oxybutynin and Restless Leg Syndrome studies

oxybutynin: RN given refers to parent cpd
oxybutynin : A racemate comprising equimolar amounts of (R)-oxybutynin and esoxybutynin. An antispasmodic used for the treatment of overactive bladder.

Research Excerpts

Excerpt	Relevance	Reference
"Patients with moderate to severe restless legs syndrome (RLS) were randomized to rotigotine (optimal dose [1-3 mg/24 h]) or placebo."	2.82	Rotigotine's effect on PLM-associated blood pressure elevations in restless legs syndrome: An RCT. ( Bauer, A; Bauer, L; Benes, H; Carney, HC; Cassel, W; Grieger, F; Joeres, L; Kesper, K; Moran, K; Oertel, W; Rye, D; Schollmayer, E; Sica, D; Trenkwalder, C; Walters, AS; Whitesides, J; Winkelman, JW, 2016)
" The full analysis set (FAS) comprised 564 patients (106 de novo; 458 pretreated [454 had complete rotigotine dosing data])."	2.78	Effectiveness and tolerability of rotigotine transdermal patch for the treatment of restless legs syndrome in a routine clinical practice setting in Germany. ( Bachmann, CG; Berg, D; Berkels, R; Grieger, F; Hofmann, WE; Lauterbach, T; Schollmayer, E; Stiasny-Kolster, K, 2013)
" The three studies reported here were conducted to determine whether the new room temperature stable patch demonstrated similar bioavailability and adhesiveness to the original and intermediate patches."	2.78	Comparison of the bioavailability and adhesiveness of different rotigotine transdermal patch formulations. ( Arth, C; Bauer, L; Brunnert, M; Elshoff, JP; Komenda, M; Schmid, M; Timmermann, L, 2013)
"Safety was assessed by adverse events (AEs) and efficacy was assessed by the International Restless Legs Syndrome Study Group Rating Scale (IRLS)."	2.78	Safety and efficacy of rotigotine transdermal patch in patients with restless legs syndrome: a post-hoc analysis of patients taking 1 - 3 mg/24 h for up to 5 years. ( Bauer, L; Dohin, E; Ferini-Strambi, L; Fichtner, A; García-Borreguero, D; Högl, B; Schollmayer, E, 2013)
" Primary safety outcomes included occurrence of adverse events and dropouts."	2.76	Long-term safety and efficacy of rotigotine transdermal patch for moderate-to-severe idiopathic restless legs syndrome: a 5-year open-label extension study. ( Beneš, H; Ferini-Strambi, L; Fichtner, A; García-Borreguero, D; Högl, B; Kohnen, R; Oertel, W; Poewe, W; Schollmayer, E; Stiasny-Kolster, K; Trenkwalder, C, 2011)
" Safety assessments included adverse events (AEs) and efficacy was measured by the International RLS Study Group Severity Rating Scale (IRLS), RLS-6 scales and Clinical Global Impression (CGI)."	2.75	Treatment of moderate to severe restless legs syndrome: 2-year safety and efficacy of rotigotine transdermal patch. ( Beneš, H; García-Borreguero, D; Geisler, P; Högl, B; Kohnen, R; Oertel, WH; Poewe, W; Schollmayer, E; Stiasny-Kolster, K; Trenkwalder, C, 2010)
", switching medications within the same class when dosing is not a one-to-one ratio."	2.55	Switching from an oral dopamine receptor agonist to rotigotine transdermal patch: a review of clinical data with a focus on patient perspective. ( Asgharnejad, M; Bauer, L; Benitez, A; Boroojerdi, B; Chung, SJ; Heidbrede, T; Kim, HJ; Little, A, 2017)
"Restless legs syndrome/Willis Ekbom disease (RLS/WED) is a sensorimotor disorder characterized by unpleasant sensations in the legs accompanied by an urge to move them, that typically occurs and tend to worsen in the evening/night or during period of inactivity."	2.53	Clinical pharmacology and efficacy of rotigotine (Neupro® patch) in the treatment of restless leg syndrome. ( Ferini-Strambi, L; Galbiati, A; Marelli, S, 2016)
"This narrative review reports on the pharmacological and pharmacokinetic properties of rotigotine, a non-ergolinic D₃/D₂/D₁ dopamine receptor agonist approved for the treatment of early- and advanced-stage Parkinson's disease (PD) and moderate to severe restless legs syndrome (RLS)."	2.52	An update on pharmacological, pharmacokinetic properties and drug-drug interactions of rotigotine transdermal system in Parkinson's disease and restless legs syndrome. ( Andreas, JO; Braun, M; Cawello, W; Elshoff, JP; Mathy, FX, 2015)

Research

Studies (20)

Authors

Clinical Trials (8)

Trial Overview

Trial Outcomes

Daytime Tiredness

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	19 (95.00)	24.3611
2020's	1 (5.00)	2.80

