carbamates has been researched along with Fatigue in 17 studies
Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli.
Excerpt | Relevance | Reference |
---|---|---|
"gov: NCT02786537) was the first comparative effectiveness study to directly compare ledipasvir/sofosbuvir (LDV/SOF) and elbasvir/grazoprevir (EBR/GZR) for the treatment of chronic hepatitis C virus (HCV)." | 9.51 | Sustainable and equivalent improvements in symptoms and functional well-being following viral cure from ledipasvir/sofosbuvir versus elbasvir/grazoprevir for chronic hepatitis C infection: Findings from the randomized PRIORITIZE trial. ( Dong, M; Evon, DM; Lok, AS; Michael, L; Nelson, DR; Peter, J; Reeve, BB; Stewart, PW, 2022) |
"gov: NCT02786537) was the first comparative effectiveness study to directly compare ledipasvir/sofosbuvir (LDV/SOF) and elbasvir/grazoprevir (EBR/GZR) for the treatment of chronic hepatitis C virus (HCV)." | 5.51 | Sustainable and equivalent improvements in symptoms and functional well-being following viral cure from ledipasvir/sofosbuvir versus elbasvir/grazoprevir for chronic hepatitis C infection: Findings from the randomized PRIORITIZE trial. ( Dong, M; Evon, DM; Lok, AS; Michael, L; Nelson, DR; Peter, J; Reeve, BB; Stewart, PW, 2022) |
"Patients with locally advanced, unresectable or metastatic BRAFV600-mutant melanoma were randomised to receive encorafenib 450 mg once daily plus binimetinib 45 mg twice daily, encorafenib 300 mg once daily or vemurafenib 960 mg twice daily." | 5.30 | Adverse events associated with encorafenib plus binimetinib in the COLUMBUS study: incidence, course and management. ( Arance, A; Ascierto, PA; de Groot, JWB; Dummer, R; Dutriaux, C; Flaherty, KT; Garbe, C; Gogas, HJ; Gollerkeri, A; Gutzmer, R; Krajsova, I; Liszkay, G; Loquai, C; Mandala, M; Pickard, MD; Robert, C; Schadendorf, D; Sileni, VC; Yamazaki, N, 2019) |
" However, information about the rate of adverse events (AEs) across different DAA regimens is limited." | 2.87 | Outcome and adverse events in patients with chronic hepatitis C treated with direct-acting antivirals: a clinical randomized study. ( Andersen, ES; Bukh, J; Christensen, PB; Fahnøe, U; Gerstoft, J; Kjær, MS; Laursen, AL; Mössner, B; Pedersen, MS; Røge, BT; Schønning, K; Sølund, C; Weis, N, 2018) |
" We calculated the risk ratio (RR) of ≥50%, ≥75% and 100% reduction in seizure frequency from baseline, as well as dropout and serious adverse events related to treatment." | 2.72 | Efficacy and safety of cenobamate in patients with uncontrolled focal seizures: A meta-analysis. ( Wang, C; Wang, J; Zhang, L, 2021) |
"Few studies have investigated restless legs syndrome (RLS) treatment effects on individual International RLS Study Group Rating Scale (IRLS) items." | 2.53 | Effect of Gabapentin Enacarbil on Individual Items of the International Restless Legs Study Group Rating Scale and Post-sleep Questionnaire in Adults with Moderate-to-Severe Primary Restless Legs Syndrome: Pooled Analysis of 3 Randomized Trials. ( Ahmed, M; Hays, R; Jaros, MJ; Kim, R; Shang, G; Steven Poceta, J, 2016) |
"Only fatigue was reported as side effect during the treatment." | 1.56 | Elbasvir/grazoprevir treatment in an HCV-infected peritoneal dialysis patient. ( Chen, J; Lei, P; Li, G; Li, Y, 2020) |
"HRQoL/fatigue was evaluated at baseline (BL), midway, and 12 weeks after the end of treatment (FU)." | 1.43 | Interferon-free regimens improve health-related quality of life and fatigue in HIV/HCV-coinfected patients with advanced liver disease: A retrospective study. ( Aichelburg, MC; Bucsics, T; Chromy, D; Grabmeier-Pfistershammer, K; Mandorfer, M; Peck-Radosavljevic, M; Reiberger, T; Scheiner, B; Schwabl, P; Steiner, S; Trauner, M, 2016) |
" To examine the potential for drug-drug interactions at these two transporters, the pharmacokinetics of gabapentin enacarbil were evaluated in healthy adults after administration alone or in combination with either naproxen (an MCT-1 substrate) or cimetidine (an OCT2 substrate)." | 1.36 | Clinical pharmacokinetic drug interaction studies of gabapentin enacarbil, a novel transported prodrug of gabapentin, with naproxen and cimetidine. ( Blumenthal, R; Cundy, KC; Ho, J; Lal, R; Luo, W; Sukbuntherng, J; Vicente, V, 2010) |
Timeframe | Studies, this research(%) | All Research% |
---|---|---|
pre-1990 | 0 (0.00) | 18.7374 |
1990's | 0 (0.00) | 18.2507 |
2000's | 0 (0.00) | 29.6817 |
2010's | 14 (82.35) | 24.3611 |
2020's | 3 (17.65) | 2.80 |
Authors | Studies |
---|---|
Evon, DM | 1 |
Dong, M | 1 |
Reeve, BB | 1 |
Peter, J | 1 |
Michael, L | 1 |
Lok, AS | 1 |
Nelson, DR | 1 |
Stewart, PW | 1 |
Gogas, HJ | 1 |
Flaherty, KT | 1 |
Dummer, R | 1 |
Ascierto, PA | 1 |
Arance, A | 1 |
Mandala, M | 1 |
Liszkay, G | 1 |
Garbe, C | 1 |
Schadendorf, D | 1 |
Krajsova, I | 1 |
Gutzmer, R | 1 |
Sileni, VC | 1 |
Dutriaux, C | 1 |
de Groot, JWB | 1 |
Yamazaki, N | 1 |
Loquai, C | 1 |
Gollerkeri, A | 1 |
Pickard, MD | 1 |
Robert, C | 1 |
Cursino, CN | 1 |
Monteiro, PGO | 1 |
Duarte, GDS | 1 |
Vieira, TBQ | 1 |
Crisante, VC | 1 |
Giordani, F | 1 |
Xavier, AR | 1 |
de Almeida, RMVR | 1 |
Calil-Elias, S | 1 |
Chen, J | 1 |
Li, Y | 1 |
Li, G | 1 |
Lei, P | 1 |
Zhang, L | 1 |
Wang, J | 2 |
Wang, C | 1 |
Sølund, C | 1 |
Andersen, ES | 1 |
Mössner, B | 1 |
Laursen, AL | 1 |
Røge, BT | 1 |
Kjær, MS | 1 |
Gerstoft, J | 1 |
Christensen, PB | 1 |
Pedersen, MS | 1 |
Schønning, K | 1 |
Fahnøe, U | 1 |
Bukh, J | 1 |
Weis, N | 1 |
Zignego, AL | 1 |
Monti, M | 1 |
Gragnani, L | 1 |
Lee, YJ | 1 |
Heo, J | 1 |
Kim, DY | 1 |
Chung, WJ | 1 |
Tak, WY | 1 |
Kim, YJ | 1 |
Paik, SW | 1 |
Sim, E | 1 |
Kulasingam, S | 1 |
Talwani, R | 1 |
Haber, B | 1 |
Hwang, P | 1 |
Zeuzem, S | 1 |
Ghalib, R | 1 |
Reddy, KR | 1 |
Pockros, PJ | 1 |
Ben Ari, Z | 1 |
Zhao, Y | 1 |
Brown, DD | 1 |
Wan, S | 1 |
DiNubile, MJ | 1 |
Nguyen, BY | 1 |
Robertson, MN | 1 |
Wahl, J | 1 |
Barr, E | 1 |
Butterton, JR | 1 |
Mangia, A | 1 |
Arleo, A | 1 |
Copetti, M | 1 |
Miscio, M | 1 |
Piazzolla, V | 1 |
Santoro, R | 1 |
Squillante, MM | 1 |
Stern, R | 1 |
Hametner, S | 1 |
Ramona, AZ | 1 |
Moser, S | 1 |
Karpi, A | 1 |
Laferl, H | 1 |
Stauber, RE | 1 |
Zoller, HM | 1 |
Maieron, A | 1 |
Vogel, W | 1 |
Graziadei, I | 1 |
Gschwantler, M | 1 |
Kozbial, K | 1 |
Freissmuth, C | 1 |
Hofer, H | 1 |
Ferenci, P | 1 |
Ahmed, M | 1 |
Hays, R | 1 |
Steven Poceta, J | 1 |
Jaros, MJ | 1 |
Kim, R | 1 |
Shang, G | 1 |
Scheiner, B | 1 |
Schwabl, P | 1 |
Steiner, S | 1 |
Bucsics, T | 1 |
Chromy, D | 1 |
Aichelburg, MC | 1 |
Grabmeier-Pfistershammer, K | 1 |
Trauner, M | 1 |
Peck-Radosavljevic, M | 1 |
Reiberger, T | 1 |
Mandorfer, M | 1 |
Yao, Y | 1 |
Yue, M | 1 |
Chen, H | 1 |
Liu, M | 1 |
Zang, F | 1 |
Li, J | 1 |
Zhang, Y | 1 |
Huang, P | 1 |
Yu, R | 1 |
Lal, R | 1 |
Sukbuntherng, J | 1 |
Luo, W | 1 |
Vicente, V | 1 |
Blumenthal, R | 1 |
Ho, J | 1 |
Cundy, KC | 1 |
Gil-Nagel, A | 1 |
Brodie, MJ | 1 |
Leroy, R | 1 |
Cyr, T | 1 |
Hall, S | 1 |
Castiglia, M | 1 |
Twomey, C | 1 |
VanLandingham, K | 1 |
Trial | Phase | Enrollment | Study Type | Start Date | Status | ||
---|---|---|---|---|---|---|---|
THE PRIORITIZE STUDY: A Pragmatic, Randomized Study of Oral Regimens for Hepatitis C: Transforming Decision-Making for Patients, Providers, and Stakeholders[NCT02786537] | Phase 4 | 1,275 participants (Actual) | Interventional | 2016-06-30 | Completed | ||
A 2-part Phase III Randomized, Open Label, Multicenter Study of LGX818 Plus MEK162 Versus Vemurafenib and LGX818 Monotherapy in Patients With Unresectable or Metastatic BRAF V600 Mutant Melanoma[NCT01909453] | Phase 3 | 921 participants (Actual) | Interventional | 2013-12-13 | Active, not recruiting | ||
Open-Labeled Trial Of Direct-Acting Antiviral Treatment Of Hepatitis C-Negative Patients Who Receive Kidney Transplants From Hepatitis C-Positive Donors[NCT02743897] | Phase 1/Phase 2 | 62 participants (Actual) | Interventional | 2016-05-01 | Completed | ||
A Prospective Cohort Study to Improve HCV Care Using Multidisciplinary Approach to the Treatment of Chronic Hepatitis C in Dialysis Patients: The MATCH-D Study[NCT03791814] | Phase 4 | 0 participants (Actual) | Interventional | 2019-01-01 | Withdrawn (stopped due to The study was stopped due to difficulty in identifying potential patients.) | ||
An Open-label, Cohort Study of Grazoprevir/Elbasvir Combination Therapy for Patients With Genotype 1b Chronic Hepatitis C After Liver or Kidney Transplantation[NCT03723824] | Phase 4 | 14 participants (Actual) | Interventional | 2019-02-14 | Terminated (stopped due to COV-19 pandemic) | ||
Open-Labeled Trial Of Zepatier For Treatment Of Hepatitis C-Negative Patients Who Receive Heart Transplants From Hepatitis C-Positive Donors[NCT03146741] | Phase 1/Phase 2 | 20 participants (Actual) | Interventional | 2017-05-16 | Completed | ||
Effect Of Interferon-Free Direct Acting Antiviral Agents For Treatment Of Hepatitis C Virus Patients On The Normal Kidney[NCT03296930] | Phase 4 | 100 participants (Anticipated) | Interventional | 2017-10-01 | Not yet recruiting | ||
A Phase III Randomized Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-5172/MK-8742 in Treatment-Naïve Subjects With Chronic HCV GT1, GT4, and GT6 Infection.[NCT02105467] | Phase 3 | 421 participants (Actual) | Interventional | 2014-06-05 | Completed | ||
A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of XP13512 in Patients With Restless Legs Syndrome.[NCT00298623] | Phase 3 | 222 participants (Actual) | Interventional | 2006-03-31 | Completed | ||
A Randomized, Double-Blind, Placebo-Controlled, Dose-Response Study to Assess the Efficacy, Safety, and Pharmacokinetics of XP13512 (GSK1838262) in Patients With Restless Legs Syndrome[NCT01332305] | Phase 2 | 217 participants (Actual) | Interventional | 2007-01-31 | Completed | ||
A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of XP13512 in Patients With Restless Legs Syndrome.[NCT00365352] | Phase 3 | 325 participants (Actual) | Interventional | 2006-08-31 | Completed | ||
[information is prepared from clinicaltrials.gov, extracted Sep-2024] |
"Efficacy of Hepatitis C Virus (HCV) Treatment with Zepatier (Elbasvir/Grazobevir) with Ribavirin (RBV) for 16 weeks when used in Genotype 1a patients with Baseline RASs (NS5a Resistance Associated Substitutions or RAPs -Resistance Associated Polymorphisms).~Efficacy defined as HCV RNA undetectable 12 weeks post treatment. Table excludes Genotype 1b patients." (NCT02786537)
Timeframe: 12 weeks post treatment
Intervention | Participants (Count of Participants) |
---|---|
EBR/GZR With RBV-16 Weeks | 34 |
Number/Percentage of patients with persistence of viral cure, SVR (SVR = Sustained Virologic Response)- defined as undetectable HCV RNA at least 24 weeks following HCV Treatment. (NCT02786537)
Timeframe: 24 weeks post-end of treatment up to 153 weeks
Intervention | Participants (Count of Participants) |
---|---|
EBR/GZR | 255 |
EBR/GZR With Ribavirin | 17 |
SOF/LDV | 146 |
SOF/LDV With RBV | 2 |
PrOD | 14 |
PrOD With RBV | 36 |
Percentage of Cirrhotic patients with persistence of viral cure, SVR, (SVR= Sustained Virologic Response) defined as undetectable HCV RNA at least 24 weeks following HCV Treatment. (NCT02786537)
Timeframe: Up to 132 weeks post HCV treatment
Intervention | Participants (Count of Participants) |
---|---|
EBR/GZR | 43 |
EBR/GZR With RBV | 7 |
SOF/LDV | 35 |
SOF/LDV With RBV | 7 |
PrOD | 6 |
PrOD With RBV | 7 |
Fatigue severity collected from validated, Patient Reported Outcomes survey (PROs), 'PROMIS Fatigue Short Form'. PROMIS® T-scores were computated to compare difference between baseline value of PROMIS score to the highest (worst) score during treatment. Results presented as computated t-score from baseline to average of on Treatment Scores. A positive (+) score suggests improvements in functional well-being. A negative (-) PRO change score is suggestive of symptom improvement or lack of drug side effect. PROMIS Fatigue Score scale per question: 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always with 7 questions for a total maximum score of 35. (NCT02786537)
Timeframe: Baseline and Average On-Treatment Score
Intervention | score on a scale (Mean) |
---|---|
EBR/GZR With RBV | -1.0 |
EBR/GZR | -2.1 |
SOF/LDV With RBV | -3.7 |
SOF/LDV | -2.2 |
Fatigue severity collected from validated, Patient Reported Outcomes survey (PROs), 'PROMIS Fatigue Short Form'. PROMIS® T-scores were computated to compare difference between baseline value of PROMIS score to the highest (worst) score during treatment. Results presented as computated t-score from baseline to average of on Treatment Scores. A positive (+) score suggests improvements in functional well-being. A negative (-) PRO change score is suggestive of symptom improvement or lack of drug side effect. PROMIS Fatigue Score scale per question: 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always with 7 questions for a total maximum score of 35. (NCT02786537)
Timeframe: Baseline to On-treatment
Intervention | units on a scale (Mean) |
---|---|
EBR/GZR With RBV | 1.5 |
EBR/GZR | -1.2 |
SOF/LDV With RBV | -7.2 |
SOF/LDV | -2.0 |
PrOD With RBV | -1.9 |
PrOD | -3.0 |
"HCV-PRO, a survey for patients with HCV that measures physical, emotional, and social functioning, productivity, intimacy, and perception of quality of life, was used to assess 'overall functioning and well-being'. In general, lower score is worst outcome and higher scores indicate greater well-being and functioning. However, for ease of interpretation, HCV-PRO scale has been transformed by using '100 - HCV-PRO' ultimately revising the score to mean 0 (lowest score) is best to 100 (worst outcome). A positive change (End of treatment to baseline) suggests improvements in functional well-being.~Total score = (SUM-N)/(4*N)*100, where N is the number of questions answered." (NCT02786537)
Timeframe: Baseline to End of Treatment
Intervention | units on a scale (Mean) |
---|---|
EBR/GZR With RBV | -0.9 |
EBR/GZR | 5.6 |
SOF/LDV With RBV | 2.5 |
SOF/LDV | 6.9 |
PrOD With RBV | 3.2 |
PrOD | 9.9 |
