of therapy, self-assessment, and various types of tapping. Six conceptual dimensions were defined; four subjectively-reported: 'walking', 'satisfied', 'dyskinesia', and 'off' and two objectively-measured: 'tapping' and 'spiral'. Each of the items was assessed in the morning and during the day. 'Off time' is when PD symptoms are not adequately controlled by the drug. Magnitude scores were 1 (worst) to 5 (best). (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | units on a scale (Mean) | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Morning, Baseline (Month -3); n=20, 0, 0 | Day, Baseline (Month -3); n=20, 0, 0 | Morning, Month 0; n=19, 20, 15 | Day, Month 0; n=19, 20, 15 | Morning, Month 3; n=19, 18, 13 | Day, Month 3; 19, 19, 13 | Morning, Month 6; n=16, 19, 11 | Day, Month 6; 16, 19, 11 | Morning, Month 9; n=16, 17, 9 | Day, Month 9; n=16, 17, 9 | Morning, Month 12; n=16, 16, 9 | Day, Month 12; n=16, 16, 9 | Morning, Month 18; n=15, 14, 10 | Day, Month 18; n=15, 14, 10 | Morning, Month 24; n=13, 13, 7 | Day, Month 24; n=13, 13, 7 | Morning, Month 30; n=9, 9, 5 | Day, Month 30; n=9, 9, 5 | Morning, Month 36; n=6, 11, 5 | Day, Month 36; n=5, 11, 5 | Morning, Endpoint; n=23, 20, 16 | Day, Endpoint; n=23, 20, 16 | |
| Duodopa Naïve | 2.7 | 2.8 | 3.6 | 3.6 | 3.5 | 3.6 | 3.4 | 3.8 | 3.7 | 3.8 | 3.7 | 3.6 | 3.7 | 3.8 | 3.6 | 3.7 | 3.8 | 3.8 | 3.1 | 3.5 | 3.3 | 3.5 |
| Duodopa Non-naïve < 2 Years | NA | NA | 3.2 | 3.5 | 2.8 | 3.6 | 3.2 | 3.7 | 3.3 | 3.6 | 3.3 | 3.6 | 3.3 | 3.7 | 3.5 | 3.6 | 3.3 | 3.6 | 3.5 | 3.8 | 3.4 | 3.6 |
| Duodopa Non-naïve ≥ 2 Years | NA | NA | 3.4 | 3.3 | 3.1 | 3.3 | 3.7 | 3.4 | 3.3 | 3.2 | 3.4 | 3.4 | 3.2 | 3.5 | 3.1 | 3.4 | 2.9 | 3.2 | 3.2 | 3.0 | 3.3 | 3.1 |
The Electronic Diary consisted of 15 items addressing motor performance, complication of therapy, self-assessment, and various types of tapping. Six conceptual dimensions were defined; four subjectively-reported: 'walking', 'satisfied', 'dyskinesia', and 'off' and two objectively-measured: 'tapping' and 'spiral'. Each of the items was assessed in the morning and during the day. Free tapping is defined as voluntary repetitive finger tapping on computer-generated fields. 'Free tapping speed' is a count of the number of taps per 20 seconds. (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | taps/20 seconds (Mean) | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Morning, Baseline (Month -3); n=20, 0, 0 | Day, Baseline (Month -3); n=20, 0, 0 | Morning, Month 0; n=19, 20, 15 | Day, Month 0; n=19, 20, 15 | Morning, Month 3; n=19, 18, 13 | Day, Month 3; n=19, 19, 13 | Morning, Month 6; n=16, 19, 11 | Day, Month 6; n=16, 19, 11 | Morning, Month 9; n=16, 17, 9 | Day, Month 9; n=16, 17, 9 | Morning, Month 12; n=16, 16, 9 | Day, Month 12; n=16, 16, 9 | Morning, Month 18; n=15, 14, 10 | Day, Month 18; n=15, 14, 10 | Morning, Month 24; n=13, 13, 7 | Day, Month 24; n=13, 13, 7 | Morning, Month 30; n=9, 9, 5 | Day, Month 30; n=9, 9, 5 | Morning, Month 36; n=6, 11, 5 | Day, Month 36; n=5, 11, 5 | Morning, Endpoint; n=23, 20, 16 | Day, Endpoint; n=23, 20, 16 | |
| Duodopa Naïve | 39.9 | 39.7 | 44.4 | 43.5 | 46.8 | 47.4 | 50.7 | 50.3 | 47.2 | 48.1 | 49.3 | 48.7 | 44.0 | 46.9 | 47.3 | 47.6 | 49.4 | 49.5 | 46.3 | 45.5 | 41.8 | 43.6 |
| Duodopa Non-naïve < 2 Years | NA | NA | 39.2 | 40.2 | 42.2 | 43.2 | 43.4 | 43.0 | 45.7 | 48.0 | 44.5 | 46.6 | 43.1 | 46.3 | 45.5 | 48.7 | 42.2 | 42.6 | 44.7 | 45.6 | 41.2 | 43.2 |
| Duodopa Non-naïve ≥ 2 Years | NA | NA | 40.6 | 40.3 | 46.3 | 43.2 | 48.0 | 47.6 | 46.8 | 47.0 | 47.0 | 46.6 | 46.7 | 45.9 | 38.7 | 41.5 | 49.3 | 52.6 | 51.4 | 50.5 | 43.1 | 41.4 |
The Electronic Diary consisted of 15 items addressing motor performance, complication of therapy, self-assessment, and various types of tapping. Six conceptual dimensions were defined; four subjectively-reported: 'walking', 'satisfied', 'dyskinesia', and 'off' and two objectively-measured: 'tapping' and 'spiral'. Each of the items was assessed in the morning and during the day. 'Free tapping' is defined as ____. 'Free tapping accuracy' is the percentage of accurate free taps per 20 seconds(?). (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | percentage of tapping accuracy (Mean) | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Morning, Baseline (Month -3); n=20, 0, 0 | Day, Baseline (Month -3); n=20, 0, 0 | Morning, Month 0; n=19, 20, 15 | Day, Month 0; n=19, 20, 15 | Morning, Month 3; n=19, 18, 13 | Day, Month 3; n=19, 19, 13 | Morning, Month 6; n=16, 19, 11 | Day, Month 6; n=16, 19, 11 | Morning, Month 9; n=16, 17, 9 | Day, Month 9; n=16, 17, 9 | Morning, Month 12; n=16, 16, 9 | Day, Month 12; n=16, 16, 9 | Morning, Month 18; n=15, 14, 10 | Day, Month 18; n=15, 14, 10 | Morning, Month 24; n=13, 13, 7 | Day, Month 24; n=13, 13, 7 | Morning, Month 30; n=9, 9, 5 | Day, Month 30; n=9, 9, 5 | Morning, Month 36; n=6, 11, 5 | Day, Month 36; n=5, 11, 5 | Morning, Endpoint; n=23, 20, 16 | Day, Endpoint; n=23, 20, 16 | |
| Duodopa Naïve | 70.7 | 71.9 | 71.4 | 70.1 | 73.4 | 70.0 | 67.6 | 65.7 | 67.0 | 65.4 | 68.7 | 64.7 | 58.9 | 61.2 | 62.3 | 64.4 | 66.3 | 66.8 | 60.7 | 50.3 | 63.7 | 60.1 |
| Duodopa Non-naïve < 2 Years | NA | NA | 69.8 | 70.7 | 70.3 | 69.7 | 66.2 | 66.1 | 63.6 | 69.9 | 71.5 | 71.7 | 65.4 | 69.1 | 66.2 | 69.1 | 67.2 | 67.3 | 60.3 | 64.6 | 58.7 | 62.7 |
| Duodopa Non-naïve ≥ 2 Years | NA | NA | 63.8 | 65.2 | 63.5 | 65.8 | 64.8 | 66.7 | 65.8 | 67.5 | 61.5 | 60.4 | 65.8 | 61.4 | 61.9 | 62.4 | 62.1 | 67.9 | 61.2 | 63.6 | 59.3 | 60.3 |
The Electronic Diary consisted of 15 items addressing motor performance, complication of therapy, self-assessment, and various types of tapping. Six conceptual dimensions were defined; four subjectively-reported: 'walking', 'satisfied', 'dyskinesia', and 'off' and two objectively-measured: 'tapping' and 'spiral'. Each of the items was assessed in the morning and during the day. 'Dyskinetic time' is time with involuntary muscle movement, and is represented as a percentage of total time of the last __ hours. (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | percentage of 'dyskinetic' time (Mean) | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Morning, Baseline (Month -3); n=20, 0, 0 | Day, Baseline (Month -3); n=20, 0, 0 | Morning, Month 0; n=19, 20, 15 | Day, Month 0; n=19, 20, 15 | Morning, Month 3; n=19, 18, 13 | Day, Month 3; n=19, 19, 13 | Morning, Month 6; n=16, 19, 11 | Day, Month 6; n=16, 19, 11 | Morning, Month 9; n=16, 17, 9 | Day, Month 9; n=16, 17, 9 | Morning, Month 12; n=16, 16, 9 | Day, Month 12; n=16, 16, 9 | Morning, Month 18; n=15, 14, 10 | Day, Month 18; n=15, 14, 10 | Morning, Month 24; n=13, 13, 7 | Day, Month 24; n=13, 13, 7 | Morning, Month 30; n=9, 9, 5 | Day, Month 30; n=9, 9, 5 | Morning, Month 36; n=6, 11, 5 | Day, Month 36; n=5, 11, 5 | Morning, Endpoint; n=23, 20, 16 | Day, Endpoint; n=23, 20, 16 | |
| Duodopa Naïve | 18.6 | 24.3 | 18.2 | 17.4 | 12.0 | 14.4 | 16.7 | 15.9 | 15.6 | 20.8 | 13.6 | 16.2 | 17.0 | 20.6 | 9.6 | 15.8 | 11.8 | 14.5 | 10.4 | 16.2 | 16.5 | 16.2 |
| Duodopa Non-naïve < 2 Years | NA | NA | 19.6 | 18.4 | 13.7 | 18.9 | 14.4 | 20.8 | 15.5 | 19.0 | 14.6 | 17.4 | 15.9 | 20.8 | 15.0 | 21.3 | 21.3 | 19.1 | 15.2 | 19.4 | 16.9 | 19.4 |
| Duodopa Non-naïve ≥ 2 Years | NA | NA | 19.7 | 27.3 | 24.5 | 24.8 | 25.6 | 25.8 | 28.5 | 26.5 | 27.2 | 25.1 | 24.0 | 27.4 | 28.2 | 32.4 | 13.4 | 18.2 | 16.6 | 21.3 | 23.0 | 21.3 |
The Electronic Diary consisted of 15 items addressing motor performance, complication of therapy, self-assessment, and various types of tapping. Six conceptual dimensions were defined; four subjectively-reported: 'walking', 'satisfied', 'dyskinesia', and 'off' and two objectively-measured: 'tapping' and 'spiral'. Each of the items was assessed in the morning and during the day. 'Dyskinetic time' is time with involuntary muscle movement. Magnitude scores were 1 (worst) to 5 (best). (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | units on a scale (Mean) | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Morning, Baseline (Month -3); n=20, 0, 0 | Day, Baseline (Month -3); n=20, 0, 0 | Morning, Month 0; n=19, 20, 15 | Day, Month 0; n=19, 20, 15 | Morning, Month 3; n=19, 18, 13 | Day, Month 3; n=19, 19, 13 | Morning, Month 6; n=16, 19, 11 | Day, Month 6; n=16, 19, 11 | Morning, Month 9; n=16, 17, 9 | Day, Month 9; n=16, 17, 9 | Morning, Month 12; n=16, 16, 9 | Day, Month 12; n=16, 16, 9 | Morning, Month 18; n=15, 14, 10 | Day, Month 18; n=15, 14, 10 | Morning, Month 24; n=13, 13, 7 | Day, Month 24; n=13, 13, 7 | Morning, Month 30; n=9, 9, 5 | Day, Month 30; n=9, 9, 5 | Morning, Month 36; n=6, 11, 5 | Day, Month 36; n=5, 11, 5 | Morning, Endpoint; n=23, 20, 16 | Day, Endpoint; 23, 20, 16 | |
| Duodopa Naïve | 4.1 | 3.6 | 4.1 | 4.0 | 4.4 | 4.2 | 4.1 | 4.2 | 4.1 | 3.8 | 4.1 | 4.1 | 3.9 | 3.9 | 4.4 | 4.1 | 4.5 | 4.5 | 4.3 | 4.0 | 4.3 | 4.0 |
| Duodopa Non-naïve < 2 Years | NA | NA | 4.1 | 4.0 | 4.2 | 4.0 | 4.1 | 3.8 | 4.2 | 4.0 | 4.2 | 3.7 | 3.8 | 3.9 | 4.2 | 3.9 | 3.9 | 3.9 | 4.0 | 3.7 | 4.0 | 3.7 |
| Duodopa Non-naïve ≥ 2 Years | NA | NA | 4.0 | 3.7 | 4.0 | 3.7 | 3.9 | 3.7 | 3.7 | 3.8 | 3.7 | 3.8 | 3.9 | 3.8 | 4.1 | 3.8 | 4.2 | 4.1 | 4.1 | 4.0 | 4.1 | 3.6 |
The Electronic Diary consisted of 15 items addressing motor performance, complication of therapy, self-assessment, and various types of tapping. Six conceptual dimensions were defined; four subjectively-reported: 'walking', 'satisfied', 'dyskinesia', and 'off' and two objectively-measured: 'tapping' and 'spiral'. Each of the items was assessed in the morning and during the day. Drawing impairment was assessed as a spiral score, where the participant is asked to draw a spiral. 1 is worst score, 10 is best. (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | units on a scale (Mean) | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Morning, Baseline (Month -3); n=20, 0, 0 | Day, Baseline (Month -3); n=20, 0, 0 | Morning, Month 0; n=19, 20, 15 | Day, Month 0; n=19, 20, 15 | Morning, Month 3; n=19, 18, 13 | Day, Month 3; n=19, 19, 13 | Morning, Month 6; n=16, 19, 11 | Day, Month 6; n=16, 19, 11 | Morning, Month 9; n=16, 17, 9 | Day, Month 9; n=16, 17, 9 | Morning, Month 12; n=16, 16, 9 | Day, Month 12; n=16, 16, 9 | Morning, Month 18; n=15, 14, 10 | Day, Month 18; n=15, 14, 10 | Morning, Month 24; n=13, 13, 7 | Day, Month 24; n=13, 13, 7 | Morning, Month 30; n=9, 9, 5 | Day, Month 30; n=9, 9, 5 | Morning, Month 36; n=6, 11, 5 | Day, Month 36; n=5, 11, 5 | Morning, Endpoint; n=23, 20, 16 | Day, Endpoint; n=23, 20, 16 | |
| Duodopa Naïve | 4.0 | 4.0 | 4.1 | 4.2 | 3.6 | 3.8 | 3.8 | 4.1 | 4.3 | 4.3 | 4.1 | 4.4 | 4.6 | 4.6 | 4.3 | 4.5 | 4.1 | 4.5 | 4.4 | 5.0 | 4.5 | 4.8 |
| Duodopa Non-naïve < 2 Years | NA | NA | 4.5 | 4.3 | 4.3 | 4.2 | 4.5 | 4.6 | 4.1 | 4.1 | 4.1 | 4.1 | 4.4 | 4.3 | 3.9 | 3.9 | 4.4 | 4.4 | 4.8 | 4.6 | 5.0 | 4.9 |
| Duodopa Non-naïve ≥ 2 Years | NA | NA | 5.0 | 5.1 | 4.7 | 4.8 | 4.5 | 4.5 | 4.6 | 4.5 | 5.0 | 4.7 | 5.4 | 4.9 | 5.2 | 5.1 | 4.9 | 4.8 | 5.3 | 5.3 | 5.3 | 5.3 |
The Electronic Diary consisted of 15 items addressing motor performance, complication of therapy, self-assessment, and various types of tapping. Six conceptual dimensions were defined; four subjectively-reported: 'walking', 'satisfied', 'dyskinesia', and 'off' and two objectively-measured: 'tapping' and 'spiral'. Each of the items was assessed in the morning and during the day. 'Cramps' scores were 1 (worst) to 5 (best). (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | units on a scale (Mean) | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Morning, Baseline (Month -3); n=20, 0, 0 | Day, Baseline (Month -3); n=20, 0, 0 | Morning, Month 0; n=19, 20, 15 | Day, Month 0; n=19, 20, 15 | Morning, Month 3; n=19, 18, 13 | Day, Month 3; n=19, 19, 13 | Morning, Month 6; n=16, 19, 11 | Day, Month 6; n=16, 19, 11 | Morning, Month 9; n=16, 17, 9 | Day, Month 9; n=16, 17, 9 | Morning, Month 12; n=16, 16, 9 | Day, Month 12; n=16, 16, 9 | Morning, Month 18; n=15, 14, 10 | Day, Month 18; n=15, 14, 10 | Morning, Month 24; n=13, 13, 7 | Day, Month 24; n=13, 13, 7 | Morning, Month 30; n=9, 9, 5 | Day, Month 30; n=9, 9, 5 | Morning, Month 36; n=6, 11, 5 | Day, Month 36; n=5, 11, 5 | Morning, Endpoint; n=23, 20, 16 | Day, Endpoint; n=23, 20, 16 | |
| Duodopa Naïve | 4.4 | 4.5 | 4.7 | 4.7 | 4.8 | 4.7 | 4.8 | 4.8 | 4.8 | 4.7 | 4.8 | 4.5 | 4.7 | 4.7 | 4.6 | 4.5 | 4.9 | 4.9 | 4.5 | 4.7 | 4.6 | 4.5 |
| Duodopa Non-naïve < 2 Years | NA | NA | 4.6 | 4.7 | 4.6 | 4.7 | 4.5 | 4.5 | 4.4 | 4.5 | 4.5 | 4.7 | 4.4 | 4.6 | 4.8 | 4.8 | 4.7 | 4.8 | 4.7 | 4.8 | 4.5 | 4.6 |
| Duodopa Non-naïve ≥ 2 Years | NA | NA | 4.6 | 4.6 | 4.5 | 4.5 | 4.3 | 4.3 | 4.4 | 4.3 | 4.2 | 4.1 | 4.1 | 4.3 | 4.0 | 4.0 | 4.1 | 3.9 | 4.1 | 4.2 | 4.4 | 4.5 |
"The Schwab and England scale was used to rate the subject's best on period during the past week by recording the percentage score, ranging between being completely independent (100%) and totally dependent (10%). On time is when PD symptoms are well controlled by the drug." (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | percentage score on a scale (Mean) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline (Month -3); n=27, 0, 0 | Month 0; n=27, 22, 18 | Month 3; n=24, 22, 18 | Month 6; n=25, 22, 18 | Month 9; n=25, 20, 17 | Month 12; n=25, 20, 17 | Month 18; n=24, 20, 17 | Month 24; n=23, 18, 15 | Month 30; n=23, 17, 13 | Month 36; n=21, 16, 12 | Endpoint; n=27, 22, 18 | |
| Duodopa Naïve | 74.4 | 80.4 | 77.9 | 75.2 | 79.2 | 77.2 | 75.8 | 72.2 | 70.4 | 66.7 | 68.9 |
| Duodopa Non-naïve < 2 Years | NA | 75.5 | 75.9 | 77.3 | 76.5 | 72.5 | 74.0 | 73.3 | 71.8 | 73.1 | 71.4 |
| Duodopa Non-naïve ≥ 2 Years | NA | 74.4 | 72.2 | 72.2 | 70.6 | 71.8 | 69.4 | 68.0 | 67.7 | 64.2 | 62.2 |
"Total monthly costs include~Direct medical costs (inpatient care, outpatient care, and drug costs [including Duodopa cost and cost of concomitant anti-PD medication]).~Direct non-medical costs (nursing home, home help, personal assistance, informal care [from family member or friend] and transportation to inpatient, outpatient visits and nursing home).~Indirect costs (sick-leave and early retirement due to PD [applied to individuals only up to the age of 65 since the main indirect cost item, early retirement due to disability, is only available for individuals 30-64 years old. Sixty-five is also a common retirement age in Sweden]).~The average rate for US Dollar (USD) to SEK on 31 December 2010 was 1 USD = 6.734 SEK." (NCT00141518)
Timeframe: Baseline (month -3) for Duodopa-naïve participants, then at Month 0, and monthly thereafter until study completion (up to 48 months) for all participants
| Intervention | SEK 2010 (Mean) |
|---|---|
| Duodopa Naïve | 78418 |
| Duodopa Non-naïve < 2 Years | 75521 |
| Duodopa Non-naïve ≥ 2 Years | 82177 |
| Total | 78464 |
Direct non-medical costs include nursing home, home help, personal assistance, informal care (from family member or friend) and transportation to inpatient, outpatient visits and nursing home. The average rate for US Dollar (USD) to SEK on 31 December 2010 was 1 USD = 6.734 SEK. (NCT00141518)
Timeframe: Baseline (month -3) for Duodopa-naïve participants, then at Month 0, and monthly thereafter until study completion (up to 48 months) for all participants
| Intervention | SEK 2010 (Mean) |
|---|---|
| Duodopa Naïve | 19274 |
| Duodopa Non-naïve < 2 Years | 27439 |
| Duodopa Non-naïve ≥ 2 Years | 25008 |
| Total | 23398 |
Direct medical costs consist of inpatient care, outpatient care (visits to physician, nurse, physiotherapist, occupational therapist, dietitian, speech therapist, counselor, and phone consultations). The average rate for US Dollar (USD) to SEK on 31 December 2010 was 1 USD = 6.734 SEK. (NCT00141518)
Timeframe: Baseline (month -3) for Duodopa-naïve participants, then at Month 0, and monthly thereafter until study completion (up to 48 months) for all participants
| Intervention | SEK 2010 (Mean) |
|---|---|
| Duodopa Naïve | 3825 |
| Duodopa Non-naïve < 2 Years | 4552 |
| Duodopa Non-naïve ≥ 2 Years | 3607 |
| Total | 4002 |
The Electronic Diary consisted of 15 items addressing motor performance, complication of therapy, self-assessment, and various types of tapping. Six conceptual dimensions were defined; four subjectively-reported: 'walking', 'satisfied', 'dyskinesia', and 'off' and two objectively-measured: 'tapping' and 'spiral'. Each of the items was assessed in the morning and during the day. Tapping: Random chase speed' is defined as the number of correct taps of fields randomly selected by the computer per 20 seconds. 'Tapping random chase - accuracy' is the percentage of accurate random chase taps. (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | percentage of accurate taps (Mean) | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Morning, Baseline (Month -3); n=20, 0, 0 | Day, Baseline (Month -3); n=20, 0, 0 | Morning, Month 0; n=19, 20, 15 | Day, Month 0; n=19, 20, 15 | Morning, Month 3; n=19, 18, 13 | Day, Month 3; n=19, 19, 13 | Morning, Month 6; n=16, 19, 11 | Day, Month 6; n=16, 19, 11 | Morning, Month 9; n=16, 17, 9 | Day, Month 9; n=16, 17, 9 | Morning, Month 12; n=16, 16, 9 | Day, Month 12; n=16, 16, 9 | Morning, Month 18; n=15, 14, 10 | Day, Month 18; n=15, 14, 10 | Morning, Month 24; n=13, 13, 7 | Day, Month 24; n=13, 13, 7 | Morning, Month 30; n=9, 9, 5 | Day, Month 30; n=9, 9, 5 | Morning, Month 36; n=6, 11, 5 | Day, Month 36; n=5, 11, 5 | Morning, Endpoint; n=23, 20, 16 | Day, Endpoint; n=23, 20, 16 | |
| Duodopa Naïve | 92.0 | 91.8 | 94.6 | 92.9 | 90.5 | 92.5 | 95.2 | 94.6 | 91.2 | 92.4 | 92.2 | 91.2 | 90.2 | 91.6 | 91.7 | 92.9 | 95.1 | 93.6 | 83.5 | 82.1 | 87.8 | 87.3 |
| Duodopa Non-naïve < 2 Years | NA | NA | 90.0 | 91.3 | 89.2 | 88.6 | 89.0 | 88.7 | 90.8 | 93.1 | 90.7 | 92.5 | 88.8 | 92.1 | 92.2 | 93.4 | 85.9 | 88.6 | 85.9 | 88.4 | 83.8 | 86.6 |
| Duodopa Non-naïve ≥ 2 Years | NA | NA | 92.6 | 92.3 | 89.1 | 89.8 | 90.5 | 89.2 | 91.8 | 92.5 | 90.6 | 89.2 | 86.8 | 85.4 | 89.0 | 90.7 | 90.5 | 91.2 | 89.7 | 88.8 | 87.5 | 86.7 |
The Electronic Diary consisted of 15 items addressing motor performance, complication of therapy, self-assessment, and various types of tapping. Six conceptual dimensions were defined; four subjectively-reported: 'walking', 'satisfied', 'dyskinesia', and 'off' and two objectively-measured: 'tapping' and 'spiral'. Each of the items was assessed in the morning and during the day. Walking scores ranged from 1 (worst) to 5 (best). (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | units on a scale (Mean) | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Morning, Baseline (Month -3); n=20, 0, 0 | Day, Baseline (Month -3); n=20, 0, 0 | Morning, Month 0; n=19, 20, 15 | Day, Month 0; n=19, 20, 15 | Morning, Month 3; n=19, 19, 13 | Day, Month 3; n=19, 19, 13 | Morning, Month 6; n=16, 19, 11 | Day, Month 6; n=16, 19, 11 | Morning, Month 9; n=16, 17, 9 | Day, Month 9; n=16, 17, 9 | Morning, Month 12; n=16, 16, 9 | Day, Month 12; n=16, 16, 9 | Morning, Month 18; n=15, 14, 10 | Day, Month 18; n=15, 14, 10 | Morning, Month 24; n=14, 13, 7 | Day, Month 24; n=13, 13, 7 | Morning, Month 30; n=9, 9, 5 | Day, Month 30; n=9, 9, 5 | Morning, Month 36; n=6, 11, 5 | Day, Month 36; n=5, 11, 5 | Morning, Endpoint; n=23, 20, 16 | Day, Endpoint; n=23, 20, 16 | |
| Duodopa Naïve | 2.7 | 3.1 | 3.3 | 3.7 | 3.5 | 3.7 | 3.5 | 4.0 | 3.6 | 4.0 | 3.6 | 3.7 | 3.3 | 3.8 | 3.4 | 3.9 | 3.4 | 3.8 | 2.3 | 3.1 | 2.8 | 3.4 |
| Duodopa Non-naïve < 2 Years | NA | NA | 3.2 | 3.7 | 3.0 | 3.6 | 3.2 | 3.7 | 3.3 | 3.8 | 3.5 | 3.8 | 3.5 | 3.9 | 3.5 | 3.9 | 3.4 | 4.0 | 3.6 | 4.0 | 3.4 | 3.8 |
| Duodopa Non-naïve ≥ 2 Years | NA | NA | 3.4 | 3.3 | 3.1 | 3.3 | 3.3 | 3.4 | 3.1 | 3.1 | 3.1 | 3.1 | 3.4 | 3.5 | 2.9 | 2.8 | 3.6 | 3.9 | 3.7 | 3.7 | 3.0 | 3.0 |
The EQ-5D is a participant-answered questionnaire scoring 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. EQ-5D health states, defined by the EQ-5D descriptive system, are converted into a single summary index by applying a formula that essentially attaches values (also called QOL weights or QOL utilities) to each of the levels in each dimension. EQ-5D Summary Index values range from -0.11 to 1.00 with positive change indicating improvement. (NCT00141518)
Timeframe: Months 0, 3, 6, 9, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | units on a scale (Mean) | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Month 0; n=27, 22, 18 | Month 3; n=24, 22, 18 | Month 6; n=25, 21, 18 | Month 9; n=25, 20, 17 | Month 18; n=24, 20, 16 | Month 24; n=21, 18, 15 | Month 30; n=22, 17, 12 | Month 36; n=21, 15, 11 | Endpoint visit; n=26, 22, 17 | |
| Duodopa Naïve | 0.67 | 0.61 | 0.64 | 0.61 | 0.64 | 0.58 | 0.55 | 0.52 | 0.54 |
| Duodopa Non-naïve < 2 Years | 0.68 | 0.70 | 0.71 | 0.66 | 0.66 | 0.67 | 0.69 | 0.57 | 0.60 |
| Duodopa Non-naïve ≥ 2 Years | 0.62 | 0.57 | 0.57 | 0.59 | 0.53 | 0.47 | 0.52 | 0.51 | 0.46 |
The EQ-5D VAS records the participant's self-rated health on a scale from 0-100 where 100 is the 'best imaginable health state' and 0 is the 'worst imaginable health state.' The scale was normalized to a scale of 0 to 1, with higher values indicating a better health state. (NCT00141518)
Timeframe: Baseline (Month -3), Month 12
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline (Month -3); n=27, 0, 0 | Month 12; n=25, 19, 17 | |
| Duodopa Naïve | 0.44 | 0.63 |
| Duodopa Non-naïve < 2 Years | NA | 0.64 |
| Duodopa Non-naïve ≥ 2 Years | NA | 0.64 |
The EQ-5D VAS records the participant's self-rated health on a scale from 0-100 where 100 is the 'best imaginable health state' and 0 is the 'worst imaginable health state.' (NCT00141518)
Timeframe: Months 0, 3, 6, 9, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | units on a scale (Mean) | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Month 0; n=27, 22, 18 | Month 3; n=24, 22, 18 | Month 6; n=25, 21, 18 | Month 9; n=25, 20, 17 | Month 18; n=24, 20, 16 | Month 24; n=21, 17, 15 | Month 30; n=22, 17, 12 | Month 36; n=21, 15, 11 | Endpoint visit; n=26, 22, 17 | |
| Duodopa Naïve | 0.68 | 0.65 | 0.60 | 0.68 | 0.62 | 0.64 | 0.56 | 0.56 | 0.57 |
| Duodopa Non-naïve < 2 Years | 0.65 | 0.63 | 0.65 | 0.69 | 0.60 | 0.60 | 0.67 | 0.61 | 0.61 |
| Duodopa Non-naïve ≥ 2 Years | 0.58 | 0.58 | 0.59 | 0.58 | 0.55 | 0.63 | 0.65 | 0.62 | 0.57 |
The EQ-5D is a participant-answered questionnaire scoring 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. EQ-5D health states, defined by the EQ-5D descriptive system, are converted into a single summary index by applying a formula that essentially attaches values (also called QOL weights or QOL utilities) to each of the levels in each dimension. EQ-5D Summary Index values range from -0.11 (worst health state) to 1.00 (perfect health state). (NCT00141518)
Timeframe: Baseline (Month -3), Month 12
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline (Month -3); n=27, 0, 0 | Month 12; n=25, 20, 17 | |
| Duodopa Naïve | 0.57 | 0.59 |
| Duodopa Non-naïve < 2 Years | NA | 0.66 |
| Duodopa Non-naïve ≥ 2 Years | NA | 0.51 |
Indirect costs consist of sick-leave and early retirement due to PD, are applied to individuals only up to the age of 65 since the main indirect cost item - early retirement due to disability - is only available for individuals 30-64 years old. Sixty-five is also a common retirement age in Sweden. The average rate for US Dollar (USD) to SEK on 31 December 2010 was 1 USD = 6.734 SEK. (NCT00141518)
Timeframe: Baseline (month -3) for Duodopa-naïve participants, then at Month 0, and monthly thereafter until Month 36
| Intervention | SEK 2010 (Mean) | |||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Month -3; n=15/37 | Month 0; n=23/67 | Month 1; n=23/67 | Month 2; n=22/65 | Month 3; n=23/65 | Month 4; n=23/65 | Month 5; n=22/65 | Month 6; n=21/65 | Month 7; n=24/65 | Month 8; n=24/63 | Month 9; n=22/62 | Month 10; n=22/62 | Month 11; n=22/62 | Month 12; n=22/62 | Month 13; n=22/62 | Month 14; n=22/62 | Month 15; n=22/61 | Month 16; n=22/61 | Month 17; n=22/61 | Month 18; n=22/61 | Month 19; n=22/60 | Month 20; n=20/59 | Month 21; n=20/58 | Month 22; n=18/57 | Month 23; n=18/57 | Month 24; n=17/56 | Month 25; n=16/54 | Month 26; n=18/54 | Month 27; n=16/53 | Month 28; n=15/53 | Month 29; n=16/53 | Month 30; n=16/53 | Month 31; n=15/50 | Month 32; n=14/50 | Month 33; n=14/50 | Month 34; n=14/49 | Month 35; n=14/49 | Month 36; n=15/49 | |
| Total | 17032 | 14109 | 14109 | 13896 | 14543 | 14543 | 13896 | 13250 | 15512 | 16005 | 14569 | 14569 | 14399 | 14399 | 14230 | 14569 | 14808 | 14808 | 14463 | 14463 | 14704 | 13529 | 13763 | 12530 | 12530 | 12003 | 12059 | 13615 | 12683 | 11890 | 12683 | 12683 | 12604 | 11763 | 11763 | 12003 | 12003 | 12432 |
MADRS is a depression rating scale consisting of 10 items representing the core symptoms of depressive illness, each rated 0 (no symptom) to 6 (severe symptom). Apparent sadness scores rate despondency, gloom and despair (more than just ordinary transient low spirits), reflected in speech, facial expression, and posture. (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | units on a scale (Mean) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline (Month -3); n=26, 0, 0 | Month 0; n=27, 22, 18 | Month 3; n=24, 22, 17 | Month 6; n=25, 21, 17 | Month 9; n=25, 20, 17 | Month 12; n=25, 20, 17 | Month 18; n=24, 19, 16 | Month 24; n=23, 18, 15 | Month 30; n=23, 17, 13 | Month 36; n=21, 16, 12 | Endpoint; n=27, 22, 17 | |
| Duodopa Naïve | 0.7 | 0.4 | 0.8 | 1.0 | 0.9 | 0.4 | 0.8 | 1.0 | 1.2 | 1.1 | 1.1 |
| Duodopa Non-naïve < 2 Years | NA | 0.5 | 0.6 | 0.6 | 0.7 | 0.9 | 0.6 | 0.6 | 1.0 | 0.8 | 0.8 |
| Duodopa Non-naïve ≥ 2 Years | NA | 0.8 | 0.5 | 0.5 | 0.9 | 0.8 | 0.8 | 0.7 | 0.6 | 1.3 | 1.0 |
MADRS is a depression rating scale consisting of 10 items representing the core symptoms of depressive illness, each rated 0 (no symptom) to 6 (severe symptom). Concentration Difficulties scores rate difficulties in collecting one's thoughts mounting to an incapacitating lack of concentration. (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | units on a scale (Mean) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline (Month -3); n=26, 0, 0 | Month 0; n=27, 22, 18 | Month 3; n=24, 22, 17 | Month 6; n=25, 21, 17 | Month 9; n=25, 20, 17 | Month 12; n=25, 20, 17 | Month 18; n=24, 19, 16 | Month 24; n=23, 18, 15 | Month 30; n=23, 17, 13 | Month 36; n=21, 16, 12 | Endpoint; n=27, 22, 17 | |
| Duodopa Naïve | 1.0 | 1.0 | 0.9 | 1.2 | 1.0 | 0.9 | 1.5 | 1.5 | 1.5 | 1.6 | 1.6 |
| Duodopa Non-naïve < 2 Years | NA | 1.5 | 1.3 | 1.4 | 1.1 | 1.2 | 1.4 | 1.7 | 2.1 | 1.9 | 1.7 |
| Duodopa Non-naïve ≥ 2 Years | NA | 0.9 | 1.2 | 1.2 | 1.3 | 1.4 | 1.4 | 1.7 | 1.5 | 1.2 | 1.6 |
MADRS is a depression rating scale consisting of 10 items representing the core symptoms of depressive illness, each rated 0 (no symptom) to 6 (severe symptom). Inability to Feel scores rate the subjective experience of reduced interest in the surroundings, or activities that normally give pleasure. The ability to react with adequate emotion to circumstances or people is reduced. (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | units on a scale (Mean) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline (Month -3); n=26, 0, 0 | Month 0; n=27, 22, 18 | Month 3; n=24, 22, 17 | Month 6; n=25, 21, 17 | Month 9; n=25, 20, 17 | Month 12; n=25, 20, 17 | Month 18; n=24, 19, 16 | Month 24; n=23, 18, 15 | Month 30; n=23, 17, 13 | Month 36; n=21, 16, 12 | Endpoint; n=27, 22, 17 | |
| Duodopa Naïve | 0.5 | 0.4 | 0.6 | 0.6 | 0.5 | 0.6 | 0.5 | 0.5 | 0.4 | 0.6 | 0.6 |
| Duodopa Non-naïve < 2 Years | NA | 0.2 | 0.6 | 0.4 | 0.6 | 0.4 | 0.5 | 0.6 | 0.7 | 0.5 | 0.6 |
| Duodopa Non-naïve ≥ 2 Years | NA | 0.8 | 0.6 | 0.8 | 0.7 | 0.5 | 0.8 | 1.1 | 0.7 | 0.7 | 0.9 |
MADRS is a depression rating scale consisting of 10 items representing the core symptoms of depressive illness, each rated 0 (no symptom) to 6 (severe symptom). Inner Tension scores rate feelings of ill-defined discomfort, edginess, inner turmoil, mental tension mounting to either panic, dread or anguish. (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | units on a scale (Mean) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline (Month -3); n=26, 0, 0 | Month 0; n=27, 22, 18 | Month 3; n=24, 22, 17 | Month 6; n=25, 21, 17 | Month 9; n=25, 20, 17 | Month 12; n=25, 20, 17 | Month 18; n=24, 19, 16 | Month 24; n=23, 18, 15 | Month 30; n=23, 17, 13 | Month 36; n=21, 16, 12 | Endpoint; n=27, 22, 17 | |
| Duodopa Naïve | 1.3 | 1.3 | 1.5 | 1.1 | 0.9 | 1.1 | 1.2 | 1.0 | 1.1 | 1.7 | 1.6 |
| Duodopa Non-naïve < 2 Years | NA | 1.0 | 0.8 | 0.9 | 0.6 | 0.7 | 0.7 | 0.8 | 1.1 | 0.6 | 0.6 |
| Duodopa Non-naïve ≥ 2 Years | NA | 0.9 | 0.9 | 1.2 | 0.9 | 1.5 | 0.8 | 1.3 | 1.5 | 1.3 | 1.5 |
MADRS is a depression rating scale consisting of 10 items representing the core symptoms of depressive illness, each rated 0 (no symptom) to 6 (severe symptom). Lassitude scores rate difficulty in getting started or slowness in initiating and performing everyday activities. (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | units on a scale (Mean) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline (Month -3); n=26, 0, 0 | Month 0; n=27, 22, 18 | Month 3; n=24, 22, 17 | Month 6; n=25, 21, 17 | Month 9; n=25, 20, 17 | Month 12; n=25, 20, 17 | Month 18; n=24, 19, 16 | Month 24; n=23, 18, 15 | Month 30; n=23, 17, 13 | Month 36; n=21, 16, 12 | Endpoint; n=27, 22, 17 | |
| Duodopa Naïve | 1.3 | 1.4 | 1.7 | 1.5 | 1.3 | 1.6 | 1.8 | 1.7 | 2.0 | 1.9 | 1.8 |
| Duodopa Non-naïve < 2 Years | NA | 1.4 | 1.5 | 1.5 | 1.5 | 1.6 | 1.4 | 1.9 | 1.7 | 1.8 | 1.7 |
| Duodopa Non-naïve ≥ 2 Years | NA | 1.7 | 2.0 | 1.3 | 1.7 | 1.4 | 1.6 | 1.7 | 1.3 | 1.7 | 1.7 |
MADRS is a depression rating scale consisting of 10 items representing the core symptoms of depressive illness, each rated 0 (no symptom) to 6 (severe symptom). Pessimistic Thoughts scores rate thoughts of guilt, inferiority, self-reproach, sinfulness, remorse and ruin. (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | units on a scale (Mean) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline (Month -3); n=26, 0, 0 | Month 0; n=27, 22, 18 | Month 3; n=24, 22, 17 | Month 6; n=25, 21, 17 | Month 9; n=25, 20, 17 | Month 12; n=25, 20, 17 | Month 18; n=24, 19, 16 | Month 24; n=23, 18, 15 | Month 30; n=22, 17, 13 | Month 36; n=21, 16, 12 | Endpoint; n=26, 22, 17 | |
| Duodopa Naïve | 0.9 | 1.0 | 0.7 | 0.9 | 0.8 | 0.9 | 1.0 | 1.0 | 1.2 | 1.0 | 1.2 |
| Duodopa Non-naïve < 2 Years | NA | 0.5 | 0.5 | 0.6 | 0.5 | 0.8 | 0.7 | 0.7 | 0.7 | 0.9 | 0.9 |
| Duodopa Non-naïve ≥ 2 Years | NA | 0.6 | 0.8 | 0.6 | 0.9 | 1.0 | 0.8 | 1.1 | 0.9 | 1.0 | 1.1 |
MADRS is a depression rating scale consisting of 10 items representing the core symptoms of depressive illness, each rated 0 (no symptom) to 6 (severe symptom). Reduced Appetite scores rate the feeling of a loss of appetite compared with when-well. Rate by loss of desire for food or the need to force oneself to eat. (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | units on a scale (Mean) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline (Month -3); n=26, 0, 0 | Month 0; n=27, 22, 18 | Month 3; n=24, 22, 17 | Month 6; n=25, 21, 17 | Month 9; n=25, 20, 17 | Month 12; n=25, 20, 17 | Month 18; n=24, 19, 16 | Month 24; n=23, 18, 15 | Month 30; n=23, 17, 13 | Month 36; n=21, 16, 12 | Endpoint; n=27, 22, 17 | |
| Duodopa Naïve | 0.8 | 0.6 | 0.7 | 0.8 | 0.5 | 0.5 | 0.5 | 0.7 | 1.0 | 0.9 | 0.9 |
| Duodopa Non-naïve < 2 Years | NA | 0.2 | 0.4 | 0.3 | 0.4 | 0.6 | 0.3 | 0.5 | 0.4 | 0.4 | 0.3 |
| Duodopa Non-naïve ≥ 2 Years | NA | 0.3 | 0.4 | 0.5 | 0.8 | 0.7 | 0.4 | 0.7 | 0.5 | 1.1 | 1.1 |
MADRS is a depression rating scale consisting of 10 items representing the core symptoms of depressive illness, each rated 0 (no symptom) to 6 (severe symptom). Reduced Sleep scores rate the experience of reduced duration or depth of sleep compared to the participant's own normal pattern when well. (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | units on a scale (Mean) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline (Month -3); n=26, 0, 0 | Month 0; n=27, 22, 18 | Month 3; n=24, 22, 17 | Month 6; n=25, 21, 17 | Month 9; n=25, 20, 17 | Month 12; n=25, 20, 17 | Month 18; n=24, 19, 16 | Month 24; n=23, 18, 15 | Month 30; n=23, 17, 13 | Month 36; n=21, 16, 12 | Endpoint; n=27, 22, 17 | |
| Duodopa Naïve | 2.5 | 1.9 | 2.0 | 1.8 | 1.8 | 1.8 | 1.7 | 1.6 | 2.3 | 1.9 | 1.6 |
| Duodopa Non-naïve < 2 Years | NA | 1.5 | 1.8 | 1.7 | 1.9 | 1.5 | 1.5 | 1.8 | 1.9 | 1.2 | 1.4 |
| Duodopa Non-naïve ≥ 2 Years | NA | 1.7 | 1.2 | 1.5 | 1.4 | 1.2 | 1.7 | 1.5 | 0.9 | 1.2 | 2.0 |
MADRS is a depression rating scale consisting of 10 items representing the core symptoms of depressive illness, each rated 0 (no symptom) to 6 (severe symptom). Reported Sadness scores rate depressed mood, regardless of whether it is reflected in appearance or not, and includes low spirits, despondency or the feeling of being beyond help and without hope. (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | units on a scale (Mean) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline (Month -3); n=26, 0, 0 | Month 0; n=27, 22, 18 | Month 3; n=24, 22, 17 | Month 6; n=25, 21, 17 | Month 9; n=25, 20, 17 | Month 12; n=25, 20, 17 | Month 18; n=24, 19, 16 | Month 24; n=23, 18, 15 | Month 30; n=23, 17, 13 | Month 36; n=21, 16, 12 | Endpoint; n=27, 22, 17 | |
| Duodopa Naïve | 0.9 | 0.6 | 0.9 | 1.1 | 0.9 | 0.6 | 1.0 | 1.0 | 1.2 | 1.1 | 1.2 |
| Duodopa Non-naïve < 2 Years | NA | 0.8 | 0.6 | 0.8 | 0.9 | 1.1 | 0.7 | 0.9 | 0.9 | 0.9 | 0.8 |
| Duodopa Non-naïve ≥ 2 Years | NA | 0.8 | 0.5 | 0.5 | 1.1 | 0.8 | 0.8 | 0.8 | 0.9 | 1.1 | 1.0 |
MADRS is a depression rating scale consisting of 10 items representing the core symptoms of depressive illness, each rated 0 (no symptom) to 6 (severe symptom). Suicidal Thoughts scores rate the feeling that life is not worth living, that a natural death would be welcome, suicidal thoughts, and preparations for suicide. (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | units on a scale (Mean) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline (Month -3); n=26, 0, 0 | Month 0; n=27, 22, 18 | Month 3; n=24, 22, 17 | Month 6; n=25, 21, 17 | Month 9; n=25, 20, 17 | Month 12; n=25, 20, 17 | Month 18; n=24, 19, 16 | Month 24; n=23, 18, 15 | Month 30; n=23, 17, 13 | Month 36; n=21, 16, 12 | Endpoint; n=27, 22, 17 | |
| Duodopa Naïve | 0.4 | 0.5 | 0.5 | 0.5 | 0.3 | 0.3 | 0.5 | 0.1 | 0.4 | 0.5 | 0.4 |
| Duodopa Non-naïve < 2 Years | NA | 0.2 | 0.0 | 0.1 | 0.0 | 0.3 | 0.3 | 0.2 | 0.1 | 0.1 | 0.2 |
| Duodopa Non-naïve ≥ 2 Years | NA | 0.3 | 0.4 | 0.2 | 0.2 | 0.2 | 0.2 | 0.4 | 0.2 | 0.1 | 0.4 |
The MMSE is used to assess orientation, attention, immediate and short term recall, language, and ability to follow simple verbal and written commands. The test consists of five sections (orientation, registration, attention-calculation, recall, and language) and results in a total possible score of 0 to 30, with higher scores indicating better function. (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint visit (Month 36 or last visit if discontinued early)
| Intervention | units on a scale (Mean) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline (Month -3); n=26, 0, 0 | Month 0; n=27, 22, 18 | Month 3; n=24, 22, 18 | Month 6; n=25, 21, 18 | Month 9; n=25, 20, 17 | Month 12; n=25, 20, 17 | Month 18; n=24, 19, 16 | Month 24; n=23, 18, 15 | Month 30; n=23, 17, 13 | Month 36; n=21, 16, 12 | Endpoint; n=27, 22, 17 | |
| Duodopa Naïve | 28.2 | 27.8 | 28.0 | 28.1 | 28.4 | 27.9 | 27.6 | 27.7 | 27.3 | 27.2 | 27.1 |
| Duodopa Non-naïve < 2 Years | NA | 28.0 | 27.2 | 27.6 | 27.6 | 28.2 | 28.5 | 27.8 | 26.4 | 26.3 | 26.4 |
| Duodopa Non-naïve ≥ 2 Years | NA | 28.2 | 28.6 | 28.1 | 28.3 | 28.2 | 28.3 | 28.0 | 28.6 | 27.9 | 27.3 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. These include: mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness. (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | units on a scale (Mean) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline (Month -3); n=27,0,0 | Month 0; n=27, 22, 17 | Month 3; n=24, 22, 18 | Month 6; n=25, 21, 17 | Month 9; n=24, 20, 16 | Month 12; n=23, 20, 17 | Month 18; n=22, 20, 16 | Month 24; n=21, 17, 14 | Month 30; n=22, 17, 12 | Month 36; n=21, 15, 11 | Endpoint; n=26, 22, 17 | |
| Duodopa Naïve | 8.3 | 10.3 | 10.8 | 12.7 | 10.2 | 12.1 | 12.7 | 15.7 | 18.2 | 18.3 | 21.8 |
| Duodopa Non-naïve < 2 Years | NA | 12.9 | 12.5 | 13.1 | 13.8 | 19.6 | 17.9 | 20.6 | 16.2 | 11.7 | 14.4 |
| Duodopa Non-naïve ≥ 2 Years | NA | 22.1 | 16.7 | 24.3 | 25.5 | 28.4 | 18.8 | 21.7 | 18.8 | 29.5 | 27.9 |
The MMSE is used to assess orientation, attention, immediate and short term recall, language, and ability to follow simple verbal and written commands. The Language subscale results in a total possible score of 0 to 9, with higher scores indicating better function. (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | units on a scale (Mean) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline (Month -3); n=26, 0, 0 | Month 0; n=27, 22, 18 | Month 3; n=24, 22, 18 | Month 6; n=25, 21, 18 | Month 9; n=25, 20, 17 | Month 12; n=25, 20, 17 | Month 18; n=24, 19, 16 | Month 24; n=23, 18, 15 | Month 30; n=23, 17, 13 | Month 36; n=21, 16, 12 | Endpoint; n=27, 22, 17 | |
| Duodopa Naïve | 8.3 | 8.5 | 8.4 | 8.3 | 8.4 | 8.2 | 8.2 | 8.0 | 7.9 | 8.3 | 8.3 |
| Duodopa Non-naïve < 2 Years | NA | 8.6 | 8.3 | 8.1 | 8.2 | 8.3 | 8.6 | 8.1 | 8.0 | 7.9 | 7.9 |
| Duodopa Non-naïve ≥ 2 Years | NA | 8.5 | 8.7 | 8.3 | 8.4 | 8.2 | 8.3 | 8.3 | 8.5 | 8.4 | 8.4 |
The MMSE is used to assess orientation, attention, immediate and short term recall, language, and ability to follow simple verbal and written commands. The orientation subscale has a total possible score of 0 to 10, with higher scores indicating better function. (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | units on a scale (Mean) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline (Month -3); n=26, 0, 0 | Month 0; n=27, 22, 18 | Month 3; n=24, 22, 18 | Month 6; n=25, 21, 18 | Month 9; n=25, 20, 17 | Month 12; n=25, 20, 17 | Month 18; n=24, 19, 16 | Month 24; n=23, 18, 15 | Month 30; n=23, 17, 13 | Month 36; n=21, 16, 12 | Endpoint; n=27, 22, 17 | |
| Duodopa Naïve | 9.8 | 9.6 | 9.4 | 9.7 | 9.8 | 9.6 | 9.7 | 9.7 | 9.4 | 9.6 | 9.5 |
| Duodopa Non-naïve < 2 Years | NA | 9.9 | 9.5 | 9.6 | 9.9 | 9.8 | 9.7 | 9.8 | 8.9 | 9.3 | 8.9 |
| Duodopa Non-naïve ≥ 2 Years | NA | 9.8 | 9.6 | 9.7 | 9.6 | 9.7 | 9.9 | 9.9 | 9.8 | 9.1 | 9.2 |
The MMSE is used to assess orientation, attention, immediate and short term recall, language, and ability to follow simple verbal and written commands. The Recall subscale results in a total possible score of 0 to 3, with higher scores indicating better function. (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | units on a scale (Mean) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline (Month -3); n=26, 0, 0 | Month 0; n=27, 22, 18 | Month 3; n=24, 22, 18 | Month 6; n=25, 21, 18 | Month 9; n=25, 20, 17 | Month 12; n=25, 20, 17 | Month 18; n=24, 19, 16 | Month 24; n=23, 18, 15 | Month 30; n=23, 17, 13 | Month 36; n=21, 16, 12 | Endpoint; n=27, 22, 17 | |
| Duodopa Naïve | 2.2 | 2.2 | 2.5 | 2.5 | 2.5 | 2.5 | 2.3 | 2.4 | 2.5 | 2.2 | 2.2 |
| Duodopa Non-naïve < 2 Years | NA | 2.1 | 2.1 | 2.4 | 2.2 | 2.5 | 2.5 | 2.3 | 2.5 | 2.4 | 2.5 |
| Duodopa Non-naïve ≥ 2 Years | NA | 2.3 | 2.5 | 2.3 | 2.5 | 2.6 | 2.6 | 2.5 | 2.6 | 2.8 | 2.5 |
The MMSE is used to assess orientation, attention, immediate and short term recall, language, and ability to follow simple verbal and written commands. The Registration subscale a total possible score of 0 to 3, with higher scores indicating better function. (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | units on a scale (Mean) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline (Month -3); n=26, 0, 0 | Month 0; n=27, 22, 18 | Month 3; n=24, 22, 18 | Month 6; n=25, 21, 18 | Month 9; n=25, 20, 17 | Month 12; n=25, 20, 17 | Month 18; n=24, 19, 16 | Month 24; n=23, 18, 15 | Month 30; n=23, 17, 13 | Month 36; n=21, 16, 12 | Endpoint; n=27, 22, 17 | |
| Duodopa Naïve | 3.0 | 3.0 | 3.0 | 3.0 | 3.0 | 3.0 | 3.0 | 3.0 | 3.0 | 3.0 | 3.0 |
| Duodopa Non-naïve < 2 Years | NA | 3.0 | 3.0 | 3.0 | 3.0 | 3.0 | 3.0 | 3.0 | 2.9 | 3.0 | 3.0 |
| Duodopa Non-naïve ≥ 2 Years | NA | 3.0 | 3.0 | 3.0 | 3.0 | 3.0 | 3.0 | 3.0 | 3.0 | 2.9 | 2.9 |
The best PD stage that the participant experienced during the last month was characterized according to Modified Hoehn and Yahr criteria, measured on the following 8-point scale for staging: 0=no signs of disease; 1=unilateral disease; 1.5=unilateral plus axial involvement; 2=bilateral disease; 2.5=mild bilateral disease; 3=mild to moderate bilateral disease; 4=severe disability; and 5=wheelchair bound or bedridden unless aided. (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | units on a scale (Mean) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline (Month -3); n=27, 0, 0 | Month 0; n=27, 22, 18 | Month 3; n=24, 22, 18 | Month 6; n=25, 22, 18 | Month 9; 25, 20, 17 | Month 12; n=25, 20, 17 | Month 18; n=24, 20, 17 | Month 24; n=23, 18, 15 | Month 30; n=23, 17, 13 | Month 36; n=21, 16, 12 | Endpoint; n=27, 22, 18 | |
| Duodopa Naïve | 2.2 | 2.0 | 2.0 | 2.0 | 2.2 | 2.2 | 2.2 | 2.3 | 2.5 | 2.5 | 2.6 |
| Duodopa Non-naïve < 2 Years | NA | 2.5 | 2.5 | 2.5 | 2.5 | 2.6 | 2.5 | 2.6 | 2.6 | 2.6 | 2.7 |
| Duodopa Non-naïve ≥ 2 Years | NA | 2.5 | 2.6 | 2.6 | 2.7 | 2.9 | 2.9 | 2.9 | 3.0 | 3.0 | 3.1 |
The current stage of PD was characterized according to Modified Hoehn and Yahr criteria, measured on the following 8-point scale for staging: 0=no signs of disease; 1=unilateral disease; 1.5=unilateral plus axial involvement; 2=bilateral disease; 2.5=mild bilateral disease; 3=mild to moderate bilateral disease; 4=severe disability; and 5=wheelchair bound or bedridden unless aided. (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | units on a scale (Mean) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline (Month -3); n=27, 0, 0 | Month 0; n=27, 22, 18 | Month 3; n=24, 22, 18 | Month 6; n=25, 22, 18 | Month 9; n=25, 20, 17 | Month 12; n=25, 20, 17 | Month 18; n=24, 20, 17 | Month 24; 23, 18, 15 | Month 30; n=23, 17, 13 | Month 36; n=21, 16, 12 | Endpoint; n=27, 22, 18 | |
| Duodopa Naïve | 2.7 | 2.5 | 2.3 | 2.4 | 2.4 | 2.4 | 2.4 | 2.5 | 2.7 | 2.7 | 2.7 |
| Duodopa Non-naïve < 2 Years | NA | 2.7 | 2.7 | 2.6 | 2.7 | 2.8 | 2.7 | 3.0 | 2.9 | 2.9 | 3.1 |
| Duodopa Non-naïve ≥ 2 Years | NA | 3.2 | 3.0 | 3.1 | 3.1 | 3.3 | 3.4 | 3.2 | 3.1 | 3.3 | 3.4 |
The worst PD stage that the participant experienced during the last month was characterized according to Modified Hoehn and Yahr criteria, measured on the following 8-point scale for staging: 0=no signs of disease; 1=unilateral disease; 1.5=unilateral plus axial involvement; 2=bilateral disease; 2.5=mild bilateral disease; 3=mild to moderate bilateral disease; 4=severe disability; and 5=wheelchair bound or bedridden unless aided. (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | units on a scale (Mean) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline (Month -3); n=27, 0, 0 | Month 0; n=27, 22, 18 | Month 3; n=24, 22, 18 | Month 6; n=25, 22, 18 | Month 9; n=25, 20, 17 | Month 12; n=25, 20, 17 | Month 18; n=24, 20, 17 | Month 24; n=23, 18, 15 | Month 30; n=23, 17, 13 | Month 36; n=21, 16, 12 | Endpoint; n=27, 22, 18 | |
| Duodopa Naïve | 3.8 | 3.6 | 3.8 | 3.7 | 3.7 | 3.6 | 3.8 | 3.9 | 4.0 | 3.9 | 3.9 |
| Duodopa Non-naïve < 2 Years | NA | 3.7 | 3.7 | 3.7 | 3.8 | 3.8 | 3.9 | 3.8 | 4.0 | 4.0 | 4.0 |
| Duodopa Non-naïve ≥ 2 Years | NA | 4.0 | 4.1 | 4.0 | 4.0 | 4.2 | 4.3 | 4.4 | 4.5 | 4.6 | 4.5 |
MADRS is a depression rating scale consisting of 10 items representing the core symptoms of depressive illness, each rated 0 (no symptom) to 6 (severe symptom). Total score ranges from 0 (no depression) to 60 (severely depressed). (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | units on a scale (Mean) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline (Month -3); n=26, 0, 0 | Month 0; n=27, 22, 18 | Month 3; n=24, 22, 17 | Month 6; n=25, 21, 17 | Month 9; n=25, 20, 17 | Month 12; n=25, 20, 17 | Month 18; n=24, 19, 16 | Month 24; n=23, 18, 15 | Month 30; n=22, 17, 13 | Month 36; n=21, 16, 12 | Endpoint; n=26, 22, 17 | |
| Duodopa Naïve | 10.3 | 9.0 | 10.2 | 10.5 | 8.8 | 8.6 | 10.6 | 10.1 | 12.0 | 12.2 | 11.6 |
| Duodopa Non-naïve < 2 Years | NA | 7.8 | 8.1 | 8.4 | 8.0 | 8.8 | 8.1 | 9.7 | 10.6 | 9.1 | 9.0 |
| Duodopa Non-naïve ≥ 2 Years | NA | 8.8 | 8.4 | 8.5 | 9.9 | 9.5 | 9.1 | 11.1 | 9.0 | 10.4 | 12.3 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. These include: mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort. The PDQ-39 Summary Index is the sum of all answers divided by the highest score possible, which is multiplied by 100 to put the score on a 0-100 scale. Higher scores are associated with more severe symptoms. (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | units on a scale (Mean) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline (Month -3); n=27, 0, 0 | Month 0; n=27, 20, 17 | Month 3; n=22, 20, 18 | Month 6; n=24, 20, 17 | Month 9; n=23, 20, 16 | Month 12; n=23, 19, 17 | Month 18; n=22, 18, 16 | Month 24; n=21, 17, 14 | Month 30; n=21, 16, 12 | Month 36; n=20, 15, 11 | Endpoint; n=25, 21, 17 | |
| Duodopa Naïve | 33.6 | 27.1 | 24.5 | 27.9 | 25.9 | 28.8 | 28.2 | 30.3 | 33.5 | 36.8 | 36.2 |
| Duodopa Non-naïve < 2 Years | NA | 30.3 | 30.0 | 33.4 | 30.9 | 33.2 | 30.4 | 36.2 | 34.8 | 31.5 | 34.0 |
| Duodopa Non-naïve ≥ 2 Years | NA | 36.6 | 34.0 | 35.5 | 35.1 | 38.3 | 34.1 | 33.6 | 34.4 | 39.2 | 40.3 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. These include: mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness. (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | units on a scale (Mean) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline (Month -3); n=27, 0, 0 | Month 0; n=27, 20, 18 | Month 3; n=24, 22, 18 | Month 6; n=25, 21, 18 | Month 9; n=25, 20, 17 | Month 12; n=25, 20, 17 | Month 18; n=24, 20, 16 | Month 24; n=21, 17, 15 | Month 30; n=22, 17, 12 | Month 36; n=21, 15, 11 | Endpoint; n=26, 22, 17 | |
| Duodopa Naïve | 38.7 | 32.1 | 26.9 | 31.8 | 29.8 | 34.7 | 33.2 | 37.1 | 38.8 | 45.4 | 43.4 |
| Duodopa Non-naïve < 2 Years | NA | 40.8 | 42.8 | 43.7 | 37.5 | 42.1 | 41.9 | 48.3 | 48.5 | 47.5 | 48.3 |
| Duodopa Non-naïve ≥ 2 Years | NA | 46.5 | 41.7 | 42.1 | 42.2 | 45.6 | 45.8 | 41.9 | 46.5 | 54.5 | 53.4 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. These include: mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness. (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | units on a scale (Mean) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline (Month -3); n=27, 0, 0 | Month 0; n=27, 22, 18 | Month 3; n=24, 22, 18 | Month 6; n=24, 21, 18 | Month 9; n=25, 20, 17 | Month 12; n=25, 20, 17 | Month 18; n=24, 20, 16 | Month 24; n=21, 17, 15 | Month 30; n=22, 17, 12 | Month 36; n=21, 15, 11 | Endpoint; n=26, 22, 17 | |
| Duodopa Naïve | 42.6 | 41.7 | 38.5 | 38.9 | 36.3 | 39.3 | 38.5 | 42.9 | 42.8 | 42.9 | 42.6 |
| Duodopa Non-naïve < 2 Years | NA | 40.2 | 39.8 | 42.1 | 42.1 | 34.6 | 37.1 | 35.3 | 39.2 | 31.7 | 36.7 |
| Duodopa Non-naïve ≥ 2 Years | NA | 43.1 | 44.0 | 39.4 | 41.2 | 46.6 | 42.7 | 38.9 | 34.7 | 37.1 | 39.7 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. These include: mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness. (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | units on a scale (Mean) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline (Month -3); n=27, 0, 0 | Month 0; n=27, 22, 18 | Month 3; n=24, 22, 18 | Month 6; n=24, 21, 18 | Month 9; n=25, 20, 17 | Month 12; n=25, 20, 17 | Month 18; n=24, 20, 16 | Month 24; n=21, 17, 15 | Month 30; n=22, 16, 12 | Month 36; n=20, 15, 11 | Endpoint; n=25, 22, 17 | |
| Duodopa Naïve | 30.6 | 22.5 | 24.2 | 25.5 | 21.5 | 26.8 | 28.6 | 24.7 | 31.5 | 34.1 | 31.5 |
| Duodopa Non-naïve < 2 Years | NA | 33.0 | 36.6 | 37.8 | 35.6 | 33.1 | 31.3 | 41.9 | 45.7 | 42.1 | 39.2 |
| Duodopa Non-naïve ≥ 2 Years | NA | 33.7 | 32.3 | 30.6 | 31.6 | 33.8 | 30.1 | 27.5 | 30.7 | 30.7 | 34.9 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. These include: mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness. (NCT00141518)