Authors	Studies
Raeder, V	1
Boura, I	1
Leta, V	1
Jenner, P	1
Reichmann, H	1
Trenkwalder, C	6
Klingelhoefer, L	1
Chaudhuri, KR	1
Chung, SJ	1
Asgharnejad, M	1
Bauer, L	4
Benitez, A	1
Boroojerdi, B	1
Heidbrede, T	2
Little, A	1
Kim, HJ	1
Takeuchi, A	1
Egawa, G	1
Nomura, T	1
Kabashima, K	1
Stiasny-Kolster, K	4
Berg, D	1
Hofmann, WE	1
Berkels, R	2
Grieger, F	2
Lauterbach, T	1
Schollmayer, E	8
Bachmann, CG	1
Elshoff, JP	2
Timmermann, L	1
Schmid, M	1
Arth, C	1
Komenda, M	1
Brunnert, M	1
Bogan, RK	1
McAfee, DA	1
Hadgraft, J	1
Lane, ME	1
Cawello, W	1
Andreas, JO	1
Mathy, FX	1
Braun, M	1
Canelo, M	1
Lang, M	1
Schroeder, H	1
Kelling, D	1
Benes, H	5
Bauer, A	1
Cassel, W	2
Kesper, K	1
Rye, D	1
Sica, D	1
Winkelman, JW	3
Joeres, L	1
Moran, K	1
Whitesides, J	1
Carney, HC	1
Walters, AS	2
Oertel, W	2
Ferini-Strambi, L	4
Marelli, S	1
Galbiati, A	1
Garnock-Jones, KP	1
Mackie, SE	1
Mei, LA	1
Platt, S	1
Schoerning, L	1
Hening, WA	1
Allen, RP	1
Ondo, WG	1
Becker, P	1
Bogan, R	1
Fry, JM	1
Kudrow, DB	1
Lesh, KW	1
Fichtner, A	4
Oertel, WH	2
Garcia-Borreguero, D	4
Högl, B	4
Poewe, W	3
Montagna, P	1
Sixel-Döring, F	1
Partinen, M	1
Saletu, B	1
Polo, O	1
Kohnen, R	3
Penzel, T	1
Geisler, P	1
Dohin, E	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
Non-Interventional Study (NIS) in Patients With Restless Legs Syndrome (RLS) to Assess the Effectiveness and Safety of Neupro® in Daily Practise[NCT01113710]		687 participants (Actual)	Observational	2010-05-31	Completed
Single-site, Open-label, Randomized, Cross-over Trial to Evaluate the Bioequivalence of Single Dose Rotigotine Transdermal Patch (4.5mg/10cm2) Comparing Two Different Formulations[NCT01059903]	Phase 1	50 participants (Actual)	Interventional	2010-01-31	Completed
Single-site, Open-label, Randomized, Cross-over Trial to Evaluate the Bioequivalence of Single Dose Rotigotine Transdermal Patch (4.5mg/10cm^2) From 2 Different Manufacturing Processes[NCT00881894]	Phase 1	52 participants (Actual)	Interventional	2008-10-31	Completed
A Multicenter, Randomized, Double-blind, Two-way Cross-over Study to Compare the Adhesiveness of Two Different Rotigotine Patch Formulations in Subjects With Parkinson's Disease[NCT01338896]	Phase 1	56 participants (Actual)	Interventional	2011-04-30	Completed
Non Interventional Observational Study to Collect Data for the Effect of Switching to Neupro® on Severity of Restless Leg Syndrome (RLS) Symptoms and Augmentation as Well as the Change in Treatment Regimen Used, in RLS Patients With Previous Augmentation[NCT01386944]		102 participants (Actual)	Observational	2011-07-31	Completed
A Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Five-Arm Parallel-Group Trial to Investigate the Efficacy and Safety of Four Different Transdermal Doses of Rotigotine in Subjects With Idiopathic Restless Legs Syndrome[NCT00135993]	Phase 3	811 participants (Actual)	Interventional	2005-05-31	Completed
A Multi-center, Double-blind, Randomized, Placebo-controlled, Two-arm, Parallel-group, Sleep Lab Trial to Investigate the Efficacy and Safety of Transdermal Rotigotine in Subjects With Idiopathic Restless Legs Syndrome[NCT00275236]	Phase 3	60 participants	Interventional	2005-11-30	Completed
An Open-label Extension Trial to Determine Safety and Tolerability of Long-term Transdermal Application of Rotigotine in Subjects With Idiopathic Restless Legs Syndrome[NCT00498186]	Phase 2	295 participants (Actual)	Interventional	2003-07-31	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

"Daytime tiredness measured as change from baseline to end of observation period (Item 6 RLS-6 scale).~The Last Observation Carried Forward (LOCF) method was utilized for all outcomes.~The RLS-6 scale is an 11-point scale (from 0 = not present/completely satisfied to 10 = very severe/completely dissatisfied) to establish an individual severity profile at various day and night times (at bedtime; during the night; during the day when the patients are resting, or during the day when the patients are involved in daily activities)." (NCT01113710)
Timeframe: From Baseline to end of Observation Period (3 months).