"HCV-PRO, a survey designed to assess functional status of patients with HCV and measures physical, emotional, and social functioning, productivity, intimacy, and perception of quality of life, was used to assess functional well-being. In general, lower score is worst outcome and higher scores indicate greater well-being and functioning. However, for ease of interpretation, HCV-PRO scale has been transformed by using '100 - HCV-PRO' ultimately revising the score to mean 0 (lowest score) is best to 100 (worst outcome). A positive change (End of treatment to baseline) suggests improvements in functional well-being.~Total score = (SUM-N)/(4*N)*100, where N is the number of questions answered. End of Treatment -Baseline were used to calculate CHANGE in outcome. Number of subjects reflects participants from both Phase 1 and 2." (NCT02786537)
Timeframe: End of Treatment - Baseline
Intervention | score on a scale (Mean) |
---|---|
EBR/GZR With RBV | 3.2 |
EBR/GZR | 6.1 |
SOF/LDV With RBV | 6.3 |
SOF/LDV | 6.8 |
Headache was evaluated by the HIT-6 score, a validated, Patient Reported Outcomes survey (PROs) 'PROMIS Headache Impact Test (HIT)' with scores ranging from 36 to 78 with higher score reflecting greater impact. Mean change in headache side effect was evaluated using difference between baseline value of HIT-6 score to the highest (worst) score during treatment. Estimates of mean change and differences obtained from a constrained longitudinal linear mixed-effects model that treated baseline score as one of outcomes. Negative values for mean change represent improvement, while negative values for 'difference' indicate LDV/SOF performed better than PrOD (NCT02786537)
Timeframe: Baseline to On-Treatment
Intervention | units on a scale (Mean) |
---|---|
EBR/GZR With RBV | -0.8 |
EBR/GZR | -0.7 |
SOF/LDV With RBV | 0.4 |
SOF/LDV | -0.8 |
Headache was evaluated by the HIT-6 score, a validated, Patient Reported Outcomes survey (PROs) 'PROMIS Headache Impact Test (HIT)' with scores ranging from 36 to 78 with higher score reflecting greater impact. Mean change in headache side effect was evaluated using difference between baseline value of HIT-6 score to the highest (worst) score during treatment. Estimates of mean change and differences obtained from a constrained longitudinal linear mixed-effects model that treated baseline score as one of outcomes. Negative values for mean change represent improvement in symptom. (NCT02786537)
Timeframe: Baseline to On-Treatment
Intervention | units on a scale (Mean) |
---|---|
EBR/GZR With Ribavirin (RBV) | 0.0 |
EBR/GZR Regimen | -0.8 |
SOF/LDV With RBV | -0.7 |
SOF/LDV | -0.5 |
PrOD With RBV Regimen | -0.2 |
PrOD | -2.2 |
"Patients completed the PROMIS® Nausea Short Form at Baseline (T1) and on-treatment. PROMIS raw scores from each of the completed questionnaires were converted to standardized T-scores. Change was calculated as the difference between baseline and on-treatment score. T-scores for the PROMIS Nausea and Vomiting 4a scale range from 45.0 - 80.1. Higher scores indicate worse nausea. Negative values for mean change represent improvement.~The estimates of mean change and differences were obtained from a constrained longitudinal linear mixed-effects model that treated the baseline score as one of the outcomes. The model expressed mean score as a function of DAA regimen, cirrhosis status, HCV genotype, sex, age, race, and previous treatment status." (NCT02786537)
Timeframe: Baseline to On-Treatment
Intervention | units on a scale (Mean) |
---|---|
EBR/GZR With RBV | 1.3 |
EBR/GZR | -1.4 |
SOF/LDV With RBV | -3.9 |
SOF/LDV | -0.7 |
PrOD With RBV | 2.5 |
PrOD | 0.7 |
"Participants completed the Patient Reported Outcomes surveys (PROs) 'PROMIS Nausea/Vomiting -4 Short Form' at baseline and during treatment. Raw scores are converted to standardized T-scores with a range of 45.0-80.1. Higher scores indicate worse nausea/vomiting.~Results presented as mean difference from baseline to average of on Treatment Scores (highest/worst) score during treatment.~A negative (-) PROMIS change score is suggestive of symptom improvement or lack of drug side effect. Estimates of mean change were obtained from a constrained longitudinal linear mixed-effects model that treated the baseline score as one of the outcomes." (NCT02786537)
Timeframe: Baseline and Average On-Treatment Score
Intervention | units on a scale (Mean) |
---|---|
EBR/GZR With RBV | -0.3 |
EBR/GZR | -0.6 |
SOF/LDV With RBV | -1.6 |
SOF/LDV | -0.4 |
Fatigue severity collected from validated, Patient Reported Outcomes survey (PROs), 'PROMIS Fatigue Short Form'. PROMIS® T-scores were computated to compare difference between baseline value of PROMIS score to the highest (worst) score during treatment. Results presented as computated t-score from baseline to average of on Treatment Scores. A positive (+) score suggests improvements in functional well-being. A negative (-) PRO change score is suggestive of symptom improvement or lack of drug side effect. PROMIS Fatigue Score scale per question: 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always with 7 questions for a total maximum score of 35. (NCT02786537)
Timeframe: Baseline to End of Treatment
Intervention | units on a scale (Median) |
---|---|
EBR/GZR With RBV | 2.2 |
EBR/GZR Regimen | -0.9 |
SOF/LDV With RBV | -10.2 |
SOF/LDV | -3.4 |
PrOD Regimen With RBV | -0.2 |
PrOD | -4.1 |
Fatigue severity collected from validated, Patient Reported Outcomes survey (PROs), 'PROMIS Fatigue Short Form'. PROMIS® T-scores were computated to compare difference between baseline value of PROMIS score to the highest (worst) score during treatment. Results presented as computated t-score from baseline to average of on Treatment Scores. A positive (+) score suggests improvements in functional well-being. A negative (-) PRO change score is suggestive of symptom improvement or lack of drug side effect. PROMIS Fatigue Score scale per question: 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always with 7 questions for a total maximum score of 35. (NCT02786537)
Timeframe: Baseline-On Treatment (up to 16 weeks)
Intervention | units on a scale (Median) |
---|---|
EBR/GZR With RBV | -1.3 |
EBR/GZR | -1.2 |
SOF/LDV With RBV | -2.4 |
SOF/LDV | -1.4 |
"HCV-PRO, a survey for patients with HCV that measures physical, emotional, and social functioning, productivity, intimacy, and perception of quality of life, was used to assess 'Overall Functioning and Well-being'. In general, lower score is worst outcome and higher scores indicate greater well-being and functioning. However, for ease of interpretation, HCV-PRO scale has been transformed by using '100 - HCV-PRO' ultimately revising the score to mean 0 (lowest score) is best to 100 (worst outcome). A positive change (End of treatment to baseline) suggests improvements in functional well-being.~Total score = (SUM-N)/(4*N)*100, where N is the number of questions answered." (NCT02786537)
Timeframe: Baseline to End of Treatment
Intervention | score on a scale (Median) |
---|---|
EBR/GZR With RBV | 0.0 |
EBR/GZR | 4.3 |
SOF/LDV With RBV | 4.7 |
SOF/LDV | 4.7 |
PrOD With RBV | 3.1 |
PrOD | 8.6 |
Headache was evaluated by the HIT-6 score, a validated, Patient Reported Outcomes survey (PROs) 'PROMIS Headache Impact Test (HIT)' with scores ranging from 36 to 78 with higher score reflecting greater impact. Median change in headache side effect was evaluated using difference between baseline value of HIT-6 score to the highest (worst) score during treatment. Estimates of mean change and differences obtained from a constrained longitudinal linear mixed-effects model that treated baseline score as one of outcomes. Negative values for change represent improvement, while negative values for 'difference' indicate LDV/SOF performed better than PrOD (NCT02786537)
Timeframe: 12 weeks (Baseline and Average On-treatment Score)
Intervention | units on a scale (Median) |
---|---|
EBR/GZR (Elbasvir/Grazoprevir) With RBV | 0.0 |
EBR/GZR (Elbasvir/Grazoprevir) | 0.0 |
SOF/LDV (Sofosbuvir/Ledipasvir) With RBV | -2.0 |
SOF/LDV (Sofosbuvir/Ledipasvir) | -1.0 |
PrOD (Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir) With RBV (Phase 1 Only) | 0.0 |
PrOD (Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir) | -1.0 |
Headache was evaluated by the HIT-6 score, a validated, Patient Reported Outcomes survey (PROs) 'PROMIS Headache Impact Test (HIT)' with scores ranging from 36 to 78 with higher score reflecting greater impact. Median change in headache side effect was evaluated using difference between baseline value of HIT-6 score to the highest (worst) score during treatment. Estimates of median change and differences obtained from a constrained longitudinal linear mixed-effects model that treated baseline score as one of outcomes. Negative values for mean change represent improvement, while negative values for 'difference' indicate LDV/SOF performed better than PrOD (NCT02786537)
Timeframe: Baseline -on Treatment (12-16 weeks)
Intervention | units on a scale (Median) |
---|---|
EBR/GZR With RBV | -1.0 |
EBR/GZR | 0.0 |
SOF/LDV With RBV | 0.5 |
SOF/LDV | -0.5 |
"Patients completed the PROMIS® Nausea Short Form at Baseline (T1) and on-treatment. PROMIS raw scores from each of the completed questionnaires were converted to standardized T-scores. Change was calculated as the difference between baseline and on-treatment score. T-scores for the PROMIS Nausea and Vomiting 4a scale range from 45.0 - 80.1. Higher scores indicate worse nausea. Negative values for mean change represent improvement.~The estimates of change and differences were obtained from a constrained longitudinal linear mixed-effects model that treated the baseline score as one of the outcomes." (NCT02786537)
Timeframe: Baseline to end of treatment
Intervention | units on a scale (Median) |
---|---|
EBR/GZR With RBV | 0.4 |
EBR/GZR | 0.0 |
SOF/LDV With RBV | -6.1 |
SOF/LDV | 0.0 |
PrOD With RBV | 0.0 |
PrOD | 0.0 |
"Patients completed the PROMIS® Nausea Short Form at Baseline (T1) and on-treatment. PROMIS raw scores from each of the completed questionnaires were converted to standardized T-scores. Change was calculated as the difference between baseline and on-treatment score. T-scores for the PROMIS Nausea and Vomiting 4a scale range from 45.0 - 80.1. Higher scores indicate worse nausea. Negative values for change represent improvement.~The estimates of change and differences were obtained from a constrained longitudinal linear mixed-effects model that treated the baseline score as one of the outcomes." (NCT02786537)
Timeframe: Baseline- On Treatment (up to 16 weeks)
Intervention | score on a scale (Median) |
---|---|
EBR/GZR With RBV | 0.0 |
EBR/GZR | 0.0 |
SOF/LDV With RBV | 0.0 |
SOF/LDV | 0.0 |
The number of participants with adverse events that led to early treatment discontinuation (defined as duration less than originally prescribed treatment regimen) (NCT02786537)
Timeframe: Treatment start date through treatment completion (up to 24 weeks)
Intervention | Participants (Count of Participants) |
---|---|
EBR/GZR Regimen | 12 |
SOF/LDV Regimen | 4 |
"SVR (Sustained Virologic Response) 12 will be defined as undetectable hepatitis C virus (HCV) RNA at 12 week follow-up visit (12 -24 weeks after HCV treatment discontinuation as dictated by standard of care at each individual site).~Number of subjects reflects participants randomized during Phase 1 only." (NCT02786537)
Timeframe: 12 -24 weeks post-treatment
Intervention | Participants (Count of Participants) |
---|---|
EBR/GZR With RBV | 9 |
EBR/GZR | 108 |
SOF/LDV With RBV | 6 |
SOF/LDV | 88 |
PrOD With RBV | 77 |
PrOD (Phase 1 Only) | 42 |
"SVR (Sustained Virologic Response) 12 will be defined as patients who have undetectable hepatitis C virus (HCV) RNA at 12 week follow-up visit (12 -24 weeks after HCV treatment discontinuation as dictated by standard of care at each individual site).~mITT with imputation (missing=failure). Total number of subjects reflects participants from Phase 1 only." (NCT02786537)
Timeframe: 12 weeks post-treatment
Intervention | Participants (Count of Participants) |
---|---|
EBR/GZR With RBV | 9 |
EBR/GZR | 108 |
SOF/LDV With RBV | 6 |
SOF/LDV | 88 |
PrOD With RBV | 77 |
PrOD | 42 |
"SVR (Sustained Virologic Response) 12 will be defined as undetectable hepatitis C virus (HCV) RNA at 12 week follow-up visit (12 -24 weeks after HCV treatment discontinuation as dictated by standard of care at each individual site).~Number of subjects reflects participants who started EBR/GZR or SOF/LDV- based treatment (with or without RBV) during Phase 1 and 2." (NCT02786537)
Timeframe: 12-24 weeks post HCV treatment
Intervention | Participants (Count of Participants) |
---|---|
EBR/GZR With RBV | 40 |
EBR/GZR | 516 |
SOF/LDV With RBV | 14 |
SOF/LDV | 335 |
Mean change (delta) in FIB-4, an indirect non-invasive measure of liver fibrosis, calculated as baseline median -long term follow up median, following SVR after any of the study treatment regimens. Change in FIB-4 where negative values indicate improvement in liver fibrosis score and positive values indicate worsening of fibrosis score. There is no upper or lower limit for change. FIB-4 = age (years) * AST(IU/L)/Platelets (10^3/L) * ALT^.5(IU/L). In general, Score of 0-1.29 is low risk for advanced fibrosis, 1.30-1.67: intermediate risk for advanced liver fibrosis, >2.67: high risk for advanced fibrosis. (NCT02786537)
Timeframe: Baseline to up to 3 years post treatment discontinuation
Intervention | score on a scale (Median) |
---|---|
EBR/GZR, SOF/LDV or PrOD Based HCV Treatment | -1.36 |
"SVR (Sustained Virologic Response) 12 will be defined as undetectable hepatitis C virus (HCV) RNA at 12 week follow-up visit (12 -24 weeks after HCV treatment discontinuation at discretion of provider).~mITT with imputation (missing=failure). Total number of subjects reflects participants from EBR/GZR with or without RBV and SOF/LDV with or without RBV randomized during Phase 1 and Phase 2." (NCT02786537)
Timeframe: 12 weeks post-treatment
Intervention | Participants (Count of Participants) |
---|---|
EBR/GZR With RBV | 40 |
EBR/GZR | 516 |
SOF/LDV With RBV | 14 |
SOF/LDV | 335 |
"The Voils Medication Adherence Survey (VMAS) was used to evaluate medication adherence during HCV treatment. Participants responded to three questions about the extent of adherence during the past seven days of treatment (during early and late on-treatment occasions). Participants responded using a five-point ordinal scale of missed dosing from 1 (none of the time) to 5 (all of the time). On each occasion participants were coded as being Non-adherent if any response was > 1, otherwise they were coded as Adherent. Probability estimates of percentage of patients reporting non-adherence were calculated per HCV treatment (Direct Acting Antiviral-DAA) regimen: 1)EBR/GZV (elbasvir/grazoprevir, 2)SOF/LDV (sofosbuvir/ledipasvir), 3)PrOD" (NCT02786537)