Timeframe: Baseline (Month -3), Months 0, 3, 6, 9, 12, 18, 24, 30, 36, endpoint (last non-missing value assigned to treatment for the participant)
| Intervention | units on a scale (Mean) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline (Month -3); n=27, 0, 0 | Month 0; n=27, 22, 18 | Month 3; n=24, 22, 18 | Month 6; n=24, 21, 18 | Month 9; n=25, 20, 17 | Month 12; n=25, 20, 17 | Month 18; n=24, 20, 16 | Month 24; n=21, 17, 15 | Month 30; n=22, 17, 12 | Month 36; n=21, 15, 11 | Endpoint; n=26, 22, 17 | |
| Duodopa Naïve | 32.4 | 24.1 | 24.7 | 24.0 | 25.3 | 29.7 | 31.6 | 28.2 | 33.7 | 33.7 | 34.0 |
| Duodopa Non-naïve < 2 Years | NA | 27.3 | 32.2 | 32.5 | 31.7 | 34.2 | 32.1 | 34.8 | 37.7 | 33.3 | 33.0 |
| Duodopa Non-naïve ≥ 2 Years | NA | 35.2 | 31.9 | 33.8 | 28.9 | 33.8 | 29.7 | 30.6 | 41.7 | 37.9 | 40.2 |
Motor function was assessed with the UPDRS part III. There are 14 items in the instrument, each measured on a 5-point scale (0-4): Speech, facial expression, tremor at rest, action tremor, rigidity, finger taps, hand movements, hand pronation and supination, leg agility, arising from chair, posture, gait, postural stability, and body bradykinesia. The sum of scores can range from 0 to 56; a higher score indicates greater disability. A negative change score indicates improvement. (NCT00219284)
Timeframe: Baseline to Week 8
| Intervention | Units on a scale (Least Squares Mean) |
|---|---|
| Immediate Switch | -3.6 |
| Delayed Switch | -3.7 |
Motor function was assessed with the UPDRS part III. There are 14 items in the instrument, each measured on a 5 point scale (0-4): Speech, facial expression, tremor at rest, action tremor, rigidity, finger taps, hand movements, hand pronation and supination, leg agility, arising from chair, posture, gait, postural stability, and body bradykinesia. The sum of scores can range from 0 to 56; a higher score indicates greater disability. A negative change score indicates improvement. (NCT00219284)
Timeframe: Baseline to Week 4
| Intervention | Units on a scale (Least Squares Mean) |
|---|---|
| Immediate Switch | -3.7 |
| Delayed Switch | -1.8 |
The PDQ-39 is another instrument used to assess quality of life in individuals with Parkinson's disease. The questionnaire provides scores on eight scales: Mobility, activities of daily living, emotions, stigma, social support, cognition, communication, and bodily discomfort. Questions are scored on a 5-point Likert scale ranging from 1 (never) to 3 (sometimes) to 5 (always). The 1 to 5 range was recoded to 0 to 4 for the analysis. The total score can range from 0 to 156. A lower score indicates better quality of life. A negative change score indicates an improvement. (NCT00219284)
Timeframe: Baseline to Week 8
| Intervention | Units on a scale (Least Squares Mean) |
|---|---|
| Immediate Switch | -5.8 |
| Delayed Switch | -1.9 |
The PDQ-39 is another instrument used to assess quality of life in individuals with Parkinson's disease. The questionnaire provides scores on eight scales: Mobility, activities of daily living, emotions, stigma, social support, cognition, communication, and bodily discomfort. Questions are scored on a 5-point Likert scale ranging from 1 (never) to 3 (sometimes) to 5 (always). The 1 to 5 range was recoded to 0 to 4 for the analysis. The total score can range from 0 to 156. A lower score indicates better quality of life. A negative change score indicates an improvement. (NCT00219284)
Timeframe: Baseline to Week 4
| Intervention | Units on a scale (Least Squares Mean) |
|---|---|
| Immediate Switch | -1.7 |
| Delayed Switch | 0.8 |
The PDQ-39 is another instrument used to assess quality of life in individuals with Parkinson's disease. The questionnaire provides scores on eight scales: Mobility, activities of daily living, emotions, stigma, social support, cognition, communication, and bodily discomfort. Questions are scored on a 5-point Likert scale ranging from 1 (never) to 3 (sometimes) to 5 (always). The 1 to 5 range was recoded to 0 to 4 for the analysis. The total score can range from 0 to 156. A lower score indicates better quality of life. A negative change score indicates an improvement. (NCT00219284)
Timeframe: Baseline to end of treatment (Week 16 in the Immediate Switch group, Week 20 in the Delayed Switch group)
| Intervention | Units on a scale (Least Squares Mean) |
|---|---|
| Immediate Switch | -2.8 |
| Delayed Switch | 0.4 |
Quality of life was assessed with the Parkinson's Disease Quality of Life Instrument (PDQUALIF), a 33-item self-reported questionnaire which includes seven domains: Social/role function, self-imaging/sexuality, sleep, outlook, physical function, independence, and urinary function. Questions are scored on a 5-point Likert scale ranging from 1 (never) to 3 (sometimes) to 5 (always). The 1 to 5 range was recoded to 0 to 4 for the analysis. The total score can range from 0 to 132. A lower score indicates better quality of life. A negative change score indicates improvement. (NCT00219284)
Timeframe: Baseline to Week 8
| Intervention | Units on a scale (Least Squares Mean) |
|---|---|
| Immediate Switch | -2.5 |
| Delayed Switch | -1.1 |
Quality of life was assessed with the Parkinson's Disease Quality of Life Instrument (PDQUALIF), a 33-item self-reported questionnaire which includes seven domains: Social/role function, self-imaging/sexuality, sleep, outlook, physical function, independence, and urinary function. Questions are scored on a 5-point Likert scale ranging from 1 (never) to 3 (sometimes) to 5 (always). The 1 to 5 range was recoded to 0 to 4 for the analysis. The total score can range from 0 to 132. A lower score indicates better quality of life. A negative change score indicates improvement. (NCT00219284)
Timeframe: Baseline to Week 4
| Intervention | Units on a scale (Least Squares Mean) |
|---|---|
| Immediate Switch | -0.4 |
| Delayed Switch | 1.1 |
Quality of life was assessed with the Parkinson's Disease Quality of Life Instrument (PDQUALIF), a 33-item self-reported questionnaire which includes seven domains: Social/role function, self-imaging/sexuality, sleep, outlook, physical function, independence, and urinary function. Questions are scored on a 5-point Likert scale ranging from 1 (never) to 3 (sometimes) to 5 (always). The 1 to 5 range was recoded to 0 to 4 for the analysis. The total score can range from 0 to 132. A lower score indicates better quality of life. A negative change score indicates improvement. (NCT00219284)
Timeframe: Baseline to end of treatment (Week 16 in the Immediate Switch group, Week 20 in the Delayed Switch group)
| Intervention | Units on a scale (Least Squares Mean) |
|---|---|
| Immediate Switch | -1.3 |
| Delayed Switch | 0.2 |
Motor function was assessed with the UPDRS part III. There are 14 items in the instrument, each measured on a 5 point scale (0-4): Speech, facial expression, tremor at rest, action tremor, rigidity, finger taps, hand movements, hand pronation and supination, leg agility, arising from chair, posture, gait, postural stability, and body bradykinesia. The sum of scores can range from 0 to 56; a higher score indicates greater disability. A negative change score indicates improvement. (NCT00219284)
Timeframe: Baseline to end of treatment (Week 16 in the Immediate Switch group, Week 20 in the Delayed Switch group)
| Intervention | Units on a scale (Least Squares Mean) |
|---|---|
| Immediate Switch | -3.6 |
| Delayed Switch | -3.3 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Activities of Daily Living (e.g., difficulty cutting food) includes 6 questions, each answered on a 5-point scale. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness. (NCT00335153)
Timeframe: Baseline, Endpoint (last post-baseline visit up to Day 378)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline | Change from Baseline at Endpoint | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 50.7 | -8.3 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Bodily Discomfort includes 3 questions, each answered on a 5-point scale. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness. (NCT00335153)
Timeframe: Baseline, Endpoint (last post-baseline visit up to Day 378)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline | Change from Baseline at Endpoint | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 46.2 | -5.8 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Cognition includes 4 questions, each answered on a 5-point scale. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness. (NCT00335153)
Timeframe: Baseline, Endpoint (last post-baseline visit up to Day 378)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline | Change from Baseline to Endpoint | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 27.2 | -4.5 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Communication includes 3 questions, each answered on a 5-point scale. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness. (NCT00335153)
Timeframe: Baseline, Endpoint (last post-baseline visit up to Day 378)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline | Change from Baseline at Endpoint | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 34.3 | -3.9 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Emotional Well-being (e.g., feelings of isolation) includes 6 questions, each answered on a 5-point scale. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness. (NCT00335153)
Timeframe: Baseline, Endpoint (last post-baseline visit up to Day 378)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline | Change from Baseline at Endpoint | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 39.4 | -4.2 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Mobility (e.g., fear of falling when walking) includes 10 questions, each answered on a 5-point scale. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness. (NCT00335153)
Timeframe: Baseline, Endpoint (last post-baseline visit up to Day 378)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline | Change from Baseline at Endpoint | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 58.8 | -11.2 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Social Support includes 3 questions, each answered on a 5-point scale. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness. (NCT00335153)
Timeframe: Baseline, Endpoint (last post-baseline visit up to Day 378)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline | Change from Baseline at Endpoint | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 17.2 | -0.3 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Stigma (e.g., social embarrassment) consists of 4 questions, each answered on a 5-point scale. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness. (NCT00335153)
Timeframe: Baseline, Endpoint (last post-baseline visit up to Day 378)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline | CHange from Baseline at Endpoint | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 32.5 | -9.1 |
The UPDRS is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The Part I Score is the sum of the answers to the 4 questions that comprise Part I, each of which are measured on a 5-point scale (0-4). The Part I score ranges from 0-16 and higher scores are associated with more disability. (NCT00335153)
Timeframe: Baseline, Endpoint (last post-baseline visit up to Day 378)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline | Change from Baseline at Endpoint | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 2.2 | 0.0 |
The UPDRS is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The Part II score is the sum of the answers to the 13 questions that comprise Part II, each of which are measured on a 5-point scale (0-4). The Part II score ranges from 0-52 and higher scores are associated with more disability. (NCT00335153)
Timeframe: Baseline, Endpoint (last post-baseline visit up to Day 378)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline | Change from Baseline at Endpoint | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 17.5 | -4.4 |
The UPDRS is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The Part III score is the sum of the 27 answers provided to the 14 Part III questions, each of which are measured on a 5-point scale (0-4). The Part III score ranges from 0-108 and higher scores are associated with more disability. (NCT00335153)
Timeframe: Baseline, Endpoint (last post-baseline visit up to Day 378)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline | Change from Baseline at Endpoint | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 28.9 | -7.4 |
The UPDRS is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The Part IV Score is the sum of the answers to the 11 questions that comprise Part IV, each of which are measured on a 5-point scale (0-4) or a 2-point scale (0 or 1). The Part IV score ranges from 0-23 and higher scores are associated with more disability. (NCT00335153)
Timeframe: Baseline, Endpoint (last post-baseline visit up to Day 378)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline | Change from Baseline at Endpoint | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 9.2 | -3.5 |
The UPDRS is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The total score is the sum of the responses to the 31 questions (44 answers) that comprise Parts I-III of the scale. The total score will range from 0-176, with 176 representing the worst (total) disability, and 0 representing no disability. (NCT00335153)
Timeframe: Baseline, Endpoint (last post-baseline visit up to Day 378)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline | Change from Baseline at Endpoint | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 48.6 | -11.7 |
The ZBI is a 22-item questionnaire regarding the caregiver/subject relationship and evaluates the caregiver's health condition, psychological well-being, finances and social life. Each question is answered on a 5-point scale (0=never, 1=rarely, 2=sometimes, 3=quite frequently, and 4=nearly always). The caregiver burden is evaluated by the total score (Range 0 to 88) obtained from the sum of the answers to the 22 questions. Higher scores are associated with a higher level of burden for the caregiver. (NCT00335153)
Timeframe: Baseline, Endpoint (last post-baseline visit up to Day 378)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline | Change from Baseline at Endpoint | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 27.1 | 0.2 |
The CGI-S is a global assessment by the Investigator of current symptomatology and impact of illness on functioning. The ratings of the CGI-S are as follows: 1 = normal, 2 = borderline ill, 3 = mildly ill, 4 = moderately ill, 5 = markedly ill, 6 = severely ill, and 7 = among the most extremely ill. The CGI-I is a global assessment by the Investigator of the change in clinical status since the start of treatment. The CGI-I ratings are as follows: 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, 7 = very much worse. (NCT00335153)
Timeframe: Baseline, Endpoint (last post-baseline visit up to Day 378)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| CGI-S Baseline | CGI-I at Endpoint | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 4.85 | 2.10 |
AE=any untoward medical occurrence which does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that: results in death; is life-threatening (an event in which the subject was at risk of death at the time of the event); requires inpatient hospitalization or prolongation of an existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or other important medical events. Treatment-emergent events (TEAE or TESAE)=those starting after the first dose of study drug. Severe=severity reported as 'severe' or missing. Possibly or Probably Treatment Related=drug-event relationship reported as 'possible', 'probable' or missing. Death=a fatal outcome of an SAE or AE. (NCT00335153)
Timeframe: Screening through Day 378 + 30 days
| Intervention | participants (Number) | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Deaths | TE Deaths | >=1 SAE | >=1TESAE | >=1 TEAE Leading to Study Termination | >=1 TEAE | >=1 Severe TEAE | >=1 Possibly or Probably Treatment Related TEAE | No TEAE | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 8 | 7 | 111 | 108 | 27 | 323 | 102 | 272 | 31 |
Complications of the infusion device were collected during the NJ Test period. Pump, intestinal tube, NJ tube, and other complications included (but were not limited to) device breakage, device leakage, device malfunction, device misuse, device occlusion, intentional and unintentional device removal by participant, complication of device insertion, device dislocation, device breakage, device dislocation, and post-procedural hemorrhage. (NCT00335153)
Timeframe: NJ Test Period (from 2 to 14 days)
| Intervention | participants (Number) | ||||
|---|---|---|---|---|---|
| >=1 Complication | Pump Complication | Intestinal Tube Complication | NJ Tube Complication | Other Complications | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 90 | 7 | 4 | 68 | 25 |
Complications of the infusion device were collected during the PEG-J Surgery and Post-PEG Long-Term Treatment periods. Pump, PEG-J, stoma, and other complications included (but were not limited to) device breakage, device leakage, device malfunction, device misuse, device occlusion, intentional and unintentional device removal by participant, complication of device insertion, device dislocation, device breakage, device dislocation, and post-procedural hemorrhage. (NCT00335153)
Timeframe: PEG-J Surgery Period (from 2 to 14 days) through the Long Term Treatment Period (Day 28 to Day 378)
| Intervention | participants (Number) | |||||
|---|---|---|---|---|---|---|
| >=1 Complication | Pump Complication | Intestinal Tube Complication | PEG-J Complication | Stoma Complication | Other Complication | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 282 | 116 | 165 | 114 | 116 | 114 |
Terms abbreviated in the table include heart rate (HR) in beats per minute (bpm), PR interval (PRI), QT interval corrected for heart rate using Bazett's formula (QTcB), and QT interval corrected for heart rate using Fridericia's formula (QTcF). Increase and decrease are signified by ↑ and ↓, respectively. (NCT00335153)
Timeframe: Screening through Day 378
| Intervention | participants (Number) | |||||||
|---|---|---|---|---|---|---|---|---|
| HR <=50 and >30 bpm ↓ from BL; n=321 | HR >=120 and >30 bpm ↑ from BL; n=321 | PR Interval <120 msec; n=321 | PR Interval >220 msec; n=321 | QTcB Interval >480 msec; n=319 | QTcB Interval >60 msec ↑ from BL; n=309 | QTcF Interval >480 msec; n=319 | QTcF Interval >60 msec ↑ from BL; n=309 | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 1 | 1 | 6 | 26 | 15 | 4 | 7 | 3 |
Terms abbreviated in the table include aspartate aminotransferase (AST), upper limit of normal (ULN), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), female (f), and male (m). (NCT00335153)
Timeframe: Screening through Day 378
| Intervention | participants (Number) | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| AST >3*ULN; n=315 | ALT >3*ULN; n=315 | GGT >3*ULN; n=315 | LDH >3*ULN; n=315 | Alkaline Phosphatase >400 U/L; n=315 | Total Protein <45 g/L; n=315 | Total Bilirubin >2*ULN; n=315 | Creatine Kinase >3*ULN; n=315 | Sodium <126 mmol/L; n=315 | Sodium >156 mmol/L; n=315 | Potassium <3.0 mmol/L; n=315 | Potassium >6.0 mmol/L; n=315 | Calcium <1.75 mmol/L; n=315 | Calcium >3.0 mmol/L; n=315 | BUN >10.8 mmol/L; n=77 | Creatinine >177 mcmol/L; n=315 | Uric Acid >500 mcmol/L (f), >590 mcmol/L (m);n=315 | Glucose (nonfasting) <2.78 mmol/L; n=315 | Glucose (nonfasting) >16.0 mmol/L; n=315 | Cholesterol >12.9 mmol/L; n=315 | Triglycerides >5.6 mmol/L; n=315 | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 1 | 0 | 3 | 0 | 0 | 0 | 0 | 7 | 2 | 2 | 1 | 1 | 2 | 0 | 4 | 3 | 0 | 1 | 1 | 0 | 2 |
Potentially clinically significant values for red blood cells (RBCs), hemoglobin, and hematocrit are specified for females (f) and males (m) separately in the category rows. (NCT00335153)
Timeframe: Screening through Day 378
| Intervention | participants (Number) | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| RBCs <2.0*10^12/L (f), <2.5*10^12/L (m); n=316 | Hemoglobin <90 g/L (f), <100 g/L (m); n=316 | Hematocrit <30% (f), <34% (m); n=315 | White Blood Cells <2.8*10^9/L; n=316 | White Blood Cells >16.0*10^9/L; n=316 | Neutrophils <1.2*10^9/L; n=316 | Lymphocytes <0.75*10^9/L; n=316 | Lymphocytes >80%; n=316 | Platelet Count <95*10^9/L; n=315 | Platelet Count >700*10^9/L; n=315 | Mean Corpuscular Volume <60 fL; n=315 | Mean Corpuscular Volume >120 fL; n=315 | Eosinophils >10%; n=316 | Monocytes >30%; n=316 | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 0 | 4 | 27 | 3 | 0 | 0 | 21 | 0 | 1 | 0 | 0 | 0 | 7 | 0 |
Terms abbreviated in the table include supine systolic blood pressure (SuSBP), standing systolic blood pressure (StSBP), orthostatic systolic blood pressure (OSBP), supine diastolic blood pressure (SuDBP), standing diastolic blood pressure (StDBP), orthostatic diastolic blood pressure (ODBP), supine pulse (SuP) in beats per minute (bpm), standing pulse (StP), and body temperature (Temp). Increase and decrease are signified by ↑ and ↓, respectively. (NCT00335153)
Timeframe: up to 56 weeks
| Intervention | participants (Number) | ||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SuSBP >=180 and >40 mm Hg ↑ from BL; n=324 | SuSBP <=90 and >30 mm Hg ↓ from BL; n=324 | StSBP >=180 and >40 mm Hg ↑ from BL; n=324 | StSBP <=90 and >30 mm Hg ↓ from BL; n=324 | OSBP: ↓ >=30 mm Hg (Supine to Standing); n=324 | SuDBP >=105 and >30 mm Hg ↑ from BL; n=324 | SuDBP <=50 and >30 mm Hg ↓ from BL; n=324 | StDBP >=105 and >30 mm Hg ↑ from BL; n=324 | StDBP <=50 and >30 mm Hg ↓ from BL; n=324 | ODBP: ↓ >=20 mm Hg (Supine to Standing); n=324 | SuP >=120 and >30 bpm ↑ from BL; n=324 | SuP <=50 and >30 bpm ↓ from BL; n=324 | StP >=120 and >30 bpm ↑ from BL; n=324 | StP <=50 and >30 bpm ↓ from BL; n=324 | Temp >=38.3 and >1.1°C ↑ from BL; n=322 | Weight >=7% ↑ from BL; n=272 | Weight <=7% ↓ from BL; n=272 | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 4 | 17 | 2 | 35 | 80 | 5 | 11 | 8 | 12 | 59 | 0 | 1 | 0 | 0 | 2 | 25 | 79 |
To prospectively monitor for the possible development of sleep attacks, participants were asked if they had experienced any events in which they fell asleep suddenly or unexpectedly, including while engaged in some activity (e.g., eating/drinking, speaking, or driving) or at rest, with or without any previous warning of sleepiness. Those participants who reported 1 or more sleep attacks were asked to report the number of sleep attacks they experienced, whether they experienced sleepiness or drowsiness prior to the sleep attack, whether they experienced a 'bad' outcome or problem due to a sleep attack, and if so, how many 'bad' outcomes or problems they experienced. (NCT00335153)
Timeframe: Baseline
| Intervention | participants (Number) | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Participants with >=1 Sleep Attacks | Number of Sleep Attacks Per Participant=1 | Number of Sleep Attacks Per Participant=2 | Number of Sleep Attacks Per Participant=3 | Number of Sleep Attacks Per Participant>3 | Number of Sleep Attacks Per Participant=Missing | Sleepiness/Drowsiness Prior to Sleep Attack | Bad Outcome/Problem Due to Sleep Attack | Number of Bad Outcomes/Problems=1 | Number of Bad Outcomes/Problems=2 | Number of Bad Outcomes/Problems=3 | Number of Bad Outcomes/Problems>3 | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 7 | 4 | 0 | 0 | 2 | 1 | 4 | 1 | 1 | 0 | 0 | 0 |
To prospectively monitor for the possible development of sleep attacks, participants were asked if they had experienced any events in which they fell asleep suddenly or unexpectedly, including while engaged in some activity (e.g., eating/drinking, speaking, or driving) or at rest, with or without any previous warning of sleepiness. Those participants who reported 1 or more sleep attacks were asked to report the number of sleep attacks they experienced, whether they experienced sleepiness or drowsiness prior to the sleep attack, whether they experienced a 'bad' outcome or problem due to a sleep attack, and if so, how many 'bad' outcomes or problems they experienced. (NCT00335153)
Timeframe: During the Post-PEG Long-Term Treatment Period (Day 28 through Day 378)
| Intervention | participants (Number) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Participants with >=1 Sleep Attacks | Number of Sleep Attacks Per Participant=1 | Number of Sleep Attacks Per Participant=2 | Number of Sleep Attacks Per Participant=3 | Number of Sleep Attacks Per Participant>3 | Sleepiness/Drowsiness Prior to Sleep Attack | Bad Outcome/Problem Due to Sleep Attack | Number of Bad Outcomes/Problems=1 | Number of Bad Outcomes/Problems=2 | Number of Bad Outcomes/Problems=3 | Number of Bad Outcomes/Problems>3 | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 27 | 11 | 2 | 5 | 9 | 11 | 2 | 2 | 0 | 0 | 0 |
The MIDI is a validated assessment of impulsive behavior consisting of a semistructured clinical interview assessing pathological gambling, trichotillomania (compulsive hair-pulling), kleptomania (compulsive stealing), pyromania (compulsive fire setting), intermittent explosive disorder, compulsive buying, and compulsive sexual behavior. (NCT00335153)
Timeframe: Baseline, during the Post-PEG Long-term Treatment Period (Day 28 through Day 378)
| Intervention | participants (Number) | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| BL Compulsive Buying; n=322 | BL Kleptomania; n=322 | BL Trichotillomania; n=322 | BL Intermittent Explosive Disorder; n=322 | BL Pyromania; n=322 | BL Pathological Gambling; n=322 | BL Compulsive Sexual Behavior; n=322 | PPLT Compulsive Buying; n=318 | PPLT Kleptomania; n=318 | PPLT Trichotillomania; n=318 | PPLT Intermittent Explosive Disorder; n=318 | PPLT Pyromania; n=318 | PPLT Pathological Gambling; n=318 | PPLT Compulsive Sexual Behavior; n=318 | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 0 | 0 | 0 | 0 | 0 | 2 | 9 | 3 | 0 | 0 | 0 | 0 | 6 | 11 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. These include: mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort. The PDQ-39 Summary Index is the sum of all answers divided by the highest score possible (i.e. number of answers multiplied by 4) which is multiplied by 100 to put the score on a 0-100 scale. Higher scores are associated with more severe symptoms. (NCT00335153)
Timeframe: Baseline, Endpoint (last post-baseline visit up to Day 378)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline | Change from Baseline at Endpoint | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 42.7 | -6.9 |
A comprehensive assessment for the presence of melanoma was performed during the screening period and at early termination or end of study by a dermatologist experienced with the diagnosis of the condition. If a suspicious lesion was present, a biopsy was obtained for proper diagnosis. (NCT00335153)
Timeframe: Screening up to Day 378
| Intervention | participants (Number) |
|---|---|
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 0 |
Concomitant medications include those started on or after the first open-label LCIG infusion as well as medications started prior to the first open-label infusion but continued during the study. (NCT00335153)
Timeframe: Screening up to Day 378
| Intervention | participants (Number) |
|---|---|
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 349 |
"Based on the Parkinson's Disease Symptom Diary. On time is when PD symptoms are well controlled by the drug. Off time is when PD symptoms are not adequately controlled by the drug. The diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected clinic visits. It reflects both time awake and time asleep. Daily totals are normalized to a 16-hour scale (i.e. 16 hours of awake time). The normalized totals for the 3 days prior to the visit are averaged for the analysis." (NCT00335153)
Timeframe: Baseline, Endpoint (last post-baseline visit up to Day 378)
| Intervention | hours (Mean) | |
|---|---|---|
| Baseline | Change from Baseline at Endpoint | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 1.60 | -0.36 |
"Based on the Parkinson's Disease Symptom Diary. On time is when PD symptoms are well controlled by the drug. Off time is when PD symptoms are not adequately controlled by the drug. The diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected clinic visits. It reflects both time awake and time asleep. Daily totals are normalized to a 16-hour scale (i.e. 16 hours of awake time). The normalized totals for the 3 days prior to the visit are averaged for the analysis. Negative change from baseline for off time indicates improvement." (NCT00335153)
Timeframe: Baseline, Endpoint (last post-baseline visit up to Day 378)
| Intervention | hours (Mean) | |
|---|---|---|
| Baseline | Change from Baseline at Endpoint | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 6.77 | -4.44 |
"Based on the Parkinson's Disease Symptom Diary. On time is when PD symptoms are well controlled by the drug. Off time is when PD symptoms are not adequately controlled by the drug. On time without troublesome dyskinesia (involuntary muscle movement) is defined as on time without dyskinesia and on time with non-troublesome dyskinesia. The diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected clinic visits. It reflects both time awake and time asleep. Daily totals are normalized to a 16-hour scale (i.e. 16 hours of awake time). The normalized totals for the 3 days prior to the visit are averaged for the analysis. Positive change from Baseline for on time without troublesome dyskinesia indicates improvement." (NCT00335153)
Timeframe: Baseline, Endpoint (last post-baseline visit up to Day 378)
| Intervention | hours (Mean) | |
|---|---|---|
| Baseline | Change from Baseline at Endpoint | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 4.83 | 3.86 |
"The AIMS is an investigator-completed rating scale that has a total of 12 items rating involuntary movements of various areas of the participant's body. Items 1 through 10 are rated on a 5-point scale of severity from 0 (none), 1 (minimal), 2 (mild), 3 (moderate), to 4 (severe), and items 11 and 12 are yes/no questions regarding issues with teeth or dentures. The total AIMS score was calculated by summing items 1-10, with a possible range of 0-40; a negative change indicates improvement. The AIMS was to be performed at consistent times, when the subject was experiencing his/her worst On time (dyskinesia [involuntary muscle movement])." (NCT00335153)
Timeframe: Baseline, Endpoint (last Post-PEG Long-Term Period visit up to Day 378)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline; n=318 | Change from Baseline at Endpoint; n=317 | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 9.6 | -1.7 |
The EQ-5D is a participant answered questionnaire scoring 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. EQ-5D health states, defined by the EQ-5D descriptive system, are converted into a single summary index by applying a formula that essentially attaches values (also called QOL weights or QOL utilities) to each of the levels in each dimension. EQ-5D Summary Index values range from -0.11 to 1.00 with positive change indicating improvement. (NCT00335153)
Timeframe: Baseline, Endpoint (last post-baseline visit up to Day 378)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline | Change from Baseline at Endpoint | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 0.588 | 0.064 |
The EQ-5D VAS records the participant's self-rated health on a scale from 0-100 where 100 is the 'best imaginable health state' and 0 is the 'worst imaginable health state'. (NCT00335153)
Timeframe: Baseline, Endpoint (last post-baseline visit up to Day 378)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline | Change from Baseline at Endpoint | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 50.2 | 14.0 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Mobility (e.g., fear of falling when walking) includes 10 questions, each answered on a 5-point scale. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness. (NCT00357994)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| LCIG + Placebo Capsules | -17.3 |
| Placebo Gel + Levodopa-Carbidopa Capsules | -6.8 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Emotional Well-being (e.g., feelings of isolation) includes 6 questions, each answered on a 5-point scale. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness. (NCT00357994)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| LCIG + Placebo Capsules | -7.1 |
| Placebo Gel + Levodopa-Carbidopa Capsules | -4.9 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Communication includes 3 questions, each answered on a 5-point scale. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness. (NCT00357994)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| LCIG + Placebo Capsules | -9.5 |
| Placebo Gel + Levodopa-Carbidopa Capsules | 4.4 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Cognition includes 4 questions, each answered on a 5-point scale. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness. (NCT00357994)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| LCIG + Placebo Capsules | -7.3 |
| Placebo Gel + Levodopa-Carbidopa Capsules | -3.2 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Bodily Discomfort includes 3 questions, each answered on a 5-point scale. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness. (NCT00357994)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| LCIG + Placebo Capsules | -13.5 |
| Placebo Gel + Levodopa-Carbidopa Capsules | -10.2 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Activities of Daily Living (e.g., difficulty cutting food) includes 6 questions, each answered on a 5-point scale. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness. (NCT00357994)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| LCIG + Placebo Capsules | -12.9 |
| Placebo Gel + Levodopa-Carbidopa Capsules | -1.3 |
The EQ-5D is a participant answered questionnaire scoring 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. EQ-5D health states, defined by the EQ-5D descriptive system, are converted into a single summary index by applying a formula that essentially attaches values (also called QOL weights or QOL utilities) to each of the levels in each dimension. EQ-5D Summary Index values range from -0.11 to 1.00 with positive change indicating improvement. (NCT00357994)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| LCIG + Placebo Capsules | 0.054 |
| Placebo Gel + Levodopa-Carbidopa Capsules | -0.016 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Social Support includes 3 questions, each answered on a 5-point scale. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness. (NCT00357994)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| LCIG + Placebo Capsules | -3.9 |
| Placebo Gel + Levodopa-Carbidopa Capsules | -0.1 |
The EQ-5D VAS records the participant's self-rated health on a scale from 0-100 where 100 is the 'best imaginable health state' and 0 is the 'worst imaginable health state.' (NCT00357994)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| LCIG + Placebo Capsules | 5.2 |
| Placebo Gel + Levodopa-Carbidopa Capsules | -6.3 |
"Based on the Parkinson's Disease Symptom Diary. On time is when PD symptoms are well controlled by the drug. Off time is when PD symptoms are not adequately controlled by the drug. The diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected clinic visits. It reflects both time awake and time asleep. Daily totals are normalized to a 16-hour scale (i.e. 16 hours of awake time). The normalized totals for the 3 days prior to the visit are averaged for the analysis. Negative change from baseline for off time indicates improvement." (NCT00357994)
Timeframe: Baseline, Week 12
| Intervention | hours (Least Squares Mean) |
|---|---|
| LCIG + Placebo Capsules | -4.04 |
| Placebo Gel + Levodopa-Carbidopa Capsules | -2.14 |
"Based on the Parkinson's Disease Symptom Diary. On time is when PD symptoms are well controlled by the drug. Off time is when PD symptoms are not adequately controlled by the drug. On time without troublesome dyskinesia (involuntary muscle movement) is defined as on time without dyskinesia and on time with non-troublesome dyskinesia. The diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected clinic visits. It reflects both time awake and time asleep. Daily totals are normalized to a 16-hour scale (i.e. 16 hours of awake time). The normalized totals for the 3 days prior to the visit are averaged for the analysis. Positive change from Baseline for on time without troublesome dyskinesia indicates improvement." (NCT00357994)
Timeframe: Baseline, Week 12
| Intervention | hours (Least Squares Mean) |
|---|---|
| LCIG + Placebo Capsules | 4.11 |
| Placebo Gel + Levodopa-Carbidopa Capsules | 2.24 |
"Based on the Parkinson's Disease Symptom Diary. On time is when PD symptoms are well controlled by the drug. Off time is when PD symptoms are not adequately controlled by the drug. The diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected clinic visits. It reflects both time awake and time asleep. Daily totals are normalized to a 16-hour scale (i.e. 16 hours of awake time). The normalized totals for the 3 days prior to the visit are averaged for the analysis." (NCT00357994)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| LCIG + Placebo Capsules | -0.11 |
| Placebo Gel + Levodopa-Carbidopa Capsules | -0.03 |
The EMP instruments are designed to collect information regarding employment and ability to run a household. EMP I questions include: Are you currently in paid employment? (If yes, at which percentage have you been working during the last 4 weeks?); Have you got someone to run your household for you? (If yes, how much time per week does he/she spend in your household?); Are you retired? (If yes, for which reason?) The retirement question (from EMP I) is excluded from the EMP II instrument. (NCT00357994)
Timeframe: Week 12 (or early termination)
| Intervention | participants (Number) | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Paid Employment (PE)=Yes | PE=Yes, 100% of Past 4 Weeks | PE=Yes, 75% of Past 4 Weeks | PE=Yes, 50% of Past 4 Weeks | PE=Yes, 25% of Past 4 Weeks | PE=Yes, Other % of Past 4 Weeks | PE=No | Someone Else Runs the Household (SRH)=Yes | SRH=Yes, 100% of Time per Week | SRH=Yes, 75% of Time per Week | SRH=Yes, 50% of Time per Week | SRH=Yes, 25% of Time per Week | SRH=Yes, Other % of Time per Week | SRH=No | |
| LCIG + Placebo Capsules | 10 | 6 | 1 | 1 | 0 | 2 | 25 | 22 | 13 | 5 | 0 | 2 | 2 | 13 |
| Placebo Gel + Levodopa-Carbidopa Capsules | 5 | 1 | 1 | 2 | 1 | 0 | 26 | 24 | 12 | 4 | 4 | 2 | 2 | 7 |
The EMP instruments are designed to collect information regarding employment and ability to run a household. EMP I questions include: Are you currently in paid employment? (If yes, at which percentage have you been working during the last 4 weeks?); Have you got someone to run your household for you? (If yes, how much time per week does he/she spend in your household?); Are you retired? (If yes, for which reason?). (NCT00357994)
Timeframe: Baseline
| Intervention | participants (Number) | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Paid Employment (PE)=Yes | PE=Yes, 100% of Past 4 Weeks | PE=Yes, 75% of Past 4 Weeks | PE=Yes, 50% of Past 4 Weeks | PE=Yes, 25% of Past 4 Weeks | PE=Yes, Other % of Past 4 Weeks | PE=No | Someone Else Runs the Household (SRH)=Yes | SRH=Yes, 100% of Time per Week | SRH=Yes, 75% of Time per Week | SRH=Yes, 50% of Time per Week | SRH=Yes, 25% of Time per Week | SRH=Yes, Other % of Time per Week | SRH=No | Are You Retired (R)=Yes | R=Yes, Old Age Pensioner | R=Yes, Premature Due to PD | R=Yes, Premature Due to Other Condition | R=Yes, Other Reason | R=No | |
| LCIG + Placebo Capsules | 10 | 6 | 2 | 0 | 1 | 1 | 25 | 24 | 15 | 3 | 3 | 2 | 1 | 11 | 24 | 8 | 13 | 1 | 2 | 11 |
| Placebo Gel + Levodopa-Carbidopa Capsules | 8 | 3 | 1 | 2 | 1 | 1 | 23 | 25 | 13 | 4 | 5 | 1 | 2 | 6 | 23 | 8 | 12 | 1 | 2 | 8 |
The CGI-S is a global assessment by the Investigator of current symptomatology and impact of illness on functioning. The ratings of the CGI-S are as follows: 1 = normal, 2 = borderline ill, 3 = mildly ill, 4 = moderately ill, 5 = markedly ill, 6 = severely ill, and 7 = among the most extremely ill. The CGI-I is a global assessment by the Investigator of the change in clinical status since the start of treatment. The CGI-I ratings are as follows: 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, 7 = very much worse. (NCT00357994)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Mean) | |
|---|---|---|
| CGI-S at Baseline | CGI-I at Week 12 | |
| LCIG + Placebo Capsules | 4.2 | 2.3 |
| Placebo Gel + Levodopa-Carbidopa Capsules | 4.6 | 3.2 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Stigma (e.g., social embarrassment) consists of 4 questions, each answered on a 5-point scale. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness. (NCT00357994)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| LCIG + Placebo Capsules | -8.9 |
| Placebo Gel + Levodopa-Carbidopa Capsules | -4.5 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. These include: mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort. The PDQ-39 Summary Index is the sum of all answers divided by the highest score possible (i.e. number of answers multiplied by 4) which is multiplied by 100 to put the score on a 0-100 scale. Higher scores are associated with more severe symptoms. (NCT00357994)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| LCIG + Placebo Capsules | -10.9 |
| Placebo Gel + Levodopa-Carbidopa Capsules | -3.9 |
The UPDRS is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The Part I Score is the sum of the answers to the 4 questions that comprise Part I, each of which are measured on a 5-point scale (0-4). The Part I score ranges from 0-16 and higher scores are associated with more disability. (NCT00357994)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| LCIG + Placebo Capsules | -0.2 |
| Placebo Gel + Levodopa-Carbidopa Capsules | -0.5 |
The UPDRS is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The Part II score is the sum of the answers to the 13 questions that comprise Part II, each of which are measured on a 5-point scale (0-4). The Part II score ranges from 0-52 and higher scores are associated with more disability. (NCT00357994)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| LCIG + Placebo Capsules | -1.8 |
| Placebo Gel + Levodopa-Carbidopa Capsules | 1.3 |
The UPDRS is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. Questions 32, 33, and 34 on UPDRS Part IV were totaled to evaluate dyskinesias. Each of these questions is measured on a 5-point scale (0-4). The Part IV dyskinesia score will range from 0-12 and higher scores are associated with more disability. (NCT00357994)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| LCIG + Placebo Capsules | 0.4 |
| Placebo Gel + Levodopa-Carbidopa Capsules | 0.8 |
The UPDRS is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The Part IV Score is the sum of the answers to the 11 questions that comprise Part IV, each of which are measured on a 5-point scale (0-4) or a 2-point scale (0 or 1). The Part IV score ranges from 0-23 and higher scores are associated with more disability. (NCT00357994)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| LCIG + Placebo Capsules | -1.1 |
| Placebo Gel + Levodopa-Carbidopa Capsules | 0.1 |
The UPDRS is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The total score is the sum of the responses to the 31 questions (44 answers) that comprise Parts I-III of the scale. The total score will range from 0-176, with 176 representing the worst (total) disability, and 0 no disability. (NCT00357994)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| LCIG + Placebo Capsules | -3.6 |
| Placebo Gel + Levodopa-Carbidopa Capsules | -2.1 |
The UPDRS is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The Part III score is the sum of the 27 answers provided to the 14 Part III questions, each of which are measured on a 5-point scale (0-4). The Part III score ranges from 0-108 and higher scores are associated with more disability. (NCT00357994)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| LCIG + Placebo Capsules | -1.5 |
| Placebo Gel + Levodopa-Carbidopa Capsules | -2.9 |
The ZBI is a 22-item questionnaire regarding the caregiver/subject relationship and evaluates the caregiver's health condition, psychological well-being, finances and social life. Each question is answered on a 5-point scale (0=Never, 1=Rarely, 2=Sometimes, 3=Quite frequently, and 4= Nearly always). The caregiver burden is evaluated by the total score (Range 0 to 88) obtained from the sum of the answers to the 22 questions. Higher scores are associated with a higher level of burden for the caregiver. (NCT00357994)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| LCIG + Placebo Capsules | -2.8 |
| Placebo Gel + Levodopa-Carbidopa Capsules | 1.7 |
The CGI-S is a global assessment by the Investigator of current symptomatology and impact of illness on functioning. The ratings of the CGI-S are as follows: 1 = normal, 2 = borderline ill, 3 = mildly ill, 4 = moderately ill, 5 = markedly ill, 6 = severely ill, and 7 = among the most extremely ill. The CGI-I is a global assessment by the Investigator of the change in clinical status since the start of treatment. The CGI-I ratings are as follows: 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, 7 = very much worse. (NCT00360568)
Timeframe: Baseline, Endpoint (Month 12 or last post-baseline visit)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| CGI-S at Baseline; n=32, 28, 60 | CGI-I at Endpoint; n=33, 29, 62 | |
| LCIG (All Participants) | 3.3 | 2.2 |
| LCIG (Previous: LCIG + Placebo Capsules) | 3.0 | 2.1 |
| LCIG (Previous: Placebo Gel + Levodopa-Carbidopa Capsules) | 3.7 | 2.3 |
The Columbia-Suicide Severity Rating Scale (C-SSRS) is a systematically administered instrument developed to track suicidal adverse events across a treatment study. The instrument is designed to assess suicidal behavior and ideation, track and assess all suicidal events, as well as the lethality of attempts. Suicidal ideation categories include the following: wish to be dead; nonspecific active suicidal thoughts; active suicidal ideation without intent to act; active suicidal ideation with some intent to act but no plan; active suicidal ideation with plan and intent. Suicidal behavior categories include the following: actual attempt; interrupted attempt; aborted attempt; preparatory acts or behavior; suicidal behavior; completed suicide. (NCT00360568)
Timeframe: up to 12 months
| Intervention | participants (Number) | |||
|---|---|---|---|---|
| Participants with Suicidal Ideations | Participants with Suicidal Ideations Only | Participants with Suicidal Behaviors | Participants with Suicidal Behaviors or Ideations | |
| LCIG (All Participants) | 0 | 0 | 0 | 0 |
| LCIG (Previous: LCIG + Placebo Capsules) | 0 | 0 | 0 | 0 |
| LCIG (Previous: Placebo Gel + Levodopa-Carbidopa Capsules) | 0 | 0 | 0 | 0 |
AE=any untoward medical occurrence which does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that: results in death; is life-threatening (an event in which the subject was at risk of death at the time of the event); requires inpatient hospitalization or prolongation of an existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or other important medical events. Treatment-emergent events (TEAE or TESAE)=those starting after the first dose of study drug. Severe=severity reported as 'severe' or missing. Possibly or Probably Treatment Related=drug-event relationship reported as 'possible', 'probable' or missing. Death=a fatal outcome of an SAE or AE. (NCT00360568)
Timeframe: From study enrollment to the end of study or early termination of treatment, including the removal of PEG-J, plus 30 days.