Satisfaction With Sleep

Intervention	units on a scale (Mean)
	Change from Baseline to End of Observation Period	Observed Value at Baseline Visit
Neupro®	-1.9	5.1

"Satisfaction with sleep measured as change from baseline to end of observation period (Item 1 RLS-6 scale).~The Last Observation Carried Forward (LOCF) method was utilized for all outcomes.~The RLS-6 scale is an 11-point scale (from 0 = not present/completely satisfied to 10 = very severe/completely dissatisfied) to establish an individual severity profile at various day and night times (at bedtime; during the night; during the day when the patients are resting, or during the day when the patients are involved in daily activities)." (NCT01113710)
Timeframe: From Baseline to end of Observation Period (3 months).

Severity of Restless Legs Syndrome (RLS) at Bedtime

Intervention	units on a scale (Mean)
	Change from Baseline to End of Observation Period	Observed Value at Baseline Visit
Neupro®	-2.4	6.4

"Severity of RLS at bedtime measured as change from baseline to end of observation period (Item 2 RLS-6 scale).~The Last Observation Carried Forward (LOCF) method was utilized for all outcomes.~The RLS-6 scale is an 11-point scale (from 0 = not present/completely satisfied to 10 = very severe/completely dissatisfied) to establish an individual severity profile at various day and night times (at bedtime; during the night; during the day when the patients are resting, or during the day when the patients are involved in daily activities)." (NCT01113710)
Timeframe: From Baseline to end of Observation Period (3 months).

Severity of Restless Legs Syndrome (RLS) at Daytime at Rest

Intervention	units on a scale (Mean)
	Change from Baseline to End of Observation Period	Observed Value at Baseline Visit
Neupro®	-2.2	5.2

"Severity of RLS at daytime at rest measured as change from baseline to end of observation period (Item 4 RLS-6 scale).~The Last Observation Carried Forward (LOCF) method was utilized for all outcomes.~The RLS-6 scale is an 11-point scale (from 0 = not present/completely satisfied to 10 = very severe/completely dissatisfied) to establish an individual severity profile at various day and night times (at bedtime; during the night; during the day when the patients are resting, or during the day when the patients are involved in daily activities)." (NCT01113710)
Timeframe: From Baseline to end of Observation Period (3 months).

Severity of Restless Legs Syndrome (RLS) at Daytime in Activity

Intervention	units on a scale (Mean)
	Change from Baseline to End of Observation Period	Observed Value at Baseline Visit
Neupro®	-2.8	5.2

"Severity of RLS at daytime in activity measured as change from baseline to end of observation period (Item 5 RLS-6 scale).~The Last Observation Carried Forward (LOCF) method was utilized for all outcomes.~The RLS-6 scale is an 11-point scale (from 0 = not present/completely satisfied to 10 = very severe/completely dissatisfied) to establish an individual severity profile at various day and night times (at bedtime; during the night; during the day when the patients are resting, or during the day when the patients are involved in daily activities)." (NCT01113710)
Timeframe: From Baseline to end of Observation Period (3 months).

Severity of Restless Legs Syndrome (RLS) During the Night

Intervention	units on a scale (Mean)
	Change from Baseline to End of Observation Period	Observed Value at Baseline Visit
Neupro®	-0.9	1.9

"Severity of RLS during the night measured as change from baseline to end of observation period (Item 3 RLS-6 scale).~The Last Observation Carried Forward (LOCF) method was utilized for all outcomes.~The RLS-6 scale is an 11-point scale (from 0 = not present/completely satisfied to 10 = very severe/completely dissatisfied) to establish an individual severity profile at various day and night times (at bedtime; during the night; during the day when the patients are resting, or during the day when the patients are involved in daily activities)." (NCT01113710)
Timeframe: From Baseline to end of Observation Period (3 months).

Apparent Dose

Intervention	units on a scale (Mean)
	Change from Baseline to End of Observation Period	Observed Value at Baseline Visit
Neupro®	-2.5	5.5

Apparent dose of unconjugated rotigotine in mg. The apparent dose was calculated by subtraction of the determined residual content of each rotigotine patch from the nominal content of rotigotine in the patch. (NCT01059903)
Timeframe: 24 hours

Apparent Total Body Clearance (CL/f) of Unconjugated Rotigotine

Intervention	mg (Mean)
Rotigotine PR2.2.1	1.970
Rotigotine PR2.1.1	2.036

The CL/f of unconjugated rotigotine is the apparent total body clearance. (NCT01059903)
Timeframe: 0 h (predose), 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h, and 48 h

AUC(0- ∞) Norm (Apparent Dose)

Intervention	L/ h (Mean)
Rotigotine PR2.2.1	1125.11
Rotigotine PR2.1.1	1041.47

The AUC(0-inf) norm (apparent dose) is the area under the plasma concentration-time curve from zero up to infinity normalized by apparent dose (mg). (NCT01059903)
Timeframe: 0 h (predose), 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h, and 48 h