Timeframe: 12-16 weeks of HCV treatment
Intervention | percentage of patients (Number) |
---|---|
EBR/GZR | 23 |
SOF/LDV | 19 |
PrOD | 26 |
"HCV-PRO score, a validated PROMIS survey used to evaluate overall functioning and well-being in HCV patients, was utilized to compare long-term 'within treatment' changes of functional well-being. In general, lower score is worst outcome and higher scores indicate greater well-being and functioning. However, for ease of interpretation, HCV-PRO scale has been transformed by using '100 - HCV-PRO' ultimately revising the score to mean 0 (lowest score) is best to 100 (worst outcome). A positive estimate (Post treatment to baseline) suggests baseline functional well-being improvement.~Total score = (SUM-N)/(4*N)*100, where N is the number of questions answered." (NCT02786537)
Timeframe: Treatment start date up to 2 years post-treatment
Intervention | score on a scale (Mean) | |
---|---|---|
9 months post treatment | 20 months post treatment | |
EBR/GZR Regimen | 8.02 | 9.87 |
SOF/LDV Regimen | 9.90 | 11.54 |
Change in HCV-associated symptoms was calculated as the mean differences of mean scores from multiple surveys from the NIH Patient-Reported Outcomes Measurement Information System (PROMIS)-- Fatigue, nausea, belly pain, sleep disturbance, and diarrhea) and functional status (well-being) when comparing baseline to early post-treatment and late post treatment surveys. Mean change scores were calculated by comparing baseline to early post-treatment (1 yr) and late post-treatment (approximately 3 years) surveys. T-scores for the PROMIS Nausea and Vomiting 4a scale range from 45.0 - 80.1. Higher scores indicate worse nausea. Negative values for mean change represent improvement.Negative numbers suggest better symptoms (improvement in HCV-associated symptoms). PROMIS Fatigue Score scale per question: 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always with 7 questions for a total maximum score of 35.HCV-PRO positive estimates suggest baseline functional well-being improvement. (NCT02786537)
Timeframe: 1 year post treatment discontinuation (Early post-tx)
Intervention | units on a scale (Mean) | ||||||
---|---|---|---|---|---|---|---|
Nausea | Belly Pain | Diarrhea | Fatigue | Sleep Disturbance | Cognitive Impairment | HCV-PRO | |
EBR/GZR Regimen | 0.00 | -0.82 | -1.12 | -2.08 | 0.65 | -0.54 | 8.02 |
SOF/LDV Regimen | -4.99 | -6.47 | -5.77 | -7.59 | -1.72 | -4.48 | 9.90 |
Number of participants who achieved SVR (sustained virologic response), defined as undetectable HCV RNA 12 weeks post-treatment with RASs (Resistant Associated Substitutions) after treatment with EBR/GZR or SOF/LDV regimen (NCT02786537)
Timeframe: 12 weeks post HCV treatment
Intervention | Participants (Count of Participants) | |
---|---|---|
With NS5a RAS | Without NS5a RAS | |
EBR/GZR Regimen | 47 | 485 |
SOF/LDV Regimen | 42 | 286 |
DCR was calculated as the percentage of participants with a best overall response (BOR) of CR, PR, or stable disease (SD). CR was defined as disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Two sets of DCR were considered, one for confirmed and one for unconfirmed responses. Results are reported for confirmed and unconfirmed responses combined. SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. DCR was based on central review. (NCT01909453)
Timeframe: From randomization until disease progression or death, whichever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)
Intervention | percentage of participants (Number) |
---|---|
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | 92.2 |
Part 1: LGX818 300 mg | 84.0 |
Part 1: Vemurafenib 960 mg BID | 81.7 |
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | 90.7 |
Part 2: LGX818 300 mg | 79.1 |
Part 1 + Part 2: LGX818 300 mg | 82.5 |
DOR was calculated, as the time from the date of first documented response (CR or PR) to the first documented progression or death due to underlying cancer. DOR was estimated for responders (i.e. participants achieving at least once CR or PR) only using a Kaplan-Meier method. CR was defined as disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. If a participant with a CR or PR had no progression or death due to underlying disease, the participant was censored at the date of last adequate tumor assessment. Results are based on confirmed BIRC response. (NCT01909453)
Timeframe: From randomization until disease progression, censoring date or death, whichever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)
Intervention | months (Median) |
---|---|
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | 16.6 |
Part 1: LGX818 300 mg | 15.2 |
Part 1: Vemurafenib 960 mg BID | 12.3 |
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | 12.7 |
Part 2: LGX818 300 mg | 7.5 |
Part 1 + Part 2: LGX818 300 mg | 12.9 |
ORR, calculated as the percentage of participants with a best overall response of complete response (CR) or partial response (PR). CR was defined as disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Results are reported for confirmed BIRC response. (NCT01909453)
Timeframe: From randomization until disease progression, censoring date or death, whichever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)
Intervention | percentage of participants (Number) |
---|---|
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | 63.0 |
Part 1: LGX818 300 mg | 50.5 |
Part 1: Vemurafenib 960 mg BID | 40.3 |
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | 65.9 |
Part 2: LGX818 300 mg | 50.0 |
Part 1 + Part 2: LGX818 300 mg | 50.4 |
ECOG: participant's performance status was measured on a 6-point scale: 0= fully active/able to carry on all pre-disease activities without restriction; 1= restricted in physically strenuous activity but ambulatory and able to carry out work of a light and sedentary nature; 2= ambulatory and capable of all self-care, but unable to carry out any work activities, up and about more than 50 percent (%) of waking hours; 3= capable of only limited self-care, confined to bed/chair >50% of waking hours; 4= completely disabled, cannot carry on any self-care, totally confined to bed/chair: 5= dead. Definitive deterioration was defined as death due to any cause or decrease in ECOG PS by at least one category from baseline score with no subsequent improvement. (NCT01909453)
Timeframe: Baseline up to 30 days from last dose of study drug (up to 30 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 36 months for Part 2 and Part 1 LGX 300 mg group)
Intervention | months (Median) |
---|---|
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | NA |
Part 1: LGX818 300 mg | 26.7 |
Part 1: Vemurafenib 960 mg BID | 18.2 |
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | NA |
Part 2: LGX818 300 mg | 10.2 |
Part 1 + Part 2: LGX818 300 mg | 19.2 |
FACT-M:melanoma specific questionnaire to assess participant health-related quality of life. Melanoma specific subscale consists of 16 items related to signs,symptoms,physical/social activities most relevant to participants with advanced-stage melanoma. Other items include physical, functional and social/family well-being (7 items each),emotional well-being (6 items),surgery specific concerns related to melanoma(8 items,not included in this study). Each item range from 0(not at all) to 4(very much), combined to produce subscale scores.Total score range for FACT-M excluding surgery specific items is 0 to 172,higher scores represent better quality of life.Melanoma subscale score range from 0(worst response) to 64(best response),higher score indicated better quality of life. Time to definitive 10% deterioration:time from date of randomization to date of event with at least 10% relative to baseline worsening of corresponding scale score with no later improvement or death due to any cause. (NCT01909453)
Timeframe: Date of randomization to date of event or death due to any cause, which ever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)
Intervention | months (Median) |
---|---|
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | NA |
Part 1: LGX818 300 mg | 30.5 |
Part 1: Vemurafenib 960 mg BID | 22.1 |
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | NA |
Part 2: LGX818 300 mg | NA |
Part 1 + Part 2: LGX818 300 mg | 20.5 |
"EORTC QLQ-C30 is 30 item questionnaire composed of 5 multi-item functional subscales (physical, role, cognitive, emotional, social functioning), 3 multi-item symptom scales (fatigue, nausea/vomiting, and pain), global health/quality of life (QOL) subscale and 6 single items assessing other cancer related symptoms (dyspnea, sleep disturbance, appetite, diarrhea, constipation and financial impact of cancer). It employed twenty-eight 4 point Likert scales with responses from not at all to very much and two 7 point Likert scales for global health and overall QOL. Global health status scale score ranged from 0 to 100. Higher score represented better level of functioning. Time to definitive 10% deterioration: time from date of randomization to date of event with at least 10% relative to baseline worsening of corresponding scale score with no later improvement or death due to any cause." (NCT01909453)
Timeframe: Date of randomization to date of event or death due to any cause, which ever occurred first (maximum up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)
Intervention | months (Median) |
---|---|
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | 23.9 |
Part 1: LGX818 300 mg | 14.7 |
Part 1: Vemurafenib 960 mg BID | 16.6 |
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | 18.4 |
Part 2: LGX818 300 mg | 9.5 |
Part 1 + Part 2: LGX818 300 mg | 11.1 |
TTR was the time between date of randomization until first documented response of CR or PR. Participants who did not achieve a PR or CR were censored at the last adequate tumor assessment date when they did not have a PFS event or at maximum follow-up (i.e. first patient first visit [FPFV] to last patient last visit [LPLV] used for the analysis) when they had a PFS event. CR was defined as disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. TTR was estimated in the treatment arms using a Kaplan-Meier method. TTR was based on central review. (NCT01909453)
Timeframe: From randomization until disease progression, censoring date or death, whichever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)
Intervention | months (Median) |
---|---|
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | 1.9 |
Part 1: LGX818 300 mg | 2.0 |
Part 1: Vemurafenib 960 mg BID | 2.1 |
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | 1.9 |
Part 2: LGX818 300 mg | 1.9 |
Part 1 + Part 2: LGX818 300 mg | 1.9 |
PFS was defined as the time from the date of randomization to the date of the first documented disease progression (PD) or death due to any cause, whichever occurs first. PFS was determined based on tumor assessment (RECIST version 1.1 criteria) as per BIRC and survival information. If a participant did not had an event at the time of the analysis cut-off or at the start of any new anti-cancer therapy, data was censored at the date of last adequate tumor assessment. PD was defined as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm^2. (NCT01909453)
Timeframe: From randomization until documented disease progression (PD), initiation of new anti-cancer therapy, censoring date or death, whichever occurred first (up to 29 months), excluding Part 1: LGX818 300 mg group; up to 35 months for Part 1: LGX 300 mg group
Intervention | months (Median) |
---|---|
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | 14.9 |
Part 1: LGX818 300 mg | 9.6 |
PFS was defined as the time from the date of randomization to the date of the first documented disease progression (PD) or death due to any cause, whichever occurs first. PFS was determined based on tumor assessment (RECIST version 1.1 criteria) as per BIRC/central review and survival information. If a participant did not had an event at the time of the analysis cut-off or at the start of any new anti-cancer therapy, data was censored at the date of last adequate tumor assessment. PD was defined as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 square millimeter (mm^2). (NCT01909453)
Timeframe: From randomization until documented disease progression (PD), initiation of new anti-cancer therapy, censoring date or death, whichever occurred first (up to 29 months)
Intervention | months (Median) |
---|---|
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | 14.9 |
Part 1: Vemurafenib 960 mg BID | 7.3 |
PFS was defined as the time from the date of randomization to the date of the first documented disease progression (PD) or death due to any cause, whichever occurs first. PFS was determined based on tumor assessment (RECIST version 1.1 criteria) as per BIRC and survival information. If a participant did not had an event at the time of the analysis cut-off or at the start of any new anti-cancer therapy, data was censored at the date of last adequate tumor assessment. PD was defined as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm^2. (NCT01909453)
Timeframe: From randomization until documented disease progression (PD), initiation of new anti-cancer therapy, censoring date or death, whichever occurred first (up to 35 months)
Intervention | months (Median) |
---|---|
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | 12.9 |
Part 2: LGX818 300 mg | 7.4 |
Part 1 + Part 2: LGX818 300 mg | 9.2 |
"EORTC QLQ-C30 contains 30 items and is composed of multi-item and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/quality of life (QOL) scale. The questionnaire employs 28 4-point Likert scales with responses from not at all to very much and two 7-point Likert scales for global health and overall QOL. Responses to all items converted to 0 to 100 scale. For functional and global QOL scales, higher scores represent a better level of functioning/QOL. For symptom-oriented scales, a higher score represented more severe symptoms." (NCT01909453)
Timeframe: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)