| Intervention | participants (Number) | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Deaths | TE Deaths | >=1 SAE | >=1 TESAE | >=1 TEAE Leading to Study Termination | >=1 TEAE | >=1 Severe TEAE | >=1 Possibly or ProbablyTreatment-Related TEAE | No TEAEs | |
| LCIG (All Participants) | 0 | 0 | 14 | 14 | 3 | 59 | 15 | 48 | 3 |
| LCIG (Previous: LCIG + Placebo Capsules) | 0 | 0 | 5 | 5 | 1 | 31 | 5 | 28 | 2 |
| LCIG (Previous: Placebo Gel + Levodopa-Carbidopa Capsules) | 0 | 0 | 9 | 9 | 2 | 28 | 10 | 20 | 1 |
"The neurologic examination was to be done during On time. The neurological examination assessed: cranial nerves - assessment of cranial nerves II - XII, excluding fundoscopic examination; motor system - assessment of tone, strength, and abnormal movements; sensory system - including light touch, pinprick, joint position, and vibratory sense; reflexes - assessment of deep tendon reflexes and plantar responses (Babinski sign); coordination - assessment of upper and lower extremities; gait - assessment of base and tandem gait; station - assessment of posture and stability." (NCT00360568)
Timeframe: up to 12 months
| Intervention | participants (Number) | ||||||
|---|---|---|---|---|---|---|---|
| Cranial Nerve | Motor System | Sensory System | Reflexes | Coordination | Gait | Station | |
| LCIG (All Participants) | 0 | 5 | 3 | 2 | 1 | 4 | 4 |
| LCIG (Previous: LCIG + Placebo Capsules) | 0 | 3 | 2 | 1 | 1 | 2 | 2 |
| LCIG (Previous: Placebo Gel + Levodopa-Carbidopa Capsules) | 0 | 2 | 1 | 1 | 0 | 2 | 2 |
Complications of the infusion device were collected. Pump, intestinal tube, PEG, stoma, and other complications included (but were not limited to) device breakage, device leakage, device malfunction, device misuse, device occlusion, intentional and unintentional device removal by participant, complication of device insertion, device dislocation, device breakage, device dislocation, and device site reaction. (NCT00360568)
Timeframe: 12 months
| Intervention | participants (Number) | |||||
|---|---|---|---|---|---|---|
| >=1 Complication | Pump Complication | Intestinal Tube Complication | PEG Complication | Stoma Complication | Other | |
| LCIG (All Participants) | 50 | 34 | 31 | 22 | 27 | 10 |
| LCIG (Previous: LCIG + Placebo Capsules) | 26 | 18 | 15 | 11 | 12 | 6 |
| LCIG (Previous: Placebo Gel + Levodopa-Carbidopa Capsules) | 24 | 16 | 16 | 11 | 15 | 4 |
Terms abbreviated in the table include heart rate (HR) in beats per minute (bpm), PR interval (PRI), QT interval corrected for heart rate using Bazett's formula (QTcB), and QT interval corrected for heart rate using Fridericia's formula (QTcF). Increase and decrease are signified by ↑ and ↓, respectively. (NCT00360568)
Timeframe: 12 months
| Intervention | participants (Number) | |||||||
|---|---|---|---|---|---|---|---|---|
| HR <=50 and >30 bpm ↓ from BL; n=33, 28, 61 | HR >=120 and >30 bpm ↑ from BL; n=33, 28, 61 | PR Interval <120 msec; n=33, 27, 60 | PR Interval >220 msec; n=33, 27, 60 | QTcB Interval >480 msec; n=33, 27, 60 | QTcB Interval >60 msec ↑ from BL; n=33, 27, 60 | QTcF Interval >480 msec; n=33, 27, 60 | QTcF Interval >60 msec ↑ from BL; n=33, 27, 60 | |
| LCIG (All Participants) | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 |
| LCIG (Previous: LCIG + Placebo Capsules) | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 |
| LCIG (Previous: Placebo Gel + Levodopa-Carbidopa Capsules) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Terms abbreviated in the table include upper limit of normal (ULN), male (m), and female (f). (NCT00360568)
Timeframe: 12 months
| Intervention | participants (Number) | ||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Sodium <126 mmol/L; n=33, 28, 61 | Sodium >156 mmol/L; n=33, 28, 61 | Albumin <25 g/L; n=27, 20, 47 | Albumin >70 g/L; n=27, 20, 47 | Potassium <3.0 mmol/L; n=33, 28, 61 | Potassium >6.0 mmol/L; n=33, 28, 61 | Creatinine >177 µmol/L; n=33, 28, 61 | Calcium <1.75 mmol/L; n=33, 28, 61 | Calcium >3.0 mmol/L; n=33, 28, 61 | Total Protein <45 g/L; n=33, 28, 61 | Total Bilirubin >2xULN; n=33, 28, 61 | Aspartate Aminotransferase >3xULN; n=33, 28, 61 | Alanine Aminotransferase >3xULN; n=33, 28, 61 | Gamma-glutamyl Transpeptidase >3x ULN;n=33, 28, 61 | Lactate dehydrogenase >3x ULN; n=33, 28, 61 | Alkaline Phosphatase >400 U/L; n=33, 28, 61 | Creatine Phosphokinase >3x ULN; n=33, 28, 61 | Non-fasting Glucose <2.78 mmol/L; n=33, 28, 61 | Non-fasting Glucose >16.0 mmol/L; n=33, 28, 61 | Uric Acid>500µmol/L(f);>590µmol/L(m);n=33, 28, 61 | Blood Urea Nitrogen >10.8 mmol/L; n=28, 22, 50 | Cholesterol >12.9 mmol/L; n=33, 28, 61 | Triglycerides >5.6 mmol/L; n=33, 28, 61 | |
| LCIG (All Participants) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 0 |
| LCIG (Previous: LCIG + Placebo Capsules) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 0 |
| LCIG (Previous: Placebo Gel + Levodopa-Carbidopa Capsules) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Terms abbreviated in the table include females (f) and males (m). (NCT00360568)
Timeframe: 12 months
| Intervention | participants (Number) | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Red Blood Cells <2.0 10^12/L (f); <2.5 10^12/L (m) | Haemoglobin <90 g/L (f); <100 g/L (m) | Haematocrit <30% (f); <34% (m) | White Blood Cells <2.8 10^9/L | White Blood Cells >16.0 10^9/L | Neutrophils, Absolute <1.2 10^9/L | Lymphocytes >80% | Lymphocytes, Absolute <.75 10^9/L | Eosinophils >10% | Monocytes >30% | Platelet Count <95 10^9/L | Platelet Count >700 10^9/L | Mean Corpuscular Volume <60 fL | Mean Corpuscular Volume >120 fL | |
| LCIG (All Participants) | 0 | 1 | 2 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
| LCIG (Previous: LCIG + Placebo Capsules) | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
| LCIG (Previous: Placebo Gel + Levodopa-Carbidopa Capsules) | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Terms abbreviated in the table include supine systolic blood pressure (SuSBP), standing systolic blood pressure (StSBP), orthostatic systolic blood pressure (OSBP), supine diastolic blood pressure (SuDBP), standing diastolic blood pressure (StDBP), orthostatic diastolic blood pressure (ODBP), supine pulse (SuP) in beats per minute (bpm), standing pulse (StP), and body temperature (Temp). Increase and decrease are signified by ↑ and ↓, respectively. (NCT00360568)
Timeframe: 12 months
| Intervention | participants (Number) | ||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SuSBP <=90 and >30 mm Hg ↓ from BL; n=33, 29, 62 | SuSBP >=180 and >40 mm Hg ↑ from BL; n=33, 29, 62 | StSBP <=90 and >30 mm Hg ↓ from BL; n=33, 29, 62 | StSBP >=180 and >40 mm Hg ↑ from BL; n=33, 29, 62 | OSBP: ↓ >=30 mm Hg Supine to Standing; n=33,29,62 | SuDBP <=50 and >30 mm Hg ↓ from BL; n=33, 29, 62 | SuDBP >=105 and >30 mm Hg ↑ from BL; n=33, 29, 62 | StDBP <=50 and >30 mm Hg ↓ from BL; n=33, 29, 62 | StDBP >=105 and >30 mm Hg ↑ from BL; (n=33,29,62) | ODBP: ↓ >=20 mm Hg Supine to Standing; n=33,29,62 | SuP <=50 and >30 bpm ↓ from BL; n=33, 29, 62 | SuP >=120 and >30 bpm ↑ from BL; n=33, 29, 62 | StP <=50 and >30 bpm ↓ from BL; n=33, 29, 62 | StP >=120 and >30 bpm ↑ from BL; n=33, 29, 62 | Temp >=38.3° and >=1.1°C ↑ from BL; n=33, 29, 62 | Weight <=7% ↓ from BL; n=33, 27, 60 | Weight >=7% ↑ from BL; n=33, 27, 60 | |
| LCIG (All Participants) | 3 | 3 | 11 | 0 | 19 | 1 | 2 | 1 | 3 | 14 | 1 | 0 | 0 | 1 | 0 | 10 | 16 |
| LCIG (Previous: LCIG + Placebo Capsules) | 3 | 1 | 4 | 0 | 8 | 0 | 1 | 1 | 2 | 7 | 1 | 0 | 0 | 0 | 0 | 5 | 8 |
| LCIG (Previous: Placebo Gel + Levodopa-Carbidopa Capsules) | 0 | 2 | 7 | 0 | 11 | 1 | 1 | 0 | 1 | 7 | 0 | 0 | 0 | 1 | 0 | 5 | 8 |
To prospectively monitor for the possible development of sleep attacks, participants were asked if they had experienced any events in which they fell asleep suddenly or unexpectedly, including while engaged in some activity (e.g., eating/drinking, speaking, or driving) or at rest, with or without any previous warning of sleepiness. (NCT00360568)
Timeframe: Baseline, Endpoint (Month 12 or last post-baseline visit)
| Intervention | participants (Number) | |
|---|---|---|
| Participants with >=1 Sleep Attacks at Baseline | Participants with >=1 Sleep Attacks at Endpoint | |
| LCIG (All Participants) | 0 | 0 |
| LCIG (Previous: LCIG + Placebo Capsules) | 0 | 0 |
| LCIG (Previous: Placebo Gel + Levodopa-Carbidopa Capsules) | 0 | 0 |
The MIDI is a validated assessment of impulsive behavior consisting of a semistructured clinical interview assessing pathological gambling, trichotillomania (compulsive hair-pulling), kleptomania (compulsive stealing), pyromania (compulsive fire-setting), intermittent explosive disorder, compulsive buying, and compulsive sexual behavior. (NCT00360568)
Timeframe: Baseline, Post-baseline (up to Month 12)
| Intervention | participants (Number) | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| BL Pathological Gambling; n=33, 29, 62 | BL Trichotillomania; n=33, 29, 62 | BL Kleptomania; n=33, 29, 62 | BL Pyromania; n=33, 29, 62 | BL Intermittent Explosive Disorder; n=33, 29, 62 | BL Compulsive Buying; n=33, 29, 62 | BL Compulsive Sexual Behavior; n=33, 29, 62 | PBL Pathological Gambling; n=33, 27, 60 | PBL Trichotillomania; n=33, 27, 60 | PBL Kleptomania; n=33, 27, 60 | PBL Pyromania; n=33, 27, 60 | PBL Intermittent Explosive Disorder; n=33, 27, 60 | PBL Compulsive Buying; n=33, 27, 60 | PBL Compulsive Sexual Behavior; n=33, 27, 60 | |
| LCIG (All Participants) | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 2 |
| LCIG (Previous: LCIG + Placebo Capsules) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 |
| LCIG (Previous: Placebo Gel + Levodopa-Carbidopa Capsules) | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Concomitant medications include medications started on or after the first open-label LCIG infusion as well as medications started prior to the first open-label infusion but continued during the study. (NCT00360568)
Timeframe: 12 months
| Intervention | participants (Number) |
|---|---|
| LCIG (Previous: LCIG + Placebo Capsules) | 33 |
| LCIG (Previous: Placebo Gel + Levodopa-Carbidopa Capsules) | 29 |
| LCIG (All Participants) | 62 |
A comprehensive assessment for the presence of melanoma was performed during the screening period and at early termination/end of study by a dermatologist experienced with the diagnosis of the condition. If a suspicious lesion was present, a biopsy was obtained for proper diagnosis. (NCT00360568)
Timeframe: up to Month 12
| Intervention | participants (Number) |
|---|---|
| LCIG (Previous: LCIG + Placebo Capsules) | 0 |
| LCIG (Previous: Placebo Gel + Levodopa-Carbidopa Capsules) | 0 |
| LCIG (All Participants) | 0 |
"Based on the Parkinson's Disease Symptom Diary. On time is when PD symptoms are well controlled by the drug. Off time is when PD symptoms are not adequately controlled by the drug. The diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected clinic visits. It reflects both time awake and time asleep. Daily totals are normalized to a 16-hour scale (i.e. 16 hours of awake time). The normalized totals for the 3 days prior to the visit are averaged for the analysis." (NCT00360568)
Timeframe: Baseline, Endpoint (Month 12 or last post-baseline visit)
| Intervention | hours (Mean) | |
|---|---|---|
| Baseline | Change from Baseline at Endpoint | |
| LCIG (All Participants) | 0.97 | -0.24 |
| LCIG (Previous: LCIG + Placebo Capsules) | 1.09 | -0.58 |
| LCIG (Previous: Placebo Gel + Levodopa-Carbidopa Capsules) | 0.82 | 0.15 |
"Based on the Parkinson's Disease Symptom Diary. On time is when PD symptoms are well controlled by the drug. Off time is when PD symptoms are not adequately controlled by the drug. The diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected clinic visits. It reflects both time awake and time asleep. Daily totals are normalized to a 16-hour scale (i.e. 16 hours of awake time). The normalized totals for the 3 days prior to the visit are averaged for the analysis. Negative change from baseline for off time indicates improvement." (NCT00360568)
Timeframe: Baseline, Endpoint (Month 12 or last post-baseline visit)
| Intervention | hours (Mean) | |
|---|---|---|
| Baseline | Change from Baseline at Endpoint | |
| LCIG (All Participants) | 3.92 | -1.30 |
| LCIG (Previous: LCIG + Placebo Capsules) | 2.87 | -0.42 |
| LCIG (Previous: Placebo Gel + Levodopa-Carbidopa Capsules) | 5.18 | -2.34 |
"Based on the Parkinson's Disease Symptom Diary. On time is when PD symptoms are well controlled by the drug. Off time is when PD symptoms are not adequately controlled by the drug. On time without troublesome dyskinesia (involuntary muscle movement) is defined as on time without dyskinesia and on time with non-troublesome dyskinesia. The diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected clinic visits. It reflects both time awake and time asleep. Daily totals are normalized to a 16-hour scale (i.e. 16 hours of awake time). The normalized totals for the 3 days prior to the visit are averaged for the analysis. Positive change from Baseline for on time without troublesome dyskinesia indicates improvement." (NCT00360568)
Timeframe: Baseline, Endpoint (Month 12 or last post-baseline visit)
| Intervention | hours (Mean) | |
|---|---|---|
| Baseline | Change from Baseline at Endpoint | |
| LCIG (All Participants) | 11.11 | 1.54 |
| LCIG (Previous: LCIG + Placebo Capsules) | 12.04 | 1.00 |
| LCIG (Previous: Placebo Gel + Levodopa-Carbidopa Capsules) | 10.00 | 2.19 |
"The AIMS is an investigator-completed rating scale that has a total of 12 items rating involuntary movements of various areas of the participant's body. Items 1 through 10 are rated on a 5-point scale of severity from 0 (none), 1 (minimal), 2 (mild), 3 (moderate), to 4 (severe), and items 11 and 12 are yes/no questions concerning problems with teeth or dentures. The total AIMS score was calculated by summing items 1-10, with a possible range of 0-40; a negative change indicates improvement. The AIMS was to be performed at consistent times, when the subject was experiencing his/her worst On time (dyskinesia [involuntary muscle movement])." (NCT00360568)
Timeframe: Baseline, Endpoint (Month 12 or last post-baseline visit)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline; n=33, 29, 62 | Change from Baseline at Endpoint; n=33, 27, 60 | |
| LCIG (All Participants) | 5.7 | 5.6 |
| LCIG (Previous: LCIG + Placebo Capsules) | 6.1 | 6.1 |
| LCIG (Previous: Placebo Gel + Levodopa-Carbidopa Capsules) | 5.3 | 5.0 |
The EQ-5D is a participant answered questionnaire scoring 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. EQ-5D health states, defined by the EQ-5D descriptive system, are converted into a single summary index by applying a formula that essentially attaches values (also called QOL weights or QOL utilities) to each of the levels in each dimension. EQ-5D Summary Index values range from -0.11 to 1.00 with positive change indicating improvement. (NCT00360568)
Timeframe: Baseline, Endpoint (Month 12 or last post-baseline visit)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline | Change from Baseline at Endpoint | |
| LCIG (All Participants) | 0.733 | -0.008 |
| LCIG (Previous: LCIG + Placebo Capsules) | 0.778 | -0.009 |
| LCIG (Previous: Placebo Gel + Levodopa-Carbidopa Capsules) | 0.676 | -0.006 |
The EQ-5D VAS records the participant's self-rated health on a scale from 0-100 where 100 is the 'best imaginable health state' and 0 is the 'worst imaginable health state.' (NCT00360568)
Timeframe: Baseline, Endpoint (Month 12 or last post-baseline visit)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline | Change from Baseline at Endpoint | |
| LCIG (All Participants) | 70.2 | 1.5 |
| LCIG (Previous: LCIG + Placebo Capsules) | 76.7 | -0.9 |
| LCIG (Previous: Placebo Gel + Levodopa-Carbidopa Capsules) | 62.1 | 4.5 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Activities of Daily Living (e.g., difficulty cutting food) includes 6 questions, each answered on a 5-point scale. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness. (NCT00360568)
Timeframe: Baseline, Endpoint (Month 12 or last post-baseline visit)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline | Change from Baseline at Endpoint | |
| LCIG (All Participants) | 31.9 | -2.8 |
| LCIG (Previous: LCIG + Placebo Capsules) | 25.9 | 0.4 |
| LCIG (Previous: Placebo Gel + Levodopa-Carbidopa Capsules) | 39.4 | -6.7 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Bodily Discomfort includes 3 questions, each answered on a 5-point scale. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness. (NCT00360568)
Timeframe: Baseline, Endpoint (Month 12 or last post-baseline visit)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Endpoint | Change from Baseline at Endpoint | |
| LCIG (All Participants) | 33.3 | -1.1 |
| LCIG (Previous: LCIG + Placebo Capsules) | 32.1 | -2.8 |
| LCIG (Previous: Placebo Gel + Levodopa-Carbidopa Capsules) | 34.9 | 1.0 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Cognition includes 4 questions, each answered on a 5-point scale. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness. (NCT00360568)
Timeframe: Baseline, Endpoint (Month 12 or last post-baseline visit)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline | Change from Baseline at Endpoint | |
| LCIG (All Participants) | 19.3 | 2.4 |
| LCIG (Previous: LCIG + Placebo Capsules) | 15.0 | 1.3 |
| LCIG (Previous: Placebo Gel + Levodopa-Carbidopa Capsules) | 24.8 | 3.8 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Communication includes 3 questions, each answered on a 5-point scale. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness. (NCT00360568)
Timeframe: Baseline, Endpoint (Month 12 or last post-baseline visit)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline | Change from Baseline at Endpoint | |
| LCIG (All Participants) | 22.9 | 3.8 |
| LCIG (Previous: LCIG + Placebo Capsules) | 15.9 | 8.3 |
| LCIG (Previous: Placebo Gel + Levodopa-Carbidopa Capsules) | 31.7 | -1.9 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Emotional Well-being (e.g., feelings of isolation) includes 6 questions, each answered on a 5-point scale. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness. (NCT00360568)
Timeframe: Baseline, Endpoint (Month 12 or last post-baseline visit)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline | Change from Baseline at Endpoint | |
| LCIG (All Participants) | 22.8 | 3.1 |
| LCIG (Previous: LCIG + Placebo Capsules) | 20.1 | 4.0 |
| LCIG (Previous: Placebo Gel + Levodopa-Carbidopa Capsules) | 26.3 | 1.9 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Mobility (e.g., fear of falling when walking) includes 10 questions, each answered on a 5-point scale. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness. (NCT00360568)
Timeframe: Baseline, Endpoint (Month 12 or last post-baseline visit)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline | Change from Baseline at Endpoint | |
| LCIG (All Participants) | 34.7 | -2.5 |
| LCIG (Previous: LCIG + Placebo Capsules) | 27.6 | 2.3 |
| LCIG (Previous: Placebo Gel + Levodopa-Carbidopa Capsules) | 43.8 | -8.5 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Social Support includes 3 questions, each answered on a 5-point scale. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness. (NCT00360568)
Timeframe: Baseline, Endpoint (Month 12 or last post-baseline visit)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline | Change from Baseline at Endpoint | |
| LCIG (All Participants) | 14.2 | -0.2 |
| LCIG (Previous: LCIG + Placebo Capsules) | 11.9 | 1.8 |
| LCIG (Previous: Placebo Gel + Levodopa-Carbidopa Capsules) | 17.1 | -2.7 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Stigma (e.g., social embarrassment) consists of 4 questions, each answered on a 5-point scale. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness. (NCT00360568)
Timeframe: Baseline, Endpoint (Month 12 or last post-baseline visit)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline | Change from Baseline at Endpoint | |
| LCIG (All Participants) | 19.7 | -2.7 |
| LCIG (Previous: LCIG + Placebo Capsules) | 16.4 | 0.2 |
| LCIG (Previous: Placebo Gel + Levodopa-Carbidopa Capsules) | 23.8 | -6.3 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. These include: mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort. The PDQ-39 Summary Index is the sum of all answers divided by the highest score possible (i.e. number of answers multiplied by 4) which is multiplied by 100 to put the score on a 0-100 scale. Higher scores are associated with more severe symptoms. (NCT00360568)
Timeframe: Baseline, Endpoint (Month 12 or last post-baseline visit)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline | Change from Baseline at Endpoint | |
| LCIG (All Participants) | 26.9 | -0.7 |
| LCIG (Previous: LCIG + Placebo Capsules) | 22.2 | 1.5 |
| LCIG (Previous: Placebo Gel + Levodopa-Carbidopa Capsules) | 32.8 | -3.5 |
The UPDRS is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The Part I Score is the sum of the answers to the 4 questions that comprise Part I, each of which are measured on a 5-point scale (0-4). The Part I score ranges from 0-16 and higher scores are associated with more disability. (NCT00360568)
Timeframe: Baseline, Endpoint (Month 12 or last post-baseline visit)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline | Change from Baseline at Endpoint | |
| LCIG (All Participants) | 1.4 | 0.5 |
| LCIG (Previous: LCIG + Placebo Capsules) | 1.6 | 0.3 |
| LCIG (Previous: Placebo Gel + Levodopa-Carbidopa Capsules) | 1.2 | 0.7 |
The UPDRS is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The Part II score is the sum of the answers to the 13 questions that comprise Part II, each of which are measured on a 5-point scale (0-4). The Part II score ranges from 0-52 and higher scores are associated with more disability. (NCT00360568)
Timeframe: Baseline, Endpoint (Month 12 or last post-baseline visit)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline | Change from Baseline at Endpoint | |
| LCIG (All Participants) | 10.1 | -0.2 |
| LCIG (Previous: LCIG + Placebo Capsules) | 8.6 | 0.5 |
| LCIG (Previous: Placebo Gel + Levodopa-Carbidopa Capsules) | 12.1 | -1.0 |
The UPDRS is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The Part III score is the sum of the 27 answers provided to the 14 Part III questions, each of which are measured on a 5-point scale (0-4). The Part III score ranges from 0-108 and higher scores are associated with more disability. (NCT00360568)
Timeframe: Baseline, Endpoint (Month 12 or last post-baseline visit)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline | Change from Baseline at Endpoint | |
| LCIG (All Participants) | 17.4 | 0.6 |
| LCIG (Previous: LCIG + Placebo Capsules) | 16.2 | 1.5 |
| LCIG (Previous: Placebo Gel + Levodopa-Carbidopa Capsules) | 19.0 | -0.5 |
The UPDRS is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The Part IV Score is the sum of the answers to the 11 questions that comprise Part IV, each of which are measured on a 5-point scale (0-4) or a 2-point scale (0 or 1). The Part IV score ranges from 0-23 and higher scores are associated with more disability. (NCT00360568)
Timeframe: Baseline, Endpoint (Month 12 or last post-baseline visit)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline | Change from Baseline at Endpoint | |
| LCIG (All Participants) | 6.3 | -1.5 |
| LCIG (Previous: LCIG + Placebo Capsules) | 5.8 | -1.6 |
| LCIG (Previous: Placebo Gel + Levodopa-Carbidopa Capsules) | 7.0 | -1.4 |
The UPDRS is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The total score is the sum of the responses to the 31 questions (44 answers) that comprise Parts I-III of the scale. The total score will range from 0-176, with 176 representing the worst (total) disability, and 0 representing no disability. (NCT00360568)
Timeframe: Baseline, Endpoint (Month 12 or last post-baseline visit)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline | Change from Baseline at Endpoint | |
| LCIG (All Participants) | 29.0 | 0.9 |
| LCIG (Previous: LCIG + Placebo Capsules) | 26.4 | 2.3 |
| LCIG (Previous: Placebo Gel + Levodopa-Carbidopa Capsules) | 32.4 | -1.0 |
The ZBI is a 22-item questionnaire regarding the caregiver/subject relationship and evaluates the caregiver's health condition, psychological well-being, finances and social life. Each question is answered on a 5-point scale (0=never, 1=rarely, 2=sometimes, 3=quite frequently, and 4=nearly always). The caregiver burden is evaluated by the total score (range 0 to 88) obtained from the sum of the answers to the 22 questions. Higher scores are associated with a higher level of burden for the caregiver. (NCT00360568)
Timeframe: Baseline, Endpoint (Month 12 months or last post-baseline visit)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline | Change from Baseline at Endpoint | |
| LCIG (All Participants) | 24.3 | -0.2 |
| LCIG (Previous: LCIG + Placebo Capsules) | 22.1 | 1.1 |
| LCIG (Previous: Placebo Gel + Levodopa-Carbidopa Capsules) | 27.0 | -1.8 |
"Time to on state (benefit with regard to mobility, stiffness and slowness) with parcopa versus carbidopa/levodopa immediate release compound. This measurement is compared between Parcopa and carbidopa/levodopa wit the first morning dose of each intervention. Study duration was 2 days." (NCT00590122)
Timeframe: first dose of day for each arm
| Intervention | minutes (Mean) |
|---|---|
| B-Parcopa Arm | 23.9 |
| A-Carbidopa/Levodopa Arm | 28.5 |
"The QWOQ-9 is a self-rated questionnaire used to assess motor and non-motor symptoms of Parkinson's disease. The 5 motor symptoms are each measured on a five item (0-4) Likert scale, reflecting the severity of the item from not present to very severe. The range of possible score values of the motor subscale of the QWOQ-9 is 0 to 20. A higher score indicates greater disability. A negative change score indicates improvement." (NCT00642356)
Timeframe: Baseline to 15 minutes prior to 2nd dose at Week 8
| Intervention | Units on a scale (Mean) |
|---|---|
| Carbidopa/Levodopa/Entacapone | -1.2 |
| Immediate Release Carbidopa/Levodopa | 0.0 |
"The QWOQ-9 is a self-rated questionnaire used to assess motor and non-motor symptoms of Parkinson's disease. The 4 non-motor symptoms are each measured on a five item (0-4) Likert scale, reflecting the severity of the item from not present to very severe. The range of possible score values of the non-motor subscale of the QWOQ-9 is 0 to 16. A higher score indicates greater disability. A negative change score indicates improvement." (NCT00642356)
Timeframe: Baseline to 15 minutes prior to 2nd dose at Week 8
| Intervention | Units on a scale (Mean) |
|---|---|
| Carbidopa/Levodopa/Entacapone | -0.9 |
| Immediate Release Carbidopa/Levodopa | -0.2 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Cognition includes 4 questions, each answered on a 5-point scale. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness. (NCT00660387)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| LCIG + Placebo Capsules | -7.3 |
| Placebo Gel + Levodopa-Carbidopa Capsules | -3.2 |
"Based on the Parkinson's Disease Symptom Diary. On time is when PD symptoms are well controlled by the drug. Off time is when PD symptoms are not adequately controlled by the drug. The diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected clinic visits. It reflects both time awake and time asleep. Daily totals are normalized to a 16-hour scale (i.e. 16 hours of awake time). The normalized totals for the 3 days prior to the visit are averaged for the analysis." (NCT00660387)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| LCIG + Placebo Capsules | -0.11 |
| Placebo Gel + Levodopa-Carbidopa Capsules | -0.03 |
"Based on the Parkinson's Disease Symptom Diary. On time is when PD symptoms are well controlled by the drug. Off time is when PD symptoms are not adequately controlled by the drug. On time without troublesome dyskinesia (involuntary muscle movement) is defined as On time without dyskinesia and On time with non-troublesome dyskinesia. The diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected clinic visits. It reflects both time awake and time asleep. Daily totals are normalized to a 16-hour scale (i.e. 16 hours of awake time). The normalized totals for the 3 days prior to the visit are averaged for the analysis. Positive change from Baseline for on time without troublesome dyskinesia indicates improvement." (NCT00660387)
Timeframe: Baseline, Week 12
| Intervention | hours (Least Squares Mean) |
|---|---|
| LCIG + Placebo Capsules | 4.11 |
| Placebo Gel + Levodopa-Carbidopa Capsules | 2.24 |
"Based on the Parkinson's Disease Symptom Diary. On time is when PD symptoms are well controlled by the drug. Off time is when PD symptoms are not adequately controlled by the drug. The diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected clinic visits. It reflects both time awake and time asleep. Daily totals are normalized to a 16-hour scale (i.e. 16 hours of awake time). The normalized totals for the 3 days prior to the visit are averaged for the analysis. Negative change from baseline for off time indicates improvement." (NCT00660387)
Timeframe: Baseline, Week 12
| Intervention | hours (Least Squares Mean) |
|---|---|
| LCIG + Placebo Capsules | -4.04 |
| Placebo Gel + Levodopa-Carbidopa Capsules | -2.14 |
The EQ VAS records the participant's self-rated health on a scale from 0-100 where 100 is the 'best imaginable health state' and 0 is the 'worst imaginable health state.' (NCT00660387)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| LCIG + Placebo Capsules | 5.2 |
| Placebo Gel + Levodopa-Carbidopa Capsules | -6.3 |
The EQ-5D is a participant answered questionnaire scoring 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. EQ-5D health states, defined by the EQ-5D descriptive system, are converted into a single summary index by applying a formula that essentially attaches values (also called QOL weights or QOL utilities) to each of the levels in each dimension. EQ-5D Summary Index values range from -0.11 to 1.00 with positive change indicating improvement. (NCT00660387)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| LCIG + Placebo Capsules | 0.054 |
| Placebo Gel + Levodopa-Carbidopa Capsules | -0.016 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Activities of Daily Living (e.g., difficulty cutting food) includes 6 questions, each answered on a 5-point scale. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness. (NCT00660387)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| LCIG + Placebo Capsules | -12.9 |
| Placebo Gel + Levodopa-Carbidopa Capsules | -1.3 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Bodily Discomfort includes 3 questions, each answered on a 5-point scale. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness. (NCT00660387)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| LCIG + Placebo Capsules | -13.5 |
| Placebo Gel + Levodopa-Carbidopa Capsules | -10.2 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Communication includes 3 questions, each answered on a 5-point scale. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness. (NCT00660387)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| LCIG + Placebo Capsules | -9.5 |
| Placebo Gel + Levodopa-Carbidopa Capsules | 4.4 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Emotional Well-being (e.g., feelings of isolation) includes 6 questions, each answered on a 5-point scale. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness. (NCT00660387)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| LCIG + Placebo Capsules | -7.1 |
| Placebo Gel + Levodopa-Carbidopa Capsules | -4.9 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Mobility (e.g., fear of falling when walking) includes 10 questions, each answered on a 5-point scale. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness. (NCT00660387)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| LCIG + Placebo Capsules | -17.3 |
| Placebo Gel + Levodopa-Carbidopa Capsules | -6.8 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Social Support includes 3 questions, each answered on a 5-point scale. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness. (NCT00660387)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| LCIG + Placebo Capsules | -3.9 |
| Placebo Gel + Levodopa-Carbidopa Capsules | -0.1 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. The PDQ-39 Domain: Stigma (e.g., social embarrassment) consists of 4 questions, each answered on a 5-point scale. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness. (NCT00660387)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| LCIG + Placebo Capsules | -8.9 |
| Placebo Gel + Levodopa-Carbidopa Capsules | -4.5 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. These include: mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort. The PDQ-39 Summary Index is the sum of all answers divided by the highest score possible (i.e. number of answers multiplied by 4) which is multiplied by 100 to put the score on a 0-100 scale. Higher scores are associated with more severe symptoms. (NCT00660387)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| LCIG + Placebo Capsules | -10.9 |
| Placebo Gel + Levodopa-Carbidopa Capsules | -3.9 |
The UPDRS is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The Part I Score is the sum of the answers to the 4 questions that comprise Part I, each of which are measured on a 5-point scale (0-4). The Part I score ranges from 0-16 and higher scores are associated with more disability. (NCT00660387)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| LCIG + Placebo Capsules | -0.2 |
| Placebo Gel + Levodopa-Carbidopa Capsules | -0.5 |
The UPDRS is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The Part II score is the sum of the answers to the 13 questions that comprise Part II, each of which are measured on a 5-point scale (0-4). The Part II score ranges from 0-52 and higher scores are associated with more disability. (NCT00660387)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| LCIG + Placebo Capsules | -1.8 |
| Placebo Gel + Levodopa-Carbidopa Capsules | 1.3 |
The UPDRS is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. Questions 32, 33, and 34 on UPDRS Part IV was totaled to evaluate dyskinesias. Each of these questions is measured on a 5-point scale (0-4). The Part IV dyskinesia score will range from 0-12 and higher scores are associated with more disability. (NCT00660387)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| LCIG + Placebo Capsules | 0.4 |
| Placebo Gel + Levodopa-Carbidopa Capsules | 0.8 |
The UPDRS is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The Part IV Score is the sum of the answers to the 11 questions that comprise Part IV, each of which are measured on a 5-point scale (0-4) or a 2-point scale (0 or 1). The Part IV score ranges from 0-23 and higher scores are associated with more disability. (NCT00660387)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| LCIG + Placebo Capsules | -1.1 |
| Placebo Gel + Levodopa-Carbidopa Capsules | 0.1 |
The UPDRS is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The total score is the sum of the responses to the 31 questions (44 answers) that comprise Parts I-III of the scale. The total score will range from 0-176, with 176 representing the worst (total) disability, and 0 no disability. (NCT00660387)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| LCIG + Placebo Capsules | -3.6 |
| Placebo Gel + Levodopa-Carbidopa Capsules | -2.1 |
The UPDRS is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The Part III score is the sum of the 27 answers provided to the 14 Part III questions, each of which are measured on a 5-point scale (0-4). The Part III score ranges from 0-108 and higher scores are associated with more disability. (NCT00660387)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| LCIG + Placebo Capsules | -1.5 |
| Placebo Gel + Levodopa-Carbidopa Capsules | -2.9 |
The ZBI is a 22-item questionnaire regarding the caregiver/subject relationship and evaluates the caregiver's health condition, psychological well-being, finances and social life. Each question is answered on a 5-point scale (0=Never, 1=Rarely, 2=Sometimes, 3=Quite frequently, and 4= Nearly always). The caregiver burden is evaluated by the total score (Range 0 to 88) obtained from the sum of the answers to the 22 questions. Higher scores are associated with a higher level of burden for the caregiver. (NCT00660387)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| LCIG + Placebo Capsules | -2.8 |
| Placebo Gel + Levodopa-Carbidopa Capsules | 1.7 |
The CGI-S is a global assessment by the Investigator of current symptomatology and impact of illness on functioning. The ratings of the CGI-S are as follows: 1 = normal, 2 = borderline ill, 3 = mildly ill, 4 = moderately ill, 5 = markedly ill, 6 = severely ill, and 7 = among the most extremely ill. The CGI-I is a global assessment by the Investigator of the change in clinical status since the start of treatment. The CGI-I ratings are as follows: 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, 7 = very much worse. (NCT00660387)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Mean) | |
|---|---|---|
| CGI-S at Baseline | CGI-I at Week 12 | |
| LCIG + Placebo Capsules | 4.2 | 2.3 |
| Placebo Gel + Levodopa-Carbidopa Capsules | 4.6 | 3.2 |
The EMP instruments are designed to collect information regarding employment and ability to run a household. EMP I questions include: Are you currently in paid employment? (If yes, at which percentage have you been working during the last 4 weeks?); Have you got someone to run your household for you? (If yes, how much time per week does he/she spend in your household?); Are you retired? (If yes, for which reason?). (NCT00660387)
Timeframe: Baseline
| Intervention | participants (Number) | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Paid Employment (PE)=Yes | PE=Yes, 100% of Past 4 Weeks | PE=Yes, 75% of Past 4 Weeks | PE=Yes, 50% of Past 4 Weeks | PE=Yes, 25% of Past 4 Weeks | PE=Yes, Other % of Past 4 Weeks | PE=No | Someone Else Runs the Household (SRH)=Yes | SRH=Yes, 100% of Time per Week | SRH=Yes, 75% of Time per Week | SRH=Yes, 50% of Time per Week | SRH=Yes, 25% of Time per Week | SRH=Yes, Other % of Time per Week | SRH=No | Are You Retired (R)=Yes | R=Yes, Old Age Pensioner | R=Yes, Premature Due to PD | R=Yes, Premature Due to Other Condition | R=Yes, Other Reason | R=No | |
| LCIG + Placebo Capsules | 10 | 6 | 2 | 0 | 1 | 1 | 25 | 24 | 15 | 3 | 3 | 2 | 1 | 11 | 24 | 8 | 13 | 1 | 2 | 11 |
| Placebo Gel + Levodopa-Carbidopa Capsules | 8 | 3 | 1 | 2 | 1 | 1 | 23 | 25 | 13 | 4 | 5 | 1 | 2 | 6 | 23 | 8 | 12 | 1 | 2 | 8 |
The EMP instruments are designed to collect information regarding employment and ability to run a household. EMP I questions include: Are you currently in paid employment? (If yes, at which percentage have you been working during the last 4 weeks?); Have you got someone to run your household for you? (If yes, how much time per week does he/she spend in your household?); Are you retired? (If yes, for which reason?) The retirement question (from EMP I) is excluded from the EMP II instrument. (NCT00660387)
Timeframe: Week 12 (or early termination)
| Intervention | participants (Number) | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Paid Employment (PE)=Yes | PE=Yes, 100% of Past 4 Weeks | PE=Yes, 75% of Past 4 Weeks | PE=Yes, 50% of Past 4 Weeks | PE=Yes, 25% of Past 4 Weeks | PE=Yes, Other % of Past 4 Weeks | PE=No | Someone Else Runs the Household (SRH)=Yes | SRH=Yes, 100% of Time per Week | SRH=Yes, 75% of Time per Week | SRH=Yes, 50% of Time per Week | SRH=Yes, 25% of Time per Week | SRH=Yes, Other % of Time per Week | SRH=No | |
| LCIG + Placebo Capsules | 10 | 6 | 1 | 1 | 0 | 2 | 25 | 22 | 13 | 5 | 0 | 2 | 2 | 13 |
| Placebo Gel + Levodopa-Carbidopa Capsules | 5 | 1 | 1 | 2 | 1 | 0 | 26 | 24 | 12 | 4 | 4 | 2 | 2 | 7 |
"The Columbia-Suicide Severity Rating Scale (C-SSRS) was implemented with Protocol Amendment 3 (20 March 2012) in order to assess suicidal behavior and ideation.~Suicidal ideation includes the wish to be dead, nonspecific active suicidal thoughts, active ideation without intent to act, active ideation with some intent to act, and active ideation with specific plan or intent. Suicidal behavior includes actual attempts, interrupted attempts, aborted attempts, completed suicide, and preparatory acts or behaviors.~The number of participants with affirmative responses on the C-SSRS at any time during the treatment period is reported." (NCT00660673)
Timeframe: Every 6 months (beginning with implementation of Protocol Amendment 3) until final visit; median duration of treatment was 1178 days.
| Intervention | Participants (Count of Participants) | |||
|---|---|---|---|---|
| Any suicidal ideation or behavior | Any suicidal ideation | Any suicidal behavior | Non-suicidal self-injurious behavior | |
| Levodopa-Carbidopa Intestinal Gel | 32 | 30 | 6 | 1 |
"The UPDRS is an Investigator-used rating tool to follow the longitudinal course of PD. It is made up of the following sections:~I) Mentation, Behavior, and Mood; II) Activities of Daily Living; III) Motor Examinations; IV) Complications of Therapy sections (including Dyskinesias); and~The UPDRS Part IV dyskinesia Score is the sum of Questions 32 (What proportion of the waking day are dyskinesias present?), 33 (How disabling are the dyskinesias? ), and 34 (How painful are the dyskinesias?) on UPDRS Part IV, each of which are measured on a 5-point scale (0-4). The Part IV dyskinesia score ranges from 0 - 12 and higher scores are associated with more disability. A negative change from Baseline indicates improvement.~The UPDRS was implemented with Protocol amendment 4 (December 2013) for participants at US sites only." (NCT00660673)
Timeframe: Prior to initial LCIG infusion (in the previous study, before the first LCIG infusion), Baseline (final assessment of the previous open-label LCIG study), and end of treatment; median duration of treatment was 1178 days.
| Intervention | score on a scale (Mean) | |
|---|---|---|
| Change from initial LCIG infusion | Change from Baseline | |
| Levodopa-Carbidopa Intestinal Gel | -0.19 | 0.55 |
Special tests for vitamin deficiencies (folic acid, vitamin B6, vitamin B12, methylmalonic acid [MMA], and homocysteine) were implemented with Protocol Amendment 2 (27 July 2011). The number of participants with vitamin levels outside of the normal range at any time post-baseline is reported for each vitamin tested. (NCT00660673)
Timeframe: Every 6 months (beginning with implementation of Protocol Amendment 2) until final visit; median duration of treatment was 1178 days.
| Intervention | Participants (Count of Participants) | |||||||
|---|---|---|---|---|---|---|---|---|
| Vitamin B12 < 148 pmol/L | Vitamin B12 > 775 pmol/L | Methylmalonic acid > 0.4 µmol/L | Homocysteine < 3.7 µmol/L | Homocysteine > 13.9 µmol/L | Vitamin B6 < 20 nmol/L | Vitamin B6 > 125 nmol/L | Folic acid < 4.5 nmol/L | |
| Levodopa-Carbidopa Intestinal Gel | 22 | 46 | 65 | 1 | 198 | 155 | 108 | 6 |
"The UPDRS is an Investigator-used rating tool to follow the longitudinal course of PD. It is made up of the following sections:~I) Mentation, Behavior, and Mood;~II) Activities of Daily Living;~III) Motor Examinations;~IV) Complications of Therapy sections (including dyskinesias).~UPDRS Part III consists of 14 questions. Questions 20 - 26 are multi-part questions in that they are evaluated separately for multiple body parts. Counting each of these assessments leads to a total of 27 answers for Part III. The UPDRS Part III score is the sum of the 27 answers provided to the 14 Part III questions, each of which are measured on a 5-Point scale (0-4). The Part III score ranges from 0-108 and higher scores are associated with more disability. A negative change from Baseline indicates improvement.~The UPDRS was implemented with Protocol amendment 4 (December 2013) for participants at US sites only." (NCT00660673)
Timeframe: Prior to initial LCIG infusion (in the previous study, before the first LCIG infusion), Baseline (final assessment of the previous open-label LCIG study), and end of treatment; median duration of treatment was 1178 days.
| Intervention | score on a scale (Mean) | |
|---|---|---|
| Change from initial LCIG infusion | Change from Baseline | |
| Levodopa-Carbidopa Intestinal Gel | 4.51 | 9.18 |
"The UPDRS is an Investigator-used rating tool to follow the longitudinal course of PD. It is made up of the following sections:~I) Mentation, Behavior, and Mood;~II) Activities of Daily Living;~III) Motor Examinations;~IV) Complications of Therapy sections (including dyskinesias).~The Part I Score is the sum of the answers to the 4 questions that comprise Part I, each of which are measured on a 5-point scale (0-4). The Part I score ranges from 0-16 and higher scores are associated with more disability. A negative change from Baseline indicates improvement.~The UPDRS was implemented with Protocol amendment 4 (December 2013) for participants at US sites only." (NCT00660673)
Timeframe: Prior to initial LCIG infusion (in the previous study, before the first LCIG infusion), Baseline (final assessment of the previous open-label LCIG study), and end of treatment; median duration of treatment was 1178 days.
| Intervention | score on a scale (Mean) | |
|---|---|---|
| Change from initial LCIG infusion | Change from Baseline | |
| Levodopa-Carbidopa Intestinal Gel | 1.51 | 1.46 |
"The PDQ-39 is a self-administered questionnaire that comprises 39 items addressing the following eight domains of health that patients consider to be adversely affected by the disease:~Mobility (e.g., fear of falling when walking) - 10 questions~Activities of daily living (e.g., difficulty cutting food) - 6 questions~Emotional well-being (e.g., feelings of isolation) - 6 questions~Stigma (e.g., social embarrassment) - 4 questions~Social support - 3 questions~Cognition - 4 questions~Communication - 3 questions~Bodily discomfort - 3 questions~Each question is answered on a 5-point scale from 0 (Never) to 4 (Always / Cannot Do At All). Scores are calculated by summing the answers to the questions in the domain and converting to a scale from 0 to 100. Higher scores are associated with the more severe symptoms of the disease such as tremor and stiffness. The PDQ-39 summary index (range 0-100) includes responses to all 39 items. A negative change indicates improvement." (NCT00660673)
Timeframe: Prior to initial LCIG infusion (in the previous study, before the first LCIG infusion), Baseline (final assessment of the previous open-label LCIG study), and end of treatment; median duration of treatment was 1178 days.
| Intervention | score on a scale (Mean) | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Summary Index: Change from initial LCIG infusion | Summary Index: Change from Baseline | Mobility Domain: Change from initial LCIG infusion | Mobility Domain: Change from Baseline | Activities of Daily Living Domain: Change from initial LCIG infusion | Activities of Daily Living Domain: Change from Baseline | Emotional Well-Being Domain: Change from initial LCIG infusion | Emotional Well-Being Domain: Change from Baseline | Stigma Domain: Change from initial LCIG infusion | Stigma Domain: Change from Baseline | Social Support Domain: Change from initial LCIG infusion | Social Support Domain: Change from Baseline | Cognition Domain: Change from initial LCIG infusion | Cognition Domain: Change from Baseline | Communication Domain: Change from initial LCIG infusion | Communication Domain: Change from Baseline | Bodily Discomfort Domain: Change from initial LCIG infusion | Bodily Discomfort Domain: Change from Baseline | |
| Levodopa-Carbidopa Intestinal Gel | -1.46 | 6.83 | -2.08 | 12.01 | -1.55 | 9.35 | -0.58 | 2.53 | -9.50 | -0.18 | 3.59 | 2.25 | 1.78 | 6.56 | 3.19 | 8.17 | -4.74 | 5.64 |
"The PD diary asks participants (or their caregivers) to indicate their status upon waking and every 30 minutes during their normal waking time according to the following categories: asleep, off, on without dyskinesia, on with non-troublesome dyskinesia, or on with troublesome dyskinesia.~On time is when medication is providing benefit with regard to mobility, slowness and stiffness. Dyskinesia is involuntary twisting, turning movements which are an effect of medication and occur during on time. Non-troublesome dyskinesia does not interfere with function or cause meaningful discomfort.~On time without troublesome dyskinesia is the sum of on time without dyskinesia and on time with non-troublesome dyskinesia. PD diary times were normalized to a 16-hour waking day and averaged for the 3 days prior to each study visit. A positive change indicates improvement.~The PD diary was implemented with Protocol amendment 4 (December 2013) for participants at US sites only." (NCT00660673)
Timeframe: Prior to initial LCIG infusion (in the previous study, before the first LCIG infusion), Baseline (final assessment of the previous open-label LCIG study), and end of treatment; median duration of treatment was 1178 days.
| Intervention | hours (Mean) | |
|---|---|---|
| Change from initial LCIG infusion | Change from Baseline | |
| Levodopa-Carbidopa Intestinal Gel | 3.86 | -0.51 |
"The PD diary asks participants (or their caregivers) to indicate their status upon waking and every 30 minutes during their normal waking time according to the following categories: asleep, off, on without dyskinesia, on with non-troublesome dyskinesia, or on with troublesome dyskinesia.~On time is when medication is providing benefit with regard to mobility, slowness and stiffness. Dyskinesia is involuntary twisting, turning movements which are an effect of medication and occur during on time. Troublesome dyskinesia interferes with function or causes meaningful discomfort.~PD diary times were normalized to a 16-hour waking day and averaged for the 3 days prior to each study visit. A positive change indicates improvement.~The PD diary was implemented with Protocol amendment 4 (December 2013) for participants at US sites only." (NCT00660673)
Timeframe: Prior to initial LCIG infusion (in the previous study, before the first LCIG infusion), Baseline (final assessment of the previous open-label LCIG study), and end of treatment; median duration of treatment was 1178 days.
| Intervention | hours (Mean) | |
|---|---|---|
| Change from initial LCIG infusion | Change from Baseline | |
| Levodopa-Carbidopa Intestinal Gel | 0.12 | 0.70 |
"The PD symptom diary asks participants (or their caregivers) to indicate their status upon waking and every 30 minutes during their normal waking time according to the following categories: asleep, off, on without dyskinesia, on with non-troublesome dyskinesia, or on with troublesome dyskinesia.~Off time was defined as time when medication had worn off and was no longer providing benefit with regard to mobility, slowness, and stiffness.~PD diary times were normalized to a 16-hour waking day and averaged for the 3 days prior to each study visit.~A negative change for off time indicates improvement. The PD diary assessment was implemented with Protocol amendment 4 (December 2013) for participants at United States (US) sites only." (NCT00660673)
Timeframe: Prior to initial LCIG infusion (in the previous study, before the first LCIG infusion), Baseline (final assessment of the previous open-label LCIG study), and end of treatment; median duration of treatment was 1178 days.
| Intervention | hours (Mean) | |
|---|---|---|
| Change from initial LCIG infusion | Change from Baseline | |
| Levodopa-Carbidopa Intestinal Gel | -3.97 | -0.19 |
"Participants could use oral levodopa-carbidopa for scheduled or supplemental bedtime/overnight doses after the pump was disconnected for the night, or as rescue medication in case of acute deterioration caused by failure of the LCIG system such as tubes and/or the pump or the onset of an acute illness.~The initiation of additional concomitant PD medication was allowed at the discretion of the Investigator if medically indicated." (NCT00660673)
Timeframe: Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9, Year 10, > Year 10 (maximum time on treatment was approximately 11.5 years).
| Intervention | Participants (Count of Participants) | ||
|---|---|---|---|
| No concomitant PD medications (LCIG only) | Concomitant oral levodopa/carbidopa | Other concomitant PD medications | |
| > Year 10 | 8 | 1 | 0 |
| Year 1 | 126 | 100 | 36 |
| Year 10 | 17 | 4 | 1 |
| Year 2 | 107 | 91 | 32 |
| Year 3 | 96 | 74 | 26 |
| Year 4 | 74 | 55 | 17 |
| Year 5 | 52 | 37 | 7 |
| Year 6 | 38 | 16 | 5 |
| Year 7 | 33 | 9 | 2 |
| Year 8 | 28 | 8 | 2 |
| Year 9 | 21 | 5 | 1 |
A comprehensive assessment for the presence of melanoma was performed at least once a year by a dermatologist. (NCT00660673)
Timeframe: Once per year during the study; median duration of treatment was 1178 days.
| Intervention | Participants (Count of Participants) |
|---|---|
| Levodopa-Carbidopa Intestinal Gel | 2 |
"The UPDRS is an Investigator-used rating tool to follow the longitudinal course of PD. It is made up of the following sections:~I) Mentation, Behavior, and Mood;~II) Activities of Daily Living;~III) Motor Examinations;~IV) Complications of Therapy sections (including dyskinesias).~The Part II score is the sum of the answers to the 13 questions that comprise Part II, each of which are measured on a 5-point scale (0-4). The Part II score ranges from 0-52 and higher scores are associated with more disability. A negative change from Baseline indicates improvement.~The UPDRS was implemented with Protocol amendment 4 (December 2013) for participants at US sites only." (NCT00660673)
Timeframe: Prior to initial LCIG infusion (in the previous study, before the first LCIG infusion), Baseline (final assessment of the previous open-label LCIG study), and end of treatment; median duration of treatment was 1178 days.
| Intervention | score on a scale (Mean) | |
|---|---|---|
| Change from initial LCIG infusion | Change from Baseline | |
| Levodopa-Carbidopa Intestinal Gel | 3.04 | 6.11 |
"The UPDRS is an Investigator-used rating tool to follow the longitudinal course of PD. It is made up of the following sections:~I) Mentation, Behavior, and Mood;~II) Activities of Daily Living;~III) Motor Examinations;~IV) Complications of Therapy sections (including dyskinesias).~The UPDRS total score is the sum of the responses to the 31 questions (44 answers) that comprise Parts I - III of the scale. The total score ranges from 0 - 176 with 176 representing the worst (total) disability, and 0 no disability. A negative change from Baseline indicates improvement.~The UPDRS was implemented with Protocol amendment 4 (December 2013) for participants at US sites only." (NCT00660673)
Timeframe: Prior to initial LCIG infusion (in the previous study, before the first LCIG infusion), Baseline (final assessment of the previous open-label LCIG study), and end of treatment; median duration of treatment was 1178 days.
| Intervention | score on a scale (Mean) | |
|---|---|---|
| Change from initial LCIG infusion | Change from Baseline | |
| Levodopa-Carbidopa Intestinal Gel | 9.12 | 16.82 |
"Adverse events of special interest (AESIs) were identified using standardized Medical Dictionary for Regulatory Activities (MedDRA) queries (SMQ) or company MedDRA queries (CMQs). The AESI in the following categories were identified on the basis of review of the clinical program and postmarketing observations where the treatment system is commercially available.~Procedure and device associated events~Polyneuropathy, included preferred terms in either the peripheral neuropathy or GuillainBarre syndrome standardized MedDRA query (narrow search), such as polyneuropathy, decreased vibratory sense, peripheral neuropathy, peripheral sensory neuropathy, neuralgia, demyelinating polyneuropathy, and sensory disturbance~Weight loss~Cardiovascular fatalities~Respiratory tract aspiration including aspiration pneumonia/pneumonitis." (NCT00660673)
Timeframe: From first dose of LCIG in this study up to 30 days after the date of last PEG-J exposure; median duration of treatment was 1178 days, with a maximum of 4217 days (11.5 years).
| Intervention | Participants (Count of Participants) | ||||
|---|---|---|---|---|---|
| TE AESI related to procedure and device | TE AESI related to polyneuropathy | TE AESI related to weight loss | TE AESI related to cardiovascular fatalities | TE AESI related to aspiration | |
| Levodopa-Carbidopa Intestinal Gel | 162 | 24 | 53 | 7 | 71 |
"Treatment-emergent adverse events (TEAEs) are defined as adverse events (AEs) which started on or after the date of the first LCIG Infusion in this study and within 30 days of the date of the last PEG-J exposure.~At least possibly drug-related is defined as TEAEs assessed as having a Possible or Probable or missing relationship to study drug.~Serious AEs included any untoward medical occurrence that:~Resulted in death~Was life-threatening~Required inpatient hospitalization or prolongation of an existing hospitalization~Resulted in persistent or significant disability/incapacity~was a congenital anomaly/birth defect~The severity of all AEs was characterized as mild, moderate or severe according to the following definitions:~Mild: usually transient and do not interfere with daily activities.~Moderate: low level of inconvenience or concern to the subject, may interfere with daily activities.~Severe: events interrupt the subject's usual daily activity." (NCT00660673)
Timeframe: From first dose of LCIG in this study up to 30 days after the date of last PEG-J exposure; median duration of treatment was 1178 days, with a maximum of 4217 days (11.5 years).
| Intervention | Participants (Count of Participants) | |||||
|---|---|---|---|---|---|---|
| Any treatment-emergent adverse event (TEAE) | TEAE at least possibly related to study drug | Serious TEAE | Severe TEAE | TEAE leading to premature study discontinuaton | TEAE leading to death | |
| Levodopa-Carbidopa Intestinal Gel | 253 | 219 | 159 | 152 | 82 | 58 |
"Participants were asked whether they experienced any events in which they fell asleep suddenly or unexpectedly, including while engaged in some activity (e.g., eating/drinking, speaking, or driving) or at rest, with or without any previous warning of sleepiness. If yes, participants were asked if they suffered any bad outcome or problem from the falling asleep event." (NCT00660673)
Timeframe: Baseline (final assessment period of the previous open-label LCIG study) and every 6 months until final visit; median duration of treatment was 1178 days.
| Intervention | Participants (Count of Participants) | |||
|---|---|---|---|---|
| Baseline: One or more sleep attacks | Baseline: One or more sleep attacks with a bad outcome | Post-baseline: One or more sleep attacks | Post-baseline: One or more sleep attacks with a bad outcome | |
| Levodopa-Carbidopa Intestinal Gel | 6 | 0 | 27 | 3 |
A vital sign value was considered potentially clinically significant if it satisfied the pre-specified criteria presented in the table and was also more extreme than the participant's corresponding Baseline value. (NCT00660673)
Timeframe: Baseline and every 6 months until final visit; median duration of treatment was 1178 days.