AUC(0- ∞) Norm (Body Weight)

Intervention	ng/ mL*h/ mg (Mean)
Rotigotine PR2.2.1	2.62042
Rotigotine PR2.1.1	2.71397

The AUC(0-inf) norm (BW) is the area under the plasma concentration-time curve from zero up to infinity normalized by body weight (kg). (NCT01059903)
Timeframe: 0 h (predose), 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h, and 48 h

AUC(0- ∞) of Unconjugated Rotigotine

Intervention	nghkg/ mL (Mean)
Rotigotine PR2.2.1	420.811
Rotigotine PR2.1.1	441.761

The AUC(0- ∞) is the area under the plasma concentration-time curve from zero up to infinity (NCT01059903)
Timeframe: 0 h (predose), 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h, and 48 h

AUC(0-tz) Norm (Apparent Dose) of Unconjugated Rotigotine

Intervention	ng/ mL*h (Mean)
Rotigotine PR2.2.1	5.36933
Rotigotine PR2.1.1	5.56925

The AUC(0-tz) norm (apparent dose) is the area under the plasma concentration-time curve from zero up to the last analytically quantifiable concentration normalized by apparent dose (mg). (NCT01059903)
Timeframe: 0 h (predose), 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h, and 48 h

AUC(0-tz) Norm (Body Weight) of Unconjugated Rotigotine

Intervention	ng/ mL*h/ mg (Mean)
Rotigotine PR2.2.1	2.56504
Rotigotine PR2.1.1	2.66067

The AUC(0-tz) norm (BW) is the area under the plasma concentration-time curve from zero up to the last analytically quantifiable concentration normalized by body weight (kg). (NCT01059903)
Timeframe: 0 h (predose), 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h, and 48 h

AUC(0-tz) of Unconjugated Rotigotine

Intervention	nghkg/ mL (Mean)
Rotigotine PR2.2.1	412.942
Rotigotine PR2.1.1	434.101

The AUC(0-tz) is the area under the concentration-time curve from zero up to the last analytically quantifiable concentration. (NCT01059903)
Timeframe: 0 h (predose), 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h, and 48 h

Cmax of Unconjugated Rotigotine

Intervention	ng/ mL*h (Mean)
Rotigotine PR2.2.1	5.2704
Rotigotine PR2.1.1	5.4724

The Cmax is the maximum plasma concentration. (NCT01059903)
Timeframe: 0 h (predose), 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h, and 48 h

Cmax, Norm (Apparent Dose) of Unconjugated Rotigotine

Intervention	ng/ mL (Mean)
Rotigotine PR2.2.1	0.26156
Rotigotine PR2.1.1	0.25774

The Cmax, norm (apparent dose) is the maximum plasma concentration normalized by apparent dose (mg). (NCT01059903)
Timeframe: 0 h (predose), 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h, and 48 h

Cmax, Norm (Body Weight) of Unconjugated Rotigotine

Intervention	ng/ mL/ mg (Mean)
Rotigotine PR2.2.1	0.128863
Rotigotine PR2.1.1	0.126144

The Cmax, norm (BW) is the maximum plasma concentration normalized by body weight (kg). (NCT01059903)
Timeframe: 0 h (predose), 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h, and 48 h

Mean Residence Time (MRT) of Unconjugated Rotigotine

Intervention	ng/ mL*kg (Mean)
Rotigotine PR2.2.1	20.4935
Rotigotine PR2.1.1	20.4489

The MRT is the mean residence time. (NCT01059903)
Timeframe: 0 h (predose), 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h, and 48 h

Rate Constant of Elimination (λz) of Unconjugated Rotigotine

Intervention	hours (h) (Mean)
Rotigotine PR2.2.1	18.473
Rotigotine PR2.1.1	18.186

The λz of unconjugated rotigotine is the rate constant of elimination. (NCT01059903)
Timeframe: 0 h (predose), 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h, and 48 h

Terminal Half-Life (t1/2) of Unconjugated Rotigotine

Intervention	1/ h (Mean)
Rotigotine PR2.2.1	0.162587
Rotigotine PR2.1.1	0.165400

the t1/2 of unconjugated rotigotine is the terminal half-life, calculated as t1/2=ln2/ λz. (NCT01059903)
Timeframe: 0 h (predose), 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h, and 48 h

Tmax of Unconjugated Rotigotine

Intervention	hours (h) (Mean)
Rotigotine PR2.2.1	4.4523
Rotigotine PR2.1.1	4.3752

The tmax is the time to reach maximum plasma concentration after patch application. (NCT01059903)
Timeframe: 0 h (predose), 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h (before patch removal in the morning of Day 2), 25 h, 26 h, 28 h, 30 h, 32 h, 36 h, 40 h, and 48 h

Apparent Dose

Intervention	hours (h) (Mean)
Rotigotine PR2.2.1	16.78
Rotigotine PR2.1.1	15.75

Apparent dose of unconjugated rotigotine in mg. The Apparent dose of unconjugated rotigotine was determined from the patches removed on Day 2. (NCT00881894)
Timeframe: 48 hours

AUC(0-∞) of Unconjugated Rotigotine

Intervention	mg (Mean)
Treatment A (Test: PR2.1.1)	1.676
Treatment B (Reference: PR1.0)	1.890

The AUC(0-∞) is the area under the plasma concentration- time curve from zero up to infinity. (NCT00881894)
Timeframe: Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application.