Intervention | units on a scale (Mean) | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Baseline | Change at Cycle 3 Day 1 | Change at Cycle 5 Day 1 | Change at Cycle 7 Day 1 | Change at Cycle 9 Day 1 | Change at Cycle 11 Day 1 | Change at Cycle 13 Day 1 | Change at Cycle 15 Day 1 | Change at Cycle 17 Day 1 | Change at Cycle 19 Day 1 | Change at Cycle 21 Day 1 | Change at End of treatment visit | |
Part 2: LGX818 300 mg | 74.20 | 1.79 | 2.96 | -3.62 | -0.60 | -2.69 | -6.41 | -2.12 | 1.79 | 2.78 | 16.67 | 5.56 |
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | 73.04 | 7.29 | 6.15 | 9.37 | 9.22 | 10.56 | 8.66 | 10.59 | 10.33 | 8.33 | 13.13 | -4.17 |
"EORTC QLQ-C30 contains 30 items and is composed of multi-item and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/quality of life (QOL) scale. The questionnaire employs 28 4-point Likert scales with responses from not at all to very much and two 7-point Likert scales for global health and overall QOL. Responses to all items converted to 0 to 100 scale. For functional and global QOL scales, higher scores represent a better level of functioning/QOL. For symptom-oriented scales, a higher score represented more severe symptoms." (NCT01909453)
Timeframe: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)
Intervention | units on a scale (Mean) | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Baseline | Change at Cycle 3 Day 1 | Change at Cycle 5 Day 1 | Change at Cycle 7 Day 1 | Change at Cycle 9 Day 1 | Change at Cycle 11 Day 1 | Change at Cycle 13 Day 1 | Change at Cycle 15 Day 1 | Change at Cycle 17 Day 1 | Change at Cycle 19 Day 1 | Change at Cycle 21 Day 1 | Change at Cycle 23 Day 1 | Change at Cycle 25 Day 1 | Change at End of treatment visit | |
Part 1 + Part 2: LGX818 300 mg | 74.38 | 0.32 | 1.98 | -0.91 | 1.26 | -0.74 | 0.83 | 1.30 | 3.26 | 1.27 | -0.76 | 2.94 | -0.32 | -0.83 |
Part 1: LGX818 300 mg | 74.46 | -0.34 | 1.54 | 0.34 | 2.15 | 0.12 | 3.78 | 2.30 | 3.64 | 1.00 | -1.16 | 2.94 | -0.32 | -3.57 |
Part 1: Vemurafenib 960 mg BID | 72.31 | 1.88 | 2.03 | 2.71 | -0.17 | 4.53 | -2.25 | -5.46 | -1.39 | 0.38 | -3.13 | -0.69 | -1.19 | 12.50 |
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | 74.68 | 3.23 | 5.37 | 5.42 | 4.47 | 4.81 | 3.52 | 7.35 | 5.33 | 4.25 | 4.17 | -1.74 | 3.92 | 41.67 |
EQ-5D-5L is a standardized participant completed questionnaire that measures health status in terms of a single index value or utility score. EQ-5D-5L consisted of two components: a health state profile (descriptive system) and a visual analogue scale (VAS) in which participants rate their overall health status from 0 (worst imaginable) to 100 (best imaginable), where higher scores indicated better health status. EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. EQ-5D-5L health status index score range between 0 to 1. Higher score indicated better health status. (NCT01909453)
Timeframe: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)
Intervention | units on a scale (Mean) | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Baseline | Change at Cycle 3 Day 1 | Change at Cycle 5 Day 1 | Change at Cycle 7 Day 1 | Change at Cycle 9 Day 1 | Change at Cycle 11 Day 1 | Change at Cycle 13 Day 1 | Change at Cycle 15 Day 1 | Change at Cycle 17 Day 1 | Change at Cycle 19 Day 1 | Change at Cycle 21 Day 1 | Change at End of treatment visit | |
Part 2: LGX818 300 mg | 0.73 | -0.06 | -0.06 | -0.16 | -0.11 | -0.16 | -0.20 | -0.26 | -0.20 | -0.11 | -0.11 | -0.06 |
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | 0.75 | 0.06 | 0.07 | 0.06 | 0.07 | 0.06 | 0.05 | 0.05 | 0.06 | 0.05 | 0.12 | -0.27 |
EQ-5D-5L is a standardized participant completed questionnaire that measures health status in terms of a single index value or utility score. EQ-5D-5L consisted of two components: a health state profile (descriptive system) and a visual analogue scale (VAS) in which participants rate their overall health status from 0 (worst imaginable) to 100 (best imaginable), where higher scores indicated better health status. EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. EQ-5D-5L health status index score range between 0 to 1. Higher score indicated better health status. (NCT01909453)
Timeframe: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)
Intervention | units on a scale (Mean) | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Baseline | Change at Cycle 3 Day 1 | Change at Cycle 5 Day 1 | Change at Cycle 7 Day 1 | Change at Cycle 9 Day 1 | Change at Cycle 11 Day 1 | Change at Cycle 13 Day 1 | Change at Cycle 15 Day 1 | Change at Cycle 17 Day 1 | Change at Cycle 19 Day 1 | Change at Cycle 21 Day 1 | Change at Cycle 23 Day 1 | Change at Cycle 25 Day 1 | Change at End of treatment visit | |
Part 1 + Part 2: LGX818 300 mg | 0.75 | -0.09 | -0.13 | -0.14 | -0.14 | -0.17 | -0.18 | -0.20 | -0.15 | -0.17 | -0.14 | -0.11 | -0.11 | -0.08 |
Part 1: LGX818 300 mg | 0.76 | -0.10 | -0.15 | -0.13 | -0.15 | -0.18 | -0.17 | -0.18 | -0.14 | -0.18 | -0.14 | -0.11 | -0.11 | -0.09 |
Part 1: Vemurafenib 960 mg BID | 0.73 | 0.00 | -0.04 | -0.03 | -0.04 | -0.01 | -0.02 | -0.07 | -0.02 | -0.02 | -0.04 | -0.05 | -0.17 | -0.14 |
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | 0.74 | 0.05 | 0.04 | 0.05 | 0.03 | 0.04 | 0.05 | 0.05 | 0.07 | 0.03 | 0.07 | 0.04 | 0.07 | 0.03 |
"EORTC QLQ-C30 contains 30 items and is composed of multi-item and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/quality of life (QOL) scale. The questionnaire employs 28 4-point Likert scales with responses from not at all to very much and two 7-point Likert scales for global health and overall QOL. Responses to all items converted to 0 to 100 scale. For functional and global QOL scales, higher scores represent a better level of functioning/QOL. For symptom-oriented scales, a higher score represents more severe symptoms." (NCT01909453)
Timeframe: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)
Intervention | units on a scale (Mean) | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Baseline | Change at Cycle 3 Day 1 | Change at Cycle 5 Day 1 | Change at Cycle 7 Day 1 | Change at Cycle 9 Day 1 | Change at Cycle 11 Day 1 | Change at Cycle 13 Day 1 | Change at Cycle 15 Day 1 | Change at Cycle 17 Day 1 | Change at Cycle 19 Day 1 | Change at Cycle 21 Day 1 | Change at End of treatment visit | |
Part 2: LGX818 300 mg | 67.39 | -4.95 | -4.72 | -7.08 | -8.73 | -7.53 | -9.29 | -12.75 | -7.14 | -0.93 | 0.00 | 4.17 |
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | 65.95 | 4.47 | 5.61 | 5.01 | 4.94 | 4.76 | 5.89 | 6.11 | 5.86 | 1.23 | 3.03 | -6.25 |
"EORTC QLQ-C30 contains 30 items and is composed of multi-item and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/quality of life (QOL) scale. The questionnaire employs 28 4-point Likert scales with responses from not at all to very much and two 7-point Likert scales for global health and overall QOL. Responses to all items converted to 0 to 100 scale. For functional and global QOL scales, higher scores represent a better level of functioning/QOL. For symptom-oriented scales, a higher score represents more severe symptoms." (NCT01909453)
Timeframe: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)
Intervention | units on a scale (Mean) | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Baseline | Change at Cycle 3 Day 1 | Change at Cycle 5 Day 1 | Change at Cycle 7 Day 1 | Change at Cycle 9 Day 1 | Change at Cycle 11 Day 1 | Change at Cycle 13 Day 1 | Change at Cycle 15 Day 1 | Change at Cycle 17 Day 1 | Change at Cycle 19 Day 1 | Change at Cycle 21 Day 1 | Change at Cycle 23 Day 1 | Change at Cycle 25 Day 1 | Change at End of treatment visit | |
Part 1 + Part 2: LGX818 300 mg | 66.48 | -6.81 | -7.87 | -8.53 | -10.96 | -10.13 | -8.80 | -10.56 | -7.85 | -8.05 | -10.80 | -5.64 | -7.05 | 4.63 |
Part 1: LGX818 300 mg | 66.07 | -7.64 | -9.24 | -9.21 | -12.03 | -11.27 | -8.59 | -9.91 | -8.03 | -9.33 | -11.05 | -5.64 | -7.05 | 4.76 |
Part 1: Vemurafenib 960 mg BID | 64.74 | -3.46 | -4.05 | -3.04 | -6.94 | -3.80 | -2.93 | -10.34 | -6.94 | -1.89 | -8.85 | -3.47 | -2.38 | -4.17 |
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | 66.72 | 3.56 | 1.55 | 1.53 | -0.55 | 0.81 | 0.42 | 5.02 | 0.41 | -0.51 | 0.74 | -1.39 | 1.96 | 0.00 |
"EORTC QLQ-C30 contains 30 items and is composed of multi-item and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/quality of life (QOL) scale. The questionnaire employs 28 4-point Likert scales with responses from not at all to very much and two 7-point Likert scales for global health and overall QOL. Responses to all items converted to 0 to 100 scale. For functional and global QOL scales, higher scores represented a better level of functioning/QOL. For symptom-oriented scales, a higher score represented more severe symptoms." (NCT01909453)
Timeframe: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)
Intervention | units on a scale (Mean) | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Baseline | Change at Cycle 3 Day 1 | Change at Cycle 5 Day 1 | Change at Cycle 7 Day 1 | Change at Cycle 9 Day 1 | Change at Cycle 11 Day 1 | Change at Cycle 13 Day 1 | Change at Cycle 15 Day 1 | Change at Cycle 17 Day 1 | Change at Cycle 19 Day 1 | Change at Cycle 21 Day 1 | Change at End of treatment visit | |
Part 2: LGX818 300 mg | 81.45 | -13.63 | -12.63 | -17.01 | -15.83 | -13.49 | -13.85 | -24.31 | -19.05 | -14.07 | -13.33 | -4.44 |
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | 80.67 | 2.94 | 2.73 | 1.22 | 3.03 | 0.50 | 0.47 | -0.40 | -0.88 | -5.71 | -8.48 | -5.00 |
"EORTC QLQ-C30 contains 30 items and is composed of multi-item and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/quality of life (QOL) scale. The questionnaire employs 28 4-point Likert scales with responses from not at all to very much and two 7-point Likert scales for global health and overall QOL. Responses to all items converted to 0 to 100 scale. For functional and global QOL scales, higher scores represented a better level of functioning/QOL. For symptom-oriented scales, a higher score represented more severe symptoms." (NCT01909453)
Timeframe: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)
Intervention | units on a scale (Mean) | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Baseline | Change at Cycle 3 Day 1 | Change at Cycle 5 Day 1 | Change at Cycle 7 Day 1 | Change at Cycle 9 Day 1 | Change at Cycle 11 Day 1 | Change at Cycle 13 Day 1 | Change at Cycle 15 Day 1 | Change at Cycle 17 Day 1 | Change at Cycle 19 Day 1 | Change at Cycle 21 Day 1 | Change at Cycle 23 Day 1 | Change at Cycle 25 Day 1 | Change at End of treatment visit | |
Part 1 + Part 2: LGX818 300 mg | 82.63 | -13.74 | -15.74 | -16.49 | -18.27 | -19.87 | -18.22 | -21.18 | -18.91 | -19.14 | -16.78 | -14.46 | -15.93 | -2.00 |
Part 1: LGX818 300 mg | 83.18 | -13.79 | -17.14 | -16.26 | -19.43 | -22.65 | -20.00 | -20.26 | -18.88 | -20.07 | -16.86 | -14.46 | -15.93 | -0.95 |
Part 1: Vemurafenib 960 mg BID | 80.71 | -2.90 | -7.45 | -6.98 | -6.82 | -4.11 | -6.30 | -6.22 | -3.27 | -1.90 | -4.90 | -2.22 | -4.76 | -15.00 |
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | 82.10 | 0.20 | 0.15 | -1.93 | -0.45 | -0.85 | -1.25 | 0.29 | -0.03 | -1.22 | -0.95 | -5.00 | -5.49 | 33.33 |
"EORTC QLQ-C30 contains 30 items and is composed of multi-item and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/quality of life (QOL) scale. The questionnaire employs 28 4-point Likert scales with responses from not at all to very much and two 7-point Likert scales for global health and overall QOL. Responses to all items converted to 0 to 100 scale. For functional and global QOL scales, higher scores represented a better level of functioning/QOL. For symptom-oriented scales, a higher score represented more severe symptoms." (NCT01909453)
Timeframe: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)
Intervention | units on a scale (Mean) | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Baseline | Change at Cycle 3 Day 1 | Change at Cycle 5 Day 1 | Change at Cycle 7 Day 1 | Change at Cycle 9 Day 1 | Change at Cycle 11 Day 1 | Change at Cycle 13 Day 1 | Change at Cycle 15 Day 1 | Change at Cycle 17 Day 1 | Change at Cycle 19 Day 1 | Change at Cycle 21 Day 1 | Change at End of treatment visit | |
Part 2: LGX818 300 mg | 78.31 | -10.00 | -5.11 | -13.89 | -9.52 | -12.37 | -5.77 | -15.69 | -7.14 | -12.96 | -33.33 | 0.00 |
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | 81.37 | 4.05 | 3.37 | 3.05 | 3.66 | 1.95 | 1.75 | 2.86 | 1.59 | 1.23 | 4.55 | -16.67 |
"EORTC QLQ-C30 contains 30 items and is composed of multi-item and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/quality of life (QOL) scale. The questionnaire employs 28 4-point Likert scales with responses from not at all to very much and two 7-point Likert scales for global health and overall QOL. Responses to all items converted to 0 to 100 scale. For functional and global QOL scales, higher scores represented a better level of functioning/QOL. For symptom-oriented scales, a higher score represented more severe symptoms." (NCT01909453)
Timeframe: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)
Intervention | units on a scale (Mean) | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Baseline | Change at Cycle 3 Day 1 | Change at Cycle 5 Day 1 | Change at Cycle 7 Day 1 | Change at Cycle 9 Day 1 | Change at Cycle 11 Day 1 | Change at Cycle 13 Day 1 | Change at Cycle 15 Day 1 | Change at Cycle 17 Day 1 | Change at Cycle 19 Day 1 | Change at Cycle 21 Day 1 | Change at Cycle 23 Day 1 | Change at Cycle 25 Day 1 | Change at End of treatment visit | |
Part 1 + Part 2: LGX818 300 mg | 80.09 | -10.59 | -9.80 | -11.11 | -13.70 | -12.54 | -9.74 | -11.78 | -10.54 | -12.43 | -15.15 | -6.37 | -7.05 | -13.33 |
Part 1: LGX818 300 mg | 80.91 | -10.86 | -11.92 | -9.80 | -15.71 | -12.62 | -11.38 | -10.63 | -11.42 | -12.33 | -14.73 | -6.37 | -7.05 | -19.05 |
Part 1: Vemurafenib 960 mg BID | 78.54 | -4.90 | -7.21 | -2.75 | -1.99 | -0.36 | -0.45 | -6.32 | 1.39 | 3.79 | -3.13 | 1.39 | 4.76 | -8.33 |
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | 80.69 | -0.66 | 3.26 | 2.82 | 1.57 | -2.72 | -4.27 | 3.73 | 1.11 | -1.04 | -1.52 | -12.32 | -5.21 | 25.00 |