| Intervention | Participants (Count of Participants) | ||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Supine Systolic Blood Pressure ≥180 mmHg and > 40 mmHg increase from Baseline | Supine Systolic Blood Pressure ≤ 90 mmHg and > 30 mmHg decrease from Baseline | Standing Systolic Blood Pressure ≥ 180 mmHg and > 40 mmHg increase from Baseline | Standing Systolic Blood Pressure ≤ 90 mmHg and > 30 mmHg decrease from Baseline | Orthostatic Change in Systolic Blood Pressure Decrease of ≥ 30 mmHg | Supine Diastolic Blood Pressure ≥ 105 mmHg and > 30 mmHg increase from Baseline | Supine Diastolic Blood Pressure ≤ 50 mmHg and > 30 mmHg decrease from Baseline | Standing Diastolic Blood Pressure ≥ 105 mmHg and > 30 mmHg increase from Baseline | Standing Diastolic Blood Pressure ≤ 50 mmHg and > 30 mmHg decrease from Baseline | Orthostatic Change in Diastolic Blood Pressure Decrease of ≥ 20 mmHg | Supine Pulse ≥ 120 bpm and > 30 bpm increase from Baseline | Supine pulse ≤ 50 bpm and > 30 bpm decrease from Baseline | Standing pulse ≥ 120 bpm and > 30 bpm increase from Baseline | Standing pulse ≤ 50 bpm and > 30 bpm decrease from Baseline | Temperature ≥ 38.3℃ and ≥ 1.1℃ increase from Baseline | Weight ≥ 7% increase from Baseline | Weight ≥ 7% decrease from Baseline | |
| Levodopa-Carbidopa Intestinal Gel | 6 | 13 | 1 | 26 | 73 | 2 | 6 | 7 | 14 | 45 | 0 | 3 | 5 | 4 | 0 | 36 | 140 |
"The UPDRS is an Investigator-used rating tool to follow the longitudinal course of PD. It is made up of the following sections:~I) Mentation, Behavior, and Mood;~II) Activities of Daily Living;~III) Motor Examinations;~IV) Complications of Therapy sections (including Dyskinesias).~The UPDRS Part IV Score is the sum of all answers to the 11 questions that comprise Part IV, 4 of which are measured on a 5-point scale (0 - 4) and 7 which are measured on a 2-point scale (0 - 1). The Part IV score ranges from 0 - 23 with higher scores associated with more disability. A negative change from Baseline indicates improvement.~The UPDRS was implemented with Protocol amendment 4 (December 2013) for participants at US sites only." (NCT00660673)
Timeframe: Prior to initial LCIG infusion (in the previous study, before the first LCIG infusion), Baseline (final assessment of the previous open-label LCIG study), and end of treatment; median duration of treatment was 1178 days.
| Intervention | score on a scale (Mean) | |
|---|---|---|
| Change from initial LCIG infusion | Change from Baseline | |
| Levodopa-Carbidopa Intestinal Gel | -2.27 | 0.77 |
"A laboratory value was considered potentially clinically significant if it satisfied the pre-specified criteria presented in the table and was also more extreme than the participant's corresponding baseline value.~ULN = upper limit of normal" (NCT00660673)
Timeframe: Baseline and every 6 months until final visit; median duration of treatment was 1178 days.
| Intervention | Participants (Count of Participants) | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Creatinine > 177 µmol/L | Calcium < 1.75 mmol/L | Calcium > 3.0 mmol/L | Total bilirubin > 2 x ULN | Aspartate aminotransferase (AST) > 3 x ULN | Alanine aminotransferase (ALT) > 3 x ULN | Gamma glutamyl-transferase (GGT) > 3 x ULN | Lactate dehydrogenase (LDH) > 3 x ULN | Alkaline phosphatase (ALP) > 400 U/L | Creatine phosphokinase (CPK) > 3 x ULN | Non-fasting glucose < 2.78 mmol/L | Non-fasting glucose > 16.0 mmol/L | Uric acid > 500 µmol/L (Female); > 590 µmol/L (Male) | Blood urea nitrogen (BUN) > 10.8 mmol/L | Cholesterol > 12.9 mmol/L | |
| Levodopa-Carbidopa Intestinal Gel | 0 | 1 | 0 | 0 | 0 | 0 | 5 | 0 | 0 | 6 | 4 | 1 | 0 | 11 | 0 |
A laboratory value was considered potentially clinically significant if it satisfied the pre-specified criteria presented in the table and was also more extreme than the participant's corresponding Baseline value. (NCT00660673)
Timeframe: Baseline and every 6 months until final visit; median duration of treatment was 1178 days.
| Intervention | Participants (Count of Participants) | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Red blood cells (RBC) < 2.0 × 10^12 cells/L (Female); < 2.5 × 10^12 cells/L (Male) | Haemoglobin < 90 g/L (Female); < 100 g/L (Male) | Haematocrit < 30% (Female); < 34% (Male) | White blood cells (WBC) < 2.8 × 10^9 cells/L | WBC > 16.0 × 10^9 cells/L | Absolute neutrophil count < 1.2 × 10^9 cells/L | Lymphocytes > 80% | Absolute lymphocyte count < 0.75 × 10^9 cells/L | Eosinophils > 10% | Monocytes > 30% | Platelet count < 95 × 10^9 cells/L | Platelet count > 700 × 10^9 cells/L | Mean corpuscular volume (MCV) < 60 fL | MCV > 120 fL | |
| Levodopa-Carbidopa Intestinal Gel | 0 | 9 | 16 | 3 | 2 | 2 | 0 | 14 | 4 | 1 | 2 | 0 | 0 | 0 |
To monitor for the development of intense impulsive behavior the Minnesota Impulsive Disorder Interview (MIDI) was administered. The MIDI is a semi-structured clinical interview assessing pathological gambling, trichotillomania, kleptomania, pyromania, intermittent explosive disorder, compulsive buying, and compulsive sexual behavior. (NCT00660673)
Timeframe: Baseline (final assessment of the previous open-label LCIG study) and every 6 months until final visit; median duration of treatment was 1178 days.
| Intervention | Participants (Count of Participants) | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline: Pathological Gambling | Baseline: Trichotillomania | Baseline: Kleptomania | Baseline: Pyromania | Baseline: Intermittent Explosive Disorder | Baseline: Compulsive Buying | Baseline: Compulsive Sexual Behavior | Post-baseline: Pathological Gambling | Post-baseline: Trichotillomania | Post-baseline: Kleptomania | Post-baseline: Pyromania | Post-baseline: Intermittent Explosive Disorder | Post-baseline: Compulsive Buying | Post-baseline: Compulsive Sexual Behavior | |
| Levodopa-Carbidopa Intestinal Gel | 1 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 2 | 14 |
Device complications include complications with the pump, intestinal tube, PEG-J or stoma. (NCT00660673)
Timeframe: From first dose of LCIG in this study up to 30 days after the date of last PEG-J exposure; median duration of treatment was 1178 days.
| Intervention | Participants (Count of Participants) | |||
|---|---|---|---|---|
| Any device complication | Device complication leading to tube replacement | Device complication with associated adverse event | Device complication with associated adverse event leading to tube replacement | |
| Levodopa-Carbidopa Intestinal Gel | 244 | 183 | 177 | 43 |
Mean sum of normalized MEP for repeated TMS (rTMS) conditions with respect to the pulse (-100, +300, placebo, zero) prior to treatment (baseline), immediately after the treatment (post-training 1), 30 minutes after the treatment (post-training 2) and 60 minutes after the treatment (post-training 3). Its amplitude is measured from peak to peak and expressed in mV. Long- lasting increases in MEP amplitude indicate increases in motor cortex excitability and are associated with motor learning. (NCT00715520)
Timeframe: Baseline, Post-Training 1(Immediately), Post-Training 2 (30 Minutes), Post-Training 3 (60 Minutes)
| Intervention | millivolts (Mean) | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline - Pulse (zero) | Post-Training 1 - Pulse (zero) | Post-Training 2 - Pulse (zero) | Post-Training 3 - Pulse (zero) | Baseline - Pulse (placebo) | Post-Training 1 - Pulse (placebo) | Post-Training 2 - Pulse (placebo) | Post-Training 3 - Pulse (placebo) | Baseline - Pulse (-100) | Post-Training 1 - Pulse (-100) | Post-Training 2 - Pulse (-100) | Post-Training 3 - Pulse (-100) | Baseline - Pulse (+300) | Post-Training 1 - Pulse (+300) | Post-Training 2 - Pulse (+300) | Post-Training 3 - Pulse (+300) | |
| Aim 2 | .39 | .66 | .63 | .69 | .40 | .54 | .51 | .52 | .39 | .56 | .60 | .61 | .38 | .54 | .48 | .51 |
Mean sum of normalized MEP for the different frequencies of rTMS treatment (placebo at 0.1 Hz, 0.1 Hz, 0.25 Hz, 0.5 Hz) prior to treatment (baseline), immediately after the treatment (post-training 1), 30 minutes after the treatment (post-training 2) and 60 minutes after the treatment (post-training 3). Increases in the mean peak acceleration of the trained wrist extension movements indicate motor learning. (NCT00715520)
Timeframe: Baseline, Post-Training 1(Immediately), Post-Training 2 (30 Minutes), Post-Training 3 (60 Minutes)
| Intervention | millivolts (Mean) | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline - Placebo | Post-Training 1 - Placebo | Post-Training 2 - Placebo | Post-Training 3 - Placebo | Baseline - .1 Hz | Post-Training 1 - .1 Hz | Post-Training 2 - .1 Hz | Post-Training 3 - .1 Hz | Baseline - .25 Hz | Post-Training 1 - .25 Hz | Post-Training 2 - .25 Hz | Post-Training 3 - .25 Hz | Baseline - .5 Hz | Post-Training 1 - .5 Hz | Post-Training 2 - .5 Hz | Post-Training 3 - .5 Hz | |
| Aim 2 | .67 | .93 | .94 | 1.02 | .71 | 1.06 | 1.06 | 1.14 | .67 | .90 | .90 | .98 | .64 | .92 | .90 | .84 |
Mean peak acceleration of wrist movements for repeated TMS (rTMS) conditions with respect of the TMS pulse (-100, +300, placebo, zero) prior to treatment (baseline), immediately after the treatment (post-training 1), 30 minutes after the treatment (post-training 2) and 60 minutes after the treatment (post-training 3). Increases in the mean peak acceleration of the trained wrist extension movements indicate motor learning. Acceleration was measured in g; a symbol for the average acceleration produced by gravity at the Earth's surface. (NCT00715520)
Timeframe: Baseline, Post-Training 1(Immediately), Post-Training 2 (30 Minutes), Post-Training 3 (60 Minutes)
| Intervention | g (Mean) | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline - Pulse (zero) | Post-Training 1 - Pulse (zero) | Post-Training 2 - Pulse (zero) | Post-Training 3 - Pulse (zero) | Baseline - Pulse (placebo) | Post-Training 1 - Pulse (placebo) | Post-Training 2 - Pulse (placebo) | Post-Training 3 - Pulse (placebo) | Baseline - Pulse (-100) | Post-Training 1 - Pulse (-100) | Post-Training 2 - Pulse (-100) | Post-Training 3 - Pulse (-100) | Baseline - Pulse (+300) | Post-Training 1 - Pulse (+300) | Post-Training 2 - Pulse (+300) | Post-Training 3 - Pulse (+300) | |
| Aim 2 | 1.33 | 1.43 | 1.51 | 1.53 | 1.44 | 1.36 | 1.35 | 1.33 | 1.51 | 1.5 | 1.46 | 1.47 | 1.40 | 1.32 | 1.38 | 1.40 |
Mean peak acceleration for the different frequencies of rTMS treatment (placebo, 0.1 Hz, 0.25 Hz, 0.5 Hz) prior to treatment (baseline), immediately after the treatment (post-training 1), 30 minutes after the treatment (post-training 2) and 60 minutes after the treatment (post-training 3). Increases in the mean peak acceleration of the trained wrist extension movements indicate motor learning. Acceleration was measured in g; a symbol for the average acceleration produced by gravity at the Earth's surface. (NCT00715520)
Timeframe: Baseline, Post-Training 1(Immediately), Post-Training 2 (30 Minutes), Post-Training 3 (60 Minutes)
| Intervention | g (Mean) | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline - Placebo | Post-Training 1 - Placebo | Post-Training 2 - Placebo | Post-Training 3 - Placebo | Baseline - .1 Hz | Post-Training 1 - .1 Hz | Post-Training 2 - .1 Hz | Post-Training 3 - .1 Hz | Baseline - .25 Hz | Post-Training 1 - .25 Hz | Post-Training 2 - .25 Hz | Post-Training 3 - .25 Hz | Baseline - .5 Hz | Post-Training 1 - .5 Hz | Post-Training 2 - .5 Hz | Post-Training 3 - .5 Hz | |
| Aim 2 | 1.44 | 1.36 | 1.35 | 1.33 | 1.33 | 1.43 | 1.50 | 1.53 | 1.38 | 1.35 | 1.40 | 1.34 | 1.32 | 1.29 | 1.25 | 1.29 |
Mean peak acceleration was measured across study drug conditions prior to treatment (baseline), immediately after the treatment (post-training 1), 30 minutes after the treatment (post-training 2) and 60 minutes after the treatment (post-training 3). Increases in the mean peak acceleration of the trained wrist extension movements indicate motor learning. Acceleration was measured in g; a symbol for the average acceleration produced by gravity at the Earth's surface. (NCT00715520)
Timeframe: Baseline, Post-Training 1 (Immediately), Post-Training 2 (30 Minutes), Post-Training 3 (60 Minutes)
| Intervention | g (Mean) | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline - Placebo | Post-Training 1 - Placebo | Post-Training 2 - Placebo | Baseline - Amphetamine Sulfate | Post-Training 1 - Amphetamine Sulfate | Post-Training 2 - Amphetamine Sulfate | Baseline - Methylphenidate | Post-Training 1 - Methylphenidate | Post-Training 2 - Methylphenidate | Baseline - Carbidopa-Levodopa | Post-Training 1 - Carbidopa-Levodopa | Post-Training 2 - Carbidopa-Levodopa | |
| Aim 1 | 1.32 | 1.33 | 1.24 | 1.24 | 1.28 | 1.29 | 1.35 | 1.27 | 1.22 | 1.22 | 1.23 | 1.37 |
Motor evoked potential (MEP) amplitudes were measured prior to treatment (baseline), immediately after the treatment (post-training 1), 30 minutes after the treatment (post-training 2), and 60 minutes after the treatment (post-training 3).The MEP is elicited by transcranial magnetic stimulation (TMS) at increased intensity. Its amplitude is measured from peak to peak and expressed in millivolts (mV). Measured MEP amplitudes were plotted against the intensity to create a stimulus response curve (SRC). SRCs were modeled by a 3- parameter sigmoid function and MEPmax was extracted. Long-lasting increases in MEP amplitude indicate increases in motor cortex excitability and are associated with motor learning. (NCT00715520)
Timeframe: Baseline, Post-Training 1 (Immediately), Post-Training 2 (30 Minutes), Post-Training 3 (60 Minutes)
| Intervention | mV (Mean) | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline Placebo - MEPmax | Post-Training 1 Placebo - MEPmax | Post-Training 2 Placebo - MEPmax | Baseline - Amphetamine Sulfate - MEPmax | Post-Training 1 Ampletamine Sulfate - MEPmax | Post-Training 2 Amphetamine Sulfate - MEPmax | Baseline Methylphenidate - MEPmax | Post-Training 1 Methylphenidate - MEPmax | Post-Training 2 Methylphenidate - MEPmax | Baseline Carbidopa-Levodopa - MEPmax | Post-Training 1 Carbidopa-Levodopa - MEPmax | Post-Training 2 Carbidopa-Levodopa - MEPmax | |
| Aim 1 | 1.01 | 1.63 | 1.29 | .73 | 1.22 | 1.08 | 1.04 | 1.10 | 1.22 | 1.81 | 1.41 | 1.53 |
"To determine 8h efficacy on Day 1 the on site investigator assessments of ON, OFF and state of dyskinesia for each subject was collected predose (-1, -0.5, and 0 hours) every 30 min for up to 8 hours after dosing . For all subjects duration of (1) OFF time (2) ON time without dyskinesia, (3) ON time with non-troublesome dyskinesia and (4) ON time with troublesome dyskinesia was calculated for both treatments. Definition of ON was based on a 20% change from predose measure, and the results were analyzed in the standard manner of a two way crossover design. The trial inclusion criteria included ability of subject to differentiate ON state from OFF state per investigator's assessment." (NCT00869791)
Timeframe: Predose and then every 30 min upto 8 h after dosing on Day of 1 of each treatment period
| Intervention | Hours (Mean) | |||
|---|---|---|---|---|
| OFF time | ON time without dyskinesia | ON time with non-troublesome dyskinesia | ON time with troublesome dyskinesia | |
| IPX066 | 1.90 | 2.94 | 2.62 | 0.54 |
| IR CD-LD | 4.44 | 2.36 | 0.90 | 0.28 |
For both treatment arms: Sequence 1 (IPX066, Washout, then IR CD-LD) and Sequence 2 (IR CD-LD, Washout, IPX066), blood samples for measurement of LD and CD plasma concentrations were collected pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, and 8 hours after dosing on Day 1 (referred to as Single-Dose data); and at pre-dose, 0.5, 1,1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 hours after dosing on Day 8 (referred to as Multiple-Dose data). Time of maximum drug concentration (Tmax in hours) was estimated using Single-Dose data and Multiple-Dose data. (NCT00869791)
Timeframe: Day 1 and on Day 8 after a week of intervention in each treatment arm: Arm 1 (IPX066 first, washout, then CD-LD IR) and Arm2 (CD-LD IR first, washout, then IPX066
| Intervention | Hours (Mean) | |||
|---|---|---|---|---|
| CD Tmax Single-Dose | CD Tmax Multiple-Dose | LD Tmax Single-Dose | LD Tmax Multiple-Dose | |
| IPX066 | 2.944 | 3.815 | 2.037 | 4.407 |
| IR CD-LD | 2.296 | 5.685 | 0.870 | 3.611 |
"Subjects recorded state of OFF time using the Parkinson's Patient Diary" (NCT00869791)
Timeframe: Last 3 days of each treatment period, every 30 minutes over a 24-hour day beginning at 6:00 AM
| Intervention | hours (Mean) |
|---|---|
| IPX066 | 3.83 |
| IR CD-LD | 5.83 |
"Improvement in Tapping: has been used as a surrogate endpoint for assessing subject being On. Finger Tapping: the number of times the subject could tap two counter keys 20 cm apart alternately in 1 minute with the most affected arm assessed every 30 minutes on Day 1. Subjects performed the 60-second tapping measurement three times prior to dosing in the clinic, and at half-hour intervals through the 8-hour measurement period on Day 1 of each treatment period. More hours On during treatment represented better outcome. For the Tapping measurement, the protocol defined a 20% change from the average of the predose measurements as the time to On. Each half-hour interval counted as 0.5 hour. Any measurement below a 20% improvement was considered time Not On. If patient required redosing then primary analyses adjusted for redosing in calculating the results." (NCT00869791)
Timeframe: Day 1 of each treatment period - three times prior to dosing in the clinic, and at half-hour intervals through the 8-hour measurement period
| Intervention | Hours (Mean) |
|---|---|
| IPX066 | 4.74 |
| IR CD-LD | 2.98 |
To determine efficacy on Day 1 the UPDRS (unified Parkinson's disease rating) Part III score, a clinician-scored measure of motor function, was collected immediately predose and 1, 2, 3, 4, 5, 6, 7 and 8 h post dose. The UPDRS Part III motor exam analyzes multiple motor functions like speech, facial expression, tremor, rigidity, movement, posture, gait etc. Each parameter is assigned values from 0 to 4, with 0 being normal and 4 being the most affected. The total range is 0 - 108, with lower scores indicating a better outcome.The average of post dose was calculated for day 1. (NCT00869791)
Timeframe: Pre dosing and at hourly intervals through the 8-hour measurement period on day 1
| Intervention | UPDRS Part III Motor Score (Mean) |
|---|---|
| IPX066 | 21.6 |
| IR CD-LD | 25.5 |
For both treatment arms: Sequence 1 (IPX066, Washout, then IR CD-LD) and Sequence 2 (IR CD-LD, Washout, IPX066), blood samples for measurement of LD and CD plasma concentrations were collected pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, and 8 hours after dosing on Day 1 (referred to as Single-Dose data); and at pre-dose, 0.5, 1,1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 hours after dosing on Day 8 (referred to as Multiple-Dose data). Area under the concentration-time curve for the dosing interval (AUC Tau) in hour*nanogram/milliliter was estimated using Single-Dose data and Multiple-Dose data. (NCT00869791)
Timeframe: Day 1 and on Day 8 after a week of intervention in each treatment arm: Arm 1 (IPX066 first, washout, then CD-LD IR) and Arm2 (CD-LD IR first, washout, then IPX066
| Intervention | hour*nanogram/milliliter (Mean) | |||
|---|---|---|---|---|
| CD AUC Tau, Single-Dose | CD AUC Tau, Multiple-Dose | LD AUC Tau, Single-Dose | LD AUC Tau, Multiple-Dose | |
| IPX066 | 917.067 | 1344.436 | 10902.194 | 13903.380 |
| IR CD-LD | 401.694 | 449.584 | 3881.298 | 4167.151 |
For both treatment arms: Sequence 1 (IPX066, Washout, then IR CD-LD) and Sequence 2 (IR CD-LD, Washout, IPX066), blood samples for measurement of LD and CD plasma concentrations were collected pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, and 8 hours after dosing on Day 1 (referred to as Single-Dose data); and at pre-dose, 0.5, 1,1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 hours after dosing on Day 8 (referred to as Multiple-Dose data). Maximum (peak) drug concentration (Cmax in nanograms/milliliter) was estimated using Single-Dose data and Multiple-Dose data. (NCT00869791)
Timeframe: Day 1 and on Day 8 after a week of intervention in each treatment arm: Arm 1 (IPX066 first, washout, then CD-LD IR) and Arm 2 (CD-LD IR first, washout, then IPX066)
| Intervention | nanogram/milliliter (Mean) | |||
|---|---|---|---|---|
| CD Cmax, Single-Dose | CD Cmax, Multiple-Dose | LD Cmax, Single-Dose | LD Cmax, Multiple-Dose | |
| IPX066 | 238.852 | 313.222 | 3000.000 | 3807.037 |
| IR CD-LD | 146.848 | 167.515 | 2356.444 | 2761.852 |
"Change from Baseline in Parkinson's disease Questionnaire 39 (PDQ-39) at Weeks 4, 9, 16, 23 and 30 or early discontinuation was collected. The PDQ-39 is a self-reported questionnaire consisting of 39 questions regarding the subjects mobility and the responses consist of Never (better in outcome), (value 0), Occasionally (value 1), Sometimes (value 2), , Often (value 3), and Always (value 4), (worse in outcome). The minimum possible score is 0 and the maximum is 156. The outcome measure calculated was the change from baseline to end of study in mean PDQ-39 score. Negative values indicate a better result." (NCT00880620)
Timeframe: Baseline and Week 30 (or End of Study)
| Intervention | score on a scale (Mean) |
|---|---|
| IPX066 145 mg LD | -4.4 |
| IPX066 245 mg LD | -3.8 |
| IPX066 390 mg LD | -6.0 |
| Placebo | 0.6 |
"Analysis of the Change from Baseline in the sum of the Unified Parkinson's Disease Rating Scale (UPDRS) Part II (Activities of Daily Living) + UPDRS Part III (Motor Examination) at Week 30 (End of Study).~Unified Parkinson's Disease Rating Scale (UPDRS) - Four Parts Higher score values represent a worse outcome.~Subscales II and III were summed:~Part I: Mentation, Behavior and Mood - 4 questions 1-4 Score range: 1-16 Part II: Activities of Daily Living - 13 questions 5-17 Score range: 0-52 Part III: Motor Examination - 19 questions 18-31 and 25 total assessments Score range: 0-100 Part IV: Complications of Therapy (In the past week) - 11 questions Score range: 0-25" (NCT00880620)
Timeframe: Week 30
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo | -0.6 |
| IPX066 145mg LD | -11.7 |
| IPX066 245 mg LD | -12.9 |
| IPX066 390 mg LD | -14.9 |
"On time without troublesome dyskinesiais measured by using the Parkinson's disease diary. On time without troublesome dyskinesia describes a period when the participant experiences decreased Parkinsonian symptoms (e.g. immobility or inability to move with ease) without dyskinesia (i.e. difficulty in performing voluntary movements) that affect daily living." (NCT00974974)
Timeframe: 22 weeks
| Intervention | hours (Mean) |
|---|---|
| IPX066 | 11.84 |
| IR CD-LD (Active Comparator) | 10.91 |
"Percentage of off time during waking hours at end of study is measured by using the Parkinson's disease diary. Off time describes a period when the participant experiences increased Parkinsonian symptoms (e.g. immobility or inability to move with ease)." (NCT00974974)
Timeframe: 22 weeks
| Intervention | percentage (Mean) |
|---|---|
| IPX066 | 23.82 |
| IR CD-LD (Active Comparator) | 29.79 |
"Off time hours is measured by using the Parkinson's disease diary. Off time describes a period when the participant experiences increased Parkinsonian symptoms (e.g. immobility or inability to move with ease)." (NCT00974974)
Timeframe: 22 weeks
| Intervention | hours (Mean) |
|---|---|
| IPX066 | 3.87 |
| IR CD-LD (Active Comparator) | 4.88 |
"Analysis of the Change from Baseline in the sum of the Unified Parkinson's Disease Rating Scale (UPDRS) Part II (Activities of Daily Living) + UPDRS Part III (Motor Examination) at End of Study.~Unified Parkinson's Disease Rating Scale (UPDRS) - Four Parts Higher score values represent a worse outcome.~Subscales II and III were summed:~Part I: Mentation, Behavior and Mood - 4 questions 1-4 Score range: 1-16 Part II: Activities of Daily Living - 13 questions 5-17 Score range: 0-52 Part III: Motor Examination - 19 questions 18-31 and 25 total assessments Score range: 0-100 Part IV: Complications of Therapy (In the past week) - 11 questions Score range: 0-25" (NCT01096186)
Timeframe: 9 months
| Intervention | units on a scale (Mean) |
|---|---|
| IPX066 | 26.4 |
"Analysis of the Change from Baseline in the sum of the Unified Parkinson's Disease Rating Scale (UPDRS) Part I (Mentation, Behavior and Mood), Part II (Activities of Daily Living), UPDRS Part III (Motor Examination), and Part IV (Complications of Therapy [In the past week]) at End of Study. Includes both scoring by a clinician and a historical report of mental functioning, activities of daily living and complications of therapy in the past week obtained by questioning the patient.~Unified Parkinson's Disease Rating Scale (UPDRS) - Four Parts Higher score values represent a worse outcome.~Subscales II and III were summed:~Part I: Mentation, Behavior and Mood - 4 questions 1-4 Score range: 1-16 Part II: Activities of Daily Living - 13 questions 5-17 Score range: 0-52 Part III: Motor Examination - 19 questions 18-31 and 25 total assessments Score range: 0-100 Part IV: Complications of Therapy (In the past week) - 11 questions Score range: 0-25" (NCT01096186)
Timeframe: 9 months
| Intervention | units on a scale (Mean) |
|---|---|
| IPX066 | 30.5 |
"Satisfaction of IPX066 using Patient Global Impression (PGI) 7-point scale.~Patient Global Impression 0-7 - higher value indicates increased improvement from study start" (NCT01096186)
Timeframe: 9 months
| Intervention | units on a scale (Mean) |
|---|---|
| IPX066 | 5.4 |
"Using a Parkinson's disease diary, subjects recorded a state of asleep, OFF, ON without dyskinesia, ON with non-troublesome dyskinesia, or ON with troublesome dyskinesia every 30 minutes over a 24-hour day for the last 3 days of each double-blind crossover treatment period.~Mean percentage of OFF Time During Waking Hours was calculated. Off Time is Time when medication has worn off and is no longer providing benefit with regard to mobility, slowness, and stiffness." (NCT01130493)
Timeframe: 3 days of data immediately prior to the end of each 2 week treatment period
| Intervention | Percent (Mean) |
|---|---|
| IPX066 | 23.98 |
| CLE (Active Comparator) | 32.48 |
"Unified Parkinson's Disease Rating Scale (UPDRS) Part II (Activities of Daily Living) and Part III (Motor Examination). Part II consists of 14 questions, each ranges from 0 (Normal/None) - 4 (Worst) with a total score of 0 - 72. Part III consists of 27 questions, each ranges from 0 (Normal/None) - 4 (Worst) with a total score of 0 - 108.~The UPDRS Part II Plus Part III scores ranged from 0 (no problems with daily living or mobility) to 180 (severe problems with daily living and mobility." (NCT01130493)
Timeframe: End of each double-blind treatment period.
| Intervention | Scores on a scale (Mean) |
|---|---|
| IPX066 | 29.3 |
| CLE (Active Comparator) | 31.7 |
Subjects who completed both treatments were asked to indicate a preference for Treatment Period 1 or Treatment Period 2 or no preference. Preferences for a particular treatment period were mapped to the associated treatment and reported. (NCT01130493)
Timeframe: End of Study (week 11)
| Intervention | Participants (Count of Participants) |
|---|---|
| Number of Participants Who Preferred IPX066 | 44 |
| Number of Participants Who Preferred CLE | 23 |
| Number of Participants Who Had no Preference | 17 |
"Using a Parkinson's disease diary, subjects recorded a state of asleep, OFF, ON without dyskinesia, ON with non-troublesome dyskinesia, or ON with troublesome dyskinesia every 30 minutes over a 24-hour day for the last 3 days of each double-blind crossover treatment period.~Mean Total On with No Troublesome Dyskinesia was calculated. On Time is when medication is providing benefit with regard to mobility, slowness, and stiffness." (NCT01130493)
Timeframe: 3 days of data immediately prior to the end of each 2 week treatment period
| Intervention | hours (Mean) |
|---|---|
| IPX066 | 11.36 |
| CLE (Active Comparator) | 9.98 |
"Using a Parkinson's disease diary, subjects recorded a state of asleep, OFF, ON without dyskinesia, ON with non-troublesome dyskinesia, or ON with troublesome dyskinesia every 30 minutes over a 24-hour day for the last 3 days of each double-blind crossover treatment period.~Mean Total Off Time During Waking Hours was calculated. Off Time is Time when medication has worn off and is no longer providing benefit with regard to mobility, slowness, and stiffness." (NCT01130493)
Timeframe: 3 days of data immediately prior to the end of each 2 week treatment period
| Intervention | hours (Mean) |
|---|---|
| IPX066 | 3.82 |
| CLE (Active Comparator) | 5.22 |
At Part 1 Week 6, Part 2 Month 3 and Month 6 or at Early Termination, the subjects rated the change in their condition with IPX066 treatment from their condition prior to Part 1 Visit 1(Baseline) using Patient Global Impression (PGI) 7-point scale. 1=very much worse and 7=very much improved. (NCT01411137)
Timeframe: 6 months
| Intervention | units on a scale (Mean) |
|---|---|
| Part 1: Conversion | 5.2 |
| Part 2: Open-Label Extension (Month 3) | 5.4 |
| Part 2: Open-Label Extension (Month 6) | 5.3 |
| Part 1 or 2 Early Termination | 2.8 |
Change from Baseline in Parkinson's disease Questionnaire-8 (PDQ-8) at End of Study or early discontinuation. The PDQ-8 is a self-reported questionnaire consisting of 8 questions regarding the subject's disease symptoms, each item ranging from 0 to 4, and the responses consist of 0=Never, 1=Occasionally, 2=Sometimes, 3=Often, and 4=Always or cannot do at all, total score ranging from 0 (never have problems/issues) to 32 (always have problems or cannot do at all). (NCT01411137)
Timeframe: 6 months
| Intervention | units on a scale (Mean) |
|---|---|
| Part 1: Conversion (Baseline) | 9.6 |
| Part 1: Conversion (Week 6) | 8.1 |
| Part 2: Open-Label Extension (Month 3) | 8.5 |
| Part 2: Open-Label Extension (Month 6) | 9.0 |
| Part 1 or 2 Early Termination | 11.8 |
"Clinician-reported satisfaction outcome of IPX066 using Clinical Global Impression (PGI) 7-point scale.~At Part 1 Week 6; Part 2 Month 3, and Month 6 or at Early Termination, the Investigator rated how much a subject's overall condition had changed since Part 1 Visit 1 (Baseline) using 7-point scale. 1=very much worse and 7=very much improved." (NCT01411137)
Timeframe: 6 months
| Intervention | units on a scale (Mean) |
|---|---|
| Part 1: Conversion | 5.5 |
| Part 2: Open-Label Extension (Month 3) | 5.7 |
| Part 2: Open-Label Extension (Month 6) | 5.6 |
| Part 1 or 2 Early Termination | 3.7 |
The number of participants who completed the 12-week medication phase of the study. (NCT01468012)
Timeframe: 12 weeks
| Intervention | participants (Number) |
|---|---|
| Levodopa Carbidopa and Entacapone (LCE) | 7 |
| Placebo | 9 |
| Non-randomized | 0 |
"The Hoehn and Yahr scale is a commonly used scale for describing how the symptoms of Parkinson's disease progress and the disease stages. Bigger numbers indicate more symptoms and disease progression. H&Y stage range from 0-5; the greater, the more severe.~The H&Y stages of patients were evaluated at baseline (1st visit, V1), and 1 year after baseline (final visit, V5)." (NCT01470859)
Timeframe: twice baseline and 1 year
| Intervention | units on a scale (Mean) | |
|---|---|---|
| H&Y at baseline（V1） | H&Y at 1 year（V5） | |
| Levodopa | 1.35 | 1.65 |
| Pramipexole | 1.43 | 1.82 |
"The brain network activity is evaluated by Parkinson's disease-related spatial covariance pattern(PDRP) value (Z score).~The change of brain network activity is calculated by the PDRP value (Z score) at V5 - the PDRP value (Z score) at V1." (NCT01470859)
Timeframe: twice, baseline and 1 year after baseline
| Intervention | Z-score in PDRP (Mean) | ||
|---|---|---|---|
| Change from baseline (V5-V1) | Z score at baseline (V1) | Z score at 1 year (V5) | |
| Levodopa | 0.41 | 2.21 | 2.29 |
| Pramipexole | 0.61 | 3.61 | 4.09 |
"The PDQ39 score was assessed at baseline (1st visit, V1) and 1 year after baseline (final visit, V5).~PDQ39 score ranges from 0-156 (0-4 each item); the more score, the more severe." (NCT01470859)
Timeframe: twice baseline and 1 year
| Intervention | units on a scale (Mean) | |
|---|---|---|
| PDQ39 at baseline (V1) | PDQ39 at 1 year (V5) | |
| Levodopa | 19.38 | 20.36 |
| Pramipexole | 20.36 | 21.07 |
"Patients with a score <= 2 (very much or much improved in relation to baseline) are considered as clinically improved.~The numbers of participants with clinical improvement are reported here. The completion of dosage titration within 10 weeks after baseline (visit 2) and 1 year after baseline (final visit)" (NCT01470859)
Timeframe: twice, at 10 weeks(V2) and 1 year(V5)
| Intervention | participants (Number) | |
|---|---|---|
| Patients with improvement at V2 | Patients with improvement at V5 | |
| Levodopa | 6 | 2 |
| Pramipexole | 4 | 4 |
baseline (1st visit, V1), completion of dosage titration within 10 weeks after baseline (2nd visit, V2), 1 year after baseline (final visit, V5) UPDRS II score 0-52 (13 items); UPDRS III score 0-56 (14 items); The more scores,the more severe; the two scales were evaluated separately. (NCT01470859)
Timeframe: three times: baseline, 10 weeks, 1 year
| Intervention | units on a scale (Mean) | |||||
|---|---|---|---|---|---|---|
| UPDRS II at baseline (V1) | UPDRS II (V2) | UPDRS II at 1 year (V5) | UPDRS III at baseline (V1) | UPDRS III (V2) | UPDRS III at 1 year (V5) | |
| Levodopa | 7.3 | 5.8 | 7.4 | 18.7 | 12.7 | 19.5 |
| Pramipexole | 7.1 | 4.9 | 8.4 | 23.1 | 20.1 | 24.3 |
"OFF indicates wearing off motor fluctuations before the next levodopa dose. Percent OFF time is calculated as the total OFF time divided by the total awake time for each day and multiplied by 100.~Patient diary-every 30min while awake for 3days prior to initial Day1 as baseline & during the last 3days before Day10 for both treatments for dyskinesia state.~Baseline is the average of the 3 days recorded in the patient diary prior to Day 1 of Period 1.~End of Period is the average of the 3 days recorded in the patient diary prior to Day 10 in each period.~Clinician-Assess efficacy at pre-dose, every 30min for Day1 and hourly for Day10 for dyskinesia state & motor fluctuations at clinic visits." (NCT01515410)
Timeframe: Baseline and 10 days for each of the 2 study periods
| Intervention | percentage of time (Least Squares Mean) |
|---|---|
| DM-1992 | -5.52 |
| Sinemet IR | 1.33 |
Correlation coefficient between UPDRS III score and independent components analysis network strength in left parietal cortex. UPDRS III is the Unified Parkinson's Disease Rating Scale composite motor score. (NCT01528592)
Timeframe: 1 hour
| Intervention | unitless (Number) |
|---|---|
| On / Off Medication | 0.5869 |
Pharmacokinetic parameters of carbidopa. For tmax = time to Cmax values are presented as median with range values. (NCT01533077)
Timeframe: Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.
| Intervention | hours (Median) |
|---|---|
| Sinemet® 100/25 mg | 3.00 |
| BIA 9-1067 50 mg + Sinemet® 100/25 mg Separated 1 h | 3.00 |
| BIA 9-1067 50 mg + Sinemet® 100/25 mg Concomitantly | 3.00 |
Mean pharmacokinetic parameters of L-beta-3,4-dihydroxyphenylalanine (levodopa) (L-DOPA) (NCT01533077)
Timeframe: pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.
| Intervention | ng.h/mL (Mean) |
|---|---|
| Sinemet® 100/25 mg | 2397 |
| BIA 9-1067 50 mg + Sinemet® 100/25 mg Separated 1 h | 2730 |
| BIA 9-1067 50 mg + Sinemet® 100/25 mg Concomitantly | 2603 |
Mean pharmacokinetic parameters of 3-O-methyl-levodopa (3-OMD) (NCT01533077)
Timeframe: Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.
| Intervention | ng.h/mL (Mean) |
|---|---|
| Sinemet® 100/25 mg | 11193 |
| BIA 9-1067 50 mg + Sinemet® 100/25 mg Separated 1 h | 7730 |
| BIA 9-1067 50 mg + Sinemet® 100/25 mg Concomitantly | 89962 |
Mean pharmacokinetic parameters of BIA 9-1067 (NCT01533077)
Timeframe: Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.
| Intervention | ng.h/mL (Mean) |
|---|---|
| BIA 9-1067 50 mg | 2165 |
| BIA 9-1067 50 mg + Sinemet® 100/25 mg Separated 1 h | 2360 |
| BIA 9-1067 50 mg + Sinemet® 100/25 mg Concomitantly | 2678 |
Pharmacokinetic parameters of carbidopa. For tmax = time to Cmax values are presented as median with range values. (NCT01533077)
Timeframe: Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose
| Intervention | ng.h/mL (Mean) |
|---|---|
| Sinemet® 100/25 mg | 668 |
| BIA 9-1067 50 mg + Sinemet® 100/25 mg Separated 1 h | 683 |
| BIA 9-1067 50 mg + Sinemet® 100/25 mg Concomitantly | 745 |
Mean pharmacokinetic parameters of 3-O-methyl-levodopa (3-OMD) (NCT01533077)
Timeframe: Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.
| Intervention | ng.h/mL (Mean) |
|---|---|
| Sinemet® 100/25 mg | 10296 |
| BIA 9-1067 50 mg + Sinemet® 100/25 mg Separated 1 h | 6940 |
| BIA 9-1067 50 mg + Sinemet® 100/25 mg Concomitantly | 8149 |
Mean pharmacokinetic parameters of BIA 9-1067 (NCT01533077)
Timeframe: Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.
| Intervention | ng.h/mL (Mean) |
|---|---|
| BIA 9-1067 50 mg | 2094 |
| BIA 9-1067 50 mg + Sinemet® 100/25 mg Separated 1 h | 2130 |
| BIA 9-1067 50 mg + Sinemet® 100/25 mg Concomitantly | 2245 |
Pharmacokinetic parameters of 3-O-methyl-levodopa (3-OMD). For tmax = time to Cmax values are presented as median with range values. (NCT01533077)
Timeframe: Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose
| Intervention | hours (Median) |
|---|---|
| Sinemet® 100/25 mg | 6.00 |
| BIA 9-1067 50 mg + Sinemet® 100/25 mg Separated 1 h | 5.00 |
| BIA 9-1067 50 mg + Sinemet® 100/25 mg Concomitantly | 5.00 |
Pharmacokinetic parameters of BIA 9-1067. For tmax = time to Cmax values are presented as median with range values. (NCT01533077)
Timeframe: Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.
| Intervention | hours (Median) |
|---|---|
| BIA 9-1067 50 mg | 2.50 |
| BIA 9-1067 50 mg + Sinemet® 100/25 mg Separated 1 h | 3.50 |
| BIA 9-1067 50 mg + Sinemet® 100/25 mg Concomitantly | 4.00 |
Mean pharmacokinetic parameters of carbidopa (NCT01533077)
Timeframe: Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.
| Intervention | ng.h/mL (Mean) |
|---|---|
| Sinemet® 100/25 mg | 656 |
| BIA 9-1067 50 mg + Sinemet® 100/25 mg Separated 1 h | 670 |
| BIA 9-1067 50 mg + Sinemet® 100/25 mg Concomitantly | 732 |
Mean pharmacokinetic parameters of L-beta-3,4-dihydroxyphenylalanine (levodopa) (L-DOPA) (NCT01533077)
Timeframe: pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.
| Intervention | ng.h/mL (Mean) |
|---|---|
| Sinemet® 100/25 mg | 2289 |
| BIA 9-1067 50 mg + Sinemet® 100/25 mg Separated 1 h | 2611 |
| BIA 9-1067 50 mg + Sinemet® 100/25 mg Concomitantly | 2459 |
Mean pharmacokinetic parameters of 3-O-methyl-levodopa (3-OMD) (NCT01533077)
Timeframe: Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose
| Intervention | ng/mL (Mean) |
|---|---|
| Sinemet® 100/25 mg | 490 |
| BIA 9-1067 50 mg + Sinemet® 100/25 mg Separated 1 h | 336 |
| BIA 9-1067 50 mg + Sinemet® 100/25 mg Concomitantly | 401 |
Mean pharmacokinetic parameters of BIA 9-1067 (NCT01533077)
Timeframe: Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.
| Intervention | ng/mL (Mean) |
|---|---|
| BIA 9-1067 50 mg | 648 |
| BIA 9-1067 50 mg + Sinemet® 100/25 mg Separated 1 h | 625 |
| BIA 9-1067 50 mg + Sinemet® 100/25 mg Concomitantly | 628 |
Mean pharmacokinetic parameters of carbidopa (NCT01533077)
Timeframe: Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.
| Intervention | ng/mL (Mean) |
|---|---|
| Sinemet® 100/25 mg | 134 |
| BIA 9-1067 50 mg + Sinemet® 100/25 mg Separated 1 h | 136 |
| BIA 9-1067 50 mg + Sinemet® 100/25 mg Concomitantly | 142 |
Mean pharmacokinetic parameters of L-beta-3,4-dihydroxyphenylalanine (levodopa) (L-DOPA) (NCT01533077)
Timeframe: pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.
| Intervention | ng/mL (Mean) |
|---|---|
| Sinemet® 100/25 mg | 1070 |
| BIA 9-1067 50 mg + Sinemet® 100/25 mg Separated 1 h | 1105 |
| BIA 9-1067 50 mg + Sinemet® 100/25 mg Concomitantly | 1198 |
Pharmacokinetic parameters of L-beta-3,4-dihydroxyphenylalanine (levodopa) (L-DOPA). For tmax = time to Cmax values are presented as median with range values. (NCT01533077)
Timeframe: pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.