AUC(0-tz) of Unconjugated Rotigotine

Intervention	(ng/ mL)*h (Mean)
Treatment A (Test: PR2.1.1)	3.12622
Treatment B (Reference: PR1.0)	3.16403

The AUC(0-tz) is the area under the plasma concentration- time curve from zero up to the last analytically quantifiable concentration. (NCT00881894)
Timeframe: Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application

AUC(0-tz)Norm (Apparent Dose) of Unconjugated Rotigotine

Intervention	(ng/ mL)*h (Mean)
Treatment A (Test: PR2.1.1)	3.0168
Treatment B (Reference: PR1.0)	3.0635

The AUC(0-tz)Norm (Apparent dose) is the area under the plasma concentration- time curve from zero up to the last analytically quantifiable concentration normalized by apparent dose (mg). (NCT00881894)
Timeframe: Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application.

AUC(0-tz)Norm (BW) of Unconjugated Rotigotine

Intervention	(ng/ mL)*(h/ mg) (Mean)
Treatment A (Test: PR2.1.1)	1.78200
Treatment B (Reference: PR1.0)	1.58900

The AUC(0-tz)Norm (BW) is the area under the plasma concentration- time curve from zero up to the last analytically quantifiable concentration normalized by body weight (kg). (NCT00881894)
Timeframe: Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application.

CL/f of Unconjugated Rotigotine

Intervention	(ng/ mL)hkg (Mean)
Treatment A (Test: PR2.1.1)	239.241
Treatment B (Reference: PR1.0)	243.841

The CL/f is the apparent total body clearance. (NCT00881894)
Timeframe: Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application.

Cmax of Unconjugated Rotigotine

Intervention	L/ h (Mean)
Treatment A (Test: PR2.1.1)	1825.38
Treatment B (Reference: PR1.0)	1822.13

The Cmax is the maximum plasma concentration. (NCT00881894)
Timeframe: Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application.

Cmax,Norm (Apparent Dose) of Unconjugated Rotigotine

Intervention	ng/ mL (Mean)
Treatment A (Test: PR2.1.1)	0.14418
Treatment B (Reference: PR1.0)	0.15155

The Cmax,Norm (Apparent dose) is the maximum plasma concentration normalized by apparent dose. (NCT00881894)
Timeframe: Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application.

Cmax,Norm (BW) of Unconjugated Rotigotine

Intervention	(ng/ mL) / mg (Mean)
Treatment A (Test: PR2.1.1)	0.085822
Treatment B (Reference: PR1.0)	0.079619

The Cmax,Norm (BW) is the maximum plasma concentration normalized by body weight (kg). (NCT00881894)
Timeframe: Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application.

MRT of Unconjugated Rotigotine

Intervention	(ng/ mL)*kg (Mean)
Treatment A (Test: PR2.1.1)	11.4391
Treatment B (Reference: PR1.0)	12.0441

The MRT is the mean residence time. (NCT00881894)
Timeframe: Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24(before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application.

t1/2 of Unconjugated Rotigotine

Intervention	hour (h) (Mean)
Treatment A (Test: PR2.1.1)	19.012
Treatment B (Reference: PR1.0)	18.882

The t1/2 is the terminal half- life. (NCT00881894)
Timeframe: Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application.

Tmax of Unconjugated Rotigotine

Intervention	hour (h) (Mean)
Treatment A (Test: PR2.1.1)	4.7665
Treatment B (Reference: PR1.0)	4.7128

The Tmax is the time to reach a maximum plasma concentration after patch application. (NCT00881894)
Timeframe: Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application.

λz of Unconjugated Rotigotine

Intervention	hour (h) (Median)
Treatment A (Test: PR2.1.1)	16.00
Treatment B (Reference: PR1.0)	16.00

The λz is the rate constant of elimination. (NCT00881894)
Timeframe: Pharmacokinetic samples were taken predose, after 1, 2, 3, 4, 6, 8, 12, 16, 24 (before patch removal), 25, 26, 28, 30, 32, 36, 40 and 48 hours after patch application.