FACT-M: melanoma specific questionnaire to assess participant health-related quality of life. Melanoma specific subscale consists of 16 items related to signs, symptoms, physical/social activities most relevant to participants with advanced-stage melanoma. Other items include physical, functional and social/family well-being (7 items each),emotional well-being (6 items),surgery specific concerns related to melanoma(8 items, not included in this study). Each item range from 0(not at all) to 4(very much), combined to produce subscale scores. Total score range for FACT-M excluding surgery specific items is 0 to 172,higher scores represented better quality of life. Melanoma subscale score range from 0(worst response) to 64(best response),higher score indicated better quality of life. (NCT01909453)
Timeframe: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)
Intervention | units on a scale (Mean) | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Baseline | Change at Cycle 3 Day 1 | Change at Cycle 5 Day 1 | Change at Cycle 7 Day 1 | Change at Cycle 9 Day 1 | Change at Cycle 11 Day 1 | Change at Cycle 13 Day 1 | Change at Cycle 15 Day 1 | Change at Cycle 17 Day 1 | Change at Cycle 19 Day 1 | Change at Cycle 21 Day 1 | Change at End of treatment visit | |
Part 2: LGX818 300 mg | 51.13 | -2.16 | -0.60 | -3.14 | -1.83 | -2.41 | -3.31 | -4.14 | -2.64 | 0.00 | -2.00 | -1.61 |
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | 52.08 | 2.79 | 2.58 | 2.64 | 3.23 | 2.54 | 1.97 | 2.08 | 2.45 | 1.23 | 2.58 | 6.58 |
FACT-M: melanoma specific questionnaire to assess participant health-related quality of life. Melanoma specific subscale consists of 16 items related to signs, symptoms, physical/social activities most relevant to participants with advanced-stage melanoma. Other items include physical, functional and social/family well-being (7 items each),emotional well-being (6 items),surgery specific concerns related to melanoma(8 items, not included in this study). Each item range from 0(not at all) to 4(very much), combined to produce subscale scores. Total score range for FACT-M excluding surgery specific items is 0 to 172,higher scores represented better quality of life. Melanoma subscale score range from 0(worst response) to 64(best response),higher score indicated better quality of life. (NCT01909453)
Timeframe: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)
Intervention | units on a scale (Mean) | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Baseline | Change at Cycle 3 Day 1 | Change at Cycle 5 Day 1 | Change at Cycle 7 Day 1 | Change at Cycle 9 Day 1 | Change at Cycle 11 Day 1 | Change at Cycle 13 Day 1 | Change at Cycle 15 Day 1 | Change at Cycle 17 Day 1 | Change at Cycle 19 Day 1 | Change at Cycle 21 Day 1 | Change at Cycle 23 Day 1 | Change at Cycle 25 Day 1 | Change at End of treatment visit | |
Part 1: Vemurafenib 960 mg BID | 52.01 | -1.55 | -1.90 | -2.19 | -1.90 | -0.51 | -0.97 | -1.72 | 0.70 | 0.23 | -3.33 | -0.17 | -0.14 | -2.31 |
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | 52.39 | 0.92 | -0.01 | 1.35 | 0.52 | 0.18 | -0.33 | 0.40 | 0.27 | -0.59 | -0.69 | -1.67 | -1.83 | 18.50 |
Part 1 + Part 2: LGX818 300 mg | 52.24 | -3.14 | -2.78 | -3.08 | -2.39 | -3.29 | -2.88 | -2.88 | -1.88 | -2.38 | -2.58 | -1.38 | -1.00 | -3.81 |
Part 1: LGX818 300 mg | 52.76 | -3.58 | -3.77 | -3.05 | -2.69 | -3.67 | -2.71 | -2.48 | -1.66 | -2.80 | -2.59 | -1.38 | -1.00 | -5.18 |
ECOG: participant's performance status was measured on a 6-point scale: 0= fully active/able to carry on all pre-disease activities without restriction; 1= restricted in physically strenuous activity but ambulatory and able to carry out work of a light and sedentary nature; 2= ambulatory and capable of all self-care, but unable to carry out any work activities, up and about more than 50% of waking hours; 3= capable of only limited self-care, confined to bed/chair >50% of waking hours; 4= completely disabled, cannot carry on any self-care, totally confined to bed/chair: 5= dead. (NCT01909453)
Timeframe: Part 1 and Part 2: Baseline, Day 1 of each cycle (Cycle 2 to Cycle 31)
Intervention | Participants (Count of Participants) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Baseline: ECOG score 0 | Baseline: ECOG score 1 | Cycle 2 Day 1: ECOG score 0 | Cycle 2 Day 1: ECOG score 1 | Cycle 2 Day 1: ECOG score 2 | Cycle 2 Day 1: ECOG score 3 | Cycle 2 Day 1: ECOG score 4 | Cycle 3 Day 1: ECOG score 0 | Cycle 3 Day 1: ECOG score 1 | Cycle 3 Day 1: ECOG score 2 | Cycle 4 Day 1: ECOG score 0 | Cycle 4 Day 1: ECOG score 1 | Cycle 4 Day 1: ECOG score 2 | Cycle 4 Day 1: ECOG score 3 | Cycle 5 Day 1: ECOG score 0 | Cycle 5 Day 1: ECOG score 1 | Cycle 5 Day 1: ECOG score 2 | Cycle 5 Day 1: ECOG score 3 | Cycle 5 Day 1: ECOG score 4 | Cycle 6 Day 1: ECOG score 0 | Cycle 6 Day 1: ECOG score 1 | Cycle 6 Day 1: ECOG score 2 | Cycle 6 Day 1: ECOG score 3 | Cycle 6 Day 1: ECOG score 4 | Cycle 7 Day 1: ECOG score 0 | Cycle 7 Day 1: ECOG score 1 | Cycle 7 Day 1: ECOG score 2 | Cycle 8 Day 1: ECOG score 0 | Cycle 8 Day 1: ECOG score 1 | Cycle 8 Day 1: ECOG score 2 | Cycle 8 Day 1: ECOG score 3 | Cycle 9 Day 1: ECOG score 0 | Cycle 9 Day 1: ECOG score 1 | Cycle 9 Day 1: ECOG score 2 | Cycle 9 Day 1: ECOG score 3 | Cycle 9 Day 1: ECOG score 4 | Cycle 9 Day 1: ECOG score 5 | Cycle 10 Day 1: ECOG score 0 | Cycle 10 Day 1: ECOG score 1 | Cycle 10 Day 1: ECOG score 2 | Cycle 10 Day 1: ECOG score 3 | Cycle 11 Day 1: ECOG score 0 | Cycle 11 Day 1: ECOG score 1 | Cycle 11 Day 1: ECOG score 2 | Cycle 11 Day 1: ECOG score 3 | Cycle 12 Day 1: ECOG score 0 | Cycle 12 Day 1: ECOG score 1 | Cycle 12 Day 1: ECOG score 2 | Cycle 12 Day 1: ECOG score 3 | Cycle 12 Day 1: ECOG score 4 | Cycle 13 Day 1: ECOG score 0 | Cycle 13 Day 1: ECOG score 1 | Cycle 13 Day 1: ECOG score 2 | Cycle 13 Day 1: ECOG score 4 | Cycle 14 Day 1: ECOG score 0 | Cycle 14 Day 1: ECOG score 1 | Cycle 14 Day 1: ECOG score 2 | Cycle 14 Day 1: ECOG score 3 | Cycle 14 Day 1: ECOG score 4 | Cycle 15 Day 1: ECOG score 0 | Cycle 15 Day 1: ECOG score 1 | Cycle 15 Day 1: ECOG score 2 | Cycle 15 Day 1: ECOG score 3 | Cycle 15 Day 1: ECOG score 4 | Cycle 16 Day 1: ECOG score 0 | Cycle 16 Day 1: ECOG score 1 | Cycle 16 Day 1: ECOG score 2 | Cycle 16 Day 1: ECOG score 3 | Cycle 17 Day 1: ECOG score 0 | Cycle 17 Day 1: ECOG score 1 | Cycle 17 Day 1: ECOG score 2 | Cycle 18 Day 1: ECOG score 0 | Cycle 18 Day 1: ECOG score 1 | Cycle 18 Day 1: ECOG score 2 | Cycle 18 Day 1: ECOG score 3 | Cycle 19 Day 1: ECOG score 0 | Cycle 19 Day 1: ECOG score 1 | Cycle 19 Day 1: ECOG score 2 | Cycle 20 Day 1: ECOG score 0 | Cycle 20 Day 1: ECOG score 1 | Cycle 20 Day 1: ECOG score 2 | Cycle 20 Day 1: ECOG score 3 | Cycle 21 Day 1: ECOG score 0 | Cycle 21 Day 1: ECOG score 1 | Cycle 21 Day 1: ECOG score 2 | Cycle 22 Day 1: ECOG score 0 | Cycle 22 Day 1: ECOG score 1 | Cycle 22 Day 1: ECOG score 3 | Cycle 22 Day 1: ECOG score 4 | Cycle 23 Day 1: ECOG score 0 | Cycle 23 Day 1: ECOG score 1 | Cycle 24 Day 1: ECOG score 0 | Cycle 24 Day 1: ECOG score 1 | Cycle 25 Day 1: ECOG score 0 | Cycle 25 Day 1: ECOG score 1 | Cycle 26 Day 1: ECOG score 0 | Cycle 26 Day 1: ECOG score 1 | Cycle 26 Day 1: ECOG score 2 | Cycle 27 Day 1: ECOG score 0 | Cycle 27 Day 1: ECOG score 1 | Cycle 28 Day 1: ECOG score 0 | Cycle 28 Day 1: ECOG score 1 | Cycle 29 Day 1: ECOG score 0 | Cycle 29 Day 1: ECOG score 1 | Cycle 30 Day 1: ECOG score 0 | Cycle 30 Day 1: ECOG score 1 | Cycle 31 Day 1: ECOG score 0 | Cycle 31 Day 1: ECOG score 1 | |
Part 1 + Part 2: LGX818 300 mg | 199 | 77 | 142 | 111 | 7 | 2 | 0 | 130 | 113 | 6 | 128 | 96 | 7 | 1 | 118 | 100 | 6 | 0 | 0 | 97 | 90 | 6 | 1 | 1 | 95 | 87 | 2 | 77 | 70 | 6 | 1 | 72 | 67 | 1 | 1 | 0 | 0 | 70 | 53 | 2 | 0 | 61 | 56 | 4 | 0 | 55 | 49 | 2 | 1 | 0 | 55 | 46 | 3 | 0 | 62 | 37 | 2 | 0 | 1 | 54 | 37 | 2 | 0 | 0 | 52 | 30 | 4 | 0 | 48 | 33 | 2 | 41 | 29 | 0 | 0 | 40 | 26 | 1 | 34 | 22 | 2 | 0 | 31 | 20 | 1 | 27 | 16 | 1 | 1 | 26 | 12 | 23 | 10 | 23 | 8 | 21 | 8 | 0 | 20 | 6 | 18 | 6 | 13 | 5 | 9 | 3 | 7 | 3 |
Part 1: LGX818 300 mg | 139 | 53 | 98 | 79 | 3 | 2 | 0 | 90 | 81 | 4 | 93 | 66 | 4 | 1 | 85 | 69 | 4 | 0 | 0 | 68 | 65 | 3 | 0 | 1 | 68 | 60 | 1 | 55 | 49 | 3 | 1 | 50 | 47 | 1 | 0 | 0 | 0 | 52 | 35 | 1 | 0 | 44 | 40 | 1 | 0 | 44 | 31 | 1 | 1 | 0 | 41 | 31 | 1 | 0 | 47 | 27 | 0 | 0 | 1 | 41 | 30 | 1 | 0 | 0 | 41 | 23 | 3 | 0 | 39 | 27 | 1 | 36 | 24 | 0 | 0 | 38 | 20 | 1 | 31 | 19 | 2 | 0 | 29 | 19 | 1 | 27 | 16 | 1 | 1 | 26 | 12 | 23 | 10 | 23 | 8 | 21 | 8 | 0 | 20 | 6 | 18 | 6 | 13 | 5 | 9 | 3 | 7 | 3 |
Part 1: Vemurafenib 960 mg BID | 135 | 51 | 113 | 64 | 4 | 0 | 0 | 107 | 64 | 4 | 98 | 52 | 4 | 4 | 82 | 52 | 7 | 1 | 1 | 78 | 46 | 1 | 1 | 0 | 74 | 35 | 2 | 58 | 33 | 4 | 0 | 55 | 30 | 4 | 1 | 0 | 0 | 43 | 26 | 2 | 1 | 39 | 20 | 2 | 1 | 32 | 16 | 2 | 1 | 0 | 27 | 18 | 2 | 0 | 25 | 19 | 2 | 0 | 0 | 22 | 18 | 1 | 0 | 0 | 24 | 10 | 1 | 0 | 21 | 11 | 1 | 18 | 11 | 1 | 1 | 20 | 9 | 1 | 19 | 8 | 0 | 0 | 15 | 8 | 0 | 11 | 6 | 0 | 0 | 10 | 5 | 9 | 5 | 9 | 2 | 7 | 2 | 0 | 3 | 4 | 4 | 1 | 5 | 0 | 4 | 0 | 2 | 0 |
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | 136 | 56 | 142 | 44 | 1 | 0 | 1 | 131 | 53 | 1 | 128 | 50 | 1 | 0 | 128 | 42 | 3 | 1 | 0 | 124 | 45 | 0 | 0 | 0 | 111 | 46 | 1 | 112 | 33 | 2 | 1 | 102 | 36 | 4 | 0 | 1 | 1 | 94 | 32 | 3 | 0 | 88 | 30 | 2 | 0 | 84 | 25 | 1 | 0 | 0 | 77 | 22 | 1 | 0 | 74 | 23 | 0 | 0 | 0 | 72 | 20 | 1 | 1 | 0 | 64 | 24 | 1 | 0 | 65 | 16 | 1 | 60 | 14 | 1 | 0 | 54 | 9 | 2 | 53 | 7 | 0 | 1 | 36 | 10 | 9 | 29 | 8 | 0 | 0 | 24 | 6 | 21 | 7 | 17 | 3 | 14 | 3 | 1 | 5 | 3 | 5 | 3 | 1 | 2 | 0 | 0 | 0 | 0 |
Part 2: LGX818 300 mg | 60 | 24 | 44 | 32 | 4 | 0 | 0 | 40 | 32 | 2 | 35 | 30 | 3 | 0 | 33 | 31 | 2 | 0 | 0 | 29 | 25 | 3 | 1 | 0 | 27 | 27 | 1 | 22 | 21 | 3 | 0 | 22 | 20 | 0 | 1 | 0 | 0 | 18 | 18 | 1 | 0 | 17 | 16 | 3 | 0 | 11 | 18 | 1 | 0 | 0 | 14 | 15 | 2 | 0 | 15 | 10 | 2 | 0 | 0 | 13 | 7 | 1 | 0 | 0 | 11 | 7 | 1 | 0 | 9 | 6 | 1 | 5 | 5 | 0 | 0 | 2 | 6 | 0 | 3 | 3 | 0 | 0 | 2 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | 189 | 68 | 193 | 62 | 1 | 0 | 0 | 197 | 55 | 1 | 189 | 56 | 4 | 1 | 181 | 55 | 2 | 1 | 0 | 168 | 58 | 3 | 1 | 1 | 158 | 58 | 2 | 140 | 58 | 1 | 1 | 135 | 52 | 0 | 0 | 1 | 0 | 121 | 46 | 3 | 1 | 116 | 42 | 0 | 0 | 113 | 38 | 0 | 0 | 1 | 102 | 39 | 1 | 1 | 100 | 33 | 2 | 1 | 0 | 82 | 27 | 1 | 0 | 1 | 64 | 23 | 0 | 1 | 52 | 15 | 1 | 34 | 11 | 1 | 0 | 22 | 7 | 1 | 15 | 5 | 0 | 0 | 11 | 2 | 0 | 4 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Number of participants with clinically notable shift from baseline in laboratory parameter values based on national cancer institute common terminology criteria (NCI-CTCAE) grade, Version 4.03 were graded from Grades 1 to 5. Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local or noninvasive intervention indicated. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death. Clinically notable shift from baseline in laboratory parameter = worsening by at least 2 grades or to >=grade 3. (NCT01909453)
Timeframe: Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group
Intervention | Participants (Count of Participants) | ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Hemoglobin (hypo) | Prothrombin international normalized ratio increased | Lymphocytes (hypo) | Lymphocytes (hyper) | Neutrophils (hypo) | Platelets (hypo) | Leukocytes (hypo) | Albumin (hypo) | Alkaline phosphatase | Alanine aminotransferase | Aspartate aminotransferase | Bilirubin | Creatine (phospho)kinase | Corrected Calcium (hypo) | Corrected Calcium (hyper) | Creatinine | Gamma-glutamyl transferase | Glucose serum fasting (hypo) | Glucose serum fasting (hyper) | Magnesium (hypo) | Magnesium (hyper) | Phosphate (hypo) | Potassium (hypo) | Potassium (hyper) | Sodium (hypo) | |
Part 1: LGX818 300 mg | 11 | 1 | 15 | 11 | 5 | 1 | 3 | 5 | 3 | 8 | 4 | 0 | 1 | 1 | 0 | 15 | 29 | 4 | 12 | 1 | 0 | 25 | 1 | 4 | 1 |
Part 1: Vemurafenib 960 mg BID | 13 | 3 | 41 | 5 | 3 | 1 | 4 | 2 | 4 | 8 | 4 | 13 | 1 | 3 | 2 | 48 | 15 | 3 | 12 | 0 | 1 | 35 | 3 | 6 | 1 |
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | 19 | 0 | 20 | 14 | 14 | 2 | 5 | 3 | 6 | 15 | 12 | 1 | 32 | 1 | 0 | 35 | 43 | 2 | 20 | 0 | 2 | 18 | 1 | 6 | 7 |
AESI consisted of events for which there was a specific clinical interest with regard to LGX818 and/or MEK162 treatment. Dermatologic-related AESI included rash, photosensitivity, nail disorders, skin infections, severe cutaneous adverse reactions and Palmar-plantar erythrodysaesthesia (PPE) syndrome. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental ADL; Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. AEs of grade 3 or 4 are reported in this outcome measure. (NCT01909453)
Timeframe: Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group
Intervention | Participants (Count of Participants) | |||||
---|---|---|---|---|---|---|
Rash | Skin infections | PPE syndrome | Photosensitivity | Nail disorders | Severe cutaneous adverse reactions | |
Part 1: LGX818 300 mg | 10 | 1 | 26 | 0 | 0 | 1 |
Part 1: Vemurafenib 960 mg BID | 25 | 0 | 2 | 3 | 0 | 5 |
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | 2 | 4 | 0 | 1 | 0 | 0 |
Newly occurring notable ECG values were reported for QT (millisecond [ms]), QTcF (millisecond), QTcB (millisecond) and heart rate (beats per minute). Newly occurring was defined as participants not meeting criterion at baseline and meeting criterion post-baseline. Ranges for newly occurring notable ECG values (QT, QTcF, QTcB) are New greater than (>) 450, New >480, New >500, Increase from baseline >30, Increase from baseline >60. Heart rate: New <60, New >100 was considered as newly occurring notable value. (NCT01909453)
Timeframe: Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group
Intervention | Participants (Count of Participants) | ||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
QT: Increase >30 ms | QT: Increase >60 ms | QT: New >450 ms | QT: New >480 ms | QT: New >500 ms | QTcF: Increase >30 ms | QTcF: Increase >60 ms | QTcF: New >450 ms | QTcF: New >480 ms | QTcF: New >500 ms | QTcB: Increase >30 ms | QTcB: Increase >60 ms | QTcB: New >450 ms | QTcB: New >480 ms | QTcB: New >500 ms | Heart rate: New <60 bpm | Heart rate: New <100 bpm | |
Part 1: LGX818 300 mg | 68 | 19 | 15 | 4 | 2 | 56 | 7 | 39 | 7 | 5 | 74 | 15 | 76 | 23 | 10 | 37 | 23 |
Part 1: Vemurafenib 960 mg BID | 81 | 24 | 17 | 3 | 2 | 76 | 10 | 42 | 5 | 3 | 78 | 14 | 65 | 20 | 8 | 16 | 18 |
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | 105 | 27 | 23 | 5 | 2 | 50 | 10 | 25 | 7 | 1 | 47 | 11 | 47 | 12 | 3 | 58 | 14 |