| Intervention | hours (Median) |
|---|---|
| Sinemet® 100/25 mg | 1.0 |
| BIA 9-1067 50 mg + Sinemet® 100/25 mg Separated 1 h | 1.0 |
| BIA 9-1067 50 mg + Sinemet® 100/25 mg Concomitantly | 0.5 |
"Use of healthcare resources was assessed by the investigator using the Health Resource Utilization Questionnaire (HRUQ), a questionnaire developed by the Sponsor regarding the use of healthcare resources due to the participant's Parkinson's disease. The standard version of the questionnaire addressed the following questions over the last 3 months:~Has the subject had a visit to an emergency room?~Has the subject had an outpatient visit to any of the following healthcare providers?~Has the subject been visited in his or her place of residence by a health care professional?~Has the subject received assistance from either of the following for their Parkinson's disease in their home?~Has the subject needed to contact either of the following for immediate assistance related to their Parkinson's disease?~Have family members or friends had to miss any paid work due to the subject's Parkinson's disease?~Has the subject fallen during the past month?" (NCT01736176)
Timeframe: Week 60
| Intervention | Participants (Count of Participants) | ||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Q1. Emergency Room Visit | Q2. Visit to Primary Care Physician | Q2. Visit to Gastroenterologist | Q2. Visit to Interventional Radiologist | Q2. Visit to Surgeon | Q2. Visit to Cardiologist | Q2. Visit to Endocrinologist | Q2. Visit to Immunologist | Q2. Visit to Internist | Q2. Visit to Psychiatrist | Q2. Visit to Urologist | Q2. Visit to Psychologist | Q2. Visit to Social Worker | Q2. Visit to Other Healthcare Provider | Q3. Visited by Physician | Q3. Visited by Nurse or Nurse Practitioner | Q3. Visited by Physical or Occupational Therapist | Q4. Received Unpaid Care From Family/Friend | Q4. Received Care From Paid Caregiver | Q5. Called 911 | Q5. Called Family/Friend | Q6. Family/Friends Missed Work | Q7. Fall During Past Month | |
| Levodopa-Carbidopa Intestinal Gel | 1 | 18 | 3 | 1 | 1 | 1 | 0 | 0 | 1 | 0 | 2 | 1 | 2 | 10 | 0 | 1 | 0 | 10 | 2 | 0 | 1 | 2 | 10 |
"Adverse events (AEs) related to treatment are those the investigator determined as having a reasonable possibility being related to study drug based on evidence to suggest a causal relationship between the study drug and the adverse event.~A severe AE was defined as an adverse event that caused considerable interference with the participant's usual activities and might be incapacitating or life-threatening.~Serious AEs were defined as those that were life-threatening or resulted in death, hospitalization or prolongation of hospitalization, a congenital anomaly, persistent or significant disability/incapacity, or important medical events requiring medical or surgical intervention to prevent a serious outcome." (NCT01736176)
Timeframe: Weeks 1-4 and Overall (from Week 1 through 30 days after the end of the LCIG Treatment Period; median duration of LCIG device exposure was 428 days)
| Intervention | Participants (Count of Participants) | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Any adverse event | AE related to LCIG | AE related to oral LC | Severe adverse event | Serious adverse event | AE leading to premature discontinuation | Gastrointestinal (GI) adverse event | Adverse event other than GI | Fatal adverse event | |
| Overall | 37 | 35 | 11 | 5 | 8 | 5 | 28 | 37 | 1 |
| Week 1-4 | 28 | 26 | 4 | 1 | 3 | 1 | 22 | 21 | 0 |
"The PGIC is a 7-point response scale. Participants were asked to rate their change in status using the following 7-point scale:~1 = Very much improved, 2 = Much improved, 3 = Minimally improved, 4 = No change, 5 = Minimally worse, 6 = Much worse, 7 = Very much worse.~The responses of Very much improved, Much improved and Minimally improved on the PGIC were used to define responders." (NCT01736176)
Timeframe: Week 12 and Week 60
| Intervention | percentage of participants (Number) | |
|---|---|---|
| Week 12 | Week 60 | |
| Levodopa-Carbidopa Intestinal Gel | 78.9 | 71.1 |
"The Unified Parkinson's Disease Rating Scale (UPDRS) is an investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The UPDRS assessment was performed by an approved, trained rater.~The UPDRS was made up of the following sections:~Part I - Mentation, Behavior, and Mood~Part II - Activities of Daily Living~Part III - Motor Examination~Part IV - Complications of Therapy (including dyskinesias)~Part V - Modified Hoehn and Yahr Staging~The Total UPDRS score includes 31 items contributing to three subscales: (I) Mentation, Behavior, and Mood; (II) Activities of Daily Living; and (III) Motor Examination. Each question is answered on a scale from 0 (None) to 4 (Severe); Some questions require multiple grades assigned to each extremity. The UPDRS Total score was computed as the sum of these 3 UPDRS subscales and ranged from 0 to 176, with 176 representing the worst (total) disability, and 0 no disability." (NCT01736176)
Timeframe: Baseline and Week 12 and Week 60
| Intervention | units on a scale (Least Squares Mean) | |
|---|---|---|
| Week 12 | Week 60 | |
| Levodopa-Carbidopa Intestinal Gel | -11.4 | -7.7 |
CANTAB is a computer-based test of the participant's ability to retain spatial information and to manipulate remembered items in working memory. The Spatial Working Memory module requires that subjects find a blue token in a series of displayed boxes and use these to fill up an empty column, while not returning to boxes where a blue token has been previously found. The between errors score is the number of times the participant revisited a box in which a token was previously found; errors are calculated for 4-, 6-, and 8-box trials. Higher numbers indicate poorer performance. (NCT01736176)
Timeframe: Baseline and Week 12
| Intervention | errors (Mean) |
|---|---|
| Levodopa-Carbidopa Intestinal Gel | -0.6 |
CANTAB is a computer-based test of the participant's ability to retain spatial information and to manipulate remembered items in working memory. The Spatial Working Memory module requires that subjects find a blue token in a series of displayed boxes and use these to fill up an empty column, while not returning to boxes where a blue token has been previously found. The Strategy score represents the number of times a participant begins a search with the same box for 6- and 8-box problems. Minimum score is 8 and maximum score is 56. Higher numbers indicate poorer performance. (NCT01736176)
Timeframe: Baseline and Week 12
| Intervention | units on a scale (Mean) |
|---|---|
| Levodopa-Carbidopa Intestinal Gel | 0.8 |
"The NMSS measures the frequency and severity of a range of non-motor symptoms in Parkinson's Disease. It consists of 30 questions grouped into 9 domains: cardiovascular, sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, gastro-intestinal tract, urinary, sexual function, and miscellaneous (pain, taste/smell, weight change, excessive sweating). Severity is rated on a scale from 0 (none) to 3 (severe) and frequency is rated on a scale from 1 (rarely) to 4 (very frequent).~Item scores are calculated as the product of severity and frequency; the total score is obtained by summing the item scores. The NMSS total score ranges from 0 to 360 with a lower score indicating fewer symptoms; a negative change from baseline indicates improvement in symptoms." (NCT01736176)
Timeframe: Baseline and Week 12
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Levodopa-Carbidopa Intestinal Gel | -17.6 |
"The NMSS measures the frequency and severity of a range of non-motor symptoms in Parkinson's Disease. It consists of 30 questions grouped into 9 domains: cardiovascular, sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, gastro-intestinal tract, urinary, sexual function, and miscellaneous (pain, taste/smell, weight change, excessive sweating). Severity is rated on a scale from 0 (none) to 3 (severe) and frequency is rated on a scale from 1 (rarely) to 4 (very frequent).~Item scores are calculated as the product of severity and frequency; the total score is obtained by summing the item scores. The NMSS total score ranges from 0 to 360 with a lower score indicating fewer symptoms; a negative change from baseline indicates improvement in symptoms." (NCT01736176)
Timeframe: Baseline and Week 60
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Levodopa-Carbidopa Intestinal Gel | -11.8 |
"The Parkinson's Disease Diary was completed by the participant for 3 consecutive days prior to each visit for the full 24 hours of each day. Participants recorded whether they had been On, Off, or Asleep and the severity of their dyskinesias (troublesome or not troublesome) for each 30-minute period during their normal waking time and upon awakening from time asleep.~Off time was defined as time when medication has worn off and was no longer providing benefit with regard to mobility, slowness, and stiffness.~Parkinson's Disease Diary times were normalized to a 16-hour waking time to account for variation in participants' sleep time. Normalized PD Diary times at a given visit were calculated as the average normalized time from the PD Diary for the 3 days prior to the visit." (NCT01736176)
Timeframe: Baseline and Week 12 and Week 60
| Intervention | hours (Least Squares Mean) | |
|---|---|---|
| Week 12 | Week 60 | |
| Levodopa-Carbidopa Intestinal Gel | -4.1 | -4.9 |
"The PD Diary was completed by the participant for 3 consecutive days prior to each visit. Participants recorded whether they had been On, Off, or Asleep and the severity of their dyskinesias (troublesome or not troublesome) for each 30-minute period during their normal waking time and upon awakening from sleep.~On was defined as time when medication was providing benefit with regard to mobility, slowness, and stiffness. On time without troublesome dyskinesia is a composite of On time without dyskinesia (involuntary twisting, turning movements which are an effect of medication) plus On time with non-troublesome dyskinesia (dyskinesia that does not interfere with function or cause meaningful discomfort).~PD Diary times were normalized to a 16-hour waking time to account for variation in participants' sleep time. Normalized PD Diary times at a given visit were calculated as the average normalized time from the PD Diary for the 3 days prior to the visit." (NCT01736176)
Timeframe: Baseline and Week 12 and Week 60
| Intervention | hours (Least Squares Mean) | |
|---|---|---|
| Week 12 | Week 60 | |
| Levodopa-Carbidopa Intestinal Gel | 3.7 | 4.3 |
"Letter fluency was assessed using a paper and pen test, in which participants were asked to generate as many words as possible in 60 seconds, starting with the letters F, A, or S.~The COWAT All Letters score is the number of words recalled in all post-baseline assessments, regardless of letter used.~The COWAT Baseline Letter score is the number of words recalled in post-baseline assessments that used the same letter as at Baseline." (NCT01736176)
Timeframe: Baseline and Week 60
| Intervention | words (Mean) | |
|---|---|---|
| All Letters Score | Baseline Letter Score | |
| Levodopa-Carbidopa Intestinal Gel | -0.5 | -1.8 |
"The Health-Related Productivity Questionnaire (HRPQ) is a generic measure of the impact of disease on the ability of the participant to be productive at paid employment or at performance of household chores. Questions inquire about the amount of time they were scheduled/planned to work, the number of the scheduled/planned hours they were able to work and their ability to be productive for the hours of work they did perform.~Absenteeism: Number of hours not worked due to PD or it's treatments;~Presenteeism: Number of hours of lost productivity while at work due to PD or it's treatments;~Total hours lost: Number of hours lost due to absenteeism and presenteeism" (NCT01736176)
Timeframe: Baseline, Week 12 and Week 60
| Intervention | hours (Mean) | |||||
|---|---|---|---|---|---|---|
| Workplace Work Lost - Absenteeism | Household Work Lost - Absenteeism | Workplace Work Lost - Presenteeism | Household Work Lost - Presenteeism | Total Workplace Work Lost | Total Household Work Lost | |
| Week 12 | -2.1 | -3.5 | -0.8 | -1.8 | -3.0 | -5.3 |
| Week 60 | -5.2 | -1.9 | -0.3 | -1.9 | -5.5 | -3.8 |
"The NMSS measures the frequency and severity of a range of non-motor symptoms in Parkinson's Disease. It consists of 30 questions grouped into 9 domains: cardiovascular, sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, gastro-intestinal tract, urinary, sexual function, and miscellaneous (pain, taste/smell, weight change, excessive sweating). Severity is rated on a scale from 0 (none) to 3 (severe) and frequency is rated on a scale from 1 (rarely) to 4 (very frequent).~Item scores are calculated as the product of severity and frequency; domain scores are obtained by summing the item scores. The NMSS attention/memory domain score ranges from 0 to 36 with a lower score indicating fewer symptoms; a negative change from baseline indicates improvement in symptoms." (NCT01736176)
Timeframe: Baseline and Week 12 and Week 60
| Intervention | units on a scale (Least Squares Mean) | |
|---|---|---|
| Week 12 | Week 60 | |
| Levodopa-Carbidopa Intestinal Gel | -2.1 | -2.2 |
"The NMSS measures the frequency and severity of a range of non-motor symptoms in Parkinson's Disease. It consists of 30 questions grouped into 9 domains: cardiovascular, sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, gastro-intestinal tract, urinary, sexual function, and miscellaneous (pain, taste/smell, weight change, excessive sweating). Severity is rated on a scale from 0 (none) to 3 (severe) and frequency is rated on a scale from 1 (rarely) to 4 (very frequent).~Item scores are calculated as the product of severity and frequency; domain scores are obtained by summing the item scores. The NMSS cardiovascular including falls domain score ranges from 0 to 24 with a lower score indicating fewer symptoms; a negative change from baseline indicates improvement in symptoms." (NCT01736176)
Timeframe: Baseline and Week 12 and Week 60
| Intervention | units on a scale (Least Squares Mean) | |
|---|---|---|
| Week 12 | Week 60 | |
| Levodopa-Carbidopa Intestinal Gel | -0.2 | 0.5 |
"The NMSS measures the frequency and severity of a range of non-motor symptoms in Parkinson's Disease. It consists of 30 questions grouped into 9 domains: cardiovascular, sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, gastro-intestinal tract, urinary, sexual function, and miscellaneous (pain, taste/smell, weight change, excessive sweating). Severity is rated on a scale from 0 (none) to 3 (severe) and frequency is rated on a scale from 1 (rarely) to 4 (very frequent).~Item scores are calculated as the product of severity and frequency; domain scores are obtained by summing the item scores. The NMSS gastrointestinal tract domain score ranges from 0 to 36 with a lower score indicating fewer symptoms; a negative change from baseline indicates improvement in symptoms." (NCT01736176)
Timeframe: Baseline and Week 12 and Week 60
| Intervention | units on a scale (Least Squares Mean) | |
|---|---|---|
| Week 12 | Week 60 | |
| Levodopa-Carbidopa Intestinal Gel | -2.0 | -1.9 |
"The NMSS measures the frequency and severity of a range of non-motor symptoms in Parkinson's Disease. It consists of 30 questions grouped into 9 domains: cardiovascular, sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, gastro-intestinal tract, urinary, sexual function, and miscellaneous (pain, taste/smell, weight change, excessive sweating). Severity is rated on a scale from 0 (none) to 3 (severe) and frequency is rated on a scale from 1 (rarely) to 4 (very frequent).~Item scores are calculated as the product of severity and frequency; domain scores are obtained by summing the item scores. The NMSS miscellaneous domain score ranges from 0 to 48 with a lower score indicating fewer symptoms; a negative change from baseline indicates improvement in symptoms." (NCT01736176)
Timeframe: Baseline and Week 12 and Week 60
| Intervention | units on a scale (Least Squares Mean) | |
|---|---|---|
| Week 12 | Week 60 | |
| Levodopa-Carbidopa Intestinal Gel | -3.4 | -3.4 |
"The NMSS measures the frequency and severity of a range of non-motor symptoms in Parkinson's Disease. It consists of 30 questions grouped into 9 domains: cardiovascular, sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, gastro-intestinal tract, urinary, sexual function, and miscellaneous (pain, taste/smell, weight change, excessive sweating). Severity is rated on a scale from 0 (none) to 3 (severe) and frequency is rated on a scale from 1 (rarely) to 4 (very frequent).~Item scores are calculated as the product of severity and frequency; domain scores are obtained by summing the item scores. The NMSS mood/cognition domain score ranges from 0 to 72 with a lower score indicating fewer symptoms; a negative change from baseline indicates improvement in symptoms." (NCT01736176)
Timeframe: Baseline and Week 12 and Week 60
| Intervention | units on a scale (Least Squares Mean) | |
|---|---|---|
| Week 12 | Week 60 | |
| Levodopa-Carbidopa Intestinal Gel | 0.0 | 0.5 |
"The NMSS measures the frequency and severity of a range of non-motor symptoms in Parkinson's Disease. It consists of 30 questions grouped into 9 domains: cardiovascular, sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, gastro-intestinal tract, urinary, sexual function, and miscellaneous (pain, taste/smell, weight change, excessive sweating). Severity is rated on a scale from 0 (none) to 3 (severe) and frequency is rated on a scale from 1 (rarely) to 4 (very frequent).~Item scores are calculated as the product of severity and frequency; domain scores are obtained by summing the item scores. The NMSS perceptual problems/hallucinations domain score ranges from 0 to 36 with a lower score indicating fewer symptoms; a negative change from baseline indicates improvement in symptoms." (NCT01736176)
Timeframe: Baseline and Week 12 and Week 60
| Intervention | units on a scale (Least Squares Mean) | |
|---|---|---|
| Week 12 | Week 60 | |
| Levodopa-Carbidopa Intestinal Gel | -0.5 | 0.4 |
"The NMSS measures the frequency and severity of a range of non-motor symptoms in Parkinson's Disease. It consists of 30 questions grouped into 9 domains: cardiovascular, sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, gastro-intestinal tract, urinary, sexual function, and miscellaneous (pain, taste/smell, weight change, excessive sweating). Severity is rated on a scale from 0 (none) to 3 (severe) and frequency is rated on a scale from 1 (rarely) to 4 (very frequent).~Item scores are calculated as the product of severity and frequency; domain scores are obtained by summing the item scores. The NMSS sexual function domain score ranges from 0 to 24 with a lower score indicating fewer symptoms; a negative change from baseline indicates improvement in symptoms." (NCT01736176)
Timeframe: Baseline and Week 12 and Week 60
| Intervention | units on a scale (Least Squares Mean) | |
|---|---|---|
| Week 12 | Week 60 | |
| Levodopa-Carbidopa Intestinal Gel | -1.8 | -1.1 |
"The NMSS measures the frequency and severity of a range of non-motor symptoms in Parkinson's Disease. It consists of 30 questions grouped into 9 domains: cardiovascular, sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, gastro-intestinal tract, urinary, sexual function, and miscellaneous (pain, taste/smell, weight change, excessive sweating). Severity is rated on a scale from 0 (none) to 3 (severe) and frequency is rated on a scale from 1 (rarely) to 4 (very frequent).~Item scores are calculated as the product of severity and frequency; domain scores are obtained by summing the item scores. The NMSS sleep/fatigue domain score ranges from 0 to 48 with a lower score indicating fewer symptoms; a negative change from baseline indicates improvement in symptoms." (NCT01736176)
Timeframe: Baseline and Week 12 and Week 60
| Intervention | units on a scale (Least Squares Mean) | |
|---|---|---|
| Week 12 | Week 60 | |
| Levodopa-Carbidopa Intestinal Gel | -6.0 | -5.4 |
"The NMSS measures the frequency and severity of a range of non-motor symptoms in Parkinson's Disease. It consists of 30 questions grouped into 9 domains: cardiovascular, sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, gastro-intestinal tract, urinary, sexual function, and miscellaneous (pain, taste/smell, weight change, excessive sweating). Severity is rated on a scale from 0 (none) to 3 (severe) and frequency is rated on a scale from 1 (rarely) to 4 (very frequent).~Item scores are calculated as the product of severity and frequency; domain scores are obtained by summing the item scores. The NMSS urinary domain score ranges from 0 to 36 with a lower score indicating fewer symptoms; a negative change from baseline indicates improvement in symptoms." (NCT01736176)
Timeframe: Baseline and Week 12 and Week 60
| Intervention | units on a scale (Least Squares Mean) | |
|---|---|---|
| Week 12 | Week 60 | |
| Levodopa-Carbidopa Intestinal Gel | -2.2 | 0.1 |
"The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing eight domains of health (mobility [10 items], activities of daily living [six items], emotional wellbeing [six items], stigma [four items], communication [three items] and bodily discomfort [three items]) which subjects consider to be adversely affected by the disease. Each item is scored on the following 5-point scale: 0 = Never, 1 = Occasionally, 2 = Sometimes, 3 = Often, 4 = Always (or cannot do at all, if applicable).~The PDQ-39 Summary Index (PDQ-SI) is the sum of all answers divided by the highest score possible (i.e., number of answers multiplied by 4) which is multiplied by 100 to put the score on a 0 - 100 scale where lower scores indicate a better perceived health status and higher scores are associated with the more severe symptoms of the disease such as tremors and stiffness." (NCT01736176)
Timeframe: Baseline and Week 12 and Week 60
| Intervention | units on a scale (Least Squares Mean) | |
|---|---|---|
| Week 12 | Week 60 | |
| Levodopa-Carbidopa Intestinal Gel | -11.2 | -10.2 |
"The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing eight domains of health (mobility [10 items], activities of daily living [six items], emotional wellbeing [six items], stigma [four items], communication [three items] and bodily discomfort [three items]) which subjects consider to be adversely affected by the disease. Each item is scored on the following 5-point scale: 0 = Never, 1 = Occasionally, 2 = Sometimes, 3 = Often, 4 = Always (or cannot do at all, if applicable).~Domain scores are calculated by summing the answers to the questions in the domain, dividing by the highest score possible and then multiplying by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status and higher scores are associated with the more severe symptoms of the disease such as tremors and stiffness." (NCT01736176)
Timeframe: Baseline and Week 12 and Week 60
| Intervention | units on a scale (Least Squares Mean) | |
|---|---|---|
| Week 12 | Week 60 | |
| Levodopa-Carbidopa Intestinal Gel | -12.1 | -11.9 |
"The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing eight domains of health (mobility [10 items], activities of daily living [six items], emotional wellbeing [six items], stigma [four items], communication [three items] and bodily discomfort [three items]) which subjects consider to be adversely affected by the disease. Each item is scored on the following 5-point scale: 0 = Never, 1 = Occasionally, 2 = Sometimes, 3 = Often, 4 = Always (or cannot do at all, if applicable).~Domain scores are calculated by summing the answers to the questions in the domain, dividing by the highest score possible and then multiplying by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status and higher scores are associated with the more severe symptoms of the disease such as tremors and stiffness." (NCT01736176)
Timeframe: Baseline and Week 12 and Week 60
| Intervention | units on a scale (Least Squares Mean) | |
|---|---|---|
| Week 12 | Week 60 | |
| Levodopa-Carbidopa Intestinal Gel | -9.6 | -3.8 |
"The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing eight domains of health (mobility [10 items], activities of daily living [six items], emotional wellbeing [six items], stigma [four items], communication [three items] and bodily discomfort [three items]) which subjects consider to be adversely affected by the disease. Each item is scored on the following 5-point scale: 0 = Never, 1 = Occasionally, 2 = Sometimes, 3 = Often, 4 = Always (or cannot do at all, if applicable).~Domain scores are calculated by summing the answers to the questions in the domain, dividing by the highest score possible and then multiplying by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status and higher scores are associated with the more severe symptoms of the disease such as tremors and stiffness." (NCT01736176)
Timeframe: Baseline and Week 12 and Week 60
| Intervention | units on a scale (Least Squares Mean) | |
|---|---|---|
| Week 12 | Week 60 | |
| Levodopa-Carbidopa Intestinal Gel | -8.4 | -7.3 |
"The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing eight domains of health (mobility [10 items], activities of daily living [six items], emotional wellbeing [six items], stigma [four items], communication [three items] and bodily discomfort [three items]) which subjects consider to be adversely affected by the disease. Each item is scored on the following 5-point scale: 0 = Never, 1 = Occasionally, 2 = Sometimes, 3 = Often, 4 = Always (or cannot do at all, if applicable).~Domain scores are calculated by summing the answers to the questions in the domain, dividing by the highest score possible and then multiplying by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status and higher scores are associated with the more severe symptoms of the disease such as tremors and stiffness." (NCT01736176)
Timeframe: Baseline and Week 12 and Week 60
| Intervention | units on a scale (Least Squares Mean) | |
|---|---|---|
| Week 12 | Week 60 | |
| Levodopa-Carbidopa Intestinal Gel | -13.0 | -10.8 |
"The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing eight domains of health (mobility [10 items], activities of daily living [six items], emotional wellbeing [six items], stigma [four items], communication [three items] and bodily discomfort [three items]) which subjects consider to be adversely affected by the disease. Each item is scored on the following 5-point scale: 0 = Never, 1 = Occasionally, 2 = Sometimes, 3 = Often, 4 = Always (or cannot do at all, if applicable).~Domain scores are calculated by summing the answers to the questions in the domain, dividing by the highest score possible and then multiplying by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status and higher scores are associated with the more severe symptoms of the disease such as tremors and stiffness." (NCT01736176)
Timeframe: Baseline and Week 12 and Week 60
| Intervention | units on a scale (Least Squares Mean) | |
|---|---|---|
| Week 12 | Week 60 | |
| Levodopa-Carbidopa Intestinal Gel | -4.9 | -6.6 |
"The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing eight domains of health (mobility [10 items], activities of daily living [six items], emotional wellbeing [six items], stigma [four items], communication [three items] and bodily discomfort [three items]) which subjects consider to be adversely affected by the disease. Each item is scored on the following 5-point scale: 0 = Never, 1 = Occasionally, 2 = Sometimes, 3 = Often, 4 = Always (or cannot do at all, if applicable).~Domain scores are calculated by summing the answers to the questions in the domain, dividing by the highest score possible and then multiplying by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status and higher scores are associated with the more severe symptoms of the disease such as tremors and stiffness." (NCT01736176)
Timeframe: Baseline and Week 12 and Week 60
| Intervention | units on a scale (Least Squares Mean) | |
|---|---|---|
| Week 12 | Week 60 | |
| Levodopa-Carbidopa Intestinal Gel | -18.5 | -19.4 |
"The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing eight domains of health (mobility [10 items], activities of daily living [six items], emotional wellbeing [six items], stigma [four items], communication [three items] and bodily discomfort [three items]) which subjects consider to be adversely affected by the disease. Each item is scored on the following 5-point scale: 0 = Never, 1 = Occasionally, 2 = Sometimes, 3 = Often, 4 = Always (or cannot do at all, if applicable).~Domain scores are calculated by summing the answers to the questions in the domain, dividing by the highest score possible and then multiplying by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status and higher scores are associated with the more severe symptoms of the disease such as tremors and stiffness." (NCT01736176)
Timeframe: Baseline and Week 12 and Week 60
| Intervention | units on a scale (Least Squares Mean) | |
|---|---|---|
| Week 12 | Week 60 | |
| Levodopa-Carbidopa Intestinal Gel | 1.6 | 3.3 |
"The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing eight domains of health (mobility [10 items], activities of daily living [six items], emotional wellbeing [six items], stigma [four items], communication [three items] and bodily discomfort [three items]) which subjects consider to be adversely affected by the disease. Each item is scored on the following 5-point scale: 0 = Never, 1 = Occasionally, 2 = Sometimes, 3 = Often, 4 = Always (or cannot do at all, if applicable).~Domain scores are calculated by summing the answers to the questions in the domain, dividing by the highest score possible and then multiplying by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status and higher scores are associated with the more severe symptoms of the disease such as tremors and stiffness." (NCT01736176)
Timeframe: Baseline and Week 12 and Week 60
| Intervention | units on a scale (Least Squares Mean) | |
|---|---|---|
| Week 12 | Week 60 | |
| Levodopa-Carbidopa Intestinal Gel | -9.5 | -5.4 |
"The UPDRS is an investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The UPDRS assessment was performed by an approved, trained rater.~The UPDRS was made up of the following sections:~Part I - Mentation, Behavior, and Mood~Part II - Activities of Daily Living~Part III - Motor Examination~Part IV - Complications of Therapy (including dyskinesias)~Part V - Modified Hoehn and Yahr Staging~The dyskinesia items score includes questions 32, 33 and 34 from the complications of therapy section of the UPDRS which address dyskinesia duration, disability, and pain. Each question was answered on a scale from 0 (Normal) to 4 (Severe); the UPDRS dyskinesia items score was computed as the sum of these items and ranged from 0 (not affected) to 12 (most severely affected)." (NCT01736176)
Timeframe: Baseline and Week 12 and Week 60
| Intervention | units on a scale (Least Squares Mean) | |
|---|---|---|
| Week 12 | Week 60 | |
| Levodopa-Carbidopa Intestinal Gel | -1.1 | -0.6 |
"The Unified Parkinson's Disease Rating Scale (UPDRS) is an investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The UPDRS assessment was performed by an approved, trained rater.~The UPDRS was made up of the following sections:~Part I - Mentation, Behavior, and Mood~Part II - Activities of Daily Living~Part III - Motor Examination~Part IV - Complications of Therapy (including dyskinesias)~Part V - Modified Hoehn and Yahr Staging~The mentation, behavior, and mood score includes 4 items addressing intellectual impairment, thought disorder, motivation/initiative, and depression. Each question is answered on a scale from 0 (None) to 4 (Severe). The UPDRS Part I: mentation, behavior, and mood score was computed as the sum of these items and ranged from 0 (not affected) to 16 (most severely affected)." (NCT01736176)
Timeframe: Baseline and Week 12 and Week 60
| Intervention | units on a scale (Least Squares Mean) | |
|---|---|---|
| Week 12 | Week 60 | |
| Levodopa-Carbidopa Intestinal Gel | -0.3 | -0.1 |
"The Unified Parkinson's Disease Rating Scale (UPDRS) is an investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The UPDRS assessment was performed by an approved, trained rater.~The UPDRS was made up of the following sections:~Part I - Mentation, Behavior, and Mood~Part II - Activities of Daily Living~Part III - Motor Examination~Part IV - Complications of Therapy (including dyskinesias)~Part V - Modified Hoehn and Yahr Staging~The activities of daily living score includes 13 items addressing speech, salivation, swallowing, handwriting, cutting food, dressing, hygiene, turning in bed, falling, freezing, walking, tremor, and sensory complaints. Each question is answered on a scale from 0 (Normal) to 4 (Severe). The UPDRS Part II: activities of daily living score was computed as the sum of these items and ranged from 0 (not affected) to 52 (most severely affected)." (NCT01736176)
Timeframe: Baseline and Week 12 and Week 60
| Intervention | units on a scale (Least Squares Mean) | |
|---|---|---|
| Week 12 | Week 60 | |
| Levodopa-Carbidopa Intestinal Gel | -5.5 | -4.7 |
"The UPDRS is an investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The UPDRS assessment was performed by an approved, trained rater.~The UPDRS was made up of the following sections:~Part I - Mentation, Behavior, and Mood~Part II - Activities of Daily Living~Part III - Motor Examination~Part IV - Complications of Therapy (including dyskinesias)~Part V - Modified Hoehn and Yahr Staging~The motor examination score includes 17 items addressing speech, facial expression, tremor at rest, action tremor, rigidity, finger taps, hand movements, hand pronation and supination, leg agility, arising from chair, posture, gait, postural stability, and body bradykinesia. Each question is answered on a scale from 0 (Normal) to 4 (Severe), some items include multiple grades for each extremity. The UPDRS Part III: motor examination score was computed as the sum of these items and ranged from 0 (not affected) to 108 (most severely affected)." (NCT01736176)
Timeframe: Baseline and Week 12 and Week 60
| Intervention | units on a scale (Least Squares Mean) | |
|---|---|---|
| Week 12 | Week 60 | |
| Levodopa-Carbidopa Intestinal Gel | -5.6 | -3.6 |
"The UPDRS is an investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The UPDRS assessment was performed by an approved, trained rater.~The UPDRS was made up of the following sections:~Part I - Mentation, Behavior, and Mood~Part II - Activities of Daily Living~Part III - Motor Examination~Part IV - Complications of Therapy (including dyskinesias)~Part V - Modified Hoehn and Yahr Staging~The complications of therapy section includes 11 items addressing dyskinesia duration, disability, and pain, early morning dystonia, offs-predictable, offs-unpredictable, offs-sudden, offs-duration, anorexia-nausea-vomiting, sleep disturbance, and symptomatic orthostasis. Four questions are answered on a scale from 0 (Normal) to 4 (Severe) and seven on a binary scale where 0=No and 1=Yes. The UPDRS Part IV: complications of therapy score was computed as the sum of these items and ranged from 0 (not affected) to 23 (most severely affected)." (NCT01736176)
Timeframe: Baseline and Week 12 and Week 60
| Intervention | units on a scale (Least Squares Mean) | |
|---|---|---|
| Week 12 | Week 60 | |
| Levodopa-Carbidopa Intestinal Gel | -3.5 | -2.9 |
"The UPDRS is an investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The UPDRS assessment was performed by an approved, trained rater.~The UPDRS was made up of the following sections:~Part I - Mentation, Behavior, and Mood~Part II - Activities of Daily Living~Part III - Motor Examination~Part IV - Complications of Therapy (including dyskinesias)~Part V - Modified Hoehn and Yahr Staging~The modified Hoehn and Yahr scale is as follows:~Stage 0: No signs of disease~Stage 1.0: Symptoms are very mild; unilateral involvement only~Stage 1.5: Unilateral and axial involvement~Stage 2: Bilateral involvement without impairment of balance~Stage 2.5: Mild bilateral disease with recovery on pull test~Stage 3: Mild to moderate bilateral disease; some postural instability; physically independent~Stage 4: Severe disability; still able to walk or stand unassisted~Stage 5: Wheelchair bound or bedridden unless aided" (NCT01736176)
Timeframe: Baseline and Week 12 and Week 60
| Intervention | units on a scale (Least Squares Mean) | |
|---|---|---|
| Week 12 | Week 60 | |
| Levodopa-Carbidopa Intestinal Gel | -0.2 | -0.2 |
"Use of healthcare resources was assessed by the investigator using the Health Resource Utilization Questionnaire (HRUQ), a questionnaire developed by the Sponsor regarding the use of healthcare resources due to the participant's Parkinson's disease. The Week 4 version of the questionnaire addressed the following questions during the first four weeks after the PEG-J procedure:~Has the subject had a visit to an emergency room?~Has the subject had a visit to an urgent care?~Has the subject had an outpatient visit to a neurologist?~Has the subject had an outpatient visit to a gastroenterologist, surgeon, or interventional radiologist?~Has the subject had an outpatient visit to a primary care physician?~Has the subject called the nursing support line?~Has the subject called a physician?" (NCT01736176)
Timeframe: Weeks 1-4
| Intervention | Participants (Count of Participants) | ||||||
|---|---|---|---|---|---|---|---|
| Q1. Emergency Room Visit | Q2. Urgent Care Visit | Q3. Neurologist Visit | Q4. Gastroenterologist, Surgeon, Radiologist Visit | Q5. Primary Care Physician Visit | Q6. Called Nursing Support Line | Q7. Called Physician | |
| Levodopa-Carbidopa Intestinal Gel | 3 | 0 | 6 | 11 | 8 | 9 | 13 |
"Patients will record daily time to on or TTO following their regularly scheduled first L-Dopa dose in the baseline period for 7 consecutive days. Following initiation on Apokyn therapy, patients will inject Apokyn at their regularly scheduled L-Dopa time (L-Dopa dosing will be delayed by 40 minutes following Apokyn injection) and record time to on or TTO from the injection. Time to on for both periods will be recorded in a standardized subject diary. Daily TTO for the baseline period will be averaged for each subject and compared to the daily TTO for the same subject during the treatment period to assess APOKYN's effect on TTO." (NCT01770145)
Timeframe: L-Dopa Baseline Days 1-7 and APOKYN Treatment Days 1-7
| Intervention | minutes (Mean) | ||
|---|---|---|---|
| Baseline | Treatment Period | Change from Baseline | |
| APOKYN | 60.86 | 23.72 | 37.14 |
Primary outcome is 20% reduction in pain intensity at p<0.1 based on pain ratings during 1 week prior to treatment and last week of study participation (at ~6months) (NCT01951105)
Timeframe: 6 months
| Intervention | Participants (Count of Participants) |
|---|---|
| Observation | 5 |
| Carbidopa/Levodopa & Naproxen | 15 |
| Placebo & Naproxen | 21 |
Residual pain is computed based on pain ratings from the week prior to treatment and last week of study participation (at ~6months) (NCT01951105)
Timeframe: 6 months
| Intervention | % residual pain (Mean) |
|---|---|
| Carbidopa/Levodopa & Naproxen (Males) | 62.97 |
| Carbidopa/Levodopa & Naproxen (Females) | 9.48 |
| Placebo & Naproxen (Males) | 37.96 |
| Placebo & Naproxen (Females) | 45.23 |
| Observation (Males) | 85.55 |
| Observation (Females) | 48.84 |
The UPDRS is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The Part IV Score is the sum of the answers to the 11 questions that comprise Part IV, each of which are measured on a 5-point scale (0-4) or a 2-point scale (0 or 1). The Part IV score ranges from 0 to 23 and higher scores are associated with more disability. (NCT01960842)
Timeframe: Baseline (end of screening period) and Final PEG-J Visit (up to week 12)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline | Last PEG-J visit | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 8.7 | 5.5 |
The UPDRS is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The Part III score is the sum of the 27 answers provided to the 14 Part III questions, each of which are measured on a 5-point scale (0-4). The Part III score ranges from 0-108 and higher scores are associated with more disability. (NCT01960842)
Timeframe: Baseline (end of screening period) and Final PEG-J Visit (up to week 12)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline | Final PEG-J visit | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 16.5 | 14.3 |
The UPDRS is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The Part I Score is the sum of the answers to the 4 questions that comprise Part I, each of which are measured on a 5-point scale (0-4). The Part I score ranges from 0 to 16 and higher scores are associated with more disability. (NCT01960842)
Timeframe: Baseline (end of screening period) and Final PEG-J Visit (up to week 12)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline | Last PEG-J visit | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 1.8 | 0.9 |
The UPDRS is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The Part II score is the sum of the answers to the 13 questions that comprise Part II, each of which are measured on a 5-point scale (0-4). The Part II score ranges from 0-52 and higher scores are associated with more disability. (NCT01960842)
Timeframe: Baseline (end of screening period) and Final PEG-J Visit (up to week 12)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline | Last PEG-J visit | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 9.4 | 7.6 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health in Parkinson's disease patients. These include: mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort. The PDQ-39 Summary Index is the sum of all answers divided by the highest score possible (i.e. number of answers multiplied by 4) which is multiplied by 100 to put the score on a 0-100 scale. Higher scores are associated with more severe symptoms. (NCT01960842)
Timeframe: Baseline (end of screening period) and Final PEG-J Visit (up to week 12)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline | Last PEG-J visit | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 35.5 | 23.5 |
The CGI-I is a global assessment by the Investigator of the change in clinical status since the start of treatment. The CGI-I ratings are as follows: 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, 7 = very much worse. (NCT01960842)
Timeframe: Final PEG-J Visit (up to week 12)
| Intervention | units on a scale (Mean) |
|---|---|
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 1.9 |
"The PGI-C is a 7-point response scale. The subjects were to rate their change in status from Screening Visit 1 using the following 7-point scale: 1 = Very much improved, 2 = Much improved, 3 = Minimally improved, 4 = No change, 5 = Minimally worse, 6 = Much worse, 7 = Very much worse. The responses of Minimally improved, Much improved, and Very much improved on the PGI-C were used to define responders." (NCT01960842)
Timeframe: Final PEG-J Visit (up to week 12)
| Intervention | units on a scale (Mean) |
|---|---|
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 2.0 |
"Based on the Parkinson's Disease Symptom Diary. On time is when PD symptoms are well controlled by the drug. Off time is when PD symptoms are not adequately controlled by the drug. The diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected clinic visits. It reflects both time awake and time asleep. Daily totals are normalized to a 16-hour scale (i.e. 16 hours of awake time). The normalized totals for the 3 days prior to the visit are averaged for the analysis. n= the number of participants with available data at each time point." (NCT01960842)
Timeframe: Baseline (end of screening period) and Weeks 2, 4, 6, 8, 10, and 12
| Intervention | hours (Mean) | ||||||
|---|---|---|---|---|---|---|---|
| Baseline (n=29) | Week 2 (n=29) | Week 4 (n=29) | Week 6 (n=29) | Week 8 (n=27) | Week 10 (n=27) | Week 12 (n=27) | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 7.37 | 3.17 | 3.68 | 2.61 | 2.77 | 2.47 | 2.45 |
"Based on the Parkinson's Disease Symptom Diary. On time is when PD symptoms are well controlled by the drug. Off time is when PD symptoms are not adequately controlled by the drug. The diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected clinic visits. It reflects both time awake and time asleep. Daily totals are normalized to a 16-hour scale (i.e. 16 hours of awake time). The normalized totals for the 3 days prior to the visit are averaged for the analysis. Negative change from baseline for off time indicates improvement." (NCT01960842)
Timeframe: Baseline (end of screening period) and Final PEG-J Visit (up to week 12)
| Intervention | hours (Mean) | |
|---|---|---|
| Baseline | Last PEG-J visit | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 7.32 | 2.67 |
"Based on the Parkinson's Disease Symptom Diary. On time is when PD symptoms are well controlled by the drug. Off time is when PD symptoms are not adequately controlled by the drug. The diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected clinic visits. It reflects both time awake and time asleep. Daily totals are normalized to a 16-hour scale (i.e. 16 hours of awake time). The normalized totals for the 3 days prior to the visit are averaged for the analysis. Negative change from baseline for off time indicates improvement." (NCT01960842)
Timeframe: Baseline (end of screening period) and Final PEG-J Visit (up to week 12)
| Intervention | hours (Mean) | |
|---|---|---|
| Baseline | Last PEG-J visit | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 7.37 | 2.78 |
The UPDRS is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The total score is the sum of the responses to the 31 questions (44 answers) that comprise Parts I-III of the scale. The total score will range from 0 to176, with 176 representing the worst (total) disability, and 0 representing no disability. (NCT01960842)
Timeframe: Baseline and Final PEG-J Visit (up to Week 12)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline | Last PEG-J visit | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 27.7 | 22.9 |
"Based on the Parkinson's Disease Symptom Diary. On time is when PD symptoms are well controlled by the drug. Off time is when PD symptoms are not adequately controlled by the drug. The diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected clinic visits. It reflects both time awake and time asleep. Daily totals are normalized to a 16-hour scale (i.e. 16 hours of awake time). The normalized totals for the 3 days prior to the visit are averaged for the analysis. Negative change from baseline for off time indicates improvement." (NCT01960842)
Timeframe: Baseline (end of screening period) and Final PEG-J Visit (up to week 12)
| Intervention | hours (Mean) | |
|---|---|---|
| Baseline | Last PEG-J visit | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 7.37 | 2.72 |
"Based on the Parkinson's Disease Symptom Diary. On time is when PD symptoms are well controlled by the drug. Off time is when PD symptoms are not adequately controlled by the drug. The diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected clinic visits. It reflects both time awake and time asleep. Daily totals are normalized to a 16-hour scale (i.e. 16 hours of awake time). The normalized totals for the 3 days prior to the visit are averaged for the analysis. Positive change from baseline for on time indicates improvement." (NCT01960842)
Timeframe: Baseline (end of screening period) and Final PEG-J Visit (up to week 12)
| Intervention | hours (Mean) | |
|---|---|---|
| Baseline | Last PEG-J visit | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 1.12 | 0.12 |
"Based on the Parkinson's Disease Symptom Diary. On time is when PD symptoms are well controlled by the drug. Off time is when PD symptoms are not adequately controlled by the drug. The diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected clinic visits. It reflects both time awake and time asleep. Daily totals are normalized to a 16-hour scale (i.e. 16 hours of awake time). The normalized totals for the 3 days prior to the visit are averaged for the analysis. Positive change from baseline for on time indicates improvement." (NCT01960842)
Timeframe: Baseline (end of screening period) and Final PEG-J Visit (up to week 12)
| Intervention | hours (Mean) | |
|---|---|---|
| Baseline | Last PEG-J visit | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 7.52 | 13.10 |
Terms abbreviated in the table include heart rate (HR) in beats per minute (bpm), PR interval (PRI), QT interval corrected for heart rate using Bazett's formula (QTcB), QT interval corrected for heart rate using Fridericia's formula (QTcF), and baseline (BL). Increase and decrease are signified by ↑ and ↓, respectively. n = the number of participants with available data at each time point. (NCT01960842)
Timeframe: From Baseline (end of screening period) to Final PEG-J Visit (up to week 12)
| Intervention | participants (Number) | |||||||
|---|---|---|---|---|---|---|---|---|
| HR <=50 and >30 bpm ↓ from BL (n=31) | HR >=120 and >30 bpm ↑ from BL (n=31) | PR Interval <120 msec (n=30) | PR Interval >220 msec (n=30) | QTcB Interval >480 msec (n=31) | QTcB Interval >60 msec ↑ from BL (n=31) | QTcF Interval >480 msec (n=31) | QTcF Interval >60 msec ↑ from BL (n=31) | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 0 | 0 | 0 | 1 | 1 | 1 | 0 | 1 |
Terms abbreviated in the table include upper limit of normal (ULN), male (m), and female (f). (NCT01960842)
Timeframe: From Baseline (end of screening period) to Final PEG-J Visit (up to week 12)
| Intervention | participants (Number) | ||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Alanine Aminotransferase >3xULN | Aspartate Aminotransferase >3xULN | Gamma-glutamyl Transferase >3x ULN | Alkaline Phosphatase >400 U/L | Total Bilirubin >2xULN | Creatine Phosphokinase >3x ULN | Creatinine >177 µmol/L | Blood Urea Nitrogen >10.8 mmol/L | Uric Acid>500µmol/L(f);>590µmol/L(m) | Calcium <1.75 mmol/L | Calcium >3.0 mmol/L | Sodium <126 mmol/L | Sodium >156 mmol/L | Potassium <3.0 mmol/L | Potassium >6.0 mmol/L | Non-fasting Glucose <2.78 mmol/L | Non-fasting Glucose >16.0 mmol/L | Albumin <25 g/L | Albumin >70 g/L | Total Protein <45 g/L | Cholesterol >12.9 mmol/L | Triglycerides >5.6 mmol/L | Lactate dehydrogenase >3x ULN | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
Terms abbreviated in the table include females (f), males (m), and femtoliters (fL). (NCT01960842)
Timeframe: From Baseline (end of screening period) to Final PEG-J Visit (up to week 12)
| Intervention | participants (Number) | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Haemoglobin <90 g/L (f); <100 g/L (m) | Haematocrit <30% (f); <34% (m) | Red Blood Cells <2.0 10^12/L (f); <2.5 10^12/L (m) | Platelet Count <95 10^9/L | Platelet Count >700 10^9/L | White Blood Cells <2.8 10^9/L | White Blood Cells >16.0 10^9/L | Lymphocytes >80% | Monocytes >30% | Eosinophils >10% | Mean Corpuscular Volume <60 fL | Mean Corpuscular Volume >120 fL | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 1 | 2 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 |
Terms abbreviated in the table include supine systolic blood pressure (SuSBP), standing systolic blood pressure (StSBP), orthostatic systolic blood pressure (OSBP), supine diastolic blood pressure (SuDBP), standing diastolic blood pressure (StDBP), orthostatic diastolic blood pressure (ODBP), supine pulse (SuP) in beats per minute (bpm), standing pulse (StP), body temperature (Temp), and baseline (BL). Increase and decrease are signified by ↑ and ↓, respectively. (NCT01960842)
Timeframe: From Baseline (end of screening period) to Final PEG-J Visit (up to week 12)
| Intervention | participants (Number) | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SuSBP <=90 and >30 mm Hg ↓ from BL | SuSBP >=180 and >40 mm Hg ↑ from BL | StSBP <=90 and >30 mm Hg ↓ from BL | StSBP >=180 and >40 mm Hg ↑ from BL | OSBP: ↓ >=30 mm Hg Supine to Standing | SuDBP <=50 and >30 mm Hg ↓ from BL | SuDBP >=105 and >30 mm Hg ↑ from BL | StDBP <=50 and >30 mm Hg ↓ from BL | StDBP >=105 and >30 mm Hg ↑ from BL | ODBP: ↓ >=20 mm Hg Supine to Standing | SuP <=50 and >30 bpm ↓ from BL | SuP >=120 and >30 bpm ↑ from BL | StP <=50 and >30 bpm ↓ from BL | StP >=120 and >30 bpm ↑ from BL | Weight <=7% ↓ from BL | Weight >=7% ↑ from BL | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 3 | 1 | 3 | 1 | 8 | 1 | 1 | 3 | 3 | 11 | 0 | 0 | 0 | 0 | 8 | 2 |
"An adverse event (AE) is any untoward medical occurrence in a participant which does not necessarily have a causal relationship with this treatment. A serious AE (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent AEs (TEAEs) are defined as any event that began or worsened in severity after N-J placement. The investigator assessed the relationship of each event to the use of study drug as Reasonable Possibility or No Reasonable Possibility.~For more details on adverse events please see the AE section below." (NCT01960842)
Timeframe: From N-J placement to the end of study or early termination of treatment, including the removal of PEG-J (up to 17 weeks), plus 30 days.
| Intervention | participants (Number) | |||||||
|---|---|---|---|---|---|---|---|---|
| Any TEAE | Any TEAE at least possibly related to LCIG | Any TEAE at least possibly related to LCIG System | Any severe TEAE | Any SAE | Any TEAE Leading to Discontinuation of Study | Death | Death related to AE | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 31 | 0 | 30 | 2 | 4 | 1 | 1 | 1 |
The PDQ-39 is a self-administered questionnaire which comprises 39 items (each question answered on a 5-point scale) addressing 8 domains of health in Parkinson's disease patients: Mobility (e.g., fear of falling when walking) includes 10 questions; Emotional Well-being (e.g., feelings of isolation) includes 6 questions; Stigma (e.g., social embarrassment) includes 4 questions; Social Support includes 3 questions; Cognition includes 4 questions; Communication includes 3 questions; and Bodily Discomfort includes 3 questions. The domain scores are calculated by first summing the answers to the questions in the domain. The sum is divided by the highest score possible (i.e., number of answers multiplied by 4) and the quotient is multiplied by 100 to put the score on a scale from 0 to 100, where lower scores indicate a better perceived health status. Higher scores are consistently associated with the more severe symptoms of the disease such as tremor and stiffness. (NCT01960842)
Timeframe: Baseline (end of screening period) and Final PEG-J Visit (up to week 12)
| Intervention | units on a scale (Mean) | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Mobility Domain-Baseline | Mobility Domain-Last PEG-J visit | Emotional Well-Being Domain-Baseline | Emotional Well-Being Domain-Last PEG-J visit | Stigma Domain-Baseline | Stigma Domain-Last PEG-J visit | Social Support Domain-Baseline | Social Support Domain-Last PEG-J visit | Cognition Domain-Baseline | Cognition Domain-Last PEG-J visit | Communication Domain-Baseline | Communication Domain-Last PEG-J visit | Bodily Discomfort Domain-Baseline | Bodily Discomfort Domain-Last PEG-J visit | |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 55.7 | 36.5 | 30.8 | 24.3 | 20.6 | 13.1 | 16.1 | 14.6 | 28.5 | 14.6 | 13.3 | 14.4 | 35.0 | 17.2 |
AUC0-t - Area under the plasma concentration-time curve to last measurable time point for levodopa (NCT02169453)
Timeframe: pre-dose, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-dose
| Intervention | ng.h/mL (Mean) |
|---|---|
| BIA 9-1067 25 mg | 1886 |
| BIA 9-1067 50 mg | 1997 |
| BIA 9-1067 100 mg | 2059 |
| Placebo | 1575 |
AUC0-∞ - Area under the plasma concentration-time curve extrapolated to infinity for levodopa (NCT02169453)
Timeframe: pre-dose, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-dose
| Intervention | ng.h/mL (Mean) |
|---|---|
| BIA 9-1067 25 mg | 1986 |
| BIA 9-1067 50 mg | 2144 |
| BIA 9-1067 100 mg | 2215 |
| Placebo | 1677 |
(NCT02169453)
Timeframe: pre-dose, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-dose
| Intervention | pmol/mg Hb/h.h (Mean) |
|---|---|
| BIA 9-1067 25 mg | 621 |
| BIA 9-1067 50 mg | 427 |
| BIA 9-1067 100 mg | 363 |
| Placebo | 1144 |
Cmax - Maximum observed plasma concentration of levodopa (NCT02169453)
Timeframe: pre-dose, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-dose
| Intervention | ng/mL (Mean) |
|---|---|
| BIA 9-1067 25 mg | 716 |
| BIA 9-1067 50 mg | 673 |
| BIA 9-1067 100 mg | 570 |
| Placebo | 554 |
Emax - Maximum inhibition of Catechol-O-Methyltransferase (COMT) activity (NCT02169453)
Timeframe: pre-dose, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-dose
| Intervention | pmol/mg Hb/h (Mean) |
|---|---|
| BIA 9-1067 25 mg | 16.5 |
| BIA 9-1067 50 mg | 7.44 |
| BIA 9-1067 100 mg | 3.16 |
| Placebo | 39.3 |
(NCT02169453)
Timeframe: pre-dose, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-dose
| Intervention | hours (Mean) |
|---|---|
| BIA 9-1067 25 mg | 4.92 |
| BIA 9-1067 50 mg | 3.59 |
| BIA 9-1067 100 mg | 2.33 |
| Placebo | 7.17 |
Levodopa maximum observed plasma concentration (Cmax) (ng/mL) (NCT02169479)
Timeframe: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-dose
| Intervention | ng/mL (Mean) |
|---|---|
| BIA 9-1067 25 mg | 896 |
| BIA 9-1067 50 mg | 1088 |
| BIA 9-1067 100 mg | 1014 |
| Placebo | 889 |
Tmax - time of occurrence of Cmax of levodopa. (NCT02169479)
Timeframe: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-dose
| Intervention | hours (Median) |
|---|---|
| BIA 9-1067 25 mg | 0.5 |
| BIA 9-1067 50 mg | 0.5 |
| BIA 9-1067 100 mg | 0.5 |
| Placebo | 0.5 |
Area under the plasma concentration-time curve for levodopa (NCT02169479)
Timeframe: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-dose
| Intervention | ng.h/mL (Mean) |
|---|---|
| BIA 9-1067 25 mg | 1629 |
| BIA 9-1067 50 mg | 1727 |
| BIA 9-1067 100 mg | 1853 |
| Placebo | 1629 |
"Dyskinesia and parkinsonism symptoms were evaluated throughout the study period as an assessment of the clinical response. To assess the ON/OFF effect the Treatment Response Scale (TRS) was used. The TRS ranges from -3 (severe OFF) to +3 (ON with severe dyskinesia). Results from the TRS recordings are presented as the mean percentage of time patients were in functional ON state (TRS: -1 to +1) during the time interval 3-14 h." (NCT02448914)
Timeframe: TRS assessments were made every 30 minutes from start of study drug administration until 3 h, every hour between 3 and 14 h and every 30 minutes between 14 and 17 h.