Change From Baseline (Visit 1) in Clinical Global Impression (CGI) (Item 1 - Severity of Illness) to Visit 2

Intervention	1/ hour (1/h) (Mean)
Treatment A (Test: PR2.1.1)	0.153848
Treatment B (Reference: PR1.0)	0.151239

"The CGI scales document a global assessment of the severity of RLS at single visits according to the treating physician. To this end the physician judges severity of disease by following a simple seven step severity rating scale:~= Normal, not ill at all~= Borderline ill~= Mildly ill~= Moderately ill~= Markedly ill~= Severely ill~= Among the most extremely ill subjects~A negative change from Baseline to Visit 2 indicates an improvement in CGI Item 1." (NCT01386944)
Timeframe: From Baseline up to 7 days

Change From Baseline (Visit 1) in Clinical Global Impression (CGI) (Item 1 - Severity of Illness) to Visit 3

Intervention	score on a scale (Mean)
Neupro® Treatment	-0.8

"The CGI scales document a global assessment of the severity of RLS at single visits according to the treating physician. To this end the physician judges severity of disease by following a simple seven step severity rating scale:~= Normal, not ill at all~= Borderline ill~= Mildly ill~= Moderately ill~= Markedly ill~= Severely ill~= Among the most extremely ill subjects~A negative change from Baseline to Visit 3 indicates an improvement in CGI Item 1." (NCT01386944)
Timeframe: From Baseline up to 28 days

Change From Baseline (Visit 1) in Clinical Global Impression (CGI) (Item 1 - Severity of Illness) to Visit 4

Intervention	score on a scale (Mean)
Neupro® Treatment	-1.4

"The CGI scales document a global assessment of the severity of RLS at single visits according to the treating physician. To this end the physician judges severity of disease by following a simple seven step severity rating scale:~= Normal, not ill at all~= Borderline ill~= Mildly ill~= Moderately ill~= Markedly ill~= Severely ill~= Among the most extremely ill subjects~A negative change from Baseline to Visit 4 indicates an improvement in CGI Item 1." (NCT01386944)
Timeframe: From Baseline up to 4 months

Change From Baseline (Visit 1) in Clinical Global Impression (CGI) (Item 1 - Severity of Illness) to Visit 5

Intervention	score on a scale (Mean)
Neupro® Treatment	-1.8

Change From Baseline (Visit 1) in Clinical Global Impression (CGI) (Item 1 - Severity of Illness) to Visit 6

Intervention	score on a scale (Mean)
Neupro® Treatment	-2.0

"The CGI scales document a global assessment of the severity of RLS at single visits according to the treating physician. To this end the physician judges severity of disease by following a simple seven step severity rating scale:~= Normal, not ill at all~= Borderline ill~= Mildly ill~= Moderately ill~= Markedly ill~= Severely ill~= Among the most extremely ill subjects~A negative change from Baseline to Visit 6 indicates an improvement in CGI Item 1." (NCT01386944)
Timeframe: From Baseline up to 10 months

Change From Baseline (Visit 1) in Clinical Global Impression (CGI) (Item 1 - Severity of Illness) to Visit 7

Intervention	score on a scale (Mean)
Neupro® Treatment	-2.0

"The CGI scales document a global assessment of the severity of RLS at single visits according to the treating physician. To this end the physician judges severity of disease by following a simple seven step severity rating scale:~= Normal, not ill at all~= Borderline ill~= Mildly ill~= Moderately ill~= Markedly ill~= Severely ill~= Among the most extremely ill subjects~A negative change from Baseline to Visit 7 indicates an improvement in CGI Item 1." (NCT01386944)
Timeframe: From Baseline up to 13 months

Change in Treatment Regimen Used for Switching to Neupro® up to 28 Days After Entering in the Study

Intervention	score on a scale (Mean)
Neupro® Treatment	-1.8

Case reports from clinical practice refer to different switching regimens for patients taking oral dopaminergics who experienced augmentation and then switched to Neupro®. The previous dopaminergic treatment might have been partly or completely down-titrated prior to switching to Neupro®. Physicians were requested to document the change of treatment at each recommended visit in the electronic Case Report Form (eCRF) considering their total clinical experience with this particular Restless Legs Syndrome (RLS) patients population. Documentation comprised changes in the RLS medication last prescribed, and the dosage of Neupro® and concomitant medications. The change of treatment regimen was entirely at the physicians' discretion. (NCT01386944)
Timeframe: From Baseline up to 28 days

Number of Subjects Who Withdrew From the Trial Due to an Adverse Event During the 5-year Open Label Extension

Intervention	participants (Number)
	"Switch after Drug holiday"	Overnight Switch	Overlapping Switch	No Switch
Neupro® Treatment	5	23	9	6

Adverse events are any untoward medical occurrences in a subject administered study treatment, whether or not these events are related to treatment. (NCT00498186)
Timeframe: Up to five years

Number of Subjects With at Least One Adverse Event, as Reported Spontaneously by the Subject or Observed by the Investigator, During the 5-year Open-label Extension.