Notably abnormal vital signs were: Low/high systolic blood pressure (SBP) (millimeter of mercury [mmHg]): less than or equal to (<=) 90 mmHg with decrease from baseline of greater than or equal to (>=) 20 mmHg/>= 160 mmHg with increase from baseline of >=20 mmHg. Low/high diastolic blood pressure (DBP) [mmHg]: <= 50 mmHg with decrease from baseline of >=15 mmHg/>=100 mmHg with increase from baseline of >=15 mmHg. Low/high Pulse rate: <=50 beats per minute (bpm) with decrease from baseline of >=15 bpm/>= 120 bpm with increase from baseline of >=15 bpm. Low/high Weight [kilogram]: >=20 percent (%) decrease from baseline/>= 10% increase from baseline. Low/high Body temperature degree Celsius (C): <= 36 degree C/>= 37.5 degree C. (NCT01909453)
Timeframe: Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group
Intervention | Participants (Count of Participants) | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Sitting Pulse Rate (bpm): High | Sitting Pulse Rate (bpm): Low | Sitting Systolic Blood Pressure (mmHg): High | Sitting Systolic Blood Pressure (mmHg): Low | Sitting Diastolic Blood Pressure (mmHg): High | Sitting Diastolic Blood Pressure (mmHg): Low | Weight (kg): High | Weight (kg): Low | Body temperature (degree C): High | Body temperature (degree C): Low | |
Part 1: LGX818 300 mg | 7 | 8 | 14 | 4 | 5 | 7 | 10 | 8 | 11 | 74 |
Part 1: Vemurafenib 960 mg BID | 8 | 2 | 31 | 1 | 13 | 5 | 8 | 13 | 17 | 57 |
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | 1 | 3 | 27 | 7 | 23 | 9 | 44 | 2 | 19 | 76 |
AESI consisted of events for which there was a specific clinical interest with regard to LGX818 and/or MEK162 treatment. Ocular-related AESI included retinopathy excluding retinal vein occlusion (RVO), RVO and uveitis-type events. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental ADL; Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. AEs of grade 3 or 4 are reported in this outcome measure. (NCT01909453)
Timeframe: Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group
Intervention | Participants (Count of Participants) | ||
---|---|---|---|
Retinopathy excluding RVO | RVO | Uveitis-type events | |
Part 1: LGX818 300 mg | 0 | 1 | 0 |
Part 1: Vemurafenib 960 mg BID | 0 | 0 | 0 |
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | 5 | 0 | 1 |
Participants with worst post-baseline LVEF Values were graded as Grade 0: Non missing value below Grade 2; Grade 2: LVEF between 40% and 50% or absolute reduction from baseline >=10% and < 20%; Grade 3: LVEF between 20% and 39% or absolute reduction from baseline >=20%; Grade 4: LVEF lower than 20%. Baseline was defined as the last non-missing value prior to the first dose of study treatment. Missing data were due to participants who died or withdrew consent prior to the first scheduled evaluation or missed evaluations as protocol deviations. (NCT01909453)
Timeframe: Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group
Intervention | Participants (Count of Participants) | ||||
---|---|---|---|---|---|
Grade 0 | Grade 2 | Grade 3 | Grade 4 | Missing | |
Part 1: LGX818 300 mg | 161 | 17 | 4 | 0 | 10 |
Part 1: LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | 127 | 56 | 3 | 0 | 6 |
Part 1: Vemurafenib 960 mg BID | 161 | 16 | 2 | 0 | 7 |
AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was any untoward medical occurrence at any dose that results in death; is life-threatening; requires inpatient hospitalization/prolongation of existing hospitalization; results in persistent/significant disability/incapacity; results in congenital anomaly/birth defect or that is considered to be important medical event. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence; Grade 5: death. AEs of all grades were reported. (NCT01909453)
Timeframe: Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group
Intervention | percentage of participants (Number) | |
---|---|---|
Participants with AEs | Participants with SAEs | |
Part 1: LGX818 300 mg | 99.5 | 34.9 |
Part 1: Vemurafenib 960 mg BID | 99.5 | 37.1 |
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | 98.4 | 34.4 |
(NCT01909453)
Timeframe: Cycle 1 Day 1: pre-dose, 0.5, 1.5, 4 to 8 hours post dose; Cycle 2 Day 1: pre-dose; Cycle 3 Day 1: pre-dose
Intervention | nanogram per milliliter (Mean) | |||||
---|---|---|---|---|---|---|
Cycle 1 Day 1: pre-dose | Cycle 1 Day 1: 0.5 hours post dose | Cycle 1 Day 1: 1.5 hours post dose | Cycle 1 Day 1: 4 to 8 hours post dose | Cycle 2 Day 1: pre-dose | Cycle 3 Day 1: pre-dose | |
Part 1: LGX818 300 mg | 58.1 | 1190 | 4090 | 1850 | 73.6 | 53.8 |
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | 18.6 | 1640 | 6860 | 3400 | 119 | 150 |
(NCT01909453)
Timeframe: Cycle 1 Day 1: pre-dose, 0.5, 1.5, 4 to 8, hours post dose; Cycle 2 Day 1: pre-dose; Cycle 3 Day 1: pre-dose
Intervention | nanogram per milliliter (Mean) | |||||
---|---|---|---|---|---|---|
Cycle 1 Day 1: pre-dose | Cycle 1 Day 1: 0.5 hours post dose | Cycle 1 Day 1: 1.5 hours post dose | Cycle 1 Day 1: 4 to 8 hours post dose | Cycle 2 Day 1: pre-dose | Cycle 3 Day 1: pre-dose | |
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | 2.95 | 426 | 832 | 330 | 81.0 | 68.1 |
Number of participants with clinically notable shift from baseline in laboratory parameter values based on national cancer institute common terminology criteria (NCI-CTCAE) grade, Version 4.0 were graded from Grades 1 to 5. Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local or noninvasive intervention indicated. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death. Clinically notable shift from baseline in laboratory parameter = worsening by at least 2 grades or to >=grade 3. (NCT01909453)
Timeframe: Baseline up to 30 days after last dose of study drug (up to 36 months)
Intervention | Participants (Count of Participants) | ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Hemoglobin (hypo) | Prothrombin international normalized ratio increased | Lymphocytes (hypo) | Lymphocytes (hyper) | Neutrophils (hypo) | Platelets (hypo) | Leukocytes (hypo) | Albumin (hypo) | Alkaline phosphatase (hyper) | Alanine aminotransferase | Aspartate aminotransferase | Bilirubin | Creatine kinase | Corrected Calcium (hypo) | Creatinine | Gamma-glutamyl transferase | Glucose serum fasting (hypo) | Glucose serum fasting (hyper) | Magnesium (hypo) | Magnesium (hyper) | Phosphate (hypo) | Potassium (hypo) | Potassium (hyper) | Sodium (hypo) | Sodium (hyper) | |
Part 1 + Part 2: LGX818 300 mg | 16 | 1 | 25 | 13 | 9 | 2 | 5 | 9 | 4 | 9 | 5 | 0 | 1 | 2 | 26 | 38 | 4 | 17 | 1 | 0 | 33 | 1 | 7 | 3 | 0 |
Part 2: LGX818 300 mg | 5 | 0 | 10 | 2 | 4 | 1 | 2 | 4 | 1 | 1 | 1 | 0 | 0 | 1 | 11 | 9 | 0 | 5 | 0 | 0 | 8 | 0 | 3 | 2 | 0 |
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | 16 | 4 | 28 | 11 | 19 | 1 | 3 | 7 | 11 | 18 | 15 | 2 | 40 | 4 | 44 | 38 | 3 | 27 | 0 | 3 | 26 | 2 | 8 | 4 | 2 |
AESI consisted of events for which there was a specific clinical interest with regard to LGX818 and/or MEK162 treatment. Dermatologic-related AESI included rash, photosensitivity, nail disorders, skin infections, severe cutaneous adverse reactions and PPE syndrome. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental ADL; Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. AEs of grade 3 or 4 are reported are reported in this outcome measure. (NCT01909453)
Timeframe: Baseline up to 30 days after last dose of study drug (up to 36 months)
Intervention | Participants (Count of Participants) | |||||
---|---|---|---|---|---|---|
Rash | Skin infection | PPE syndrome | Photosensitivity | Nail disorders | Severe cutaneous adverse reactions | |
Part 1 + Part 2: LGX818 300 mg | 13 | 1 | 30 | 0 | 0 | 1 |
Part 2: LGX818 300 mg | 3 | 0 | 4 | 0 | 0 | 0 |
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | 2 | 7 | 1 | 0 | 0 | 0 |
Newly occurring notable ECG values were reported for QT (ms), QTcF (ms), QTcB (ms) and heart rate (bpm). Newly occurring was defined as participants not meeting criterion at baseline and meeting criterion post-baseline. Ranges for newly occurring notable ECG values (QT, QTcF, QTcB) are New >450, New >480, New >500, increase from baseline >30, Increase from baseline >60. Heart rate: New < 60, New >100 was considered as newly occurring notable value. (NCT01909453)
Timeframe: Baseline up to 30 days after last dose of study drug (up to 36 months)
Intervention | Participants (Count of Participants) | ||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
QT (ms): Increase from baseline > 30 | QT (ms): Increase from baseline > 60 | QT (ms): New > 450 | QT (ms): New > 480 | QT (ms): New > 500 | QTcF (ms): Increase from baseline > 30 | QTcF (ms): Increase from baseline > 60 | QTcF (ms): New > 450 | QTcF (ms): New > 480 | QTcF (ms): New > 500 | QTcB (ms): New > 450 | QTcB (ms): New > 480 | QTcB (ms): New > 500 | QTcB (ms): Increase from baseline > 30 | QTcB (ms): Increase from baseline > 60 | Heart rate (bpm): New < 60 | Heart rate (bpm): New > 100 | |
Part 1 + Part 2: LGX818 300 mg | 95 | 25 | 20 | 6 | 2 | 76 | 14 | 50 | 12 | 6 | 104 | 29 | 11 | 98 | 23 | 42 | 33 |
Part 2: LGX818 300 mg | 27 | 6 | 5 | 2 | 0 | 20 | 7 | 11 | 5 | 1 | 28 | 6 | 1 | 24 | 8 | 5 | 10 |
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | 132 | 34 | 34 | 9 | 4 | 59 | 13 | 36 | 11 | 2 | 70 | 23 | 10 | 69 | 22 | 82 | 8 |
Notably abnormal vital signs were: Low/high systolic blood pressure (SBP) in millimeter of mercury (mmHg): less than or equal to (<=) 90 mmHg with decrease from baseline of greater than or equal to (>=) 20 mmHg/>= 160 mmHg with increase from baseline of >=20 mmHg, Low/high diastolic blood pressure (DBP) [mmHg]: <=50 mmHg with decrease from baseline of >=15 mmHg/>=100 mmHg with increase from baseline of >=15 mmHg, Low/high pulse rate [bpm]: <=50 bpm with decrease from baseline of >=15 bpm/>=120 bpm with increase from baseline of >=15 bpm, Low/high weight (kg): >=20 % decrease from baseline/>= 10% increase from baseline Low/high Body temperature degree C): <= 36°C/>= 37.5 degree C. (NCT01909453)
Timeframe: Baseline up to 30 days after last dose of study drug (up to 36 months)
Intervention | Participants (Count of Participants) | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Sitting Pulse Rate (bpm): High | Sitting Pulse Rate (bpm): Low | Sitting Systolic Blood Pressure (mmHg): High | Sitting Systolic Blood Pressure (mmHg): Low | Sitting Diastolic Blood Pressure (mmHg): High | Sitting Diastolic Blood Pressure (mmHg): Low | Weight (kg): High | Weight (kg): Low | Body temperature (°C): High | Body temperature (°C): Low | |
Part 1 + Part 2: LGX818 300 mg | 10 | 9 | 17 | 8 | 7 | 9 | 11 | 9 | 16 | 96 |
Part 2: LGX818 300 mg | 3 | 1 | 3 | 4 | 2 | 2 | 1 | 1 | 5 | 22 |
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | 7 | 11 | 40 | 10 | 41 | 7 | 46 | 0 | 14 | 120 |
AESI consisted of events for which there was a specific clinical interest with regard to LGX818 and/or MEK162 treatment. Ocular-related AESI included retinopathy excluding RVO, RVO and uveitis-type events. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental ADL; Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. AEs of grade 3 or 4 are reported in this outcome measure. (NCT01909453)
Timeframe: Baseline up to 30 days after last dose of study drug (up to 36 months)
Intervention | Participants (Count of Participants) | ||
---|---|---|---|
Retinopathy excluding RVO | RVO | Uveitis-type events | |
Part 1 + Part 2: LGX818 300 mg | 0 | 1 | 0 |
Part 2: LGX818 300 mg | 0 | 0 | 0 |
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | 4 | 0 | 4 |
Participants with worst post-baseline LVEF Values were graded as Grade 0: Non missing value below Grade 2; Grade 2: LVEF between 40% and 50% or absolute reduction from baseline >=10% and < 20%;Grade 3: LVEF between 20% and 39% or absolute reduction from baseline >=20%; Grade 4: LVEF lower than 20%. Baseline was defined as the last non-missing value prior to the first dose of study treatment. Missing data were due to participants who died or withdrew consent prior to the first scheduled evaluation or missed evaluations as protocol deviations. (NCT01909453)
Timeframe: Baseline up to 30 days after last dose of study drug (up to 36 months)
Intervention | Participants (Count of Participants) | ||||
---|---|---|---|---|---|
Grade 0 | Grade 2 | Grade 3 | Grade 4 | Missing | |
Part 1 + Part 2: LGX818 300 mg | 235 | 22 | 4 | 0 | 15 |
Part 2: LGX818 300 mg | 74 | 5 | 0 | 0 | 5 |
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | 181 | 71 | 3 | 0 | 2 |
AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was any untoward medical occurrence at any dose that results in death; is life-threatening; requires inpatient hospitalization/prolongation of existing hospitalization; results in persistent/significant disability/incapacity; results in congenital anomaly/birth defect or that is considered to be important medical event. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence; Grade 5: death. AEs of all grades were reported. (NCT01909453)
Timeframe: Baseline up to 30 days after last dose of study drug (up to 36 months)
Intervention | percentage of Participants (Number) | |
---|---|---|
AEs | SAEs | |
Part 1 + Part 2: LGX818 300 mg | 98.6 | 33.3 |
Part 2: LGX818 300 mg | 96.4 | 29.8 |
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | 98.1 | 29.2 |
(NCT01909453)
Timeframe: Cycle 1 Day 1: pre-dose, 0.5, 1.5, 4 to 8 hours post dose; Cycle 2 Day 1: pre-dose; Cycle 3 Day 1: pre-dose
Intervention | nanogram per milliliter (Mean) | |||||
---|---|---|---|---|---|---|
Cycle 1 Day 1: pre-dose | Cycle 1 Day 1: 0.5 hours post dose | Cycle 1 Day 1: 1.5 hours post dose | Cycle 1 Day 1: 4 to 8 hours post dose | Cycle 2 Day 1: pre-dose | Cycle 3 Day 1: pre-dose | |
Part 1 + Part 2: LGX818 300 mg | 39.7 | 1250 | 4170 | 1980 | 60.1 | 60.6 |
Part 2: LGX818 300 mg | 0.0145 | 1370 | 4310 | 2250 | 29.5 | 79.5 |
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | 5.02 | 1360 | 4390 | 2420 | 121 | 74.1 |
(NCT01909453)
Timeframe: Cycle 1 Day 1: pre-dose, 0.5, 1.5, 4 to 8, hours post dose; Cycle 2 Day 1: pre-dose; Cycle 3 Day 1: pre-dose
Intervention | nanogram per milliliter (Mean) | |||||
---|---|---|---|---|---|---|
Cycle 1 Day 1: pre-dose | Cycle 1 Day 1: 0.5 hours post dose | Cycle 1 Day 1: 1.5 hours post dose | Cycle 1 Day 1: 4 to 8 hours post dose | Cycle 2 Day 1: pre-dose | Cycle 3 Day 1: pre-dose | |