| Intervention | Mean % of time (Mean) |
|---|---|
| TRIGEL | 91.7 |
| Duodopa | 91.0 |
(NCT02448914)
Timeframe: During 14 h infusion on 2 consecutive days
| Intervention | h*ng/mL/mg (Least Squares Mean) |
|---|---|
| TRIGEL | 40.6 |
| Duodopa | 29.4 |
(NCT02448914)
Timeframe: During 14 h infusion on 2 consecutive days
| Intervention | h*ng/mL/mg (Least Squares Mean) |
|---|---|
| TRIGEL | 155 |
| Duodopa | 131 |
(NCT02448914)
Timeframe: During 14 h infusion on 2 consecutive days
| Intervention | h*ng/mL/mg (Least Squares Mean) |
|---|---|
| TRIGEL | 22.1 |
| Duodopa | 18.8 |
The individual patient's coefficient of variation (CV) of levodopa plasma concentration during administration of TRIGEL and Duodopa respectively between 3 and 14 h after start of study drug. CV=100*sqrt (exp (SDlog*SDlog)-1) were SDlog denotes the standard deviation computed on logged plasma concentrations. (NCT02448914)
Timeframe: During 3-14h infusion on 2 consecutive days
| Intervention | percentage of variability (Least Squares Mean) |
|---|---|
| TRIGEL | 13.8 |
| Duodopa | 10.6 |
(NCT02448914)
Timeframe: Patients will be followed for the duration of the hospital stay, an expected average of 3 days
| Intervention | adverse events (Number) |
|---|---|
| TRIGEL | 10 |
| Duodopa | 6 |
The NMSS consists of 30 questions in 9 domains (cardiovascular/falls, sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, GI tract, urinary, sexual function, miscellaneous). Score of each question is calculated by multiplying severity*frequency. Severity and frequency are rated using a scale ranging from 0 (none) to 3 (severe) for severity and from 1 (rarely) to 4 (very frequent) for frequency. Total score is the sum of 9 domains, and ranges from 0 to 360, with a lower value indicating a more desirable outcome. Repeated-measure analysis. (NCT02549092)
Timeframe: Baseline, Week 26
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Optimized Medical Treatment | -23.83 |
| LCIG | -32.04 |
The PDSS-2 addresses PD-specific sleep disturbances such as restless leg syndrome (RLS), morning akinesia, pain, and sleep apnea. The frequency is assessed for the 15 sleep problems based on a 5-point Likert-type scale (ranging from 0 [never] to 4 [very often]). Scores are calculated for each of the 3 domains (motor symptoms at night, PD symptoms at night, and disturbed sleep) as well as a total score. The PDSS-2 domain scores range from 0 to 20 and the total score is a sum of the 3 domains and ranges from 0 to 60. Repeated measure analysis. (NCT02549092)
Timeframe: Baseline, Week 26
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Optimized Medical Treatment | -8.98 |
| LCIG | -7.41 |
The PDQ-8 is a disease-specific instrument designed to measure aspects of health relevant to PD. Eight questions including the mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort are assessed on a 5-point scale: 0 = Never, 1 = Occasionally, 2 = Sometimes, 3 = Often, 4 = Always (or cannot do at all, if applicable). Summary index score is the sum of each question divided by 32 and multiplied by 100. Scores range from 0 to 100 with lower values desirable. (NCT02549092)
Timeframe: Baseline, Week 26
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Optimized Medical Treatment | -1.75 |
| LCIG | -5.56 |
"The GDS-15 is a short, self-report reliable and valid screening instrument for depression in the elderly of 15 yes/no questions: 1) Satisfied with life 2) Dropped many activities and interests 3) Life is empty 4) Often get bored 5) In good spirits most of the time 6) Afraid that something bad is going to happen 7) Feel happy most of the time 8) Often feel helpless 9) Prefer to stay at home, rather than going out and doing things 10) Feel that have more problems with memory than most 11) Think it is wonderful to be alive now 12) Feel worthless 13) Feel full of energy 14) Situation is hopeless 15) Most subjects are better off. Answers of 'yes' to questions 2, 3, 4, 6, 8, 9, 10, 12, 14, 15 are scored 1 point. Answers of 'no' to questions 1, 5, 7, 11, 13 are scored~1 point. The 15 items are summed and scores range from 0 - 15 with lower value desirable." (NCT02549092)
Timeframe: Baseline, Week 26
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Optimized Medical Treatment | 0.25 |
| LCIG | 0.17 |
UPDRS is an investigator-used rating tool to follow the longitudinal course of Parkinson's disease of 42 total questions. Part I (Questions 1 - 4), Part II (Questions 5 - 17), Part III (Questions 18 - 31), and Part IV (Questions 32 - 42). Questions 35 - 38 and 40 - 42 are 2-point (0 and 1), all other questions are 5-point (0 - 4). Part II scores range from 0 to 52 with lower value desirable. (NCT02549092)
Timeframe: Baseline, Week 26
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Optimized Medical Treatment | 0.53 |
| LCIG | -2.26 |
PAS is a 12-item scale developed specifically to measure severity in anxiety in Parkinson's disease for the following items: Feeling anxious or nervous; Feeling tense or stressed; Being unable to relax; Excessive worrying about everyday matters; Fear of something bad, or even the worst, happening; Panic or intense fear; Shortness of breath; Heart palpitations or heart beating fast; Fear of losing control; Social situations; Public settings; Specific objects or situations. Severity for each item is rated as: 0, Never; 1 Rarely; 2, Sometimes; 3, Often; 4, Nearly always. Total score is the sum of the12 item scores, with a range of 0 to 48; a lower value is desirable. (NCT02549092)
Timeframe: Baseline, Week 26
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Optimized Medical Treatment | -0.75 |
| LCIG | -2.29 |
The PDSS-2 addresses PD-specific sleep disturbances such as restless leg syndrome (RLS), morning akinesia, pain, and sleep apnea. The frequency is assessed for the 15 sleep problems based on a 5-point Likert-type scale (ranging from 0 [never] to 4 [very often]). Scores are calculated for each of the 3 domains (motor symptoms at night, PD symptoms at night, and disturbed sleep) as well as a total score. The PDSS-2 domain scores range from 0 to 20 and the total score is a sum of the 3 domains and ranges from 0 to 60. Repeated measure analysis. (NCT02549092)
Timeframe: Baseline, Week 26
| Intervention | score on a scale (Least Squares Mean) | ||
|---|---|---|---|
| Motor symptoms at night | PD symptoms at night | Disturbed sleep | |
| LCIG | -2.79 | -1.53 | -2.89 |
| Optimized Medical Treatment | -2.21 | -1.77 | -4.88 |
The NMSS consists of 30 questions in 9 domains. Score of each question is calculated by multiplying severity*frequency. Severity and frequency are rated using a scale ranging from 0 (none) to 3 (severe) for severity and from 1 (rarely) to 4 (very frequent) for frequency. Cardiovascular/falls scores range from 0 - 24 with lower value desirable. Sleep/fatigue scores range from 0 - 48 with lower value desirable. Mood/cognition scores range from 0 - 72 with lower value desirable. Perceptual problems/hallucinations scores range from 0 - 36 with lower value desirable. Attention/memory scores range from 0 - 36 with lower value desirable. Gastrointestinal tract scores range from 0 - 36 with lower value desirable. Urinary scores range from 0 - 36 with lower value desirable. Sexual function scores range from 0 - 24 with lower value desirable. Miscellaneous scores range from 0 - 48 with lower value desirable. Repeated-measure analysis. (NCT02549092)
Timeframe: Baseline, Week 26
| Intervention | score on a scale (Least Squares Mean) | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Cardiovascular including falls | Sleep/fatigue | Mood/cognition | Perceptual problems/hallucinations | Attention/memory | Gastrointestinal tract | Urinary | Sexual function | Miscellaneous | |
| LCIG | -1.76 | -6.06 | -7.84 | -1.14 | -2.15 | -3.43 | -4.83 | 0.10 | -5.16 |
| Optimized Medical Treatment | -1.84 | -7.11 | -5.99 | -1.53 | -1.20 | -0.85 | -3.65 | 0.88 | -3.87 |
UPDRS is an investigator-used rating tool to follow the longitudinal course of Parkinson's disease of 42 total questions. Part I (Questions 1 - 4), Part II (Questions 5 - 17), Part III (Questions 18 - 31), and Part IV (Questions 32 - 42). Questions 35 - 38 and 40 - 42 are 2-point (0 and 1), all other questions are 5-point (0 - 4). Part I is the sum of Questions 1 - 4; scores range from 0 to 16 with lower value desirable. Part III is the sum of Questions 18 - 31 (Questions 20 - 26 apply to multiple body parts, resulting in 27 answers total); scores range from 0 to 108 with lower value desirable. Part IV is the sum of Questions 32 - 42; scores range from 0 to 23 with lower value desirable. (NCT02549092)
Timeframe: Baseline, Week 26
| Intervention | score on a scale (Least Squares Mean) | ||
|---|---|---|---|
| Part I | Part III | Part IV | |
| LCIG | 0.39 | -0.89 | -2.31 |
| Optimized Medical Treatment | 0.20 | 1.32 | -0.61 |
The KPPS score is a clinical PD-specific pain scale of 14 items addressing the following 7 domains: musculoskeletal pain, chronic pain, fluctuation-related pain, nocturnal pain, orofacial pain, neuropathic pain, radicular pain. Each domain item is scored by severity (0, none to 3, very severe) multiplied by frequency (0, never to 4, all the time) resulting in a subscore of 0 - 12 (with lower value desirable), the sum of the 14 items gives the total score with a range from 0 to 168 with lower value desirable. (NCT02549092)
Timeframe: Baseline, Week 26
| Intervention | score on a scale (Least Squares Mean) | |||||||
|---|---|---|---|---|---|---|---|---|
| Total score | Musculoskeletal Pain Score | Chronic pain score | Fluctuation related pain score | Nocturnal pain score | Orofacial pain score | Discoloration and edema score | Radicular pain score | |
| LCIG | -12.46 | -1.79 | -0.77 | -3.14 | -2.78 | -0.87 | -2.27 | -1.47 |
| Optimized Medical Treatment | -11.32 | -1.72 | -0.84 | -3.77 | -2.41 | -0.74 | -0.47 | -1.43 |
The PGIC is a 7-point response scale. The participant was asked by the Investigator or qualified designee to rate their change in status using the following 7-point scale: 1 = Very much improved, 2 = Much improved, 3 = Minimally improved, 4 = No change, 5 = Minimally worse, 6 = Much worse, 7 = Very much worse. PGIC score ranges from 1 to 7 with lower score desirable. (NCT02549092)
Timeframe: End of Treatment Period (up to Week 26)
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Optimized Medical Treatment | 4.9 |
| LCIG | 2.5 |
CGI-C score is a clinician's impression of a subject's change in status on a 7-point scale (1 = very much improved, 2 = much improved, 3 = minimally Improved, 4 = no change, 5 = minimally worse, 6 = much worse, 7 = very much worse). Scores range from 1 to 7, with lower score desirable. (NCT02549092)
Timeframe: End of Treatment Period (up to Week 26)
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Optimized Medical Treatment | 4.9 |
| LCIG | 2.5 |
The Parkinson's Disease (PD) Symptom Diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected study visits. It reflects both time awake and time asleep. Daily totals are normalized to a 16-hour scale (i.e., 16 hours of awake time). The normalized totals for the 3 days prior to the visit are averaged for the analysis. ON time is when PD symptoms are well controlled by the drug, and OFF time is when PD symptoms are not adequately controlled by the drug. Positive change from baseline for ON time without troublesome dyskinesia indicates improvement. (NCT02799381)
Timeframe: Baseline, Week 12
| Intervention | hours (Least Squares Mean) |
|---|---|
| Optimized Medical Treatment (OMT) | -0.12 |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 3.15 |
The Parkinson's Disease Questionnaire-8 (PDQ-8) is a disease-specific instrument designed to measure aspects of health that are relevant to participants with PD, and which may not be included in general health status questionnaires. The PDQ-8 is a self-administered questionnaire. Each item is scored on the following 5-point scale: 0 = Never, 1 = Occasionally, 2 = Sometimes, 3 = Often, 4 = Always (or cannot do at all, if applicable). Higher scores are consistently associated with the more severe symptoms of the disease such as tremors and stiffness. The results are presented as a summary index. The PDQ-8 summary index ranges from 0 to 100, where lower scores indicate a better perceived health status. Negative changes from baseline indicate improvement. (NCT02799381)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Optimized Medical Treatment (OMT) | -4.95 |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | -21.62 |
The Parkinson's Disease (PD) Symptom Diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected study visits. It reflects both time awake and time asleep. Daily totals are normalized to a 16-hour scale (i.e., 16 hours of awake time). The normalized totals for the 3 days prior to the visit are averaged for the analysis. ON time is when PD symptoms are well controlled by the drug, and OFF time is when PD symptoms are not adequately controlled by the drug. Negative change from baseline for OFF time indicates improvement. (NCT02799381)
Timeframe: Baseline, Week 12
| Intervention | hours (Least Squares Mean) |
|---|---|
| Optimized Medical Treatment (OMT) | 0.18 |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | -2.17 |
The Unified Dyskinesia Rating Scale (UDysRS) is a tool used to assess dyskinesia in Parkinson's disease (PD) and contains both self-evaluation questions and items that are assessed directly by the physician to objectively rate the abnormal movements associated with PD. Part 1 contains 11 questions about the ON time dyskinesia and the impact of ON-dyskinesia on experiences of daily living. Part 2 contains 4 questions about OFF-dystonia rating. Part 3 contains 7 questions about objective evaluation of dyskinesia impairment and Part 4 contains 4 questions regarding dyskinesia disability. Each question is scored with respect to severity, which is rated on a scale where 0 = normal, 1 = slight, 2 = mild, 3= moderate and 4 = severe. The UDysRS total score is obtained by summing the item scores, ranging from 0 to 104. Higher scores are associated with more disability. Negative changes from baseline indicate improvement. (NCT02799381)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Optimized Medical Treatment (OMT) | -2.33 |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | -17.37 |
The Unified Parkinson's Disease Rating Scale (UPDRS) is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The Part II score is the sum of the answers to the 13 questions related to Activities of Daily Living, and ranges from 0-52. Higher scores are associated with more disability. Negative values indicate improvement from baseline. (NCT02799381)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Optimized Medical Treatment (OMT) | 0.21 |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | -5.33 |
The Unified Parkinson's Disease Rating Scale (UPDRS) is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The Part III score is the sum of the 27 answers related to Motor Examination, and ranges from 0-108. Higher scores are associated with more disability. Negative values indicate improvement from baseline. (NCT02799381)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Optimized Medical Treatment (OMT) | -0.87 |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | -4.93 |
The Clinical Global Impression of Change (CGI-C) score is a clinician's rating scale for assessing Global Improvement of Change. The CGI-C rates improvement by 7 categories: very much improved (1), much improved (2), minimally improved (3), no change (4), minimally worse (5), much worse (6), very much worse (7). The CGI-C score ranges from 1 to 7, with lower scores indicating improvement. (NCT02799381)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Optimized Medical Treatment (OMT) | 4.58 |
| Levodopa-Carbidopa Intestinal Gel (LCIG) | 2.48 |
Multiple Dose predose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, and 10 hours postdose. (NCT03007888)
Timeframe: Day 15
| Intervention | hour (Mean) |
|---|---|
| IPX203 | 1.91 |
| Sinemet | 0.83 |
Single Dose predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 5.5, 6, 6.5, 7, 7.5, and 8 hours postdose (NCT03007888)
Timeframe: Day 1
| Intervention | hour (Mean) |
|---|---|
| IPX203 | 1.658 |
| Sinemet | 1.420 |
Multiple Dose predose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, and 10 hours postdose. (NCT03007888)
Timeframe: Day 15
| Intervention | ng/mL (Mean) |
|---|---|
| IPX203 | 2767.96 |
| Sinemet | 2356.85 |
Single Dose predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 5.5, 6, 6.5, 7, 7.5, and 8 hours postdose (NCT03007888)
Timeframe: Day 1
| Intervention | ng/mL (Mean) |
|---|---|
| IPX203 | 2857.56 |
| Sinemet | 2173.30 |
Single Dose predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 5.5, 6, 6.5, 7, 7.5, and 8 hours postdose (NCT03007888)
Timeframe: Day 1
| Intervention | Percentage (Mean) |
|---|---|
| IPX203 | 88.965 |
| Sinemet | 0 |
Multiple Dose predose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, and 10 hours postdose. (NCT03007888)
Timeframe: Day 15
| Intervention | ng.h/ML (Mean) |
|---|---|
| IPX203 | 11213.76 |
| Sinemet | 3879.39 |
Single Dose predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 5.5, 6, 6.5, 7, 7.5, and 8 hours postdose (NCT03007888)
Timeframe: Day 1
| Intervention | ng.h/mL (Mean) |
|---|---|
| IPX203 | 12107.60 |
| Sinemet | 3747.61 |
Single Dose predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 5.5, 6, 6.5, 7, 7.5, and 8 hours postdose (NCT03007888)
Timeframe: Day 1
| Intervention | ng.h/mL (Mean) |
|---|---|
| IPX203 | 13968.57 |
| Sinemet | 4308.37 |
Multiple Dose predose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, and 10 hours postdose. (NCT03007888)
Timeframe: Day 15
| Intervention | hour (Mean) |
|---|---|
| IPX203 | 2.52 |
| Sinemet | 2.20 |
Single Dose predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 5.5, 6, 6.5, 7, 7.5, and 8 hours postdose (NCT03007888)
Timeframe: Day 1
| Intervention | hour (Mean) |
|---|---|
| IPX203 | 2.61 |
| Sinemet | 2.07 |
Single Dose predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 5.5, 6, 6.5, 7, 7.5, and 8 hours postdose (NCT03007888)
Timeframe: Day 1
| Intervention | hour (Mean) |
|---|---|
| IPX203 | 2.015 |
| Sinemet | 1.969 |
Multiple Dose predose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, and 10 hours postdose. (NCT03007888)
Timeframe: Day 15
| Intervention | ng/mL (Mean) |
|---|---|
| IPX203 | 478.66 |
| Sinemet | 145.67 |
Single Dose predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 5.5, 6, 6.5, 7, 7.5, and 8 hours postdose (NCT03007888)
Timeframe: Day 1
| Intervention | ng/mL (Mean) |
|---|---|
| IPX203 | 500.35 |
| Sinemet | 151.50 |
Single Dose predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 5.5, 6, 6.5, 7, 7.5, and 8 hours postdose (NCT03007888)
Timeframe: Day 1
| Intervention | Percentage (Mean) |
|---|---|
| IPX203 | 117.442 |
| Sinemet | 0 |
Multiple Dose predose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, and 10 hours postdose. (NCT03007888)
Timeframe: Day 15
| Intervention | ng.h/mL (Mean) |
|---|---|
| IPX203 | 1892.39 |
| Sinemet | 415.83 |
Single Dose predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 5.5, 6, 6.5, 7, 7.5, and 8 hours postdose (NCT03007888)
Timeframe: Day 1
| Intervention | ng.h/mL (Mean) |
|---|---|
| IPX203 | 1940.51 |
| Sinemet | 436.63 |
Single Dose predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 5.5, 6, 6.5, 7, 7.5, and 8 hours postdose (NCT03007888)
Timeframe: Day 1
| Intervention | ng.h/mL (Mean) |
|---|---|
| IPX203 | 2239.61 |
| Sinemet | 610.44 |
Single Dose predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 5.5, 6, 6.5, 7, 7.5, and 8 hours postdose (NCT03007888)
Timeframe: Day 1
| Intervention | hour (Mean) |
|---|---|
| IPX203 | 2.07 |
| Sinemet | 0.94 |
MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. (Part I; 13 items) non-motor experiences of daily living, (Part II; 13 items) motor experiences of daily living completed by the participants, (Part III; 34 items) motor examination of PD and was administered by the rater, and (Part IV; 6 items) motor complication integrates participant-derived information with the rater's clinical observations and judgements and is completed by the rater. For each question a numeric score was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. MDS-UPDRS Total Score equals the sum of Parts I, II, and III and IV (Range 0-234). Part III score ranges from 0 to 136. A higher score indicated more severe symptoms of PD. Baseline was defined as data obtained from PD Diary collected over 3 days prior to Week 7/Randomization. (NCT03670953)
Timeframe: Baseline (Week 7) and Week 20/ET
| Intervention | score on a scale (Mean) | |
|---|---|---|
| Baseline (Week 7) | Change at Week 20/ET | |
| IPX203 - Double-Blind Maintenance | 26.9 | 1.1 |
| IR CD-LD - Double -Blind Maintenance | 27.0 | 0.9 |
MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. (Part I; 13 items) non-motor experiences of daily living, (Part II; 13 items) motor experiences of daily living completed by the participants, (Part III; 34 items) motor examination of PD and was administered by the rater, and (Part IV; 6 items) motor complication integrates participant-derived information with the rater's clinical observations and judgements and is completed by the rater. For each question a numeric score was assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. MDS-UPDRS Total Score equals the sum of Parts I, II, and III and IV (Range 0-234). The scale range for Part II+III score is 0-188. A higher score indicated more severe symptoms of PD. Baseline was defined as data obtained from PD Diary collected over 3 days prior to Week 7/Randomization. (NCT03670953)
Timeframe: Baseline (Week 7) and Week 20/ET
| Intervention | score on a scale (Mean) | |
|---|---|---|
| Baseline (Week 7) | Change at Week 20/ET | |
| IPX203 - Double-Blind Maintenance | 38.9 | 2.0 |
| IR CD-LD - Double -Blind Maintenance | 39.3 | 1.8 |
"Off time was derived from the 3-day PD Diaries. For each day, Off time was calculated by adding the number of half-hour intervals in which the Status Off was checked. Baseline was defined as data obtained from PD Diary collected over 3 days prior to Week 7/Randomization." (NCT03670953)
Timeframe: Baseline (Week 7) and Week 20/ET
| Intervention | hours/day (Mean) | |
|---|---|---|
| Baseline (Week 7) | Change at Week 20/ET | |
| IPX203 - Double-Blind Maintenance | 3.95 | 0.29 |
| IR CD-LD - Double -Blind Maintenance | 4.02 | 0.76 |
"The Patient Global Impression of Change (PGIC) is self assessment questionnaire which was used by participants to compare his/her condition on a 7-point scale ranging from 1-Very Much Worse, 2-Much Worse, 3-Minimally Worse, 4-No Change, 5-Minimally Improved, 6-Much Improved, 7-Very Much Improved. Percentage of participants with either Much Improved or Very Much Improved was reported." (NCT03670953)
Timeframe: Week 20/ET
| Intervention | percentage of participants (Number) |
|---|---|
| IPX203 - Double-Blind Maintenance | 29.7 |
| IR CD-LD - Double -Blind Maintenance | 18.8 |
"Good on time was derived from the 3-day PD Diaries. For each day, Good on time was calculated by adding the number of half-hour intervals in which either an On without dyskinesia or On with nontroublesome dyskinesia was checked.~Baseline was defined as data obtained from PD Diary collected over 3 days prior to Week 7/Randomization.~Least square mean (LSM), standard error (SE), confidence interval (CI), Mixed model repeated measures (MMRM), Change from baseline (CFB)." (NCT03670953)
Timeframe: Baseline (Week 7) and Week 20/ET
| Intervention | hours/day (Mean) | |
|---|---|---|
| Baseline (Week 7) | Change at Week 20/ET | |
| IPX203 - Double-Blind Maintenance | 11.67 | -0.39 |
| IR CD-LD - Double -Blind Maintenance | 11.72 | -0.97 |
Patients' gait was assessed as walking speed in cm/s on a 15' walking course. Patients walked at their usual or normal speed for a total of 27' (starting and ending at a point 6 feet prior to and after the 15' course to eliminate acceleration and deceleration effects). Two trials were completed, and gait speed was based on the average of 2 trials. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations. (NCT03761030)
Timeframe: Change from Baseline to 8 Weeks
| Intervention | cm/s (Mean) |
|---|---|
| L-DOPA Arm | 3.7 |
| Placebo Arm | -3.8 |
The Digit Symbol test is a neuropsychological test measuring information processing speed. It consists of digit-symbol pairs (e.g. 1/-,2/┴ ... 7/Λ,8/X,9/=) followed by a list of digits. Under each digit the subject should write down the corresponding symbol as fast as possible. The number of correct symbols within the allowed time is measured. Score ranges from 0-133, with higher scores indicating higher information processing speed. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations. (NCT03761030)
Timeframe: Change from Baseline to 8 Weeks
| Intervention | Number of items correctly completed (Mean) |
|---|---|
| L-DOPA Arm | 2.8 |
| Placebo Arm | 5.0 |
The Inventory of Depressive Symptomatology--Self Report (IDS-SR) is a rating scale for depressive symptoms based on standard diagnostic criteria for Major Depressive Disorder. The scale ranges from 0-84 with higher scores indicating more severe depression. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations. (NCT03761030)
Timeframe: Change from Baseline to 8 Weeks
| Intervention | units on a scale (Mean) |
|---|---|
| L-DOPA Arm | -9.8 |
| Placebo Arm | -12.1 |
Subjects were asked to determine whether two strings of letters are the same or different. There are 3 pages and the subject is given 30 seconds per page. Scoring is based on the number answered correctly. Scores range from 0 to 21, with the higher the number, the better the score. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations. (NCT03761030)
Timeframe: Change from Baseline to 8 Weeks
| Intervention | Number of items correctly completed (Mean) |
|---|---|
| L-DOPA Arm | 1.2 |
| Placebo Arm | 0.7 |
"This test required participants to identify whether two visual patterns are the same or not the same (responses were made by pressing a yes or no button). Patterns were either identical or varied on one of three dimensions: color (all ages), adding/taking something away (all ages), or one versus many. Scores reflect the number of correct items completed in 90 s, with scores ranging from a minimum of 0 to a maximum of 30. Items were designed to minimize the number of errors that were made. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations." (NCT03761030)
Timeframe: Change from Baseline to 8 Weeks
| Intervention | Number of items correctly completed (Mean) |
|---|---|
| L-DOPA Arm | 0.6 |
| Placebo Arm | 1.2 |
The Hamilton Rating Scale for Depression (HRSD) is a 24-item questionnaire used as an indication of depression and a guide to evaluate recovery. Total scores range from 0-74, not including atypical symptoms sub-scale. A score of 16 or above is typically considered to indicate the presence of depressive symptoms. Higher scores indicate greater severity. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations. (NCT03761030)
Timeframe: Change from Baseline to 8 Weeks
| Intervention | units on a scale (Mean) |
|---|---|
| L-DOPA Arm | -2.2 |
| Placebo Arm | -3.6 |
"In this task participants decide whether to work harder for a larger reward (high number of finger presses with their pinky) or expend less energy (low number of presses with a dominant index finger) for a lesser reward, with lower rewards being $1 dollar and higher rewards ranging from $1.20 to $5. Participants receive information about the probability of winning on each trial regardless of their pick and one trial from each run is randomly picked for payout. The primary output on this task is the percentage of time participants choose the high cost / high reward option on the EEfRT. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations.~This task was not completed following Step 2 of the study, so there are no EEfRT data reported for change in task performance following Step 2." (NCT04493320)
Timeframe: Change from Baseline to 3 weeks (post Step 1)
| Intervention | percentage of high effort choices (Mean) |
|---|---|
| L-DOPA, Then Placebo | 0.18 |
| Placebo, Then L-DOPA | 0.0 |
The Digit Symbol test is a neuropsychological test measuring information processing speed. It consists of digit-symbol pairs (e.g. 1/-,2/┴ ... 7/Λ,8/X,9/=) followed by a list of digits. Under each digit the subject should write down the corresponding symbol as fast as possible. The number of correct symbols within the allowed time is measured. Score ranges from 0-133, with higher scores indicating higher information processing speed. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations. (NCT04493320)
Timeframe: Change from Week 3 to Week 7 (post-Step 2)
| Intervention | Number of items correctly completed (Number) |
|---|---|
| L-DOPA, Then Placebo | 5.0 |
| Placebo, Then L-DOPA | 4.0 |
QIDS-16-item, a participant-rated measure of depressive symptomatology. The total score ranges from 0 to 27, with higher scores indicative of greater severity. In contrast to other measures, which were not available at Week 4, Week 4 was selected as the baseline for post-Step 2 change on the QIDS since it followed the taper period taking place between study Steps. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations. (NCT04493320)
Timeframe: Change from Week 4 to Week 7 (post-Step 2)
| Intervention | units on a scale (Number) |
|---|---|
| L-DOPA, Then Placebo | -1.0 |
| Placebo, Then L-DOPA | 0.0 |
QIDS-16-item, a participant-rated measure of depressive symptomatology. The total score ranges from 0 to 27, with higher scores indicative of greater severity. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations. (NCT04493320)
Timeframe: Change from Baseline to 3 weeks (post Step 1)
| Intervention | units on a scale (Mean) |
|---|---|
| L-DOPA, Then Placebo | -1.0 |
| Placebo, Then L-DOPA | -5.0 |
"This test required participants to identify whether two visual patterns are the same or not the same (responses were made by pressing a yes or no button). Patterns were either identical or varied on one of three dimensions: color (all ages), adding/taking something away (all ages), or one versus many. Scores reflect the number of correct items completed in 90 s, with scores ranging from a minimum of 0 to a maximum of 30. Items were designed to minimize the number of errors that were made. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations." (NCT04493320)
Timeframe: Change from Week 3 to Week 7 (post-Step 2)
| Intervention | Number of items correctly completed (Number) |
|---|---|
| L-DOPA, Then Placebo | 1.0 |
| Placebo, Then L-DOPA | -3.5 |
"This test required participants to identify whether two visual patterns are the same or not the same (responses were made by pressing a yes or no button). Patterns were either identical or varied on one of three dimensions: color (all ages), adding/taking something away (all ages), or one versus many. Scores reflect the number of correct items completed in 90 s, with scores ranging from a minimum of 0 to a maximum of 30. Items were designed to minimize the number of errors that were made. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations." (NCT04493320)
Timeframe: Change from Baseline to 3 weeks (post Step 1)
| Intervention | Number of items correctly completed (Mean) |
|---|---|
| L-DOPA, Then Placebo | -1.0 |
| Placebo, Then L-DOPA | 1.75 |
Secondary outcome measured by the total score of the clinician rated MADRS, a measure of depression severity. The MADRS total score range is 0-60, where higher scores indicate greater depression severity. In contrast to other measures, which were not available at Week 4, Week 4 was selected as the baseline for post-Step 2 change on the MADRS since it followed the taper period taking place between study Steps. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations. (NCT04493320)
Timeframe: Change from Week 4 to Week 7 (post-Step 2)
| Intervention | units on a scale (Number) |
|---|---|
| L-DOPA, Then Placebo | 4.0 |
| Placebo, Then L-DOPA | 2.0 |
The Digit Symbol test is a neuropsychological test measuring information processing speed. It consists of digit-symbol pairs (e.g. 1/-,2/┴ ... 7/Λ,8/X,9/=) followed by a list of digits. Under each digit the subject should write down the corresponding symbol as fast as possible. The number of correct symbols within the allowed time is measured. Score ranges from 0-133, with higher scores indicating higher information processing speed. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations. (NCT04493320)
Timeframe: Change from Baseline to 3 weeks (post Step 1)
| Intervention | Number of items correctly completed (Mean) |
|---|---|
| L-DOPA, Then Placebo | -0.5 |
| Placebo, Then L-DOPA | 9.0 |
Patients' gait was assessed as walking speed in cm/s on a 15' walking course. Patients walked at their usual or normal speed for a total of 27' (starting and ending at a point 6 feet prior to and after the 15' course to eliminate acceleration and deceleration effects). Two trials were completed, and gait speed was based on the average of 2 trials. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations. (NCT04493320)
Timeframe: Change from Baseline to 3 weeks (post Step 1)
| Intervention | cm/s (Mean) |
|---|---|
| L-DOPA, Then Placebo | 4.6 |
| Placebo, Then L-DOPA | 11.9 |
Subjects were asked to determine whether two strings of letters are the same or different. There are 3 pages and the subject is given 30 seconds per page. Scoring is based on the number answered correctly. Scores range from 0 to 21, with the higher the number, the better the score. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations. (NCT04493320)
Timeframe: Change from Week 3 to Week 7 (post-Step 2)
| Intervention | Number of items correctly completed (Number) |
|---|---|
| L-DOPA, Then Placebo | 0.5 |
| Placebo, Then L-DOPA | -1.5 |
"[18F]-FDOPA PET quantifies dopamine synthesis capacity in specific brain regions. Lower [18F]-FDOPA uptake in the striatum has been associated with increased depression severity and worse cognitive and motor function in patients. Because [18F]-FDOPA uptake may be sensitive to deficits in dopamine synthesis capacity in older depressed patients, in this study depressed participants at baseline underwent a PET scan to quantify relative [18F]-FDOPA influx rate in the nucleus accumbens bilaterally. Time activity curves (TACs) were extracted within the nucleus accumbens region of interest (ROI) as the average radioactivity in the ROI over time. The occipital lobe, which has the lowest dopamine concentration in the brain, was used as the reference region to yield the Kocc measure of [18F]-FDOPA influx rate. Higher [18F]-FDOPA influx rate (kocc) numbers indicate greater relative influx rate and therefore greater dopamine synthesis capacity." (NCT04493320)
Timeframe: Baseline (prior to LDOPA or placebo administration)
| Intervention | min^-1 (Number) |
|---|---|
| L-DOPA, Then Placebo | 0.0107 |
Subjects were asked to determine whether two strings of letters are the same or different. There are 3 pages and the subject is given 30 seconds per page. Scoring is based on the number answered correctly. Scores range from 0 to 21, with the higher the number, the better the score. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations. (NCT04493320)
Timeframe: Change from Baseline to 3 weeks (post Step 1)
| Intervention | Number of items correctly completed (Mean) |
|---|---|
| L-DOPA, Then Placebo | -0.5 |
| Placebo, Then L-DOPA | -0.25 |
Patients' gait was assessed as walking speed in cm/s on a 15' walking course. Patients walked at their usual or normal speed for a total of 27' (starting and ending at a point 6 feet prior to and after the 15' course to eliminate acceleration and deceleration effects). Two trials were completed, and gait speed was based on the average of 2 trials. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations. (NCT04493320)
Timeframe: Change from Week 3 to Week 7 (post-Step 2)
| Intervention | cm/s (Number) |
|---|---|
| L-DOPA, Then Placebo | -17.2 |
| Placebo, Then L-DOPA | 7.0 |
Secondary outcome measured by the total score of the clinician rated MADRS, a measure of depression severity. The MADRS total score range is 0-60, where higher scores indicate greater depression severity. Because the full sample was not enrolled and the results are considered unreliable, no statistical analysis was performed other than calculating means and standard deviations. (NCT04493320)
Timeframe: Change from Baseline to 3 weeks (post Step 1)
| Intervention | units on a scale (Mean) |
|---|---|
| L-DOPA, Then Placebo | -1.0 |
| Placebo, Then L-DOPA | -3.0 |
"The MADRS is a standard rater-administered measure of depression severity that will be used to measure changes in depressive symptoms during the study.~The total MADRS score ranges from a minimum score of 0 to a maximum score of 60. Higher scores indicate more severe depression." (NCT04650217)
Timeframe: Week 0 (Baseline)
| Intervention | score on a scale (Number) |
|---|---|
| Non-randomized Participants | 25 |
| Substance | Relationship Strength | Studies | Trials | Classes | Roles |
|---|---|---|---|---|---|
| gamma-aminobutyric acid gamma-Aminobutyric Acid: The most common inhibitory neurotransmitter in the central nervous system.. gamma-aminobutyric acid : A gamma-amino acid that is butanoic acid with the amino substituent located at C-4. | 3.5 | 1 | 1 | amino acid zwitterion; gamma-amino acid; monocarboxylic acid | human metabolite; neurotransmitter; Saccharomyces cerevisiae metabolite; signalling molecule |
| 5-hydroxytryptophan 5-Hydroxytryptophan: The immediate precursor in the biosynthesis of SEROTONIN from tryptophan. It is used as an antiepileptic and antidepressant.. 5-hydroxytryptophan : A tryptophan derivative that is tryptophan substituted by a hydroxy group at position 5. | 2.55 | 2 | 0 | hydroxytryptophan | human metabolite; neurotransmitter |
| choline [no description available] | 3.37 | 1 | 1 | cholines | allergen; Daphnia magna metabolite; Escherichia coli metabolite; human metabolite; mouse metabolite; neurotransmitter; nutrient; plant metabolite; Saccharomyces cerevisiae metabolite |
| coumarin 2H-chromen-2-one: coumarin derivative | 2.21 | 1 | 0 | coumarins | fluorescent dye; human metabolite; plant metabolite |
| 3,4-dihydroxyphenylacetic acid 3,4-Dihydroxyphenylacetic Acid: A deaminated metabolite of LEVODOPA.. (3,4-dihydroxyphenyl)acetic acid : A dihydroxyphenylacetic acid having the two hydroxy substituents located at the 3- and 4-positions. It is a metabolite of dopamine.. dihydroxyphenylacetic acid : A dihydroxy monocarboxylic acid consisting of phenylacetic acid having two phenolic hydroxy substituents. | 3.1 | 5 | 0 | catechols; dihydroxyphenylacetic acid | human metabolite |
| dihydroxyphenylalanine Dihydroxyphenylalanine: A beta-hydroxylated derivative of phenylalanine. The D-form of dihydroxyphenylalanine has less physiologic activity than the L-form and is commonly used experimentally to determine whether the pharmacological effects of LEVODOPA are stereospecific.. dopa : A hydroxyphenylalanine carrying hydroxy substituents at positions 3 and 4 of the benzene ring. | 3.99 | 4 | 0 | hydroxyphenylalanine; non-proteinogenic alpha-amino acid; tyrosine derivative | human metabolite |
| melatonin [no description available] | 1.99 | 1 | 0 | acetamides; tryptamines | anticonvulsant; central nervous system depressant; geroprotector; hormone; human metabolite; immunological adjuvant; mouse metabolite; radical scavenger |
| nitrites Nitrites: Salts of nitrous acid or compounds containing the group NO2-. The inorganic nitrites of the type MNO2 (where M=metal) are all insoluble, except the alkali nitrites. The organic nitrites may be isomeric, but not identical with the corresponding nitro compounds. (Grant & Hackh's Chemical Dictionary, 5th ed) | 2.02 | 1 | 0 | monovalent inorganic anion; nitrogen oxoanion; reactive nitrogen species | human metabolite |
| pyridoxal phosphate Pyridoxal Phosphate: This is the active form of VITAMIN B 6 serving as a coenzyme for synthesis of amino acids, neurotransmitters (serotonin, norepinephrine), sphingolipids, aminolevulinic acid. During transamination of amino acids, pyridoxal phosphate is transiently converted into pyridoxamine phosphate (PYRIDOXAMINE).. pyridoxal 5'-phosphate : The monophosphate ester obtained by condensation of phosphoric acid with the primary hydroxy group of pyridoxal. | 2.25 | 1 | 0 | methylpyridines; monohydroxypyridine; pyridinecarbaldehyde; vitamin B6 phosphate | coenzyme; cofactor; EC 2.7.7.7 (DNA-directed DNA polymerase) inhibitor; Escherichia coli metabolite; human metabolite; mouse metabolite; Saccharomyces cerevisiae metabolite |
| thiamine thiamine(1+) : A primary alcohol that is 1,3-thiazol-3-ium substituted by (4-amino-2-methylpyrimidin-5-yl)methyl, methyl and 2-hydroxyethyl groups at positions 3, 4 and 5, respectively. | 2.15 | 1 | 0 | primary alcohol; vitamin B1 | Escherichia coli metabolite; human metabolite; mouse metabolite; Saccharomyces cerevisiae metabolite |
| vanilmandelic acid Vanilmandelic Acid: A 3-O-methyl ether of 3,4-dihydroxymandelic acid. It is an end-stage metabolite of CATECHOLAMINES; EPINEPHRINE; and NOREPINEPHRINE.. vanillylmandelic acid : An aromatic ether that is the 3-O-methyl ether of 3,4-dihydroxymandelic acid. | 2.68 | 3 | 0 | 2-hydroxy monocarboxylic acid; aromatic ether; phenols | human metabolite |
| 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine: A dopaminergic neurotoxic compound which produces irreversible clinical, chemical, and pathological alterations that mimic those found in Parkinson disease.. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine : A tetrahydropyridine that is 1,2,3,6-tetrahydropyridine substituted by a methyl group at position 1 and a phenyl group at position 4. | 4.87 | 11 | 0 | methylpyridines; phenylpyridine; tetrahydropyridine | neurotoxin |
| 3-methoxytyramine 3-methoxytyramine: RN given refers to parent cpd. 3-methoxytyramine : A monomethoxybenzene that is dopamine in which the hydroxy group at position 3 is replaced by a methoxy group. It is a metabolite of the neurotransmitter dopamine and considered a potential biomarker of pheochromocytomas and paragangliomas. | 2.15 | 1 | 0 | monomethoxybenzene; phenols; phenylethylamine; primary amino compound | biomarker; human blood serum metabolite; human urinary metabolite |
| 3-methoxytyrosine [no description available] | 7.29 | 9 | 5 | tyrosine derivative | |
| homovanillic acid Homovanillic Acid: A 3-O-methyl ETHER of (3,4-dihydroxyphenyl)acetic acid.. homovanillate : A hydroxy monocarboxylic acid anion which is obtained by deprotonation of the carboxy group of homovanillic acid.. homovanillic acid : A monocarboxylic acid that is the 3-O-methyl ether of (3,4-dihydroxyphenyl)acetic acid. It is a catecholamine metabolite. | 3.37 | 7 | 0 | guaiacols; monocarboxylic acid | human metabolite; mouse metabolite |
| hydroxyindoleacetic acid (5-hydroxyindol-3-yl)acetic acid : A member of the class of indole-3-acetic acids that is indole-3-acetic acid substituted by a hydroxy group at C-5. | 1.97 | 1 | 0 | indole-3-acetic acids | drug metabolite; human metabolite; mouse metabolite |
| amantadine amant: an antiviral compound consisting of an adamantane derivative chemically linked to a water-solube polyanioic matrix; structure in first source | 6.49 | 19 | 0 | adamantanes; primary aliphatic amine | analgesic; antiparkinson drug; antiviral drug; dopaminergic agent; NMDA receptor antagonist; non-narcotic analgesic |
| amitriptyline Amitriptyline: Tricyclic antidepressant with anticholinergic and sedative properties. It appears to prevent the re-uptake of norepinephrine and serotonin at nerve terminals, thus potentiating the action of these neurotransmitters. Amitriptyline also appears to antagonize cholinergic and alpha-1 adrenergic responses to bioactive amines.. amitriptyline : An organic tricyclic compound that is 10,11-dihydro-5H-dibenzo[a,d][7]annulene substituted by a 3-(dimethylamino)propylidene group at position 5. | 1.96 | 1 | 0 | carbotricyclic compound; tertiary amine | adrenergic uptake inhibitor; antidepressant; environmental contaminant; tropomyosin-related kinase B receptor agonist; xenobiotic |
| amoxapine Amoxapine: The N-demethylated derivative of the antipsychotic agent LOXAPINE that works by blocking the reuptake of norepinephrine, serotonin, or both; it also blocks dopamine receptors. Amoxapine is used for the treatment of depression.. amoxapine : A dibenzooxazepine compound having a chloro substituent at the 2-position and a piperazin-1-yl group at the 11-position. | 1.99 | 1 | 0 | dibenzooxazepine | adrenergic uptake inhibitor; antidepressant; dopaminergic antagonist; geroprotector; serotonin uptake inhibitor |
| baclofen [no description available] | 2.07 | 1 | 0 | amino acid zwitterion; gamma-amino acid; monocarboxylic acid; monochlorobenzenes; primary amino compound | central nervous system depressant; GABA agonist; muscle relaxant |
| benserazide Benserazide: An inhibitor of DOPA DECARBOXYLASE that does not enter the central nervous system. It is often given with LEVODOPA in the treatment of parkinsonism to prevent the conversion of levodopa to dopamine in the periphery, thereby increasing the amount that reaches the central nervous system and reducing the required dose. It has no antiparkinson actions when given alone.. benserazide : A carbohydrazide that results from the formal condensation of the carboxy group of DL-serine with the primary amino group of 4-(hydrazinylmethyl)benzene-1,2,3-triol. An aromatic-L-amino-acid decarboxylase inhibitor (DOPA decarboxylase inhibitor) that does not enter the central nervous system, it is used as its hydrochloride salt as an adjunct to levodopa in the treatment of parkinsonism. By preventing the conversion of levodopa to dopamine in the periphery, it causes an increase in the amount of levodopa reaching the central nervous system and so reduces the required dose. Benserazide has no antiparkinson actions when given alone. | 8.59 | 26 | 7 | carbohydrazide; catechols; primary alcohol; primary amino compound | antiparkinson drug; dopaminergic agent; EC 4.1.1.28 (aromatic-L-amino-acid decarboxylase) inhibitor |
| biperiden Biperiden: A muscarinic antagonist that has effects in both the central and peripheral nervous systems. It has been used in the treatment of arteriosclerotic, idiopathic, and postencephalitic parkinsonism. It has also been used to alleviate extrapyramidal symptoms induced by phenothiazine derivatives and reserpine.. biperiden : A member of the class of piperidines that is N-propylpiperidine in which the methyl hydrogens have been replaced by hydroxy, phenyl, and 5-norbornen-2-yl groups. A muscarinic antagonist affecting both the central and peripheral nervous systems, it is used in the treatment of all forms of Parkinson's disease. | 2.92 | 4 | 0 | piperidines; tertiary alcohol; tertiary amino compound | antidote to sarin poisoning; antidyskinesia agent; antiparkinson drug; muscarinic antagonist; parasympatholytic |
| carbamazepine Carbamazepine: A dibenzazepine that acts as a sodium channel blocker. It is used as an anticonvulsant for the treatment of grand mal and psychomotor or focal SEIZURES. It may also be used in the management of BIPOLAR DISORDER, and has analgesic properties.. carbamazepine : A dibenzoazepine that is 5H-dibenzo[b,f]azepine carrying a carbamoyl substituent at the azepine nitrogen, used as an anticonvulsant. | 2 | 1 | 0 | dibenzoazepine; ureas | analgesic; anticonvulsant; antimanic drug; drug allergen; EC 3.5.1.98 (histone deacetylase) inhibitor; environmental contaminant; glutamate transporter activator; mitogen; non-narcotic analgesic; sodium channel blocker; xenobiotic |
| chlorpromazine Chlorpromazine: The prototypical phenothiazine antipsychotic drug. Like the other drugs in this class chlorpromazine's antipsychotic actions are thought to be due to long-term adaptation by the brain to blocking DOPAMINE RECEPTORS. Chlorpromazine has several other actions and therapeutic uses, including as an antiemetic and in the treatment of intractable hiccup.. chlorpromazine : A substituted phenothiazine in which the ring nitrogen at position 10 is attached to C-3 of an N,N-dimethylpropanamine moiety. | 2.87 | 3 | 0 | organochlorine compound; phenothiazines; tertiary amine | anticoronaviral agent; antiemetic; dopaminergic antagonist; EC 3.4.21.26 (prolyl oligopeptidase) inhibitor; phenothiazine antipsychotic drug |
| ciprofloxacin Ciprofloxacin: A broad-spectrum antimicrobial carboxyfluoroquinoline.. ciprofloxacin : A quinolone that is quinolin-4(1H)-one bearing cyclopropyl, carboxylic acid, fluoro and piperazin-1-yl substituents at positions 1, 3, 6 and 7, respectively. | 2.25 | 1 | 0 | aminoquinoline; cyclopropanes; fluoroquinolone antibiotic; N-arylpiperazine; quinolinemonocarboxylic acid; quinolone antibiotic; quinolone; zwitterion | antibacterial drug; antiinfective agent; antimicrobial agent; DNA synthesis inhibitor; EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor; environmental contaminant; topoisomerase IV inhibitor; xenobiotic |
| clonazepam Clonazepam: An anticonvulsant used for several types of seizures, including myotonic or atonic seizures, photosensitive epilepsy, and absence seizures, although tolerance may develop. It is seldom effective in generalized tonic-clonic or partial seizures. The mechanism of action appears to involve the enhancement of GAMMA-AMINOBUTYRIC ACID receptor responses.. clonazepam : 1,3-Dihydro-2H-1,4-benzodiazepin-2-one in which the hydrogens at positions 5 and 7 are substituted by 2-chlorophenyl and nitro groups, respectively. It is used in the treatment of all types of epilepsy and seizures, as well as myoclonus and associated abnormal movements, and panic disorders. However, its use can be limited by the development of tolerance and by sedation. | 2.91 | 4 | 0 | 1,4-benzodiazepinone; monochlorobenzenes | anticonvulsant; anxiolytic drug; GABA modulator |
| dantrolene Dantrolene: Skeletal muscle relaxant that acts by interfering with excitation-contraction coupling in the muscle fiber. It is used in spasticity and other neuromuscular abnormalities. Although the mechanism of action is probably not central, dantrolene is usually grouped with the central muscle relaxants.. dantrolene : The hydrazone resulting from the formal condensation of 5-(4-nitrophenyl)furfural with 1-aminohydantoin. A ryanodine receptor antagonist used for the relief of chronic severe spasticity and malignant hyperthermia. | 1.98 | 1 | 0 | hydrazone; imidazolidine-2,4-dione | muscle relaxant; neuroprotective agent; ryanodine receptor antagonist |
| dapi DAPI: RN given refers to parent cpd. | 2.02 | 1 | 0 | indoles | fluorochrome |
| amphetamine Amphetamine: A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is DEXTROAMPHETAMINE.. 1-phenylpropan-2-amine : A primary amine that is isopropylamine in which a hydrogen attached to one of the methyl groups has been replaced by a phenyl group.. amphetamine : A racemate comprising equimolar amounts of (R)-amphetamine (also known as levamphetamine or levoamphetamine) and (S)-amphetamine (also known as dexamfetamine or dextroamphetamine. | 3.47 | 2 | 0 | primary amine | |
| diazepam Diazepam: A benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of GAMMA-AMINOBUTYRIC ACID activity.. diazepam : A 1,4-benzodiazepinone that is 1,3-dihydro-2H-1,4-benzodiazepin-2-one substituted by a chloro group at position 7, a methyl group at position 1 and a phenyl group at position 5. | 1.97 | 1 | 0 | 1,4-benzodiazepinone; organochlorine compound | anticonvulsant; anxiolytic drug; environmental contaminant; sedative; xenobiotic |
| valproic acid Valproic Acid: A fatty acid with anticonvulsant and anti-manic properties that is used in the treatment of EPILEPSY and BIPOLAR DISORDER. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of VOLTAGE-GATED SODIUM CHANNELS.. valproic acid : A branched-chain saturated fatty acid that comprises of a propyl substituent on a pentanoic acid stem. | 2.49 | 2 | 0 | branched-chain fatty acid; branched-chain saturated fatty acid | anticonvulsant; antimanic drug; EC 3.5.1.98 (histone deacetylase) inhibitor; GABA agent; neuroprotective agent; psychotropic drug; teratogenic agent |
| racemetirosine alpha-Methyltyrosine: An inhibitor of the enzyme TYROSINE 3-MONOOXYGENASE, and consequently of the synthesis of catecholamines. It is used to control the symptoms of excessive sympathetic stimulation in patients with PHEOCHROMOCYTOMA. (Martindale, The Extra Pharmacopoeia, 30th ed) | 2.31 | 1 | 0 | ||
| domperidone Domperidone: A specific blocker of dopamine receptors. It speeds gastrointestinal peristalsis, causes prolactin release, and is used as antiemetic and tool in the study of dopaminergic mechanisms.. domperidone : 1-[3-(Piperidin-1-yl)propyl]-1,3-dihydro-2H-benzimidazol-2-one in which the 4-position of the piperidine ring is substituted by a 5-chloro-1,3-dihydro-2H-benzimidazol-2-on-1-yl group. A dopamine antagonist, it is used as an antiemetic for the short-term treatment of nausea and vomiting, and to control gastrointestinal effects of dopaminergic drugs given in the management of parkinsonism. The free base is used in oral suspensions, while the maleate salt is used in tablet preparations. | 1.96 | 1 | 0 | benzimidazoles; heteroarylpiperidine | antiemetic; dopaminergic antagonist |
| donepezil Donepezil: An indan and piperidine derivative that acts as a selective and reversible inhibitor of ACETYLCHOLINESTERASE. Donepezil is highly selective for the central nervous system and is used in the management of mild to moderate DEMENTIA in ALZHEIMER DISEASE.. donepezil : A racemate comprising equimolar amounts of (R)- and (S)-donepezil. A centrally acting reversible acetylcholinesterase inhibitor, its main therapeutic use is in the treatment of Alzheimer's disease where it is used to increase cortical acetylcholine.. 2-[(1-benzylpiperidin-4-yl)methyl]-5,6-dimethoxyindan-1-one : A member of the class of indanones that is 5,6-dimethoxyindan-1-one which is substituted at position 2 by an (N-benzylpiperidin-4-yl)methyl group. | 3.93 | 3 | 0 | aromatic ether; indanones; piperidines; racemate | EC 3.1.1.7 (acetylcholinesterase) inhibitor; EC 3.1.1.8 (cholinesterase) inhibitor; nootropic agent |
| fluoxetine Fluoxetine: The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants.. fluoxetine : A racemate comprising equimolar amounts of (R)- and (S)-fluoxetine. A selective serotonin reuptake inhibitor (SSRI), it is used (generally as the hydrochloride salt) for the treatment of depression (and the depressive phase of bipolar disorder), bullimia nervosa, and obsessive-compulsive disorder.. N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propan-1-amine : An aromatic ether consisting of 4-trifluoromethylphenol in which the hydrogen of the phenolic hydroxy group is replaced by a 3-(methylamino)-1-phenylpropyl group. | 4.06 | 2 | 0 | (trifluoromethyl)benzenes; aromatic ether; secondary amino compound | |
| gabapentin Gabapentin: A cyclohexane-gamma-aminobutyric acid derivative that is used for the treatment of PARTIAL SEIZURES; NEURALGIA; and RESTLESS LEGS SYNDROME.. gabapentin : A gamma-amino acid that is cyclohexane substituted at position 1 by aminomethyl and carboxymethyl groups. Used for treatment of neuropathic pain and restless legs syndrome. | 3.5 | 1 | 1 | gamma-amino acid | anticonvulsant; calcium channel blocker; environmental contaminant; xenobiotic |
| haloperidol Haloperidol: A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279). haloperidol : A compound composed of a central piperidine structure with hydroxy and p-chlorophenyl substituents at position 4 and an N-linked p-fluorobutyrophenone moiety. | 4.22 | 5 | 0 | aromatic ketone; hydroxypiperidine; monochlorobenzenes; organofluorine compound; tertiary alcohol | antidyskinesia agent; antiemetic; dopaminergic antagonist; first generation antipsychotic; serotonergic antagonist |
| lidocaine Lidocaine: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of PROCAINE but its duration of action is shorter than that of BUPIVACAINE or PRILOCAINE.. lidocaine : The monocarboxylic acid amide resulting from the formal condensation of N,N-diethylglycine with 2,6-dimethylaniline. | 2.17 | 1 | 0 | benzenes; monocarboxylic acid amide; tertiary amino compound | anti-arrhythmia drug; drug allergen; environmental contaminant; local anaesthetic; xenobiotic |
| imipramine Imipramine: The prototypical tricyclic antidepressant. It has been used in major depression, dysthymia, bipolar depression, attention-deficit disorders, agoraphobia, and panic disorders. It has less sedative effect than some other members of this therapeutic group.. imipramine : A dibenzoazepine that is 5H-dibenzo[b,f]azepine substituted by a 3-(dimethylamino)propyl group at the nitrogen atom. | 1.96 | 1 | 0 | dibenzoazepine | adrenergic uptake inhibitor; antidepressant; EC 3.4.21.26 (prolyl oligopeptidase) inhibitor |