Intervention	participants (Number)
Rotigotine	93

Adverse events are any untoward medical occurrences in a subject administered study treatment, whether or not these events are related to treatment. (NCT00498186)
Timeframe: Up to five years

Article	Year
Rotigotine Transdermal Patch for Motor and Non-motor Parkinson's Disease: A Review of 12 Years' Clinical Experience. CNS drugs, 2021, Volume: 35, Issue:2 Topics: Administration, Cutaneous; Dopamine Agonists; Humans; Parkinson Disease; Quality of Life; Restless L	2021
Switching from an oral dopamine receptor agonist to rotigotine transdermal patch: a review of clinical data with a focus on patient perspective. Expert review of neurotherapeutics, 2017, Volume: 17, Issue:7 Topics: Dopamine Agonists; Drug Substitution; Humans; Parkinson Disease; Restless Legs Syndrome; Tetrahydron	2017
From bench to bedside: An overview of rotigotine for the treatment of restless legs syndrome. Clinical therapeutics, 2014, Mar-01, Volume: 36, Issue:3 Topics: Administration, Cutaneous; Dopamine Agonists; Drug Delivery Systems; Humans; PubMed; Restless Legs S	2014
Rotigotine: the first new chemical entity for transdermal drug delivery. European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 2014, Volume: 88, Issue:3 Topics: Administration, Cutaneous; Chemical Phenomena; Clinical Trials as Topic; Dopamine Agonists; Drug Del	2014
An update on pharmacological, pharmacokinetic properties and drug-drug interactions of rotigotine transdermal system in Parkinson's disease and restless legs syndrome. Drugs, 2015, Volume: 75, Issue:5 Topics: Animals; Anti-Dyskinesia Agents; Antiparkinson Agents; Comorbidity; Dopamine Agonists; Drug Interact	2015
Clinical pharmacology and efficacy of rotigotine (Neupro® patch) in the treatment of restless leg syndrome. Expert opinion on drug metabolism & toxicology, 2016, Volume: 12, Issue:8 Topics: Administration, Cutaneous; Animals; Dopamine Agonists; Drug Delivery Systems; Humans; Randomized Con	2016
Rotigotine Transdermal Patch: A Review in Restless Legs Syndrome. Drugs, 2016, Volume: 76, Issue:10 Topics: Dopamine Agonists; Dose-Response Relationship, Drug; Humans; Randomized Controlled Trials as Topic;	2016

Article	Year
Effectiveness and tolerability of rotigotine transdermal patch for the treatment of restless legs syndrome in a routine clinical practice setting in Germany. Sleep medicine, 2013, Volume: 14, Issue:6 Topics: Aged; Benzothiazoles; Dopamine Agonists; Female; Germany; Humans; Levodopa; Male; Middle Aged; Prami	2013
Comparison of the bioavailability and adhesiveness of different rotigotine transdermal patch formulations. Current medical research and opinion, 2013, Volume: 29, Issue:12 Topics: Adult; Biological Availability; Cross-Over Studies; Dopamine Agonists; Double-Blind Method; Humans;	2013
Comparison of the bioavailability and adhesiveness of different rotigotine transdermal patch formulations. Current medical research and opinion, 2013, Volume: 29, Issue:12 Topics: Adult; Biological Availability; Cross-Over Studies; Dopamine Agonists; Double-Blind Method; Humans;	2013
Comparison of the bioavailability and adhesiveness of different rotigotine transdermal patch formulations. Current medical research and opinion, 2013, Volume: 29, Issue:12 Topics: Adult; Biological Availability; Cross-Over Studies; Dopamine Agonists; Double-Blind Method; Humans;	2013
Comparison of the bioavailability and adhesiveness of different rotigotine transdermal patch formulations. Current medical research and opinion, 2013, Volume: 29, Issue:12 Topics: Adult; Biological Availability; Cross-Over Studies; Dopamine Agonists; Double-Blind Method; Humans;	2013
Comparison of the bioavailability and adhesiveness of different rotigotine transdermal patch formulations. Current medical research and opinion, 2013, Volume: 29, Issue:12 Topics: Adult; Biological Availability; Cross-Over Studies; Dopamine Agonists; Double-Blind Method; Humans;	2013
Comparison of the bioavailability and adhesiveness of different rotigotine transdermal patch formulations. Current medical research and opinion, 2013, Volume: 29, Issue:12 Topics: Adult; Biological Availability; Cross-Over Studies; Dopamine Agonists; Double-Blind Method; Humans;	2013
Comparison of the bioavailability and adhesiveness of different rotigotine transdermal patch formulations. Current medical research and opinion, 2013, Volume: 29, Issue:12 Topics: Adult; Biological Availability; Cross-Over Studies; Dopamine Agonists; Double-Blind Method; Humans;	2013
Comparison of the bioavailability and adhesiveness of different rotigotine transdermal patch formulations. Current medical research and opinion, 2013, Volume: 29, Issue:12 Topics: Adult; Biological Availability; Cross-Over Studies; Dopamine Agonists; Double-Blind Method; Humans;	2013
Comparison of the bioavailability and adhesiveness of different rotigotine transdermal patch formulations. Current medical research and opinion, 2013, Volume: 29, Issue:12 Topics: Adult; Biological Availability; Cross-Over Studies; Dopamine Agonists; Double-Blind Method; Humans;	2013
Rotigotine's effect on PLM-associated blood pressure elevations in restless legs syndrome: An RCT. Neurology, 2016, May-10, Volume: 86, Issue:19 Topics: Adolescent; Adult; Aged; Blood Pressure; Blood Pressure Determination; Dopamine Agonists; Double-Bli	2016
Rotigotine improves restless legs syndrome: a 6-month randomized, double-blind, placebo-controlled trial in the United States. Movement disorders : official journal of the Movement Disorder Society, 2010, Aug-15, Volume: 25, Issue:11 Topics: Adolescent; Adult; Aged; Dopamine Agonists; Dose-Response Relationship, Drug; Double-Blind Method; F	2010
Rotigotine transdermal patch in moderate to severe idiopathic restless legs syndrome: a randomized, placebo-controlled polysomnographic study. Sleep medicine, 2010, Volume: 11, Issue:9 Topics: Adolescent; Adult; Aged; Double-Blind Method; Female; Humans; Male; Middle Aged; Movement; Polysomno	2010
Treatment of moderate to severe restless legs syndrome: 2-year safety and efficacy of rotigotine transdermal patch. BMC neurology, 2010, Sep-28, Volume: 10 Topics: Adult; Aged; Dopamine Agonists; Female; Humans; Male; Middle Aged; Patient Compliance; Restless Legs	2010
Long-term safety and efficacy of rotigotine transdermal patch for moderate-to-severe idiopathic restless legs syndrome: a 5-year open-label extension study. The Lancet. Neurology, 2011, Volume: 10, Issue:8 Topics: Administration, Cutaneous; Adolescent; Adult; Aged; Double-Blind Method; Female; Follow-Up Studies;	2011
Safety and efficacy of rotigotine transdermal patch in patients with restless legs syndrome: a post-hoc analysis of patients taking 1 - 3 mg/24 h for up to 5 years. Expert opinion on pharmacotherapy, 2013, Volume: 14, Issue:1 Topics: Administration, Cutaneous; Adult; Aged; Dopamine Agonists; Dose-Response Relationship, Drug; Double-	2013