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | 1.68 | 366 | 642 | 287 | 72.3 | 73.2 |
Subjects with post-treatment sustained virologic response (SVR) = Number of subjects with negative HCV RNA 12 weeks after completing therapy / number of subjects treated post-kidney transplantation (NCT02743897)
Timeframe: Baseline to 24 weeks
Intervention | Participants (Count of Participants) |
---|---|
Direct-acting Antiviral Treatment for HCV | 62 |
Number of subjects with major adverse events attributable to HCV therapy in post-kidney transplant (NCT02743897)
Timeframe: Baseline to 52 weeks
Intervention | Participants (Count of Participants) |
---|---|
Direct-acting Antiviral Treatment for HCV | 1 |
The primary analysis will be based on a calculation of SVR rates (number of subjects with SVR; negative HCV RNA after completing Zepatier therapy) / (number of subjects treated with Zepatier post-heart transplantation) (NCT03146741)
Timeframe: Baseline to 24 weeks
Intervention | Participants (Count of Participants) |
---|---|
Zepatier (Grazoprevir 100mg and Elbasvir 50 mg) | 9 |
(NCT03146741)
Timeframe: Baseline to 52 weeks
Intervention | Severe adverse event (Number) |
---|---|
Zepatier (Grazoprevir 100mg and Elbasvir 50 mg) | 0 |
Hepatitis C Virus (HCV) ribonucleic acid (RNA) was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay. SVR12 was defined as HCV RNA
Timeframe: Week 24 (12 weeks after the end of treatment)
Intervention | Percentage of participants (Number) |
---|---|
Immediate Treatment Group | 94.6 |
Hepatitis C Virus RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay. SVR24 was defined as HCV RNA
Timeframe: Week 36 (24 weeks after the end of treatment)
Intervention | Percentage of participants (Number) |
---|---|
Immediate Treatment Group | 94.3 |
Hepatitis C Virus RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay. SVR4 was defined as HCV RNA
Timeframe: Week 16 (4 weeks after the end of treatment)
Intervention | Percentage of participants (Number) |
---|---|
Immediate Treatment Group | 97.2 |
An adverse event is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. (NCT02105467)
Timeframe: Up to Week 12 (end of Blinded Treatment)
Intervention | Percentage of participants (Number) |
---|---|
Immediate Treatment Group | 0.9 |
Deferred Treatment Group | 1.0 |
An adverse event is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. (NCT02105467)
Timeframe: Up to Week 14 (14 days after the Blinded Treatment was completed)
Intervention | Percentage of participants (Number) |
---|---|
Immediate Treatment Group | 67.4 |
Deferred Treatment Group | 68.6 |
The area under the plot of plasma concentration of drug against time after drug administration is defined as the area under the curve (AUC). The AUCss is the area under the curve during the steady-state period. The AUCss is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. AUCss used concentration data from 0 to 24 hours at steady-state for Weeks 4 and 12. (NCT01332305)
Timeframe: Weeks 4 and 12
Intervention | ng*hour/ml (Mean) | |
---|---|---|
Week 4, n=0, 38, 33, 33, 35 | Week 12, n=0, 32, 30, 30, 30 | |
GEn 1200 mg | 96.1 | 95.7 |
GEn 1800 mg | 141 | 146 |
GEn 2400 mg | 176 | 173 |
GEn 600 mg | 49.3 | 51.4 |
"Css, max is defined as the maximum or peak concentration of a drug observed after multiple administration, at steady state. Css, max is one of the parameters of particular use in estimating the bioavailability of drugs, by measuring the total amount of drug absorbed. Css, min is defined as the minimum concentration of a drug observed after its administration, in steady state. ng, nanograms; PK, pharmacokinetic; W, week; BLQ, below limit of quantitation." (NCT01332305)
Timeframe: Weeks 4 and 12
Intervention | nanograms per milliliter (ng/ml) (Mean) | |||
---|---|---|---|---|
Css, max; Week 4, n=0, 39, 33, 33, 36 | Css, max; Week 12, n=0, 32, 30, 30, 31 | Css, min; Week 4, n=0, 39, 33, 33, 36 | Css, min; Week 12, n=0, 32, 30, 30, 31 | |
GEn 1200 mg | 7.14 | 7.15 | 1.37 | 1.32 |
GEn 1800 mg | 11.4 | 12.0 | 1.63 | 1.60 |
GEn 2400 mg | 14.0 | 13.3 | 2.34 | 2.41 |
GEn 600 mg | 3.86 | 4.14 | 0.690 | 0.600 |
"Tmax is defined as the time to the maximum or peak concentration of a drug observed after multiple administration. T1/2 is defined as the time to when half of the total amount of a particular substance is eliminated from the body." (NCT01332305)
Timeframe: Weeks 4 and 12
Intervention | hours (Mean) | |||
---|---|---|---|---|
Tmax; Week 4, n=0, 39, 33, 33, 36 | Tmax; Week 12, n=0, 32, 30, 30, 31 | T1/2; Week 4, n=0, 38, 33, 33, 35 | T1/2, Week 12, n=0, 32, 30, 30, 30 | |
GEn 1200 mg | 8.57 | 8.72 | 6.67 | 6.63 |
GEn 1800 mg | 7.61 | 8.00 | 5.82 | 5.89 |
GEn 2400 mg | 8.01 | 8.13 | 6.05 | 6.09 |
GEn 600 mg | 8.76 | 6.96 | 5.82 | 6.27 |
"The investigator -rated Clinical Global Impression of Improvement (CGI-I) scale is an assessment designed to allow investigators to rate the change of a participant's disease severity over time based on a seven-point scale, with a score of 1 being very much improved, a score of 2 being much improved, a score of 3 being minimally improved, a score of 4 being no change, a score of 5 being minimally improved,a score of 6 being much worse, and a score of 7 being very much worse. Participants with a response of much improved or very much improved were classified as responders." (NCT00365352)
Timeframe: Week 12
Intervention | participants (Number) |
---|---|
Placebo | 43 |
GEn (XP13512/GSK1838262) 1200 mg | 86 |
The International Restless Legs Syndrome (IRLS) Rating scale is a measure of RLS disease severity. The scale reflects the participant-reported assessment of primary sensory and motor features and associated sleep problems in RLS. Ten items (individually scored from 0 to 4) are included that assess the impact of symptoms on participants' mood, daily life, and activities. The total scale score is a sum of all of the individual item scores and ranges from 0-40 points, with 40 being the most severe. The scale assesses symptoms over the week prior to measurement. (NCT00365352)
Timeframe: Baseline and Week 12
Intervention | scores on a scale (Mean) |
---|---|
Placebo | -9.8 |
GEn (XP13512/GSK1838262) 1200 mg | -13.0 |
"The MOS Sleep Scale measures most constructs of sleep. The scale has a battery of questions to measure specific aspects of sleep in participants with co-morbidities. The four domains scored from the MOS Sleep Scale were sleep disturbance,' sleep quantity,' sleep adequacy, and daytime somnolence. The scores of the sleep adequacy domain ranged from 1 to 100, with a high score indicating greater adequacy. The assessment was completed at Baseline (Day 1) and end of Weeks, 4, 8, and 12 (or end of Treatment)." (NCT00365352)
Timeframe: Basline and Week 12
Intervention | scores on a scale (Mean) |
---|---|
Placebo | 13.6 |
GEn (XP13512/GSK1838262) 600 mg | 29.1 |
GEn (XP13512/GSK1838262) 1200 mg | 27.7 |
"The MOS Sleep Scale measures most constructs of sleep. The scale has a battery of questions to measure specific aspects of sleep in participants with co-morbidities. The four domains scored from the MOS Sleep Scale were sleep disturbance,' sleep quantity,' sleep adequacy, and daytime somnolence. The scores of the sleep quantity domain were measured in time (number of hours of sleep each night). The assessment was completed at Baseline (Day 1) and end of Weeks, 4, 8, and 12 (or end of Treatment)." (NCT00365352)
Timeframe: Baseline and Week 12
Intervention | hours (Mean) |
---|---|
Placebo | 0.3 |
GEn (XP13512/GSK1838262) 600 mg | 0.6 |
GEn (XP13512/GSK1838262) 1200 mg | 0.8 |
The Daily RLS pain score was assessed by participants reporting whether they experienced any pain associated with RLS in the last 24 hours and rating their pain levels on an 11-point numerical rating scale, with 0 being no pain and 10 the most intense pain imaginable. The assessment was performed for 7 days prior to Baseline and pre-defined study visits. The change from baseline was calculated as the End of Treatment (Week 12) value minus the Baseline (Day 1) value. (NCT00365352)
Timeframe: Baseline and End of Treatment (Week 12)
Intervention | scores on a scale (Mean) |
---|---|
Placebo | -1.7 |
GEn (XP13512/GSK1838262) 600 mg | -2.5 |
GEn (XP13512/GSK1838262) 1200 mg | -2.6 |
The Average Daily RLS pain was assessed by participants reporting whether they experienced any pain associated with RLS in the last 24 hours and rating their pain levels on an 11-point numerical rating scale, with 0 being no pain and 10 the most intense pain imaginable. The assessment was performed for 7 days prior to Baseline and pre-defined visits. The change from baseline was calculated as the End of Treatment (Week 12) value minus the Baseline (Day 1) value. (NCT00365352)
Timeframe: Baseline and Week 12
Intervention | scores on a scale (Mean) |
---|---|
Placebo | -2.3 |
GEn (XP13512/GSK1838262) 600 mg | -3.5 |
GEn (XP13512/GSK1838262) 1200 mg | -3.5 |
"The MOS Sleep Scale measures most constructs of sleep. The scale has a battery of questions to measure specific aspects of sleep in participants with co-morbidities. The four domains scored from the MOS Sleep Scale were sleep disturbance,' sleep quantity,' sleep adequacy, and daytime somnolence. The scores of the daytime somnolence domain ranged from 1 to 100, with a high score indicating greater daytime somnolence. The assessment was completed at Baseline (Day 1) and end of Weeks, 4, 8, and 12 (or end of Treatment)." (NCT00365352)
Timeframe: Baseline and Week 12
Intervention | scores on a scale (Mean) |
---|---|
Placebo | -9.7 |
GEn (XP13512/GSK1838262) 600 mg | -9.8 |
GEn (XP13512/GSK1838262) 1200 mg | -16.1 |
The Restless Legs Syndrome Quality of Life (RLS-QoL) questionnaire is a disease-specific, participant-rated questionnaire that assesses the impact of RLS on daily life, emotional well-being, social life, and work life of the participants. The RLS-QoL Questionnaire is presented on a 0 (lowest possible score) to 100 (highest possible score) scale. It was completed at Day 1 and at the end of Weeks 4, 8, and 12 (or Early Termination). (NCT00365352)
Timeframe: Baseline and Week 12
Intervention | scores on a scale (Mean) |
---|---|
Placebo | 14.5 |
GEn (XP13512/GSK1838262) 600 mg | 19.3 |
GEn (XP13512/GSK1838262) 1200 mg | 20.4 |
"The Profile of Mood States (POMS) Brief Form contains 30 adjectives; each participant is asked to rate the degree to which each adjective describes themselves based on how they felt during the past week including the date on which the adjective was rated. The possible ratings range from 0 (Not all all) to 4 (Extremely). The Total Mood Disturbance Score (range of 0 to 120) is obtained by summing the values of six domains. Higher scores indicate a more negative mood disturbance. The POMS was completed at Baseline (Day 1), and at the end of Weeks 4, 8, and 12 (or Early Termination)." (NCT00365352)
Timeframe: Baseline to End of Treatment (Week 12)
Intervention | scores on a scale (Mean) |
---|---|
Placebo | -7.3 |
GEn (XP13512/GSK1838262) 600 mg | -10.9 |
GEn (XP13512/GSK1838262) 1200 mg | -11.5 |
"The MOS Sleep Scale measures most constructs of sleep. The scale has a battery of questions to measure specific aspects of sleep in participants with co-morbidities. The four domains scored from the MOS Sleep Scale were sleep disturbance,' sleep quantity,' sleep adequacy, and daytime somnolence. The scores of the sleep disturbance domain ranged from 1 to 100, with a high score indicating greater impairment of sleep. The assessment was completed at Baseline (Day 1) and end of Weeks, 4, 8, and 12 (or end of Treatment)." (NCT00365352)
Timeframe: Baseline and Week 12
Intervention | scores on a scale (Mean) |
---|---|
Placebo | -17.0 |
GEn (XP13512/GSK1838262) 600 mg | -29.5 |
GEn (XP13512/GSK1838262) 1200 mg | -30.7 |
The IRLS Rating scale is a measure of RLS disease severity. The scale reflects the participant-reported assessment of primary sensory and motor features and associated sleep problems in RLS. Items (individually scored from 0 to 4) are included that assess the impact of symptoms on participants' mood, daily life, and activities. The total scale score is a sum of all of the individual item scores and ranges from 0-40 points, with 40 being the most severe. The scale assesses symptoms over the week prior to measurement. (NCT00365352)
Timeframe: Baseline (Day 1) and End of Treatment (Week 12)
Intervention | scores on a scale (Mean) |
---|---|
Placebo | -9.8 |
GEn (XP13512/GSK1838262) 600 mg | -13.8 |
Average daily total sleep time was derived from the Pittsburgh Sleep Diary (PghSD; an instrument with separate components to be completed [self-reported] at bedtime and waketime) as the mean of non-missing total sleep time over the 7 days before each visit, where total sleep time = [(wake up time - lights out time) - time to fall asleep - time awake during the night] in hours. The change was calculated as the end of treatment (Week 12) value minus the Baseline value. (NCT00365352)
Timeframe: Baseline to End of Treatment (Week 12)
Intervention | hours (Mean) |
---|---|
Placebo | 0.6 |
GEn (XP13512/GSK1838262) 600 mg | 0.7 |
GEn (XP13512/GSK1838262) 1200 mg | 1.0 |
Average daily wake time after sleep onset was derived from the Pittsburgh Sleep Diary (PghSD) as the mean of non-missing total hours awake during the night after falling asleep over the 7 days before each visit. The change was calculated as the end of treatment (Week 12) value minus the Baseline value. (NCT00365352)
Timeframe: Baseline to End of Treatment (Week 12)
Intervention | minutes (Mean) |
---|---|
Placebo | -12.5 |
GEn (XP13512/GSK1838262) 600 mg | -16.4 |
GEn (XP13512/GSK1838262) 1200 mg | -18.5 |
The IRLS Rating scale is a measure of RLS disease severity. The scale reflects the participant-reported assessment of primary sensory and motor features and associated sleep problems in RLS. Items (individually scored from 0 to 4) are included that assess the impact of symptoms on participants' mood, daily life, and activities. The total scale score is a sum of all of the individual item scores and ranges from 0-40 points, with 40 being the most severe. The scale assesses symptoms over the week prior to measurement. (NCT00365352)
Timeframe: Baseline and the End of Week 1
Intervention | scores on a scale (Mean) |
---|---|
Placebo | -6.0 |
GEn (XP13512/GSK1838262) 600 mg | -9.8 |