| methylphenidate Methylphenidate: A central nervous system stimulant used most commonly in the treatment of ATTENTION DEFICIT DISORDER in children and for NARCOLEPSY. Its mechanisms appear to be similar to those of DEXTROAMPHETAMINE. The d-isomer of this drug is referred to as DEXMETHYLPHENIDATE HYDROCHLORIDE.. methylphenidate : A racemate comprising equimolar amounts of the two threo isomers of methyl phenyl(piperidin-2-yl)acetate. A central stimulant and indirect-acting sympathomimetic, is used (generally as the hydrochloride salt) in the treatment of hyperactivity disorders in children and for the treatment of narcolepsy.. methyl phenyl(piperidin-2-yl)acetate : A amino acid ester that is methyl phenylacetate in which one of the hydrogens alpha to the carbonyl group is replaced by a piperidin-2-yl group. | 4.18 | 3 | 1 | beta-amino acid ester; methyl ester; piperidines | |
| modafinil Modafinil: A benzhydryl acetamide compound, central nervous system stimulant, and CYP3A4 inducing agent that is used in the treatment of NARCOLEPSY and SLEEP WAKE DISORDERS.. modafinil : A racemate comprising equimolar amounts of armodafinil and (S)-modafinil. A central nervous system stimulant, it is used for the treatment of sleeping disorders such as narcolepsy, obstructive sleep apnoea, and shift-work sleep disorder. The optical enantiomers of modafinil have similar pharmacological actions in animals.. 2-[(diphenylmethyl)sulfinyl]acetamide : A sulfoxide that is dimethylsulfoxide in which two hydrogens attached to one of the methyl groups are replaced by phenyl groups, while one hydrogen attached to the other methyl group is replaced by a carbamoyl (aminocarbonyl) group. | 2.31 | 1 | 0 | monocarboxylic acid amide; sulfoxide | |
| nefazodone nefazodone: may be useful as an opiate adjunct | 1.99 | 1 | 0 | aromatic ether; monochlorobenzenes; N-alkylpiperazine; N-arylpiperazine; triazoles | alpha-adrenergic antagonist; analgesic; antidepressant; serotonergic antagonist; serotonin uptake inhibitor |
| orphenadrine Orphenadrine: A muscarinic antagonist used to treat drug-induced parkinsonism and to relieve pain from muscle spasm.. orphenadrine : A tertiary amino compound which is the phenyl-o-tolylmethyl ether of 2-(dimethylamino)ethanol. | 1.97 | 1 | 0 | ether; tertiary amino compound | antidyskinesia agent; antiparkinson drug; H1-receptor antagonist; muscarinic antagonist; muscle relaxant; NMDA receptor antagonist; parasympatholytic |
| oxidopamine Oxidopamine: A neurotransmitter analogue that depletes noradrenergic stores in nerve endings and induces a reduction of dopamine levels in the brain. Its mechanism of action is related to the production of cytolytic free-radicals.. oxidopamine : A benzenetriol that is phenethylamine in which the hydrogens at positions 2, 4, and 5 on the phenyl ring are replaced by hydroxy groups. It occurs naturally in human urine, but is also produced as a metabolite of the drug DOPA (used for the treatment of Parkinson's disease). | 3.42 | 7 | 0 | benzenetriol; catecholamine; primary amino compound | drug metabolite; human metabolite; neurotoxin |
| propranolol Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for MYOCARDIAL INFARCTION; ARRHYTHMIA; ANGINA PECTORIS; HYPERTENSION; HYPERTHYROIDISM; MIGRAINE; PHEOCHROMOCYTOMA; and ANXIETY but adverse effects instigate replacement by newer drugs.. propranolol : A propanolamine that is propan-2-ol substituted by a propan-2-ylamino group at position 1 and a naphthalen-1-yloxy group at position 3. | 3.1 | 1 | 0 | naphthalenes; propanolamine; secondary amine | anti-arrhythmia drug; antihypertensive agent; anxiolytic drug; beta-adrenergic antagonist; environmental contaminant; human blood serum metabolite; vasodilator agent; xenobiotic |
| ritanserin Ritanserin: A selective and potent serotonin-2 antagonist that is effective in the treatment of a variety of syndromes related to anxiety and depression. The drug also improves the subjective quality of sleep and decreases portal pressure.. ritanserin : A thiazolopyrimidine that is 5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one which is substituted at position 7 by a methyl group and at position 6 by a 2-{4-[bis(4-fluorophenyl)methylidene]piperidin-1-yl}ethyl group. A potent and long-acting seratonin (5-hydroxytryptamine, 5-HT) antagonist of the subtype 5-HT2 (Ki = 0.39 nM), it is used in the treatment of a variety of disorders including anxiety, depression and schizophrenia. It has little sedative action. | 3.38 | 1 | 1 | organofluorine compound; piperidines; thiazolopyrimidine | antidepressant; antipsychotic agent; anxiolytic drug; dopaminergic antagonist; EC 3.4.21.26 (prolyl oligopeptidase) inhibitor; serotonergic antagonist |
| ropinirole [no description available] | 8.94 | 11 | 4 | indolones; tertiary amine | antidyskinesia agent; antiparkinson drug; central nervous system drug; dopamine agonist |
| sulfasalazine Sulfasalazine: A drug that is used in the management of inflammatory bowel diseases. Its activity is generally considered to lie in its metabolic breakdown product, 5-aminosalicylic acid (see MESALAMINE) released in the colon. (From Martindale, The Extra Pharmacopoeia, 30th ed, p907). sulfasalazine : An azobenzene consisting of diphenyldiazene having a carboxy substituent at the 4-position, a hydroxy substituent at the 3-position and a 2-pyridylaminosulphonyl substituent at the 4'-position. | 2.15 | 1 | 0 | ||
| trihexyphenidyl Trihexyphenidyl: One of the centrally acting MUSCARINIC ANTAGONISTS used for treatment of PARKINSONIAN DISORDERS and drug-induced extrapyramidal movement disorders and as an antispasmodic. | 4.47 | 5 | 1 | amine | |
| tyramine [no description available] | 1.96 | 1 | 0 | monoamine molecular messenger; primary amino compound; tyramines | EC 3.1.1.8 (cholinesterase) inhibitor; Escherichia coli metabolite; human metabolite; mouse metabolite; neurotransmitter |
| reserpine Reserpine: An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria. Reserpine inhibits the uptake of norepinephrine into storage vesicles resulting in depletion of catecholamines and serotonin from central and peripheral axon terminals. It has been used as an antihypertensive and an antipsychotic as well as a research tool, but its adverse effects limit its clinical use.. reserpine : An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria. | 2.44 | 2 | 0 | alkaloid ester; methyl ester; yohimban alkaloid | adrenergic uptake inhibitor; antihypertensive agent; EC 3.4.21.26 (prolyl oligopeptidase) inhibitor; environmental contaminant; first generation antipsychotic; plant metabolite; xenobiotic |
| thyroxine Thyroxine: The major hormone derived from the thyroid gland. Thyroxine is synthesized via the iodination of tyrosines (MONOIODOTYROSINE) and the coupling of iodotyrosines (DIIODOTYROSINE) in the THYROGLOBULIN. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroxine is peripherally deiodinated to form TRIIODOTHYRONINE which exerts a broad spectrum of stimulatory effects on cell metabolism.. thyroxine : An iodothyronine compound having iodo substituents at the 3-, 3'-, 5- and 5'-positions. | 1.96 | 1 | 0 | 2-halophenol; iodophenol; L-phenylalanine derivative; non-proteinogenic L-alpha-amino acid; thyroxine zwitterion; thyroxine | antithyroid drug; human metabolite; mouse metabolite; thyroid hormone |
| dextroamphetamine Dextroamphetamine: The d-form of AMPHETAMINE. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic.. (S)-amphetamine : A 1-phenylpropan-2-amine that has S configuration. | 4.42 | 2 | 2 | 1-phenylpropan-2-amine | adrenergic agent; adrenergic uptake inhibitor; dopamine uptake inhibitor; dopaminergic agent; neurotoxin; sympathomimetic agent |
| triiodothyronine Triiodothyronine: A T3 thyroid hormone normally synthesized and secreted by the thyroid gland in much smaller quantities than thyroxine (T4). Most T3 is derived from peripheral monodeiodination of T4 at the 5' position of the outer ring of the iodothyronine nucleus. The hormone finally delivered and used by the tissues is mainly T3.. 3,3',5-triiodo-L-thyronine : An iodothyronine compound having iodo substituents at the 3-, 3'- and 5-positions. Although some is produced in the thyroid, most of the 3,3',5-triiodo-L-thyronine in the body is generated by mono-deiodination of L-thyroxine in the peripheral tissues. Its metabolic activity is about 3 to 5 times that of L-thyroxine. The sodium salt is used in the treatment of hypothyroidism. | 2.36 | 2 | 0 | 2-halophenol; amino acid zwitterion; iodophenol; iodothyronine | human metabolite; mouse metabolite; thyroid hormone |
| aspartic acid Aspartic Acid: One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter.. aspartic acid : An alpha-amino acid that consists of succinic acid bearing a single alpha-amino substituent. L-aspartic acid : The L-enantiomer of aspartic acid. | 3.37 | 1 | 1 | aspartate family amino acid; aspartic acid; L-alpha-amino acid; proteinogenic amino acid | Escherichia coli metabolite; mouse metabolite; neurotransmitter |
| apomorphine Apomorphine: A derivative of morphine that is a dopamine D2 agonist. It is a powerful emetic and has been used for that effect in acute poisoning. It has also been used in the diagnosis and treatment of parkinsonism, but its adverse effects limit its use. | 7.49 | 23 | 0 | aporphine alkaloid | alpha-adrenergic drug; antidyskinesia agent; antiparkinson drug; dopamine agonist; emetic; serotonergic drug |
| adenosine diphosphate Adenosine Diphosphate: Adenosine 5'-(trihydrogen diphosphate). An adenine nucleotide containing two phosphate groups esterified to the sugar moiety at the 5'-position. | 2.01 | 1 | 0 | adenosine 5'-phosphate; purine ribonucleoside 5'-diphosphate | fundamental metabolite; human metabolite |
| levodopa Levodopa: The naturally occurring form of DIHYDROXYPHENYLALANINE and the immediate precursor of DOPAMINE. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to DOPAMINE. It is used for the treatment of PARKINSONIAN DISORDERS and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system.. L-dopa : An optically active form of dopa having L-configuration. Used to treat the stiffness, tremors, spasms, and poor muscle control of Parkinson's disease | 22.86 | 690 | 143 | amino acid zwitterion; dopa; L-tyrosine derivative; non-proteinogenic L-alpha-amino acid | allelochemical; antidyskinesia agent; antiparkinson drug; dopaminergic agent; hapten; human metabolite; mouse metabolite; neurotoxin; plant growth retardant; plant metabolite; prodrug |
| edetic acid Edetic Acid: A chelating agent that sequesters a variety of polyvalent cations such as CALCIUM. It is used in pharmaceutical manufacturing and as a food additive. | 2.15 | 1 | 0 | ethylenediamine derivative; polyamino carboxylic acid; tetracarboxylic acid | anticoagulant; antidote; chelator; copper chelator; geroprotector |
| tyrosine Tyrosine: A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.. tyrosine : An alpha-amino acid that is phenylalanine bearing a hydroxy substituent at position 4 on the phenyl ring. | 7.65 | 11 | 6 | amino acid zwitterion; erythrose 4-phosphate/phosphoenolpyruvate family amino acid; L-alpha-amino acid; proteinogenic amino acid; tyrosine | EC 1.3.1.43 (arogenate dehydrogenase) inhibitor; fundamental metabolite; micronutrient; nutraceutical |
| lactose Lactose: A disaccharide of GLUCOSE and GALACTOSE in human and cow milk. It is used in pharmacy for tablets, in medicine as a nutrient, and in industry.. lactose : A glycosylglucose disaccharide, found most notably in milk, that consists of D-galactose and D-glucose fragments bonded through a beta-1->4 glycosidic linkage. The glucose fragment can be in either the alpha- or beta-pyranose form, whereas the galactose fragment can only have the beta-pyranose form.. beta-lactose : The beta-anomer of lactose. | 1.98 | 1 | 0 | lactose | |
| methionine Methionine: A sulfur-containing essential L-amino acid that is important in many body functions.. methionine : A sulfur-containing amino acid that is butyric acid bearing an amino substituent at position 2 and a methylthio substituent at position 4. | 2.21 | 1 | 0 | aspartate family amino acid; L-alpha-amino acid; methionine zwitterion; methionine; proteinogenic amino acid | antidote to paracetamol poisoning; human metabolite; micronutrient; mouse metabolite; nutraceutical |
| phenylalanine Phenylalanine: An essential aromatic amino acid that is a precursor of MELANIN; DOPAMINE; noradrenalin (NOREPINEPHRINE), and THYROXINE.. L-phenylalanine : The L-enantiomer of phenylalanine.. phenylalanine : An aromatic amino acid that is alanine in which one of the methyl hydrogens is substituted by a phenyl group. | 3.42 | 1 | 1 | amino acid zwitterion; erythrose 4-phosphate/phosphoenolpyruvate family amino acid; L-alpha-amino acid; phenylalanine; proteinogenic amino acid | algal metabolite; EC 3.1.3.1 (alkaline phosphatase) inhibitor; Escherichia coli metabolite; human xenobiotic metabolite; micronutrient; mouse metabolite; nutraceutical; plant metabolite; Saccharomyces cerevisiae metabolite |
| cytarabine [no description available] | 1.97 | 1 | 0 | beta-D-arabinoside; monosaccharide derivative; pyrimidine nucleoside | antimetabolite; antineoplastic agent; antiviral agent; immunosuppressive agent |
| tryptophan Tryptophan: An essential amino acid that is necessary for normal growth in infants and for NITROGEN balance in adults. It is a precursor of INDOLE ALKALOIDS in plants. It is a precursor of SEROTONIN (hence its use as an antidepressant and sleep aid). It can be a precursor to NIACIN, albeit inefficiently, in mammals.. tryptophan : An alpha-amino acid that is alanine bearing an indol-3-yl substituent at position 3. | 3.8 | 2 | 1 | erythrose 4-phosphate/phosphoenolpyruvate family amino acid; L-alpha-amino acid zwitterion; L-alpha-amino acid; proteinogenic amino acid; tryptophan zwitterion; tryptophan | antidepressant; Escherichia coli metabolite; human metabolite; micronutrient; mouse metabolite; nutraceutical; plant metabolite; Saccharomyces cerevisiae metabolite |
| rotenone Derris: A plant genus of the family FABACEAE. The root is a source of rotenoids (ROTENONE) and flavonoids. Some species of Pongamia have been reclassified to this genus and some to MILLETTIA. Some species of Deguelia have been reclassified to this genus.. rotenoid : Members of the class of tetrahydrochromenochromene that consists of a cis-fused tetrahydrochromeno[3,4-b]chromene skeleton and its substituted derivatives. The term was originally restricted to natural products, but is now also used to describe semi-synthetic and fully synthetic compounds. | 2.87 | 3 | 0 | organic heteropentacyclic compound; rotenones | antineoplastic agent; metabolite; mitochondrial NADH:ubiquinone reductase inhibitor; phytogenic insecticide; piscicide; toxin |
| thiophenes Thiophenes: A monocyclic heteroarene furan in which the oxygen atom is replaced by a sulfur.. thiophenes : Compounds containing at least one thiophene ring. | 3.9 | 3 | 0 | mancude organic heteromonocyclic parent; monocyclic heteroarene; thiophenes; volatile organic compound | non-polar solvent |
| vanillic acid Vanillic Acid: A flavoring agent. It is the intermediate product in the two-step bioconversion of ferulic acid to vanillin. (J Biotechnol 1996;50(2-3):107-13).. vanillic acid : A monohydroxybenzoic acid that is 4-hydroxybenzoic acid substituted by a methoxy group at position 3. | 2.31 | 1 | 0 | methoxybenzoic acid; monohydroxybenzoic acid | plant metabolite |
| 1-naphthylamine 1-Naphthylamine: A suspected industrial carcinogen (and listed as such by OSHA). Its N-hydroxy metabolite is strongly carcinogenic and mutagenic.. naphthylamine : A primary arylamine that is naphthalene substituted by an amino group at unspecified position.. 1-naphthylamine : A naphthylamine that is naphthalene substituted by an amino group at position 1. | 1.99 | 1 | 0 | naphthylamine | human xenobiotic metabolite |
| thiazoles [no description available] | 4.66 | 3 | 2 | 1,3-thiazoles; mancude organic heteromonocyclic parent; monocyclic heteroarene | |
| hydrazine diamine : Any polyamine that contains two amino groups. | 5.05 | 10 | 1 | azane; hydrazines | EC 4.3.1.10 (serine-sulfate ammonia-lyase) inhibitor |
| methoxyhydroxyphenylglycol Methoxyhydroxyphenylglycol: Synthesized from endogenous epinephrine and norepinephrine in vivo. It is found in brain, blood, CSF, and urine, where its concentrations are used to measure catecholamine turnover. | 1.98 | 1 | 0 | methoxybenzenes; phenols | |
| methamphetamine Methamphetamine: A central nervous system stimulant and sympathomimetic with actions and uses similar to DEXTROAMPHETAMINE. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed.. methamphetamine : A member of the class of amphetamines in which the amino group of (S)-amphetamine carries a methyl substituent. | 1.96 | 1 | 0 | amphetamines; secondary amine | central nervous system stimulant; environmental contaminant; neurotoxin; psychotropic drug; xenobiotic |
| lithium carbonate Lithium Carbonate: A lithium salt, classified as a mood-stabilizing agent. Lithium ion alters the metabolism of BIOGENIC MONOAMINES in the CENTRAL NERVOUS SYSTEM, and affects multiple neurotransmission systems. | 1.98 | 1 | 0 | carbonate salt; lithium salt | antimanic drug |
| cytidine diphosphate choline Cytidine Diphosphate Choline: Donor of choline in biosynthesis of choline-containing phosphoglycerides. | 3.27 | 1 | 0 | nucleotide-(amino alcohol)s; phosphocholines | human metabolite; mouse metabolite; neuroprotective agent; psychotropic drug; Saccharomyces cerevisiae metabolite |
| d-alpha tocopherol Vitamin E: A generic descriptor for all TOCOPHEROLS and TOCOTRIENOLS that exhibit ALPHA-TOCOPHEROL activity. By virtue of the phenolic hydrogen on the 2H-1-benzopyran-6-ol nucleus, these compounds exhibit varying degree of antioxidant activity, depending on the site and number of methyl groups and the type of ISOPRENOIDS.. tocopherol : A collective name for a group of closely related lipids that contain a chroman-6-ol nucleus substituted at position 2 by a methyl group and by a saturated hydrocarbon chain consisting of three isoprenoid units. They are designated as alpha-, beta-, gamma-, and delta-tocopherol depending on the number and position of additional methyl substituents on the aromatic ring. Tocopherols occur in vegetable oils and vegetable oil products, almost exclusively with R,R,R configuration. Tocotrienols differ from tocopherols only in having three double bonds in the hydrocarbon chain.. vitamin E : Any member of a group of fat-soluble chromanols that exhibit biological activity against vitamin E deficiency. The vitamers in this class consists of a chroman-6-ol core which is substituted at position 2 by a methyl group and (also at position 2) either a saturated or a triply-unsaturated hydrocarbon chain consisting of three isoprenoid units. The major function of vitamin E is to act as a natural antioxidant by scavenging free radicals and molecular oxygen.. (R,R,R)-alpha-tocopherol : An alpha-tocopherol that has R,R,R configuration. The naturally occurring stereoisomer of alpha-tocopherol, it is found particularly in sunflower and olive oils. | 2.1 | 1 | 0 | alpha-tocopherol | algal metabolite; antiatherogenic agent; anticoagulant; antioxidant; antiviral agent; EC 2.7.11.13 (protein kinase C) inhibitor; immunomodulator; micronutrient; nutraceutical; plant metabolite |
| tetrahydropapaveroline Tetrahydropapaveroline: A leukomaine (animal alkaloid) formed in brain and liver from dopamine and L-dopa; it may be implicated in psychiatric problems. | 1.98 | 1 | 0 | benzylisoquinoline alkaloid; benzyltetrahydroisoquinoline; isoquinolinol | human metabolite |
| tranylcypromine Tranylcypromine: A propylamine formed from the cyclization of the side chain of amphetamine. This monoamine oxidase inhibitor is effective in the treatment of major depression, dysthymic disorder, and atypical depression. It also is useful in panic and phobic disorders. (From AMA Drug Evaluations Annual, 1994, p311). tranylcypromine : A racemate comprising equal amounts of (1R,2S)- and (1S,2R)-2-phenylcyclopropan-1-amine. An irreversible monoamine oxidase inhibitor that is used as an antidepressant (INN tranylcypromine).. (1R,2S)-tranylcypromine : A 2-phenylcyclopropan-1-amine that is the (1R,2S)-enantiomer of tranylcypromine. | 1.97 | 1 | 0 | 2-phenylcyclopropan-1-amine | |
| levodopa methyl ester levodopa methyl ester: RN given refers to parent cpd(L)-isomer | 1.98 | 1 | 0 | tyrosine derivative | |
| ferrous sulfate ferrous sulfate: Ferro-Gradumet is ferrous sulfate in controlled release form; RN given refers to Fe(+2)[1:1] salt. iron(2+) sulfate (anhydrous) : A compound of iron and sulfate in which the ratio of iron(2+) to sulfate ions is 1:1. Various hydrates occur naturally - most commonly the heptahydrate, which loses water to form the tetrahydrate at 57degreeC and the monohydrate at 65degreeC. | 1.97 | 1 | 0 | iron molecular entity; metal sulfate | reducing agent |
| selegiline Selegiline: A selective, irreversible inhibitor of Type B monoamine oxidase that is used for the treatment of newly diagnosed patients with PARKINSON DISEASE, and for the treatment of depressive disorders. The compound without isomeric designation is Deprenyl. | 9.14 | 17 | 4 | selegiline; terminal acetylenic compound | geroprotector |
| lisuride Lisuride: An ergot derivative that acts as an agonist at dopamine D2 receptors (DOPAMINE AGONISTS). It may also act as an antagonist at dopamine D1 receptors, and as an agonist at some serotonin receptors (SEROTONIN RECEPTOR AGONISTS). | 2.67 | 3 | 0 | monocarboxylic acid amide | antidyskinesia agent; antiparkinson drug; dopamine agonist; serotonergic agonist |
| bromocriptine Bromocriptine: A semisynthetic ergotamine alkaloid that is a dopamine D2 agonist. It suppresses prolactin secretion. | 8.24 | 21 | 5 | indole alkaloid | antidyskinesia agent; antiparkinson drug; dopamine agonist; hormone antagonist |
| methyldopa Methyldopa: An alpha-2 adrenergic agonist that has both central and peripheral nervous system effects. Its primary clinical use is as an antihypertensive agent.. alpha-methyl-L-dopa : A derivative of L-tyrosine having a methyl group at the alpha-position and an additional hydroxy group at the 3-position on the phenyl ring. | 4.36 | 2 | 2 | L-tyrosine derivative; non-proteinogenic L-alpha-amino acid | alpha-adrenergic agonist; antihypertensive agent; hapten; peripheral nervous system drug; sympatholytic agent |
| pergolide Pergolide: A long-acting dopamine agonist which has been used to treat PARKINSON DISEASE and HYPERPROLACTINEMIA but withdrawn from some markets due to potential for HEART VALVE DISEASES.. pergolide : A diamine that is ergoline in which the beta-hydrogen at position 8 is replaced by a (methylthio)methyl group and the hydrogen attached to the piperidine nitrogen (position 6) is replaced by a propyl group. A dopamine D2 receptor agonist which also has D1 and D2 agonist properties, it is used as the mesylate salt in the management of Parkinson's disease, although it was withdrawn from the U.S. and Canadian markets in 2007 due to an increased risk of cardiac valve dysfunction. | 8.32 | 14 | 6 | diamine; methyl sulfide; organic heterotetracyclic compound | antiparkinson drug; dopamine agonist |
| cabergoline Cabergoline: An ergoline derivative and dopamine D2-agonist that inhibits PROLACTIN secretion. It is used in the management of HYPERPROLACTINEMIA, and to suppress lactation following childbirth for medical reasons. Cabergoline is also used in the management of PARKINSON DISEASE.. cabergoline : An N-acylurea that is (8R)-ergoline-8-carboxamide in which the hydrogen attached to the piperidine nitrogen (position 6) is substituted by an allyl group and the hydrogens attached to the carboxamide nitrogen are substituted by a 3-(dimethylamino)propyl group and an N-ethylcarbamoyl group. A dopamine D2 receptor agonist, cabergoline is used in the management of Parkinson's disease and of disorders associated with hyperprolactinaemia. | 2.96 | 4 | 0 | N-acylurea | antineoplastic agent; antiparkinson drug; dopamine agonist |
| finasteride Finasteride: An orally active 3-OXO-5-ALPHA-STEROID 4-DEHYDROGENASE inhibitor. It is used as a surgical alternative for treatment of benign PROSTATIC HYPERPLASIA.. finasteride : An aza-steroid that is a synthetic drug for the treatment of benign prostatic hyperplasia. | 2.07 | 1 | 0 | 3-oxo steroid; aza-steroid; delta-lactam | androgen antagonist; antihyperplasia drug; EC 1.3.1.22 [3-oxo-5alpha-steroid 4-dehydrogenase (NADP(+))] inhibitor |
| mk 458 MK 458: a sustained release formulation of a naphthoxazine compoud with selective D-2 dopamine receptor agonism. naxagolide hydrochloride : The hydrochloride salt of naxagolide. | 1.98 | 1 | 0 | hydrochloride | anticonvulsant; antiparkinson drug; dopamine agonist |
| naxagolide naxagolide: structure given in first source. naxagolide : An organic heterotricyclic compound that is (4aR,10bR)-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazine substituted by propyl and hydroxy groups at positions 4 and 9, respectively. It is a potent dopamine D2-receptor agonist and its hydrochloride salt was under clinical development by Merck & Co as a potential antiparkinsonian agent (now discontinued). | 2.37 | 2 | 0 | organic heterotricyclic compound; phenols; tertiary amino compound | anticonvulsant; antiparkinson drug; dopamine agonist |
| n 0437, (-)-isomer rotigotine: Antiparkinson Agent and dopamine receptor agonist; structure given in first source; RN given refers to cpd without isomeric designation | 3.9 | 3 | 0 | tetralins | |
| remacemide remacemide: structure given in first source | 1.98 | 1 | 0 | stilbenoid | |
| n-acetylaspartic acid N-acetyl-L-aspartic acid : An N-acyl-L-aspartic acid in which the acyl group is specified as acetyl. | 3.37 | 1 | 1 | N-acetyl-L-amino acid; N-acyl-L-aspartic acid | antioxidant; human metabolite; mouse metabolite; nutraceutical; rat metabolite |
| triazoles Triazoles: Heterocyclic compounds containing a five-membered ring with two carbon atoms and three nitrogen atoms with the molecular formula C2H3N3.. triazoles : An azole in which the five-membered heterocyclic aromatic skeleton contains three N atoms and two C atoms. | 1.99 | 1 | 0 | 1,2,3-triazole | |
| fluorodeoxyglucose f18 Fluorodeoxyglucose F18: The compound is given by intravenous injection to do POSITRON-EMISSION TOMOGRAPHY for the assessment of cerebral and myocardial glucose metabolism in various physiological or pathological states including stroke and myocardial ischemia. It is also employed for the detection of malignant tumors including those of the brain, liver, and thyroid gland. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1162) | 3.5 | 2 | 0 | 2-deoxy-2-((18)F)fluoro-D-glucose; 2-deoxy-2-fluoro-aldehydo-D-glucose | |
| sertraline Sertraline: A selective serotonin uptake inhibitor that is used in the treatment of depression.. sertraline : A member of the class of tetralins that is tetralin which is substituted at positions 1 and 4 by a methylamino and a 3,4-dichlorophenyl group, respectively (the S,S diastereoisomer). A selective serotonin-reuptake inhibitor (SSRI), it is administered orally as the hydrochloride salt as an antidepressant for the treatment of depression, obsessive-compulsive disorder, panic disorder and post-traumatic stress disorder. | 1.99 | 1 | 0 | dichlorobenzene; secondary amino compound; tetralins | antidepressant; serotonin uptake inhibitor |
| lazabemide lazabemide: structure given in first source | 2.15 | 1 | 0 | ||
| homocysteine Homocysteine: A thiol-containing amino acid formed by a demethylation of METHIONINE.. homocysteine : A sulfur-containing amino acid consisting of a glycine core with a 2-mercaptoethyl side-chain.. L-homocysteine : A homocysteine that has L configuration. | 4.41 | 2 | 2 | amino acid zwitterion; homocysteine; serine family amino acid | fundamental metabolite; mouse metabolite |
| droxidopa Droxidopa: A synthetic precursor of norepinephrine that is used in the treatment of PARKINSONIAN DISORDERS and ORTHOSTATIC HYPOTENSION.. droxidopa : A serine derivative that is L-serine substituted at the beta-position by a 3,4-dihydroxyphenyl group. A prodrug for noradrenalone, it is used for treatment of neurogenic orthostatic hypotension | 2.52 | 2 | 0 | catechols; L-tyrosine derivative | antihypertensive agent; prodrug; vasoconstrictor agent |
| vitamin b 6 Vitamin B 6: VITAMIN B 6 refers to several PICOLINES (especially PYRIDOXINE; PYRIDOXAL; & PYRIDOXAMINE) that are efficiently converted by the body to PYRIDOXAL PHOSPHATE which is a coenzyme for synthesis of amino acids, neurotransmitters (serotonin, norepinephrine), sphingolipids, and aminolevulinic acid. During transamination of amino acids, pyridoxal phosphate is transiently converted into PYRIDOXAMINE phosphate. Although pyridoxine and Vitamin B 6 are still frequently used as synonyms, especially by medical researchers, this practice is erroneous and sometimes misleading (EE Snell; Ann NY Acad Sci, vol 585 pg 1, 1990). Most of vitamin B6 is eventually degraded to PYRIDOXIC ACID and excreted in the urine. | 2.08 | 1 | 0 | ||
| deoxyglucose Deoxyglucose: 2-Deoxy-D-arabino-hexose. An antimetabolite of glucose with antiviral activity.. deoxyglucose : A deoxyhexose comprising glucose having at least one hydroxy group replaced by hydrogen. | 3.08 | 1 | 0 | ||
| pramipexole Pramipexole: A benzothiazole derivative and dopamine agonist with antioxidant properties that is used in the treatment of PARKINSON DISEASE and RESTLESS LEGS SYNDROME.. pramipexole : A member of the class of benzothiazoles that is 4,5,6,7-tetrahydro-1,3-benzothiazole in which the hydrogens at the 2 and 6-pro-S-positions are substituted by amino and propylamino groups, respectively. | 8.59 | 13 | 4 | benzothiazoles; diamine | antidyskinesia agent; antiparkinson drug; dopamine agonist; radical scavenger |
| 5-fluorodopa 5-fluorodopa: RN given refers to (DL)-isomer; DOPA might be a specific substance which would allow a distinction to be made between normal & abnormal brain capillaries by means of external gamma-ray detection; structure | 3.08 | 1 | 0 | ||
| imatinib mesylate imatinib methanesulfonate : A methanesulfonate (mesylate) salt that is the monomesylate salt of imatinib. Used for treatment of chronic myelogenous leukemia and gastrointestinal stromal tumours. | 2.17 | 1 | 0 | methanesulfonate salt | anticoronaviral agent; antineoplastic agent; apoptosis inducer; tyrosine kinase inhibitor |
| ro 8-0576 benserazide, levodopa drug combination: combination of L-Dopa and seryltrihydroxybenzylhydrazine; used in treatment of parkinsonism | 8.33 | 23 | 6 | ||
| dopamine 4-o-sulfate dopamine 4-O-sulfate: possible precursor of free norepinephrin; see also record for dopamine 3-O-sulfate. dopamine 4-O-sulfate : An aryl sulfate that is dopamine in which the phenolic hydrogen at position 4 has been replaced by a sulfo group. | 2.15 | 1 | 0 | aryl sulfate; phenols; primary amino compound; zwitterion | human blood serum metabolite; human urinary metabolite |
| 6-fluoro-3-tyrosine 6-fluoro-3-tyrosine: used as a probe for central dopamine metabolism with positron emission tomography | 2 | 1 | 0 | ||
| ciladopa [no description available] | 3.35 | 1 | 1 | ||
| adenosine 3'-phosphate-5'-phosphate adenosine 3',5'-bismonophosphate : An adenosine bisphosphate having two monophosphate groups at the 3'- and 5'-positions. | 2.01 | 1 | 0 | adenosine bisphosphate | Escherichia coli metabolite; mouse metabolite |
| biotin vitamin B7 : Any member of a group of vitamers that belong to the chemical structural class called biotins that exhibit biological activity against vitamin B7 deficiency. Vitamin B7 deficiency is very rare in individuals who take a normal balanced diet. Foods rich in biotin are egg yolk, liver, cereals, vegetables (spinach, mushrooms) and rice. Symptoms associated with vitamin B7 deficiency include thinning hair, scaly skin rashes around eyes, nose and mouth, and brittle nails. The vitamers include biotin and its ionized and salt forms. | 2.15 | 1 | 0 | biotins; vitamin B7 | coenzyme; cofactor; Escherichia coli metabolite; fundamental metabolite; human metabolite; mouse metabolite; nutraceutical; prosthetic group; Saccharomyces cerevisiae metabolite |
| cysteinylglycine cysteinylglycine: RN given refers to (L)-isomer; RN for cpd without isomeric designation not in Chemlne 7/13/83. L-cysteinylglycine : A dipeptide consisting of glycine having an L-cysteinyl attached to its alpha-amino group. It is an intermediate metabolite in glutathione metabolism. | 3.51 | 1 | 1 | dipeptide zwitterion; dipeptide | Escherichia coli metabolite; human metabolite; Saccharomyces cerevisiae metabolite |
| linezolid [no description available] | 2.13 | 1 | 0 | acetamides; morpholines; organofluorine compound; oxazolidinone | antibacterial drug; protein synthesis inhibitor |
| cocaine Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.. cocaine : A tropane alkaloid obtained from leaves of the South American shrub Erythroxylon coca. | 6.01 | 3 | 2 | benzoate ester; methyl ester; tertiary amino compound; tropane alkaloid | adrenergic uptake inhibitor; central nervous system stimulant; dopamine uptake inhibitor; environmental contaminant; local anaesthetic; mouse metabolite; plant metabolite; serotonin uptake inhibitor; sodium channel blocker; sympathomimetic agent; vasoconstrictor agent; xenobiotic |
| glycosides [no description available] | 2.21 | 1 | 0 | ||
| arginine vasopressin Arginine Vasopressin: The predominant form of mammalian antidiuretic hormone. It is a nonapeptide containing an ARGININE at residue 8 and two disulfide-linked cysteines at residues of 1 and 6. Arg-vasopressin is used to treat DIABETES INSIPIDUS or to improve vasomotor tone and BLOOD PRESSURE.. argipressin : The predominant form of mammalian vasopressin (antidiuretic hormone). It is a nonapeptide containing an arginine at residue 8 and two disulfide-linked cysteines at residues of 1 and 6. | 3.46 | 1 | 1 | vasopressin | cardiovascular drug; hematologic agent; mitogen |
| benztropine Benztropine: A centrally active muscarinic antagonist that has been used in the symptomatic treatment of PARKINSON DISEASE. Benztropine also inhibits the uptake of dopamine.. benzatropine : Tropane in which a hydrogen at position 3 is substituted by a diphenylmethoxy group (endo-isomer). An acetylcholine receptor antagonist, it is used (particularly as its methanesulphonate salt) in the treatment of Parkinson's disease, and to reduce parkinsonism and akathisia side effects of antipsychotic treatments. | 3.34 | 1 | 1 | diarylmethane | |
| lithium Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight [6.938; 6.997]. Salts of lithium are used in treating BIPOLAR DISORDER. | 3.06 | 1 | 0 | alkali metal atom | |
| raclopride Raclopride: A substituted benzamide that has antipsychotic properties. It is a dopamine D2 receptor (see RECEPTORS, DOPAMINE D2) antagonist. | 4.75 | 2 | 1 | salicylamides | |
| rasagiline [no description available] | 2.47 | 2 | 0 | indanes; secondary amine; terminal acetylenic compound | EC 1.4.3.4 (monoamine oxidase) inhibitor; neuroprotective agent |
| quinagolide quinagolide: structure & RN given in first source; a non-ergot dopamine D(2)-agonist | 3.36 | 1 | 1 | organic heterotricyclic compound; organonitrogen heterocyclic compound | |
| tolcapone Tolcapone: A benzophenone and nitrophenol compound that acts as an inhibitor of CATECHOL O-METHYLTRANSFERASE, an enzyme involved in the metabolism of DOPAMINE and LEVODOPA. It is used in the treatment of PARKINSON DISEASE in patients for whom levodopa is ineffective or contraindicated.. tolcapone : Benzophenone substituted on one of the phenyl rings at C-3 and C-4 by hydroxy groups and at C-5 by a nitro group, and on the other phenyl ring by a methyl group at C-4. It is an inhibitor of catechol O-methyltransferase. | 6.66 | 6 | 3 | 2-nitrophenols; benzophenones; catechols | antiparkinson drug; EC 2.1.1.6 (catechol O-methyltransferase) inhibitor |
| harmine Harmine: Alkaloid isolated from seeds of PEGANUM HARMALA; ZYGOPHYLLACEAE. It is identical to banisterine, or telepathine, from Banisteria caapi and is one of the active ingredients of hallucinogenic drinks made in the western Amazon region from related plants. It has no therapeutic use, but (as banisterine) was hailed as a cure for postencephalitic PARKINSON DISEASE in the 1920's.. harmine : A harmala alkaloid in which the harman skeleton is methoxy-substituted at C-7. | 3.46 | 1 | 1 | harmala alkaloid | anti-HIV agent; EC 1.4.3.4 (monoamine oxidase) inhibitor; metabolite |
| entacapone entacapone: structure given in first source. entacapone : A monocarboxylic acid amide that is N,N-diethylprop-2-enamide in which the hydrogen at position 2 is substituted by a cyano group and the hydrogen at the 3E position is substituted by a 3,4-dihydroxy-5-nitrophenyl group. | 10.8 | 20 | 11 | 2-nitrophenols; catechols; monocarboxylic acid amide; nitrile | antidyskinesia agent; antiparkinson drug; central nervous system drug; EC 2.1.1.6 (catechol O-methyltransferase) inhibitor |
| etretinate retinoid : Oxygenated derivatives of 3,7-dimethyl-1-(2,6,6-trimethylcyclohex-1-enyl)nona-1,3,5,7-tetraene and derivatives thereof. | 1.97 | 1 | 0 | enoate ester; ethyl ester; retinoid | keratolytic drug |
| barium Barium: An element of the alkaline earth group of metals. It has an atomic symbol Ba, atomic number 56, and atomic weight 138. All of its acid-soluble salts are poisonous. | 2.15 | 1 | 0 | alkaline earth metal atom; elemental barium | |
| cysteine Cysteine: A thiol-containing non-essential amino acid that is oxidized to form CYSTINE.. L-cysteinium : The L-enantiomer of cysteinium.. cysteine : A sulfur-containing amino acid that is propanoic acid with an amino group at position 2 and a sulfanyl group at position 3. | 3.89 | 2 | 1 | cysteinium | fundamental metabolite |
| octadecylsilane [no description available] | 1.98 | 1 | 0 | ||
| dizocilpine maleate Dizocilpine Maleate: A potent noncompetitive antagonist of the NMDA receptor (RECEPTORS, N-METHYL-D-ASPARTATE) used mainly as a research tool. The drug has been considered for the wide variety of neurodegenerative conditions or disorders in which NMDA receptors may play an important role. Its use has been primarily limited to animal and tissue experiments because of its psychotropic effects.. dizocilpine maleate : A maleate salt obtained by reaction of dizocilpine with one equivalent of maleic acid. | 1.98 | 1 | 0 | maleate salt; tetracyclic antidepressant | anaesthetic; anticonvulsant; neuroprotective agent; nicotinic antagonist; NMDA receptor antagonist |
| ergoline Ergolines: A series of structurally-related alkaloids that contain the ergoline backbone structure.. ergoline : An indole alkaloid whose structural skeleton is found in many naturally occurring and synthetic ergolines which are known to bind to neurotransmitter receptors, such as dopamine, noradrenaline and serotonin receptors and function as unselective agonists or antagonists at these receptors. | 5.16 | 11 | 1 | diamine; ergoline alkaloid; indole alkaloid fundamental parent; indole alkaloid; organic heterotetracyclic compound | |
| stalevo Stalevo: Levodopa, carbidopa & entacapone (Catechols), intended as improved therapy for Parkinson Disease | 3.5 | 1 | 1 | ||
| aluminum oxide Aluminum Oxide: An oxide of aluminum, occurring in nature as various minerals such as bauxite, corundum, etc. It is used as an adsorbent, desiccating agent, and catalyst, and in the manufacture of dental cements and refractories. | 1.98 | 1 | 0 | ||
| 2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane 2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane: used in PET and SPECT imaging of dopamine transporters; structure in first source | 2.11 | 1 | 0 | ||
| linagliptin Linagliptin: A purine and quinazoline derivative that functions as an INCRETIN and DIPEPTIDYL-PEPTIDASE IV INHIBTOR. It is used as a HYPOGLYCEMIC AGENT in the treatment of TYPE II DIABETES MELLITUS.. linagliptin : A xanthine that is 7H-xanthine bearing (4-methylquinazolin-2-yl)methyl, methyl, but-2-yn-1-yl and 3-aminopiperidin-1-yl substituents at positions 1, 3, 7 and 8 respectively (the R-enantiomer). Used for treatment of type II diabetes. | 2.17 | 1 | 0 | aminopiperidine; quinazolines | EC 3.4.14.5 (dipeptidyl-peptidase IV) inhibitor; hypoglycemic agent |
| oxadiazoles Oxadiazoles: Compounds containing five-membered heteroaromatic rings containing two carbons, two nitrogens, and one oxygen atom which exist in various regioisomeric forms. | 3.97 | 2 | 1 | ||
| sitagliptin phosphate Sitagliptin Phosphate: A pyrazine-derived DIPEPTIDYL-PEPTIDASE IV INHIBITOR and HYPOGLYCEMIC AGENT that increases the levels of the INCRETIN hormones GLUCAGON-LIKE PEPTIDE-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). It is used in the treatment of TYPE 2 DIABETES. | 2.21 | 1 | 0 | ||
| liraglutide [no description available] | 2.21 | 1 | 0 | lipopeptide; polypeptide | glucagon-like peptide-1 receptor agonist; neuroprotective agent |
| glucagon-like peptide 1 Glucagon-Like Peptide 1: A peptide of 36 or 37 amino acids that is derived from PROGLUCAGON and mainly produced by the INTESTINAL L CELLS. GLP-1(1-37 or 1-36) is further N-terminally truncated resulting in GLP-1(7-37) or GLP-1-(7-36) which can be amidated. These GLP-1 peptides are known to enhance glucose-dependent INSULIN release, suppress GLUCAGON release and gastric emptying, lower BLOOD GLUCOSE, and reduce food intake. | 2.17 | 1 | 0 | ||
| s-adenosylmethionine (R)-S-adenosyl-L-methionine : An S-adenosyl-L-methionine that has R-configuration.. S-adenosyl-L-methionine zwitterion : A zwitterionic tautomer of S-adenosyl-L-methionine arising from shift of the proton from the carboxy group to the amino group.. (R)-S-adenosyl-L-methionine zwitterion : An S-adenosyl-L-methionine zwitterion that has R-configuration; major species at pH 7.3.. (S)-S-adenosyl-L-methionine zwitterion : An S-adenosyl-L-methionine zwitterion that has S-configuration; major species at pH 7.3.. S-adenosyl-L-methionine : A sulfonium compound that is the S-adenosyl derivative of L-methionine. It is an intermediate in the metabolic pathway of methionine. | 2.01 | 1 | 0 | organic cation; sulfonium compound | coenzyme; cofactor; human metabolite; micronutrient; Mycoplasma genitalium metabolite; nutraceutical; Saccharomyces cerevisiae metabolite |
| piperidines Piperidines: A family of hexahydropyridines. | 6.55 | 5 | 1 | ||
| methylcellulose Methylcellulose: Methylester of cellulose. Methylcellulose is used as an emulsifying and suspending agent in cosmetics, pharmaceutics and the chemical industry. It is used therapeutically as a bulk laxative. | 1.98 | 1 | 0 | ||
| ascorbic acid Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant.. L-ascorbic acid : The L-enantiomer of ascorbic acid and conjugate acid of L-ascorbate.. L-ascorbate : The L-enantiomer of ascorbate and conjugate base of L-ascorbic acid, arising from selective deprotonation of the 3-hydroxy group. Required for a range of essential metabolic reactions in all animals and plants.. vitamin C : Any member of a group of vitamers that belong to the chemical structural class called butenolides that exhibit biological activity against vitamin C deficiency in animals. The vitamers include L-ascorbic acid and its salt, ionized and oxidized forms. | 2.44 | 2 | 0 | ascorbic acid; vitamin C | coenzyme; cofactor; flour treatment agent; food antioxidant; food colour retention agent; geroprotector; plant metabolite; skin lightening agent |
| minocycline Minocycline: A TETRACYCLINE analog, having a 7-dimethylamino and lacking the 5 methyl and hydroxyl groups, which is effective against tetracycline-resistant STAPHYLOCOCCUS infections.. minocycline : A tetracycline analogue having a dimethylamino group at position 7 and lacking the methyl and hydroxy groups at position 5. | 2.1 | 1 | 0 | ||
| warfarin Warfarin: An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide.. warfarin : A racemate comprising equal amounts of (R)- and (S)-warfarin. Extensively used as both an anticoagulant drug and as a pesticide against rats and mice.. 4-hydroxy-3-(3-oxo-1-phenylbutyl)-1-benzopyran-2-one : A member of the class of coumarins that is 4-hydroxycoumarin which is substituted at position 3 by a 1-phenyl-3-oxo-1-butyl group. | 2.21 | 1 | 0 | benzenes; hydroxycoumarin; methyl ketone | |
| transforming growth factor beta Transforming Growth Factor beta: A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGF-beta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins. | 2.1 | 1 | 0 | ||
| nitrophenols Nitrophenols: PHENOLS carrying nitro group substituents. | 6.66 | 6 | 3 | ||
| epoetin alfa Epoetin Alfa: A recombinant glycosylated form of erythropoietin which stimulates the differentiation and proliferation of erythroid precursors. It is used for the treatment of ANEMIA associated with CHRONIC RENAL FAILURE in dialysis and predialysis patients. | 3.27 | 1 | 0 | ||
| vitamin b 12 Vitamin B 12: A cobalt-containing coordination compound produced by intestinal micro-organisms and found also in soil and water. Higher plants do not concentrate vitamin B 12 from the soil and so are a poor source of the substance as compared with animal tissues. INTRINSIC FACTOR is important for the assimilation of vitamin B 12. | 3.89 | 2 | 1 | ||
| sapropterin sapropterin: RN given refers to parent cpd; co-factor required for catalytic activity of nitric oxide synthases. (6R)-5,6,7,8-tetrahydrobiopterin : A 5,6,7,8-tetrahydrobiopterin in which the stereocentre at position 6 has R-configuration.. sapropterin : A tetrahydropterin that is 2-amino-5,6,7,8-tetrahydropteridin-4(3H)-one in which a hydrogen at position 6 is substituted by a 1,2-dihydroxypropyl group (6R,1'R,2'S-enantiomer). | 1.99 | 1 | 0 | 5,6,7,8-tetrahydrobiopterin | coenzyme; cofactor; diagnostic agent; human metabolite |
| folic acid folcysteine: used to promote fertility in chickens. vitamin B9 : Any B-vitamin that exhibits biological activity against vitamin B9 deficiency. Vitamin B9 refers to the many forms of folic acid and its derivatives, including tetrahydrofolic acid (the active form), methyltetrahydrofolate (the primary form found in blood), methenyltetrahydrofolate, folinic acid amongst others. They are present in abundance in green leafy vegetables, citrus fruits, and animal products. Lack of vitamin B9 leads to anemia, a condition in which the body cannot produce sufficient number of red blood cells. Symptoms of vitamin B9 deficiency include fatigue, muscle weakness, and pale skin. | 2.21 | 1 | 0 | folic acids; N-acyl-amino acid | human metabolite; mouse metabolite; nutrient |
| neopterin [no description available] | 1.97 | 1 | 0 | ||
| clozapine Clozapine: A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent.. clozapine : A benzodiazepine that is 5H-dibenzo[b,e][1,4]diazepine substituted by a chloro group at position 8 and a 4-methylpiperazin-1-yl group at position 11. It is a second generation antipsychotic used in the treatment of psychiatric disorders like schizophrenia. | 2.68 | 3 | 0 | benzodiazepine; N-arylpiperazine; N-methylpiperazine; organochlorine compound | adrenergic antagonist; dopaminergic antagonist; EC 3.4.21.26 (prolyl oligopeptidase) inhibitor; environmental contaminant; GABA antagonist; histamine antagonist; muscarinic antagonist; second generation antipsychotic; serotonergic antagonist; xenobiotic |
| sildenafil citrate Sildenafil Citrate: A PHOSPHODIESTERASE TYPE-5 INHIBITOR; VASODILATOR AGENT and UROLOGICAL AGENT that is used in the treatment of ERECTILE DYSFUNCTION and PRIMARY PULMONARY HYPERTENSION.. sildenafil citrate : The citrate salt of sildenafil. | 2.05 | 1 | 0 | citrate salt | EC 3.1.4.35 (3',5'-cyclic-GMP phosphodiesterase) inhibitor; vasodilator agent |
| opicapone opicapone: structure in first source | 3.97 | 2 | 1 | oxadiazole; ring assembly | |
| lipoteichoic acid lipoteichoic acid: lipopolysaccharides with an acyl group anchored to the cell membrane of gram-positive bacteria; functions as an adhesion molecule to facilitate the binding of bacteria to cells, colonization, and invasion; interacts with CD14 to induce NF-κB activation and inflammatory cytokine production; can function as surface antigen; inhibits remineraliztion of artificial lesions and surface-softened enamels;. lipoteichoic acid : A teichoic acid which is covalently bound to a lipid. | 2.02 | 1 | 0 | ||
| carbidopa Carbidopa: An inhibitor of DOPA DECARBOXYLASE that prevents conversion of LEVODOPA to dopamine. It is used in PARKINSON DISEASE to reduce peripheral adverse effects of LEVODOPA. It has no anti-parkinson activity by itself.. carbidopa : The hydrate of 3-(3,4-dihydroxyphenyl)propanoic acid in which the hydrogens alpha- to the carboxyl group are substituted by hydrazinyl and methyl groups (S-configuration). Carbidopa is a dopa decarboxylase inhibitor, so prevents conversion of levodopa to dopamine. It has no antiparkinson activity by itself, but is used in the management of Parkinson's disease to reduce peripheral adverse effects of levodopa. | 22.86 | 690 | 143 |
| Condition | Indicated | Relationship Strength | Studies | Trials |
|---|---|---|---|---|
| Idiopathic Parkinson Disease [description not available] | 0 | 22.52 | 521 | 122 |
| Parkinson Disease A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75) | 0 | 22.52 | 521 | 122 |
| Adult-Onset Dystonias [description not available] | 0 | 5.72 | 11 | 0 |
| Dystonic Disorders Acquired and inherited conditions that feature DYSTONIA as a primary manifestation of disease. These disorders are generally divided into generalized dystonias (e.g., dystonia musculorum deformans) and focal dystonias (e.g., writer's cramp). They are also classified by patterns of inheritance and by age of onset. | 0 | 5.72 | 11 | 0 |
| Chronic Inflammatory Demyelinating Polyradiculoneuropathy [description not available] | 0 | 2.54 | 2 | 0 |
| Polyradiculoneuropathy, Chronic Inflammatory Demyelinating A slowly progressive autoimmune demyelinating disease of peripheral nerves and nerve roots. Clinical manifestations include weakness and sensory loss in the extremities and enlargement of peripheral nerves. The course may be relapsing-remitting or demonstrate a step-wise progression. Protein is usually elevated in the spinal fluid and cranial nerves are typically spared. GUILLAIN-BARRE SYNDROME features a relatively rapid progression of disease which distinguishes it from this condition. (Adams et al., Principles of Neurology, 6th ed, p1337) | 0 | 2.54 | 2 | 0 |
| Anochlesia [description not available] | 0 | 3.11 | 4 | 0 |
| Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. | 0 | 4.9 | 13 | 0 |
| Atherosclerotic Parkinsonism [description not available] | 0 | 6.75 | 32 | 0 |
| Parkinson Disease, Secondary Conditions which feature clinical manifestations resembling primary Parkinson disease that are caused by a known or suspected condition. Examples include parkinsonism caused by vascular injury, drugs, trauma, toxin exposure, neoplasms, infections and degenerative or hereditary conditions. Clinical features may include bradykinesia, rigidity, parkinsonian gait, and masked facies. In general, tremor is less prominent in secondary parkinsonism than in the primary form. (From Joynt, Clinical Neurology, 1998, Ch38, pp39-42) | 0 | 6.75 | 32 | 0 |
| Adverse Drug Event [description not available] | 0 | 4.55 | 4 | 1 |
| Drug-Related Side Effects and Adverse Reactions Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals. | 0 | 4.55 | 4 | 1 |
| Dyskinesia, Medication-Induced [description not available] | 0 | 12.12 | 40 | 6 |
| Dyskinesia, Drug-Induced Abnormal movements, including HYPERKINESIS; HYPOKINESIA; TREMOR; and DYSTONIA, associated with the use of certain medications or drugs. Muscles of the face, trunk, neck, and extremities are most commonly affected. Tardive dyskinesia refers to abnormal hyperkinetic movements of the muscles of the face, tongue, and neck associated with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS). (Adams et al., Principles of Neurology, 6th ed, p1199) | 0 | 12.12 | 40 | 6 |
| Benign Neoplasms, Brain [description not available] | 0 | 3.93 | 2 | 1 |
| Brain Neoplasms Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain. | 0 | 3.93 | 2 | 1 |
| Autosomal Dominant Juvenile Parkinson Disease [description not available] | 0 | 5.82 | 20 | 1 |
| Action Tremor [description not available] | 0 | 5.18 | 11 | 1 |
| Sensitivity and Specificity Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed) | 0 | 3.83 | 2 | 1 |
| Tremor Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of CEREBELLAR DISEASES, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of PARKINSON DISEASE. | 0 | 5.18 | 11 | 1 |
| Parkinsonian Disorders A group of disorders which feature impaired motor control characterized by bradykinesia, MUSCLE RIGIDITY; TREMOR; and postural instability. Parkinsonian diseases are generally divided into primary parkinsonism (see PARKINSON DISEASE), secondary parkinsonism (see PARKINSON DISEASE, SECONDARY) and inherited forms. These conditions are associated with dysfunction of dopaminergic or closely related motor integration neuronal pathways in the BASAL GANGLIA. | 0 | 5.82 | 20 | 1 |
| Dysarthosis [description not available] | 0 | 2.77 | 3 | 0 |
| Infections, Legionella pneumophila [description not available] | 0 | 2.25 | 1 | 0 |
| Acute Hypercapnic Respiratory Failure [description not available] | 0 | 2.25 | 1 | 0 |
| Respiratory Insufficiency Failure to adequately provide oxygen to cells of the body and to remove excess carbon dioxide from them. (Stedman, 25th ed) | 0 | 2.25 | 1 | 0 |
| Cognitive Decline [description not available] | 0 | 2.94 | 3 | 0 |
| Cognitive Dysfunction Diminished or impaired mental and/or intellectual function. | 0 | 2.94 | 3 | 0 |
| Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms. | 0 | 2.73 | 3 | 0 |
| Disease Exacerbation [description not available] | 0 | 11.07 | 23 | 0 |
| Diabetic Retinopathy Disease of the RETINA as a complication of DIABETES MELLITUS. It is characterized by the progressive microvascular complications, such as ANEURYSM, interretinal EDEMA, and intraocular PATHOLOGIC NEOVASCULARIZATION. | 0 | 4.55 | 1 | 1 |
| Break-Bone Fever [description not available] | 0 | 2.25 | 1 | 0 |
| Dengue An acute febrile disease transmitted by the bite of AEDES mosquitoes infected with DENGUE VIRUS. It is self-limiting and characterized by fever, myalgia, headache, and rash. SEVERE DENGUE is a more virulent form of dengue. | 0 | 2.25 | 1 | 0 |
| Ambulation Disorders, Neurologic [description not available] | 0 | 3.95 | 4 | 0 |
| Abnormal Movements [description not available] | 0 | 7.91 | 12 | 4 |
| Age-Related Macular Degeneration [description not available] | 0 | 2.31 | 1 | 0 |
| Macular Degeneration Degenerative changes in the RETINA usually of older adults which results in a loss of vision in the center of the visual field (the MACULA LUTEA) because of damage to the retina. It occurs in dry and wet forms. | 0 | 2.31 | 1 | 0 |
| Abdomen, Acute A clinical syndrome with acute abdominal pain that is severe, localized, and rapid in onset. Acute abdomen may be caused by a variety of disorders, injuries, or diseases. | 0 | 2.31 | 1 | 0 |
| Dysphagia [description not available] | 0 | 2.31 | 1 | 0 |
| Deglutition Disorders Difficulty in SWALLOWING which may result from neuromuscular disorder or mechanical obstruction. Dysphagia is classified into two distinct types: oropharyngeal dysphagia due to malfunction of the PHARYNX and UPPER ESOPHAGEAL SPHINCTER; and esophageal dysphagia due to malfunction of the ESOPHAGUS. | 0 | 2.31 | 1 | 0 |
| Acute Symptom Flare [description not available] | 0 | 2.31 | 1 | 0 |
| Hypermelanosis [description not available] | 0 | 2.31 | 1 | 0 |
| Malignant Melanoma [description not available] | 0 | 2.31 | 1 | 0 |
| Cancer of Skin [description not available] | 0 | 2.31 | 1 | 0 |
| Melanoma A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445) | 0 | 2.31 | 1 | 0 |
| Skin Neoplasms Tumors or cancer of the SKIN. | 0 | 2.31 | 1 | 0 |
| Hyperpigmentation Excessive pigmentation of the skin, usually as a result of increased epidermal or dermal melanin pigmentation, hypermelanosis. Hyperpigmentation can be localized or generalized. The condition may arise from exposure to light, chemicals or other substances, or from a primary metabolic imbalance. | 0 | 2.31 | 1 | 0 |
| Bradykinesia [description not available] | 0 | 4.16 | 3 | 1 |
| Acute Ischemic Stroke [description not available] | 0 | 2.31 | 1 | 0 |
| 2019 Novel Coronavirus Disease [description not available] | 0 | 2.31 | 1 | 0 |
| Brain Disorders [description not available] | 0 | 2.7 | 3 | 0 |