GEn (XP13512/GSK1838262) 1200 mg | -8.7 |
"The CGI-I scale is a standardized tool that is widely used in psychopharmacologic trials. For the CGI-I, the investigator was asked to rate the participant's overall change in RLS symptoms from Baseline. Scores ranged from 1 (very much improved) to 7 (very much worse). Participants who were much improved (score of 2) or very much improved on the CGI-I scale at the end of treatment (Week 12) are classified as Responders." (NCT00365352)
Timeframe: Week 12
Intervention | participants (Number) |
---|---|
Placebo | 43 |
GEn (XP13512/GSK1838262) 600 mg | 83 |
"The IRLS Rating scale is a measure of RLS disease severity. Items (individually scored from 0 to 4) are included that assess the impact of symptoms on participants' mood, daily life, and activities. The total scale score is a sum of all of the individual item scores and ranges from 0-40 points, with 40 being the most severe. Response was defined by an IRLS Rating Scale total score at the end of Week 1 < 15 and at least a 6-point reduction from the participant's Baseline score and an investigator-rated CGI-I response of much improved or very much improved." (NCT00365352)
Timeframe: End of Week 1
Intervention | participants (Number) |
---|---|
Placebo | 13 |
GEn (XP13512/GSK1838262) 600 mg | 36 |
GEn (XP13512/GSK1838262) 1200 mg | 40 |
The Mood Assessment is a non-disease-specific question surveying global change in a participant's overall mood. Participants were asked to rate their overall change in mood since the start of the study by choosing a score in a range from 1 (Very Much Improved) to 7 (Very Much Worse). The assessment was completed at Day 1 and the ends of Weeks 4, 8, and 12 or (Early Termination). (NCT00365352)
Timeframe: Week 12
Intervention | participants (Number) |
---|---|
Placebo | 19 |
GEn (XP13512/GSK1838262) 600 mg | 35 |
GEn (XP13512/GSK1838262) 1200 mg | 39 |
"The Post-Sleep Questionnaire (PSQ) was designed to evaluate overall sleep quality, ability to function, and RLS symptoms' interference with sleep over the past week. Participants were asked to rate overall sleep quality (as either Excellent, Reasonable, or Poor), ability to function, number of nights with RLS symptoms, number of nights awakened by RLS symptoms, and the number of hours spent awake due to RLS symptoms over the past week." (NCT00365352)
Timeframe: End of Treatment (Week 12)
Intervention | participants (Number) |
---|---|
Placebo | 14 |
GEn (XP13512/GSK1838262) 600 mg | 24 |
GEn (XP13512/GSK1838262) 1200 mg | 30 |
"The CGI-I scale is a standardized tool that is widely used in psychopharmacologic trials. For the CGI-I, the investigator was asked to rate the participant's overall change in RLS symptoms from Baseline. Scores ranged from 1 (very much improved) to 7 (very much worse). Participants who were much improved (score of 2) or very much improved on the CGI-I scale at the end of treatment (Week 12) are classified as Responders." (NCT00365352)
Timeframe: End of Week 1
Intervention | responders (Number) |
---|---|
Placebo | 26 |
GEn (XP13512/GSK1838262) 600 mg | 54 |
GEn (XP13512/GSK1838262) 1200 mg | 59 |
The Response was defined by an IRLS Rating Scale total score at the end of Week 1 < 15 and at least a 6-point reduction from the participant's Baseline score and an investigator-rated CGI-I response of much improved or very much improved. The median time to onset is estimated using the product-limit estimation method. (NCT00365352)
Timeframe: Baseline (Day 1) to End of Treatment (Week 12)
Intervention | weeks (Median) |
---|---|
Placebo | NA |
GEn (XP13512/GSK1838262) 600 Milligrams(mg) Taken Orally | 4.1 |
GEn (XP13512/GSK1838262) 1200 mg Taken Orally Once a Day | 2.1 |
The time to onset of the first RLS symptoms from the 24-hour RLS Record is defined as the length of time from the start of the 24-hour assessment period (8:00 AM) to the time when 50% of participants experienced their first symptom. (NCT00365352)
Timeframe: Week 12
Intervention | hours (Median) |
---|---|
Placebo | 12.8 |
GEn (XP13512/GSK1838262) 600 mg | 13.5 |
GEn (XP13512/GSK1838262) 1200 mg | 13.8 |
The IRLS Rating scale is a measure of RLS disease severity. The scale reflects the participant-reported assessment of primary sensory and motor features and associated sleep problems in RLS. Ten items (individually scored from 0 to 4) are included that assess the impact of symptoms on participants' mood, daily life, and activities. The total scale score is a sum of all of the individual item scores and ranges from 0-40 points, with 40 being the most severe. The scale assesses symptoms over the week prior to measurement. (NCT00365352)
Timeframe: Baseline (Day 1) and Week 12
Intervention | scores on a scale (Mean) | |||
---|---|---|---|---|
IRLS Total Score < 17.5 | IRLS Total Score 17.5 to < 22.5 | IRLS Total Score 22.5 to < 27.5 | IRLS Total Score >= 27.5 | |
GEn (XP13512/GSK1838262) 1200 mg | -7.9 | -8.8 | -15.5 | -19.6 |
GEn (XP13512/GSK1838262) 600 mg | -8.9 | -11.9 | -15.1 | -18.2 |
Placebo | -6.3 | -8.5 | -9.6 | -13.3 |
The IRLS Rating scale is a measure of RLS disease severity. The scale reflects the participant-reported assessment of primary sensory and motor features and associated sleep problems in RLS. Ten items (individually scored from 0 to 4) are included that assess the impact of symptoms on participants' mood, daily life, and activities. The total scale score is a sum of all of the individual item scores and ranges from 0-40 points, with 40 being the most severe. The scale assesses symptoms over the week prior to measurement. (NCT00365352)
Timeframe: Baseline (Day 1) and Week 12
Intervention | scores on a scale (Mean) | ||
---|---|---|---|
No RLS Treatment History | Treatment terminated | Treatment within 1 month of study start | |
GEn (XP13512/GSK1838262) 1200 mg | -12.5 | -17.1 | -12.1 |
GEn (XP13512/GSK1838262) 600 mg | -13.7 | -12.4 | -14.6 |
Placebo | -8.8 | -13.3 | -10.7 |
"The CGI-I scale is a standardized tool that is widely used in psychopharmacologic trials. For the CGI-I, the investigator was asked to rate the participant's overall change in RLS symptoms from Baseline. Scores ranged from 1 (very much improved) to 7 (very much worse). Participants who were much improved (score of 2) or very much improved on the CGI-I scale at the end of treatment (Week 12) are classified as Responders." (NCT00365352)
Timeframe: Basline and Week 12
Intervention | participants (Number) | ||
---|---|---|---|
No RLS Treatment History | Treatment terminated | Treatment within 1 month of study start | |
GEn (XP13512/GSK1838262) 1200 mg | 57 | 13 | 15 |
GEn (XP13512/GSK1838262) 600 mg | 54 | 9 | 18 |
Placebo | 26 | 5 | 11 |
"The CGI-I scale is a standardized tool that is widely used in psychopharmacologic trials. For the CGI-I, the investigator was asked to rate the participant's overall change in RLS symptoms from Baseline. Scores ranged from 1 (very much improved) to 7 (very much worse). Participants who were much improved (score of 2) or very much improved on the CGI-I scale at the end of treatment (Week 12) are classified as Responders." (NCT00365352)
Timeframe: Week 1 and Week 12
Intervention | participants (Number) | |
---|---|---|
Responders at the End of Treatment (Week 12) | Responders at the End of One Week | |
GEn (XP13512/GSK1838262) 1200 mg | 83 | 52 |
GEn (XP13512/GSK1838262) 600 mg | 90 | 55 |
Placebo | 46 | 20 |
"The Mean Daily RLS pain was assessed by participants reporting whether they experienced any pain associated with RLS in the last 24 hours and rating their pain levels on an 11-point numerical rating scale, with 0 being no pain and 10 the most intense pain imaginable. The assessment was performed for 7 days prior to Baseline and pre-defined visits A Responder is a participant with a score of much improved or very much improved on the investigator rated CGI I Scale at the end of treatment (Week 12 using LOCF)." (NCT00365352)
Timeframe: Week 12
Intervention | participants (Number) | |
---|---|---|
> or equal to 30% response | > or equal to 50% response | |
GEn (XP13512/GSK1838262) 1200 mg | 76 | 66 |
GEn (XP13512/GSK1838262) 600 mg | 75 | 62 |
Placebo | 48 | 41 |
RLS severity ratings were summarized in 6 non-overlapping 4-hour periods beginning at 8 AM. A 4-hour period from 6 PM to 10 PM was also prospectively included to reflect the time frame when the most participants would experience their first symptoms of the day. (NCT00365352)
Timeframe: Week 12
Intervention | participants (Number) | ||||||
---|---|---|---|---|---|---|---|
8 AM to 12 PM | 12 PM to 4 PM | 4 PM to 8 PM | 6 PM to 10 PM | 8 PM to 12 AM | 12 AM to 4 AM | 4 AM to 8 AM | |
GEn (XP13512/GSK1838262) 1200 mg | 74 | 69 | 61 | 55 | 48 | 67 | 72 |
GEn (XP13512/GSK1838262) 600 mg | 85 | 74 | 68 | 55 | 49 | 74 | 79 |
Placebo | 52 | 51 | 45 | 39 | 27 | 38 | 56 |
4 reviews available for carbamates and Fatigue
5 trials available for carbamates and Fatigue
Article | Year |
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Sustainable and equivalent improvements in symptoms and functional well-being following viral cure from ledipasvir/sofosbuvir versus elbasvir/grazoprevir for chronic hepatitis C infection: Findings from the randomized PRIORITIZE trial.
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Adverse events associated with encorafenib plus binimetinib in the COLUMBUS study: incidence, course and management.
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Outcome and adverse events in patients with chronic hepatitis C treated with direct-acting antivirals: a clinical randomized study.
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Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes; | 2015 |
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes; | 2015 |
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes; | 2015 |
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes; | 2015 |
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes; | 2015 |
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes; | 2015 |
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes; | 2015 |
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes; | 2015 |
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes; | 2015 |
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes; | 2015 |
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes; | 2015 |
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes; | 2015 |
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes; | 2015 |
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes; | 2015 |
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes; | 2015 |
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes; | 2015 |
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes; | 2015 |
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes; | 2015 |
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes; | 2015 |
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes; | 2015 |
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes; | 2015 |
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes; | 2015 |
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes; | 2015 |
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes; | 2015 |
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes; | 2015 |
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes; | 2015 |
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes; | 2015 |
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes; | 2015 |
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes; | 2015 |
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes; | 2015 |
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes; | 2015 |
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes; | 2015 |
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes; | 2015 |
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes; | 2015 |
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes; | 2015 |
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.
Topics: Administration, Oral; Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes; | 2015 |
Safety and efficacy of ezogabine (retigabine) in adults with refractory partial-onset seizures: Interim results from two ongoing open-label studies.
Topics: Adult; Anticonvulsants; Carbamates; Dizziness; Drug Resistance; Epilepsies, Partial; Fatigue; Female | 2012 |
8 other studies available for carbamates and Fatigue
Article | Year |
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Predictors of adverse drug reactions associated with ribavirin in direct-acting antiviral therapies for chronic hepatitis C.
Topics: Adult; Aged; Aged, 80 and over; Anemia; Antiviral Agents; Brazil; Carbamates; Drug Therapy, Combinat | 2019 |
Elbasvir/grazoprevir treatment in an HCV-infected peritoneal dialysis patient.
Topics: Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes; Drug Therapy, Combination; Fatigue | 2020 |
An integrated analysis of elbasvir/grazoprevir in Korean patients with hepatitis C virus genotype 1b infection.
Topics: Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Clinical Trials, Phase III as Topic; | 2019 |
The combination of daclatasvir and sofosbuvir for curing genotype 2 patients who cannot tolerate ribavirin.
Topics: Aged; Antiviral Agents; Carbamates; Drug Administration Schedule; Drug Therapy, Combination; Fatigue | 2016 |
Interferon/Ribavirin-Free Antiviral Treatment in Septuagenarians and Octogenarians With Chronic Hepatitis C.
Topics: Aged; Aged, 80 and over; Antiviral Agents; Benzimidazoles; Carbamates; Drug Therapy, Combination; Fa | 2016 |
Interferon-free regimens improve health-related quality of life and fatigue in HIV/HCV-coinfected patients with advanced liver disease: A retrospective study.
Topics: Antiviral Agents; Austria; Benzimidazoles; Carbamates; Coinfection; Fatigue; Female; Fluorenes; Hepa | 2016 |
Grazoprevir and Elbasvir in Patients with Genotype 1 Hepatitis C Virus Infection: A Comprehensive Efficacy and Safety Analysis.
Topics: Amides; Antiviral Agents; Asthenia; Benzofurans; Carbamates; Cyclopropanes; Drug Therapy, Combinatio | 2017 |
Clinical pharmacokinetic drug interaction studies of gabapentin enacarbil, a novel transported prodrug of gabapentin, with naproxen and cimetidine.
Topics: Adolescent; Adult; Biological Transport; Carbamates; Cimetidine; Constipation; Dose-Response Relatio | 2010 |