| Ischemic Stroke Stroke due to BRAIN ISCHEMIA resulting in interruption or reduction of blood flow to a part of the brain. When obstruction is due to a BLOOD CLOT formed within in a cerebral blood vessel it is a thrombotic stroke. When obstruction is formed elsewhere and moved to block a cerebral blood vessel (see CEREBRAL EMBOLISM) it is referred to as embolic stroke. Wake-up stroke refers to ischemic stroke occurring during sleep while cryptogenic stroke refers to ischemic stroke of unknown origin. | 0 | 2.31 | 1 | 0 |
| Brain Diseases Pathologic conditions affecting the BRAIN, which is composed of the intracranial components of the CENTRAL NERVOUS SYSTEM. This includes (but is not limited to) the CEREBRAL CORTEX; intracranial white matter; BASAL GANGLIA; THALAMUS; HYPOTHALAMUS; BRAIN STEM; and CEREBELLUM. | 0 | 2.7 | 3 | 0 |
| Complication, Postoperative [description not available] | 0 | 4.64 | 6 | 1 |
| Postoperative Complications Pathologic processes that affect patients after a surgical procedure. They may or may not be related to the disease for which the surgery was done, and they may or may not be direct results of the surgery. | 0 | 4.64 | 6 | 1 |
| Nearsightedness [description not available] | 0 | 2.31 | 1 | 0 |
| Myopia A refractive error in which rays of light entering the EYE parallel to the optic axis are brought to a focus in front of the RETINA when accommodation (ACCOMMODATION, OCULAR) is relaxed. This results from an overly curved CORNEA or from the eyeball being too long from front to back. It is also called nearsightedness. | 0 | 2.31 | 1 | 0 |
| Microscopic Colitis [description not available] | 0 | 2.31 | 1 | 0 |
| Colitis, Microscopic A condition characterized by chronic watery DIARRHEA of unknown origin, a normal COLONOSCOPY but abnormal histopathology on BIOPSY. This syndrome was first described in 1980 by Read and associates. Subtypes include COLLAGENOUS COLITIS and LYMPHOCYTIC COLITIS. Both have similar clinical symptoms and are distinguishable only by histology. | 0 | 2.31 | 1 | 0 |
| Muscle Disorders [description not available] | 0 | 2.92 | 4 | 0 |
| Muscular Diseases Acquired, familial, and congenital disorders of SKELETAL MUSCLE and SMOOTH MUSCLE. | 0 | 2.92 | 4 | 0 |
| Ileal Diseases Pathological development in the ILEUM including the ILEOCECAL VALVE. | 0 | 2.17 | 1 | 0 |
| Foreign-Body Migration Migration of a foreign body from its original location to some other location in the body. | 0 | 2.57 | 2 | 0 |
| Intestinal Obstruction Any impairment, arrest, or reversal of the normal flow of INTESTINAL CONTENTS toward the ANAL CANAL. | 0 | 2.17 | 1 | 0 |
| Long Sleeper Syndrome [description not available] | 0 | 4.5 | 5 | 1 |
| Sleep Wake Disorders Abnormal sleep-wake schedule or pattern associated with the CIRCADIAN RHYTHM which affect the length, timing, and/or rigidity of the sleep-wake cycle relative to the day-night cycle. | 0 | 4.5 | 5 | 1 |
| Peripheral Nerve Diseases [description not available] | 0 | 5.11 | 5 | 2 |
| Peripheral Nervous System Diseases Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves. | 0 | 5.11 | 5 | 2 |
| Deficiency, Vitamin D [description not available] | 0 | 2.15 | 1 | 0 |
| Vitamin D Deficiency A nutritional condition produced by a deficiency of VITAMIN D in the diet, insufficient production of vitamin D in the skin, inadequate absorption of vitamin D from the diet, or abnormal conversion of vitamin D to its bioactive metabolites. It is manifested clinically as RICKETS in children and OSTEOMALACIA in adults. (From Cecil Textbook of Medicine, 19th ed, p1406) | 0 | 2.15 | 1 | 0 |
| Polyneuropathy, Acquired [description not available] | 0 | 5.13 | 3 | 1 |
| Polyneuropathies Diseases of multiple peripheral nerves simultaneously. Polyneuropathies usually are characterized by symmetrical, bilateral distal motor and sensory impairment with a graded increase in severity distally. The pathological processes affecting peripheral nerves include degeneration of the axon, myelin or both. The various forms of polyneuropathy are categorized by the type of nerve affected (e.g., sensory, motor, or autonomic), by the distribution of nerve injury (e.g., distal vs. proximal), by nerve component primarily affected (e.g., demyelinating vs. axonal), by etiology, or by pattern of inheritance. | 0 | 5.13 | 3 | 1 |
| Acute Kidney Failure [description not available] | 0 | 2.15 | 1 | 0 |
| Colitis, Granulomatous [description not available] | 0 | 2.53 | 2 | 0 |
| Kidney Stones [description not available] | 0 | 2.15 | 1 | 0 |
| Crohn Disease A chronic transmural inflammation that may involve any part of the DIGESTIVE TRACT from MOUTH to ANUS, mostly found in the ILEUM, the CECUM, and the COLON. In Crohn disease, the inflammation, extending through the intestinal wall from the MUCOSA to the serosa, is characteristically asymmetric and segmental. Epithelioid GRANULOMAS may be seen in some patients. | 0 | 2.53 | 2 | 0 |
| Kidney Calculi Stones in the KIDNEY, usually formed in the urine-collecting area of the kidney (KIDNEY PELVIS). Their sizes vary and most contains CALCIUM OXALATE. | 0 | 2.15 | 1 | 0 |
| Acute Kidney Injury Abrupt reduction in kidney function. Acute kidney injury encompasses the entire spectrum of the syndrome including acute kidney failure; ACUTE KIDNEY TUBULAR NECROSIS; and other less severe conditions. | 0 | 2.15 | 1 | 0 |
| Weight Reduction [description not available] | 0 | 5.53 | 5 | 1 |
| Weight Loss Decrease in existing BODY WEIGHT. | 0 | 5.53 | 5 | 1 |
| Gastric Diseases [description not available] | 0 | 2.15 | 1 | 0 |
| Amino Acid Metabolism Disorders, Inborn [description not available] | 0 | 2.15 | 1 | 0 |
| Infusion Site Adverse Event [description not available] | 0 | 2.15 | 1 | 0 |
| Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. | 0 | 2.15 | 1 | 0 |
| Pain, Chronic [description not available] | 0 | 2.17 | 1 | 0 |
| Nerve Pain [description not available] | 0 | 2.17 | 1 | 0 |
| Neuralgia Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve. | 0 | 2.17 | 1 | 0 |
| Chronic Pain Aching sensation that persists for more than a few months. It may or may not be associated with trauma or disease, and may persist after the initial injury has healed. Its localization, character, and timing are more vague than with acute pain. | 0 | 2.17 | 1 | 0 |
| Dengue Hemorrhagic Fever [description not available] | 0 | 2.15 | 1 | 0 |
| Encephalitis Lethargica Type Parkinsonism [description not available] | 0 | 2.4 | 2 | 0 |
| Parkinson Disease, Postencephalitic Parkinsonism following encephalitis, historically seen as a sequella of encephalitis lethargica (Von Economo Encephalitis). The early age of onset, the rapid progression of symptoms followed by stabilization, and the presence of a variety of other neurological disorders (e.g., sociopathic behavior; TICS; MUSCLE SPASMS; oculogyric crises; hyperphagia; and bizarre movements) distinguish this condition from primary PARKINSON DISEASE. Pathologic features include neuronal loss and gliosis concentrated in the MESENCEPHALON; SUBTHALAMUS; and HYPOTHALAMUS. (From Adams et al., Principles of Neurology, 6th ed, p754) | 0 | 2.4 | 2 | 0 |
| Severe Dengue A virulent form of dengue characterized by THROMBOCYTOPENIA and an increase in vascular permeability (grades I and II) and distinguished by a positive pain test (e.g., TOURNIQUET PAIN TEST). When accompanied by SHOCK (grades III and IV), it is called dengue shock syndrome. | 0 | 2.15 | 1 | 0 |
| Basal Ganglia Diseases Diseases of the BASAL GANGLIA including the PUTAMEN; GLOBUS PALLIDUS; claustrum; AMYGDALA; and CAUDATE NUCLEUS. DYSKINESIAS (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include CEREBROVASCULAR DISORDERS; NEURODEGENERATIVE DISEASES; and CRANIOCEREBRAL TRAUMA. | 0 | 4.33 | 4 | 1 |
| Dystonia An attitude or posture due to the co-contraction of agonists and antagonist muscles in one region of the body. It most often affects the large axial muscles of the trunk and limb girdles. Conditions which feature persistent or recurrent episodes of dystonia as a primary manifestation of disease are referred to as DYSTONIC DISORDERS. (Adams et al., Principles of Neurology, 6th ed, p77) | 0 | 4.88 | 13 | 0 |
| Inborn Errors of Metabolism [description not available] | 0 | 2.54 | 2 | 0 |
| Absence Seizure [description not available] | 0 | 2.52 | 2 | 0 |
| Metabolism, Inborn Errors Errors in metabolic processes resulting from inborn genetic mutations that are inherited or acquired in utero. | 0 | 2.54 | 2 | 0 |
| Seizures Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or seizure disorder. | 0 | 2.52 | 2 | 0 |
| Deficiency, Mental [description not available] | 0 | 2.17 | 1 | 0 |
| Symptom Cluster [description not available] | 0 | 3.29 | 6 | 0 |
| Intellectual Disability Subnormal intellectual functioning which originates during the developmental period. This has multiple potential etiologies, including genetic defects and perinatal insults. Intelligence quotient (IQ) scores are commonly used to determine whether an individual has an intellectual disability. IQ scores between 70 and 79 are in the borderline range. Scores below 67 are in the disabled range. (from Joynt, Clinical Neurology, 1992, Ch55, p28) | 0 | 2.17 | 1 | 0 |
| Syndrome A characteristic symptom complex. | 0 | 3.29 | 6 | 0 |
| Esophageal Hernia [description not available] | 0 | 2.17 | 1 | 0 |
| Disruptive, Impulse Control, and Conduct Disorders Disorders whose essential features are the failure to resist an impulse, drive, or temptation to perform an act that is harmful to the individual or to others. Individuals experience an increased sense of tension prior to the act and pleasure, gratification or release of tension at the time of committing the act. | 0 | 5.37 | 4 | 1 |
| Intestinal Volvulus A twisting in the intestine (INTESTINES) that can cause INTESTINAL OBSTRUCTION. | 0 | 2.17 | 1 | 0 |
| Bezoars Concretions of swallowed hair, fruit or vegetable fibers, or similar substances found in the alimentary canal. | 0 | 3.22 | 5 | 0 |
| Acute Cholecystitis [description not available] | 0 | 2.17 | 1 | 0 |
| Biliary Calculi [description not available] | 0 | 2.17 | 1 | 0 |
| Cholecystitis, Acute Acute inflammation of the GALLBLADDER wall. It is characterized by the presence of ABDOMINAL PAIN; FEVER; and LEUKOCYTOSIS. Gallstone obstruction of the CYSTIC DUCT is present in approximately 90% of the cases. | 0 | 2.17 | 1 | 0 |
| Gallstones Solid crystalline precipitates in the BILIARY TRACT, usually formed in the GALLBLADDER, resulting in the condition of CHOLELITHIASIS. Gallstones, derived from the BILE, consist mainly of calcium, cholesterol, or bilirubin. | 0 | 2.17 | 1 | 0 |
| Amblyopia, Developmental [description not available] | 0 | 5.53 | 3 | 1 |
| Amblyopia A nonspecific term referring to impaired vision. Major subcategories include stimulus deprivation-induced amblyopia and toxic amblyopia. Stimulus deprivation-induced amblyopia is a developmental disorder of the visual cortex. A discrepancy between visual information received by the visual cortex from each eye results in abnormal cortical development. STRABISMUS and REFRACTIVE ERRORS may cause this condition. Toxic amblyopia is a disorder of the OPTIC NERVE which is associated with ALCOHOLISM, tobacco SMOKING, and other toxins and as an adverse effect of the use of some medications. | 0 | 5.53 | 3 | 1 |
| Dermatitis, Contact, Phototoxic [description not available] | 0 | 2.17 | 1 | 0 |
| Excessive Periodic Sleep-Related Leg Movements [description not available] | 0 | 2.46 | 2 | 0 |
| Aging The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time. | 0 | 5.21 | 4 | 1 |
| Ache [description not available] | 0 | 3.8 | 2 | 1 |
| Pain An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS. | 0 | 3.8 | 2 | 1 |
| Curling Ulcer Acute stress DUODENAL ULCER, usually observed in patients with extensive third-degree burns. | 0 | 3.34 | 6 | 0 |
| Duodenal Ulcer A PEPTIC ULCER located in the DUODENUM. | 0 | 3.34 | 6 | 0 |
| Exanthem [description not available] | 0 | 2.17 | 1 | 0 |
| Exanthema Diseases in which skin eruptions or rashes are a prominent manifestation. Classically, six such diseases were described with similar rashes; they were numbered in the order in which they were reported. Only the fourth (Duke's disease), fifth (ERYTHEMA INFECTIOSUM), and sixth (EXANTHEMA SUBITUM) numeric designations survive as occasional synonyms in current terminology. | 0 | 2.17 | 1 | 0 |
| Gastrointestinal Stromal Neoplasm [description not available] | 0 | 2.17 | 1 | 0 |
| Cancer of Liver [description not available] | 0 | 2.17 | 1 | 0 |
| Cancer of Stomach [description not available] | 0 | 2.17 | 1 | 0 |
| Liver Neoplasms Tumors or cancer of the LIVER. | 0 | 2.17 | 1 | 0 |
| Stomach Neoplasms Tumors or cancer of the STOMACH. | 0 | 2.17 | 1 | 0 |
| Gastrointestinal Stromal Tumors All tumors in the GASTROINTESTINAL TRACT arising from mesenchymal cells (MESODERM) except those of smooth muscle cells (LEIOMYOMA) or Schwann cells (SCHWANNOMA). | 0 | 2.17 | 1 | 0 |
| Deficiency, Pyridoxine [description not available] | 0 | 2.52 | 2 | 0 |
| Hypotension, Postural [description not available] | 0 | 2.41 | 2 | 0 |
| Hypotension, Orthostatic A significant drop in BLOOD PRESSURE after assuming a standing position. Orthostatic hypotension is a finding, and defined as a 20-mm Hg decrease in systolic pressure or a 10-mm Hg decrease in diastolic pressure 3 minutes after the person has risen from supine to standing. Symptoms generally include DIZZINESS, blurred vision, and SYNCOPE. | 0 | 2.41 | 2 | 0 |
| Hypoventilation A reduction in the amount of air entering the pulmonary alveoli. | 0 | 2.21 | 1 | 0 |
| Depression Depressive states usually of moderate intensity in contrast with MAJOR DEPRESSIVE DISORDER present in neurotic and psychotic disorders. | 0 | 2.94 | 4 | 0 |
| Apoplexy [description not available] | 0 | 5.15 | 3 | 1 |
| Stroke A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810) | 0 | 5.15 | 3 | 1 |
| Encephalopathy, Traumatic [description not available] | 0 | 2.21 | 1 | 0 |
| Affective Psychosis, Bipolar [description not available] | 0 | 2.74 | 3 | 0 |
| Brain Injuries, Traumatic A form of acquired brain injury which occurs when a sudden trauma causes damage to the brain. | 0 | 2.21 | 1 | 0 |
| Bipolar Disorder A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence. | 0 | 2.74 | 3 | 0 |
| Primary Peritonitis [description not available] | 0 | 2.21 | 1 | 0 |
| Dermatoses [description not available] | 0 | 2.21 | 1 | 0 |
| Intestinal Perforation Opening or penetration through the wall of the INTESTINES. | 0 | 2.21 | 1 | 0 |
| Duodenal Diseases Pathological conditions in the DUODENUM region of the small intestine (INTESTINE, SMALL). | 0 | 2.21 | 1 | 0 |
| Peritonitis INFLAMMATION of the PERITONEUM lining the ABDOMINAL CAVITY as the result of infectious, autoimmune, or chemical processes. Primary peritonitis is due to infection of the PERITONEAL CAVITY via hematogenous or lymphatic spread and without intra-abdominal source. Secondary peritonitis arises from the ABDOMINAL CAVITY itself through RUPTURE or ABSCESS of intra-abdominal organs. | 0 | 2.21 | 1 | 0 |
| Skin Diseases Diseases involving the DERMIS or EPIDERMIS. | 0 | 2.21 | 1 | 0 |
| Infectious Skin Diseases [description not available] | 0 | 2.21 | 1 | 0 |
| Skin Diseases, Infectious Skin diseases caused by bacteria, fungi, parasites, or viruses. | 0 | 2.21 | 1 | 0 |
| Central Pontine Myelinolysis [description not available] | 0 | 2.81 | 3 | 0 |
| Adenoma, Basal Cell [description not available] | 0 | 2.21 | 1 | 0 |
| Cancer of Pituitary [description not available] | 0 | 2.21 | 1 | 0 |
| Adenoma A benign epithelial tumor with a glandular organization. | 0 | 2.21 | 1 | 0 |
| Hyponatremia Deficiency of sodium in the blood; salt depletion. (Dorland, 27th ed) | 0 | 2.94 | 4 | 0 |
| Pituitary Neoplasms Neoplasms which arise from or metastasize to the PITUITARY GLAND. The majority of pituitary neoplasms are adenomas, which are divided into non-secreting and secreting forms. Hormone producing forms are further classified by the type of hormone they secrete. Pituitary adenomas may also be characterized by their staining properties (see ADENOMA, BASOPHIL; ADENOMA, ACIDOPHIL; and ADENOMA, CHROMOPHOBE). Pituitary tumors may compress adjacent structures, including the HYPOTHALAMUS, several CRANIAL NERVES, and the OPTIC CHIASM. Chiasmal compression may result in bitemporal HEMIANOPSIA. | 0 | 2.21 | 1 | 0 |
| Pyrexia [description not available] | 0 | 2.41 | 2 | 0 |
| Hyperactivity, Motor [description not available] | 0 | 2.21 | 1 | 0 |
| Fever An abnormal elevation of body temperature, usually as a result of a pathologic process. | 0 | 2.41 | 2 | 0 |
| Chemical Dependence [description not available] | 0 | 2.9 | 4 | 0 |
| Substance-Related Disorders Disorders related to substance use or abuse. | 0 | 2.9 | 4 | 0 |
| Brain Hemorrhage [description not available] | 0 | 3.94 | 2 | 1 |
| Cerebral Ischemia [description not available] | 0 | 3.83 | 2 | 1 |
| Ambulation Difficulty [description not available] | 0 | 3.59 | 1 | 1 |
| Brain Ischemia Localized reduction of blood flow to brain tissue due to arterial obstruction or systemic hypoperfusion. This frequently occurs in conjunction with brain hypoxia (HYPOXIA, BRAIN). Prolonged ischemia is associated with BRAIN INFARCTION. | 0 | 3.83 | 2 | 1 |
| Intracranial Hemorrhages Bleeding within the SKULL, including hemorrhages in the brain and the three membranes of MENINGES. The escape of blood often leads to the formation of HEMATOMA in the cranial epidural, subdural, and subarachnoid spaces. | 0 | 3.94 | 2 | 1 |
| Depression, Involutional Form of depression in those MIDDLE AGE with feelings of ANXIETY. | 0 | 6.51 | 3 | 2 |
| Depressive Disorder, Major Disorder in which five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure. Symptoms include: depressed mood most of the day, nearly every daily; markedly diminished interest or pleasure in activities most of the day, nearly every day; significant weight loss when not dieting or weight gain; Insomnia or hypersomnia nearly every day; psychomotor agitation or retardation nearly every day; fatigue or loss of energy nearly every day; feelings of worthlessness or excessive or inappropriate guilt; diminished ability to think or concentrate, or indecisiveness, nearly every day; or recurrent thoughts of death, recurrent suicidal ideation without a specific plan, or a suicide attempt. (DSM-5) | 0 | 6.51 | 3 | 2 |
| Adult Spinal Muscular Atrophy [description not available] | 0 | 2.21 | 1 | 0 |
| Spinal Curvatures Deformities of the SPINE characterized by abnormal bending or flexure in the vertebral column. They may be bending forward (KYPHOSIS), backward (LORDOSIS), or sideway (SCOLIOSIS). | 0 | 2.21 | 1 | 0 |
| Muscular Atrophy, Spinal A group of disorders marked by progressive degeneration of motor neurons in the spinal cord resulting in weakness and muscular atrophy, usually without evidence of injury to the corticospinal tracts. Diseases in this category include Werdnig-Hoffmann disease and later onset SPINAL MUSCULAR ATROPHIES OF CHILDHOOD, most of which are hereditary. (Adams et al., Principles of Neurology, 6th ed, p1089) | 0 | 2.21 | 1 | 0 |
| Developmental Coordination Disorder [description not available] | 0 | 5.62 | 3 | 2 |
| Mydriasis Dilation of pupils to greater than 6 mm combined with failure of the pupils to constrict when stimulated with light. This condition may occur due to injury of the pupillary fibers in the oculomotor nerve, in acute angle-closure glaucoma, and in ADIE SYNDROME. | 0 | 2.08 | 1 | 0 |
| Ectopic Ossification [description not available] | 0 | 2.08 | 1 | 0 |
| Radius Fractures Fractures of the RADIUS. | 0 | 2.08 | 1 | 0 |
| Deficiency, Vitamin B 12 [description not available] | 0 | 3.48 | 1 | 1 |
| Vitamin B 12 Deficiency A nutritional condition produced by a deficiency of VITAMIN B 12 in the diet, characterized by megaloblastic anemia. Since vitamin B 12 is not present in plants, humans have obtained their supply from animal products, from multivitamin supplements in the form of pills, and as additives to food preparations. A wide variety of neuropsychiatric abnormalities is also seen in vitamin B 12 deficiency and appears to be due to an undefined defect involving myelin synthesis. (From Cecil Textbook of Medicine, 19th ed, p848) | 0 | 3.48 | 1 | 1 |
| Acute Autoimmune Neuropathy [description not available] | 0 | 2.1 | 1 | 0 |
| Guillain-Barre Syndrome An acute inflammatory autoimmune neuritis caused by T cell- mediated cellular immune response directed towards peripheral myelin. Demyelination occurs in peripheral nerves and nerve roots. The process is often preceded by a viral or bacterial infection, surgery, immunization, lymphoma, or exposure to toxins. Common clinical manifestations include progressive weakness, loss of sensation, and loss of deep tendon reflexes. Weakness of respiratory muscles and autonomic dysfunction may occur. (From Adams et al., Principles of Neurology, 6th ed, pp1312-1314) | 0 | 2.1 | 1 | 0 |
| Restless Leg Syndrome [description not available] | 0 | 5.92 | 9 | 1 |
| Restless Legs Syndrome A disorder characterized by aching or burning sensations in the lower and rarely the upper extremities that occur prior to sleep or may awaken the patient from sleep. | 0 | 5.92 | 9 | 1 |
| Anhedonia Inability to experience pleasure due to impairment or dysfunction of normal psychological and neurobiological mechanisms. It is a symptom of many PSYCHOTIC DISORDERS (e.g., DEPRESSIVE DISORDER, MAJOR; and SCHIZOPHRENIA). | 0 | 2.51 | 2 | 0 |
| Behavior Disorders [description not available] | 0 | 2.48 | 2 | 0 |
| Cognition Disorders Disorders characterized by disturbances in mental processes related to learning, thinking, reasoning, and judgment. | 0 | 3.41 | 7 | 0 |
| Mental Disorders Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. | 0 | 2.48 | 2 | 0 |
| Cerebral Palsy, Athetoid [description not available] | 0 | 4.3 | 4 | 1 |
| Developmental Psychomotor Disorders [description not available] | 0 | 2.74 | 3 | 0 |
| Cerebral Palsy A heterogeneous group of nonprogressive motor disorders caused by chronic brain injuries that originate in the prenatal period, perinatal period, or first few years of life. The four major subtypes are spastic, athetoid, ataxic, and mixed cerebral palsy, with spastic forms being the most common. The motor disorder may range from difficulties with fine motor control to severe spasticity (see MUSCLE SPASTICITY) in all limbs. Spastic diplegia (Little disease) is the most common subtype, and is characterized by spasticity that is more prominent in the legs than in the arms. Pathologically, this condition may be associated with LEUKOMALACIA, PERIVENTRICULAR. (From Dev Med Child Neurol 1998 Aug;40(8):520-7) | 0 | 4.3 | 4 | 1 |
| Autosomal Dominant Hereditary Spastic Paraplegia [description not available] | 0 | 3.01 | 1 | 0 |
| Spastic Paraplegia, Hereditary A group of inherited diseases that share similar phenotypes but are genetically diverse. Different genetic loci for autosomal recessive, autosomal dominant, and x-linked forms of hereditary spastic paraplegia have been identified. Clinically, patients present with slowly progressive distal limb weakness and lower extremity spasticity. Peripheral sensory neurons may be affected in the later stages of the disease. (J Neurol Neurosurg Psychiatry 1998 Jan;64(1):61-6; Curr Opin Neurol 1997 Aug;10(4):313-8) | 0 | 3.01 | 1 | 0 |
| Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with ANXIETY DISORDERS. | 0 | 4.38 | 4 | 1 |
| Scoliosis An appreciable lateral deviation in the normally straight vertical line of the spine. (Dorland, 27th ed) | 0 | 2.1 | 1 | 0 |
| Serotonin Syndrome An adverse drug interaction characterized by altered mental status, autonomic dysfunction, and neuromuscular abnormalities. It is most frequently caused by use of both serotonin reuptake inhibitors and monoamine oxidase inhibitors, leading to excess serotonin availability in the CNS at the serotonin 1A receptor. | 0 | 3.67 | 3 | 0 |
| Apnea, Obstructive Sleep [description not available] | 0 | 3.51 | 1 | 1 |
| Sleep Apnea, Obstructive A disorder characterized by recurrent apneas during sleep despite persistent respiratory efforts. It is due to upper airway obstruction. The respiratory pauses may induce HYPERCAPNIA or HYPOXIA. Cardiac arrhythmias and elevation of systemic and pulmonary arterial pressures may occur. Frequent partial arousals occur throughout sleep, resulting in relative SLEEP DEPRIVATION and daytime tiredness. Associated conditions include OBESITY; ACROMEGALY; MYXEDEMA; micrognathia; MYOTONIC DYSTROPHY; adenotonsilar dystrophy; and NEUROMUSCULAR DISEASES. (From Adams et al., Principles of Neurology, 6th ed, p395) | 0 | 3.51 | 1 | 1 |
| Drug Withdrawal Symptoms [description not available] | 0 | 3.38 | 7 | 0 |
| Substance Withdrawal Syndrome Physiological and psychological symptoms associated with withdrawal from the use of a drug after prolonged administration or habituation. The concept includes withdrawal from smoking or drinking, as well as withdrawal from an administered drug. | 0 | 3.38 | 7 | 0 |
| Dissociation [description not available] | 0 | 2.11 | 1 | 0 |
| Chorea Disorders [description not available] | 0 | 3.1 | 5 | 0 |
| Catatonic Rigidity [description not available] | 0 | 6.35 | 11 | 4 |
| Chorea Involuntary, forcible, rapid, jerky movements that may be subtle or become confluent, markedly altering normal patterns of movement. Hypotonia and pendular reflexes are often associated. Conditions which feature recurrent or persistent episodes of chorea as a primary manifestation of disease are referred to as CHOREATIC DISORDERS. Chorea is also a frequent manifestation of BASAL GANGLIA DISEASES. | 0 | 3.1 | 5 | 0 |
| Muscle Rigidity Continuous involuntary sustained muscle contraction which is often a manifestation of BASAL GANGLIA DISEASES. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from MUSCLE SPASTICITY. (From Adams et al., Principles of Neurology, 6th ed, p73) | 0 | 6.35 | 11 | 4 |
| Dyskinesia Syndromes [description not available] | 0 | 7.72 | 18 | 4 |
| Movement Disorders Syndromes which feature DYSKINESIAS as a cardinal manifestation of the disease process. Included in this category are degenerative, hereditary, post-infectious, medication-induced, post-inflammatory, and post-traumatic conditions. | 0 | 7.72 | 18 | 4 |
| Anasarca [description not available] | 0 | 2.13 | 1 | 0 |
| Edema Abnormal fluid accumulation in TISSUES or body cavities. Most cases of edema are present under the SKIN in SUBCUTANEOUS TISSUE. | 0 | 2.13 | 1 | 0 |
| Acquired Communication Disorders [description not available] | 0 | 2.13 | 1 | 0 |
| Communication Disorders Disorders of verbal and nonverbal communication caused by receptive or expressive LANGUAGE DISORDERS, cognitive dysfunction (e.g., MENTAL RETARDATION), psychiatric conditions, and HEARING DISORDERS. | 0 | 2.13 | 1 | 0 |
| Diseases in Twins Disorders affecting TWINS, one or both, at any age. | 0 | 2.13 | 1 | 0 |
| Emergencies Situations or conditions requiring immediate intervention to avoid serious adverse results. | 0 | 2.15 | 1 | 0 |
| Abnormal Deep Tendon Reflex [description not available] | 0 | 2.13 | 1 | 0 |
| Reflex, Abnormal An abnormal response to a stimulus applied to the sensory components of the nervous system. This may take the form of increased, decreased, or absent reflexes. | 0 | 2.13 | 1 | 0 |
| Jejunal Diseases Pathological development in the JEJUNUM region of the SMALL INTESTINE. | 0 | 2.13 | 1 | 0 |
| Degenerative Diseases, Central Nervous System [description not available] | 0 | 2.15 | 1 | 0 |
| Calcification, Pathologic [description not available] | 0 | 2.15 | 1 | 0 |
| Calcinosis Pathologic deposition of calcium salts in tissues. | 0 | 2.15 | 1 | 0 |
| Neurodegenerative Diseases Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures. | 0 | 2.15 | 1 | 0 |
| Disbacteriosis [description not available] | 0 | 3.06 | 1 | 0 |
| Dysautonomia [description not available] | 0 | 2.15 | 1 | 0 |
| Blood Pressure, High [description not available] | 0 | 5.21 | 4 | 1 |
| Hypertension Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more. | 0 | 5.21 | 4 | 1 |
| Athetoid Movements [description not available] | 0 | 2.4 | 2 | 0 |
| Hemorrhage, Subarachnoid [description not available] | 0 | 2.05 | 1 | 0 |
| Subarachnoid Hemorrhage Bleeding into the intracranial or spinal SUBARACHNOID SPACE, most resulting from INTRACRANIAL ANEURYSM rupture. It can occur after traumatic injuries (SUBARACHNOID HEMORRHAGE, TRAUMATIC). Clinical features include HEADACHE; NAUSEA; VOMITING, nuchal rigidity, variable neurological deficits and reduced mental status. | 0 | 2.05 | 1 | 0 |
| Deficiency Diseases A condition produced by dietary or metabolic deficiency. The term includes all diseases caused by an insufficient supply of essential nutrients, i.e., protein (or amino acids), vitamins, and minerals. It also includes an inadequacy of calories. (From Dorland, 27th ed; Stedman, 25th ed) | 0 | 2.06 | 1 | 0 |
| BH4 Deficiency [description not available] | 0 | 2.42 | 2 | 0 |
| Phenylketonurias A group of autosomal recessive disorders marked by a deficiency of the hepatic enzyme PHENYLALANINE HYDROXYLASE or less frequently by reduced activity of DIHYDROPTERIDINE REDUCTASE (i.e., atypical phenylketonuria). Classical phenylketonuria is caused by a severe deficiency of phenylalanine hydroxylase and presents in infancy with developmental delay; SEIZURES; skin HYPOPIGMENTATION; ECZEMA; and demyelination in the central nervous system. (From Adams et al., Principles of Neurology, 6th ed, p952). | 0 | 2.42 | 2 | 0 |
| Tauopathies Neurodegenerative disorders involving deposition of abnormal tau protein isoforms (TAU PROTEINS) in neurons and glial cells in the brain. Pathological aggregations of tau proteins are associated with mutation of the tau gene on chromosome 17 in patients with ALZHEIMER DISEASE; DEMENTIA; PARKINSONIAN DISORDERS; progressive supranuclear palsy (SUPRANUCLEAR PALSY, PROGRESSIVE); and corticobasal degeneration. | 0 | 2.06 | 1 | 0 |
| Hyperhomocysteinemia Condition in which the plasma levels of homocysteine and related metabolites are elevated ( | 0 | 3.45 | 1 | 1 |
| Atrophy Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. | 0 | 4.09 | 3 | 1 |
| Hypertrichosis Excessive hair growth at inappropriate locations, such as on the extremities, the head, and the back. It is caused by genetic or acquired factors, and is an androgen-independent process. This concept does not include HIRSUTISM which is an androgen-dependent excess hair growth in WOMEN and CHILDREN. | 0 | 2.06 | 1 | 0 |
| Respiration Disorders Diseases of the respiratory system in general or unspecified or for a specific respiratory disease not available. | 0 | 2.06 | 1 | 0 |
| Hallucination of Body Sensation [description not available] | 0 | 3.38 | 7 | 0 |
| Hallucinations Subjectively experienced sensations in the absence of an appropriate stimulus, but which are regarded by the individual as real. They may be of organic origin or associated with MENTAL DISORDERS. | 0 | 3.38 | 7 | 0 |
| Multiple System Atrophy Syndrome [description not available] | 0 | 2.43 | 2 | 0 |
| Multiple System Atrophy A syndrome complex composed of three conditions which represent clinical variants of the same disease process: STRIATONIGRAL DEGENERATION; SHY-DRAGER SYNDROME; and the sporadic form of OLIVOPONTOCEREBELLAR ATROPHIES. Clinical features include autonomic, cerebellar, and basal ganglia dysfunction. Pathologic examination reveals atrophy of the basal ganglia, cerebellum, pons, and medulla, with prominent loss of autonomic neurons in the brain stem and spinal cord. (From Adams et al., Principles of Neurology, 6th ed, p1076; Baillieres Clin Neurol 1997 Apr;6(1):187-204; Med Clin North Am 1999 Mar;83(2):381-92) | 0 | 2.43 | 2 | 0 |
| Bone Fractures [description not available] | 0 | 2.06 | 1 | 0 |
| Anesthesia Awareness [description not available] | 0 | 2.06 | 1 | 0 |
| Anesthesia A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. | 0 | 2.06 | 1 | 0 |
| Fractures, Bone Breaks in bones. | 0 | 2.06 | 1 | 0 |
| Burning Mouth Syndrome A group of painful oral symptoms associated with a burning or similar sensation. There is usually a significant organic component with a degree of functional overlay; it is not limited to the psychophysiologic group of disorders. | 0 | 2.07 | 1 | 0 |
| Gambling, Pathologic [description not available] | 0 | 2.47 | 2 | 0 |
| Gambling An activity distinguished primarily by an element of risk in trying to obtain a desired goal, e.g., playing a game of chance for money. | 0 | 2.47 | 2 | 0 |
| Encephalopathy, Toxic [description not available] | 0 | 2.07 | 1 | 0 |
| Aggression Behavior which may be manifested by destructive and attacking action which is verbal or physical, by covert attitudes of hostility or by obstructionism. | 0 | 2.07 | 1 | 0 |
| Aprosodia [description not available] | 0 | 2.07 | 1 | 0 |
| Acathisia, Drug-Induced [description not available] | 0 | 2.42 | 2 | 0 |
| Acute Disease Disease having a short and relatively severe course. | 0 | 2.68 | 3 | 0 |
| Cholera Infantum [description not available] | 0 | 2.07 | 1 | 0 |
| Brachial Paresis [description not available] | 0 | 3.47 | 1 | 1 |
| Antidiuretic Hormone, Inappropriate Secretion [description not available] | 0 | 3.46 | 1 | 1 |
| Inappropriate ADH Syndrome A condition of HYPONATREMIA and renal salt loss attributed to overexpansion of BODY FLUIDS resulting from sustained release of ANTIDIURETIC HORMONES which stimulates renal resorption of water. It is characterized by normal KIDNEY function, high urine OSMOLALITY, low serum osmolality, and neurological dysfunction. Etiologies include ADH-producing neoplasms, injuries or diseases involving the HYPOTHALAMUS, the PITUITARY GLAND, and the LUNG. This syndrome can also be drug-induced. | 0 | 3.46 | 1 | 1 |
| Benign Essential Tremor [description not available] | 0 | 2.01 | 1 | 0 |
| Essential Tremor A relatively common disorder characterized by a fairly specific pattern of tremors which are most prominent in the upper extremities and neck, inducing titubations of the head. The tremor is usually mild, but when severe may be disabling. An autosomal dominant pattern of inheritance may occur in some families (i.e., familial tremor). (Mov Disord 1988;13(1):5-10) | 0 | 2.01 | 1 | 0 |
| Muscular Weakness [description not available] | 0 | 3.33 | 2 | 0 |
| Muscle Weakness A vague complaint of debility, fatigue, or exhaustion attributable to weakness of various muscles. The weakness can be characterized as subacute or chronic, often progressive, and is a manifestation of many muscle and neuromuscular diseases. (From Wyngaarden et al., Cecil Textbook of Medicine, 19th ed, p2251) | 0 | 3.33 | 2 | 0 |
| Stammering [description not available] | 0 | 2.01 | 1 | 0 |
| Stuttering A disturbance in the normal fluency and time patterning of speech that is inappropriate for the individual's age. This disturbance is characterized by frequent repetitions or prolongations of sounds or syllables. Various other types of speech dysfluencies may also be involved including interjections, broken words, audible or silent blocking, circumlocutions, words produced with an excess of physical tension, and monosyllabic whole word repetitions. Stuttering may occur as a developmental condition in childhood or as an acquired disorder which may be associated with BRAIN INFARCTIONS and other BRAIN DISEASES. (From DSM-IV, 1994) | 0 | 2.01 | 1 | 0 |
| Cleft Spine [description not available] | 0 | 2.02 | 1 | 0 |
| Low Back Ache [description not available] | 0 | 2.02 | 1 | 0 |
| Low Back Pain Acute or chronic pain in the lumbar or sacral regions, which may be associated with musculo-ligamentous SPRAINS AND STRAINS; INTERVERTEBRAL DISK DISPLACEMENT; and other conditions. | 0 | 2.02 | 1 | 0 |
| Chronic Illness [description not available] | 0 | 4.28 | 4 | 1 |
| Chronic Disease Diseases which have one or more of the following characteristics: they are permanent, leave residual disability, are caused by nonreversible pathological alteration, require special training of the patient for rehabilitation, or may be expected to require a long period of supervision, observation, or care (Dictionary of Health Services Management, 2d ed). For epidemiological studies chronic disease often includes HEART DISEASES; STROKE; CANCER; and diabetes (DIABETES MELLITUS, TYPE 2). | 0 | 4.28 | 4 | 1 |
| Heart Valve Diseases Pathological conditions involving any of the various HEART VALVES and the associated structures (PAPILLARY MUSCLES and CHORDAE TENDINEAE). | 0 | 2.02 | 1 | 0 |
| Akinetic-Rigid Variant of Huntington Disease [description not available] | 0 | 2.39 | 2 | 0 |
| Huntington Disease A familial disorder inherited as an autosomal dominant trait and characterized by the onset of progressive CHOREA and DEMENTIA in the fourth or fifth decade of life. Common initial manifestations include paranoia; poor impulse control; DEPRESSION; HALLUCINATIONS; and DELUSIONS. Eventually intellectual impairment; loss of fine motor control; ATHETOSIS; and diffuse chorea involving axial and limb musculature develops, leading to a vegetative state within 10-15 years of disease onset. The juvenile variant has a more fulminant course including SEIZURES; ATAXIA; dementia; and chorea. (From Adams et al., Principles of Neurology, 6th ed, pp1060-4) | 0 | 2.39 | 2 | 0 |
| Nerve Degeneration Loss of functional activity and trophic degeneration of nerve axons and their terminal arborizations following the destruction of their cells of origin or interruption of their continuity with these cells. The pathology is characteristic of neurodegenerative diseases. Often the process of nerve degeneration is studied in research on neuroanatomical localization and correlation of the neurophysiology of neural pathways. | 0 | 2.4 | 2 | 0 |
| Manganese Poisoning Manganese poisoning is associated with chronic inhalation of manganese particles by individuals who work with manganese ore. Clinical features include CONFUSION; HALLUCINATIONS; and an extrapyramidal syndrome (PARKINSON DISEASE, SECONDARY) that includes rigidity; DYSTONIA; retropulsion; and TREMOR. (Adams, Principles of Neurology, 6th ed, p1213) | 0 | 2.39 | 2 | 0 |
| Dermatitis Medicamentosa [description not available] | 0 | 2.67 | 3 | 0 |
| Allergy, Drug [description not available] | 0 | 2.03 | 1 | 0 |
| Drug Hypersensitivity Immunologically mediated adverse reactions to medicinal substances used legally or illegally. | 0 | 2.03 | 1 | 0 |
| Chronic Insomnia [description not available] | 0 | 2.39 | 2 | 0 |
| Sleep Initiation and Maintenance Disorders Disorders characterized by impairment of the ability to initiate or maintain sleep. This may occur as a primary disorder or in association with another medical or psychiatric condition. | 0 | 2.39 | 2 | 0 |
| Agitation, Psychomotor [description not available] | 0 | 2.04 | 1 | 0 |
| Psychoses, Drug [description not available] | 0 | 2.9 | 4 | 0 |
| Tachyarrhythmia [description not available] | 0 | 2.04 | 1 | 0 |
| Psychomotor Agitation A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions. | 0 | 2.04 | 1 | 0 |
| Tachycardia Abnormally rapid heartbeat, usually with a HEART RATE above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. | 0 | 2.04 | 1 | 0 |
| Drug Overdose Accidental or deliberate use of a medication or street drug in excess of normal dosage. | 0 | 2.04 | 1 | 0 |
| Atrophy, Muscle [description not available] | 0 | 3.29 | 2 | 0 |
| Muscular Dystrophy [description not available] | 0 | 2.65 | 3 | 0 |
| Muscular Atrophy Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. | 0 | 3.29 | 2 | 0 |
| Muscular Dystrophies A heterogeneous group of inherited MYOPATHIES, characterized by wasting and weakness of the SKELETAL MUSCLE. They are categorized by the sites of MUSCLE WEAKNESS; AGE OF ONSET; and INHERITANCE PATTERNS. | 0 | 2.65 | 3 | 0 |
| Adrenal Cancer [description not available] | 0 | 2.67 | 3 | 0 |
| Pheochromocytoma, Extra-Adrenal [description not available] | 0 | 2.67 | 3 | 0 |
| Pheochromocytoma A usually benign, well-encapsulated, lobular, vascular tumor of chromaffin tissue of the ADRENAL MEDULLA or sympathetic paraganglia. The cardinal symptom, reflecting the increased secretion of EPINEPHRINE and NOREPINEPHRINE, is HYPERTENSION, which may be persistent or intermittent. During severe attacks, there may be HEADACHE; SWEATING, palpitation, apprehension, TREMOR; PALLOR or FLUSHING of the face, NAUSEA and VOMITING, pain in the CHEST and ABDOMEN, and paresthesias of the extremities. The incidence of malignancy is as low as 5% but the pathologic distinction between benign and malignant pheochromocytomas is not clear. (Dorland, 27th ed; DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1298) | 0 | 2.67 | 3 | 0 |
| Childhood Torsion Disease [description not available] | 0 | 4.05 | 3 | 1 |
| Nervous System Disorders [description not available] | 0 | 2.37 | 2 | 0 |
| Neuroses [description not available] | 0 | 1.96 | 1 | 0 |
| Nervous System Diseases Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle. | 0 | 2.37 | 2 | 0 |
| Neurotic Disorders Disorders in which the symptoms are distressing to the individual and recognized by him or her as being unacceptable. Social relationships may be greatly affected but usually remain within acceptable limits. The disturbance is relatively enduring or recurrent without treatment. | 0 | 1.96 | 1 | 0 |
| Blood Pressure, Low [description not available] | 0 | 1.96 | 1 | 0 |
| Hypotension Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients. | 0 | 1.96 | 1 | 0 |
| Amentia [description not available] | 0 | 2.37 | 2 | 0 |
| Dementia An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. | 0 | 2.37 | 2 | 0 |
| Bewilderment [description not available] | 0 | 2.66 | 3 | 0 |
| ADDH [description not available] | 0 | 3.34 | 1 | 1 |
| Attention Deficit Disorder with Hyperactivity A behavior disorder originating in childhood in which the essential features are signs of developmentally inappropriate inattention, impulsivity, and hyperactivity. Although most individuals have symptoms of both inattention and hyperactivity-impulsivity, one or the other pattern may be predominant. The disorder is more frequent in males than females. Onset is in childhood. Symptoms often attenuate during late adolescence although a minority experience the full complement of symptoms into mid-adulthood. (From DSM-V) | 0 | 3.34 | 1 | 1 |
| Muscle Contraction A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. | 0 | 1.96 | 1 | 0 |
| Obesity A status with BODY WEIGHT that is grossly above the recommended standards, usually due to accumulation of excess FATS in the body. The standards may vary with age, sex, genetic or cultural background. In the BODY MASS INDEX, a BMI greater than 30.0 kg/m2 is considered obese, and a BMI greater than 40.0 kg/m2 is considered morbidly obese (MORBID OBESITY). | 0 | 1.95 | 1 | 0 |
| Brain Damage, Chronic A condition characterized by long-standing brain dysfunction or damage, usually of three months duration or longer. Potential etiologies include BRAIN INFARCTION; certain NEURODEGENERATIVE DISORDERS; CRANIOCEREBRAL TRAUMA; ANOXIA, BRAIN; ENCEPHALITIS; certain NEUROTOXICITY SYNDROMES; metabolic disorders (see BRAIN DISEASES, METABOLIC); and other conditions. | 0 | 1.98 | 1 | 0 |
| Closed Head Injuries [description not available] | 0 | 1.98 | 1 | 0 |
| Hemiplegia, Crossed [description not available] | 0 | 2.9 | 1 | 0 |
| Decreased Muscle Tone [description not available] | 0 | 3.32 | 2 | 0 |
| Hemiplegia Severe or complete loss of motor function on one side of the body. This condition is usually caused by BRAIN DISEASES that are localized to the cerebral hemisphere opposite to the side of weakness. Less frequently, BRAIN STEM lesions; cervical SPINAL CORD DISEASES; PERIPHERAL NERVOUS SYSTEM DISEASES; and other conditions may manifest as hemiplegia. The term hemiparesis (see PARESIS) refers to mild to moderate weakness involving one side of the body. | 0 | 2.9 | 1 | 0 |
| Flaccid Quadriplegia [description not available] | 0 | 2.39 | 2 | 0 |
| Psychoses [description not available] | 0 | 1.98 | 1 | 0 |
| Psychotic Disorders Disorders in which there is a loss of ego boundaries or a gross impairment in reality testing with delusions or prominent hallucinations. (From DSM-IV, 1994) | 0 | 1.98 | 1 | 0 |
| Neuroleptic Malignant Syndrome A potentially fatal syndrome associated primarily with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS) which are in turn associated with dopaminergic receptor blockade (see RECEPTORS, DOPAMINE) in the BASAL GANGLIA and HYPOTHALAMUS, and sympathetic dysregulation. Clinical features include diffuse MUSCLE RIGIDITY; TREMOR; high FEVER; diaphoresis; labile blood pressure; cognitive dysfunction; and autonomic disturbances. Serum CPK level elevation and a leukocytosis may also be present. (From Adams et al., Principles of Neurology, 6th ed, p1199; Psychiatr Serv 1998 Sep;49(9):1163-72) | 0 | 3.81 | 4 | 0 |
| Aqueductal Stenosis [description not available] | 0 | 2.38 | 2 | 0 |
| Myoclonic Jerk [description not available] | 0 | 2.67 | 3 | 0 |
| Complications, Pregnancy [description not available] | 0 | 2.4 | 2 | 0 |
| Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. | 0 | 2.4 | 2 | 0 |
| Depression, Endogenous [description not available] | 0 | 3.22 | 6 | 0 |
| Depressive Disorder An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent. | 0 | 3.22 | 6 | 0 |
| Autosomal Dominant Striatonigral Degeneration [description not available] | 0 | 1.99 | 1 | 0 |
| Machado-Joseph Disease A dominantly-inherited ATAXIA first described in people of Azorean and Portuguese descent, and subsequently identified in Brazil, Japan, China, and Australia. This disorder is classified as one of the SPINOCEREBELLAR ATAXIAS (Type 3) and has been associated with a mutation of the MJD1 gene on chromosome 14. Clinical features include progressive ataxia, DYSARTHRIA, postural instability, nystagmus, eyelid retraction, and facial FASCICULATIONS. DYSTONIA is prominent in younger patients (referred to as Type I Machado-Joseph Disease). Type II features ataxia and ocular signs; Type III features MUSCULAR ATROPHY and a sensorimotor neuropathy; and Type IV features extrapyramidal signs combined with a sensorimotor neuropathy. (From Clin Neurosci 1995;3(1):17-22; Ann Neurol 1998 Mar;43(3):288-96) | 0 | 1.99 | 1 | 0 |
| IgA Vasculitis A systemic non-thrombocytopenic purpura caused by HYPERSENSITIVITY VASCULITIS and deposition of IGA-containing IMMUNE COMPLEXES within the blood vessels throughout the body, including those in the kidney (KIDNEY GLOMERULUS). Clinical symptoms include URTICARIA; ERYTHEMA; ARTHRITIS; GASTROINTESTINAL HEMORRHAGE; and renal involvement. Most cases are seen in children after acute upper respiratory infections. | 0 | 1.99 | 1 | 0 |
| Hyperprolactinaemia [description not available] | 0 | 1.99 | 1 | 0 |
| Hyperprolactinemia Increased levels of PROLACTIN in the BLOOD, which may be associated with AMENORRHEA and GALACTORRHEA. Relatively common etiologies include PROLACTINOMA, medication effect, KIDNEY FAILURE, granulomatous diseases of the PITUITARY GLAND, and disorders which interfere with the hypothalamic inhibition of prolactin release. Ectopic (non-pituitary) production of prolactin may also occur. (From Joynt, Clinical Neurology, 1992, Ch36, pp77-8) | 0 | 1.99 | 1 | 0 |
| Central Nervous System Disease [description not available] | 0 | 2.39 | 2 | 0 |
| Central Nervous System Diseases Diseases of any component of the brain (including the cerebral hemispheres, diencephalon, brain stem, and cerebellum) or the spinal cord. | 0 | 2.39 | 2 | 0 |
| Electrolytes Substances that dissociate into two or more ions, to some extent, in water. Solutions of electrolytes thus conduct an electric current and can be decomposed by it (ELECTROLYSIS). (Grant & Hackh's Chemical Dictionary, 5th ed) | 0 | 1.99 | 1 | 0 |
| Anterior Ischemic Optic Neuropathy [description not available] | 0 | 3.39 | 1 | 1 |
| Arterial Inflammation [description not available] | 0 | 3.39 | 1 | 1 |
| Day Blindness [description not available] | 0 | 3.39 | 1 | 1 |
| Optic Neuropathy, Ischemic Ischemic injury to the OPTIC NERVE which usually affects the OPTIC DISK (optic neuropathy, anterior ischemic) and less frequently the retrobulbar portion of the nerve (optic neuropathy, posterior ischemic). The injury results from occlusion of arterial blood supply which may result from TEMPORAL ARTERITIS; ATHEROSCLEROSIS; COLLAGEN DISEASES; EMBOLISM; DIABETES MELLITUS; and other conditions. The disease primarily occurs in the sixth decade or later and presents with the sudden onset of painless and usually severe monocular visual loss. Anterior ischemic optic neuropathy also features optic disk edema with microhemorrhages. The optic disk appears normal in posterior ischemic optic neuropathy. (Glaser, Neuro-Ophthalmology, 2nd ed, p135) | 0 | 3.39 | 1 | 1 |
| Abnormalities, Autosome [description not available] | 0 | 2 | 1 | 0 |
| Autosomal Chromosome Disorders [description not available] | 0 | 2 | 1 | 0 |
| Emesis [description not available] | 0 | 3.34 | 1 | 1 |
| Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. | 0 | 3.34 | 1 | 1 |
| Vomiting The forcible expulsion of the contents of the STOMACH through the MOUTH. | 0 | 3.34 | 1 | 1 |
| Charcot-Marie-Tooth Disease, Demyelinating, Type 4f [description not available] | 0 | 3.36 | 1 | 1 |
| Paranoia [description not available] | 0 | 2.38 | 2 | 0 |
| Hakim Syndrome [description not available] | 0 | 2.38 | 2 | 0 |
| Hydrocephalus, Normal Pressure A form of compensated hydrocephalus characterized clinically by a slowly progressive gait disorder (see GAIT DISORDERS, NEUROLOGIC), progressive intellectual decline, and URINARY INCONTINENCE. Spinal fluid pressure tends to be in the high normal range. This condition may result from processes which interfere with the absorption of CSF including SUBARACHNOID HEMORRHAGE, chronic MENINGITIS, and other conditions. (From Adams et al., Principles of Neurology, 6th ed, pp631-3) | 0 | 2.38 | 2 | 0 |
| Acute Brain Injuries [description not available] | 0 | 1.97 | 1 | 0 |
| Coma A profound state of unconsciousness associated with depressed cerebral activity from which the individual cannot be aroused. Coma generally occurs when there is dysfunction or injury involving both cerebral hemispheres or the brain stem RETICULAR FORMATION. | 0 | 1.97 | 1 | 0 |
| Brain Injuries Acute and chronic (see also BRAIN INJURIES, CHRONIC) injuries to the brain, including the cerebral hemispheres, CEREBELLUM, and BRAIN STEM. Clinical manifestations depend on the nature of injury. Diffuse trauma to the brain is frequently associated with DIFFUSE AXONAL INJURY or COMA, POST-TRAUMATIC. Localized injuries may be associated with NEUROBEHAVIORAL MANIFESTATIONS; HEMIPARESIS, or other focal neurologic deficits. | 0 | 1.97 | 1 | 0 |
| Alogia [description not available] | 0 | 1.97 | 1 | 0 |
| Aphasia A cognitive disorder marked by an impaired ability to comprehend or express language in its written or spoken form. This condition is caused by diseases which affect the language areas of the dominant hemisphere. Clinical features are used to classify the various subtypes of this condition. General categories include receptive, expressive, and mixed forms of aphasia. | 0 | 1.97 | 1 | 0 |
| Anti-MuSK Myasthenia Gravis [description not available] | 0 | 3.36 | 1 | 1 |
| Myasthenia Gravis A disorder of neuromuscular transmission characterized by fatigable weakness of cranial and skeletal muscles with elevated titers of ACETYLCHOLINE RECEPTORS or muscle-specific receptor tyrosine kinase (MuSK) autoantibodies. Clinical manifestations may include ocular muscle weakness (fluctuating, asymmetric, external ophthalmoplegia; diplopia; ptosis; and weakness of eye closure) and extraocular fatigable weakness of facial, bulbar, respiratory, and proximal limb muscles. The disease may remain limited to the ocular muscles (ocular myasthenia). THYMOMA is commonly associated with this condition. | 0 | 3.36 | 1 | 1 |
| Age-Related Memory Disorders [description not available] | 0 | 2.38 | 2 | 0 |
| Memory Disorders Disturbances in registering an impression, in the retention of an acquired impression, or in the recall of an impression. Memory impairments are associated with DEMENTIA; CRANIOCEREBRAL TRAUMA; ENCEPHALITIS; ALCOHOLISM (see also ALCOHOL AMNESTIC DISORDER); SCHIZOPHRENIA; and other conditions. | 0 | 2.38 | 2 | 0 |
| Chondromalacia Softening and degeneration of the CARTILAGE. | 0 | 1.96 | 1 | 0 |
| Incontinentia Pigmenti Achromians [description not available] | 0 | 1.96 | 1 | 0 |
| Cartilage Diseases Pathological processes involving the chondral tissue (CARTILAGE). | 0 | 1.96 | 1 | 0 |
| Palmoplantaris Pustulosis [description not available] | 0 | 1.97 | 1 | 0 |
| Psoriasis A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. | 0 | 1.97 | 1 | 0 |
| Acute Confusional Senile Dementia [description not available] | 0 | 1.97 | 1 | 0 |
| Alzheimer Disease A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57) | 0 | 1.97 | 1 | 0 |
| Bile Duct Obstruction [description not available] | 0 | 1.97 | 1 | 0 |
| Cholestasis Impairment of bile flow due to obstruction in small bile ducts (INTRAHEPATIC CHOLESTASIS) or obstruction in large bile ducts (EXTRAHEPATIC CHOLESTASIS). | 0 | 1.97 | 1 | 0 |
| Affective Disorders [description not available] | 0 | 1.97 | 1 | 0 |
| Mood Disorders Those disorders that have a disturbance in mood as their predominant feature. | 0 | 1.97 | 1 | 0 |
| Leukemia, Myeloid, Acute, M4 [description not available] | 0 | 1.97 | 1 | 0 |
| Leukemia, Myelomonocytic, Acute A pediatric acute myeloid leukemia involving both myeloid and monocytoid precursors. At least 20% of non-erythroid cells are of monocytic origin. | 0 | 1.97 | 1 | 0 |
| Ophthalmoplegia, Progressive Supranuclear [description not available] | 0 | 1.97 | 1 | 0 |
| Supranuclear Palsy, Progressive A degenerative disease of the central nervous system characterized by balance difficulties; OCULAR MOTILITY DISORDERS (supranuclear ophthalmoplegia); DYSARTHRIA; swallowing difficulties; and axial DYSTONIA. Onset is usually in the fifth decade and disease progression occurs over several years. Pathologic findings include neurofibrillary degeneration and neuronal loss in the dorsal MESENCEPHALON; SUBTHALAMIC NUCLEUS; RED NUCLEUS; pallidum; dentate nucleus; and vestibular nuclei. (From Adams et al., Principles of Neurology, 6th ed, pp1076-7) | 0 | 1.97 | 1 | 0 |
| Breathing Sounds [description not available] | 0 | 1.97 | 1 | 0 |
| Respiratory Sounds Noises, normal and abnormal, heard on auscultation over any part of the RESPIRATORY TRACT. | 0 | 1.97 | 1 | 0 |
| Uremia A clinical syndrome associated with the retention of renal waste products or uremic toxins in the blood. It is usually the result of RENAL INSUFFICIENCY. Most uremic toxins are end products of protein or nitrogen CATABOLISM, such as UREA or CREATININE. Severe uremia can lead to multiple organ dysfunctions with a constellation of symptoms. | 0 | 1.97 | 1 | 0 |
| Clasp-Knife Spasticity [description not available] | 0 | 1.96 | 1 | 0 |
| Cervical Dystonia A common form of DYSTONIA due to involuntary sustained or spasmodic, repetitive muscle contractions in the neck region. According to the position of the twisted neck and head, cervical dystonia can be categorized as torticollis, laterocollis, retrocollis, and a combination of these abnormal postures. | 0 | 1.96 | 1 | 0 |
| Muscle Spasticity A form of muscle hypertonia associated with upper MOTOR NEURON DISEASE. Resistance to passive stretch of a spastic muscle results in minimal initial resistance (a free interval) followed by an incremental increase in muscle tone. Tone increases in proportion to the velocity of stretch. Spasticity is usually accompanied by HYPERREFLEXIA and variable degrees of MUSCLE WEAKNESS. (From Adams et al., Principles of Neurology, 6th ed, p54) | 0 | 1.96 | 1 | 0 |
| Torticollis A symptom, not a disease, of a twisted neck. In most instances, the head is tipped toward one side and the chin rotated toward the other. The involuntary muscle contractions in the neck region of patients with torticollis can be due to congenital defects, trauma, inflammation, tumors, and neurological or other factors. | 0 | 1.96 | 1 | 0 |
| Diseases, Occupational [description not available] | 0 | 1.96 | 1 | 0 |
| Anesthesia Related Hyperthermia [description not available] | 0 | 1.96 | 1 | 0 |
| Bone Cancer [description not available] | 0 | 1.96 | 1 | 0 |
| Pain, Intractable Persistent pain that is refractory to some or all forms of treatment. | 0 | 1.96 | 1 | 0 |
| Bone Neoplasms Tumors or cancer located in bone tissue or specific BONES. | 0 | 1.96 | 1 | 0 |
| ANS (Autonomic Nervous System) Diseases [description not available] | 0 | 1.96 | 1 | 0 |
| Autonomic Failure, Progressive [description not available] | 0 | 1.96 | 1 | 0 |
| Cramp [description not available] | 0 | 1.96 | 1 | 0 |
| Muscle Cramp A sustained and usually painful contraction of muscle fibers. This may occur as an isolated phenomenon or as a manifestation of an underlying disease process (e.g., UREMIA; HYPOTHYROIDISM; MOTOR NEURON DISEASE; etc.). (From Adams et al., Principles of Neurology, 6th ed, p1398) | 0 | 1.96 | 1 | 0 |