Article	Year
Contact leukoderma induced by rotigotine transdermal patch (Neupro®). European journal of dermatology : EJD, 2019, 04-01, Volume: 29, Issue:2 Topics: Dopamine Agonists; Female; Humans; Hypopigmentation; Middle Aged; Restless Legs Syndrome; Tetrahydro	2019
Transdermal rotigotine in restless legs syndrome: impulse control disorders. Prescrire international, 2014, Volume: 23, Issue:153 Topics: Administration, Cutaneous; Disruptive, Impulse Control, and Conduct Disorders; Dopamine Agonists; Hu	2014
Management of augmentation of restless legs syndrome with rotigotine: a 1-year observational study. Sleep medicine, 2017, Volume: 30 Topics: Adult; Aged; Dopamine Agonists; Female; Humans; Male; Middle Aged; Restless Legs Syndrome; Tetrahydr	2017
A method to switch from oral dopamine agonists to rotigotine in patients with restless legs syndrome and mild augmentation. Sleep medicine, 2016, Volume: 24 Topics: Administration, Oral; Aged; Benzothiazoles; Dopamine Agonists; Drug Synergism; Female; Humans; Indol	2016
In brief: transdermal rotigotine (Neupro). The Medical letter on drugs and therapeutics, 2012, Aug-20, Volume: 54, Issue:1397 Topics: Antiparkinson Agents; Parkinson Disease; Restless Legs Syndrome; Tetrahydronaphthalenes; Thiophenes;	2012

oxybutynin and Restless Leg Syndrome

Research Excerpts

Research

Studies (20)

Authors

Clinical Trials (8)

Trial Overview

Trial Outcomes

Daytime Tiredness

Satisfaction With Sleep

Severity of Restless Legs Syndrome (RLS) at Bedtime

Severity of Restless Legs Syndrome (RLS) at Daytime at Rest

Severity of Restless Legs Syndrome (RLS) at Daytime in Activity

Severity of Restless Legs Syndrome (RLS) During the Night

Apparent Dose

Apparent Total Body Clearance (CL/f) of Unconjugated Rotigotine

AUC(0- ∞) Norm (Apparent Dose)

AUC(0- ∞) Norm (Body Weight)

AUC(0- ∞) of Unconjugated Rotigotine

AUC(0-tz) Norm (Apparent Dose) of Unconjugated Rotigotine

AUC(0-tz) Norm (Body Weight) of Unconjugated Rotigotine

AUC(0-tz) of Unconjugated Rotigotine

Cmax of Unconjugated Rotigotine

Cmax, Norm (Apparent Dose) of Unconjugated Rotigotine

Cmax, Norm (Body Weight) of Unconjugated Rotigotine

Mean Residence Time (MRT) of Unconjugated Rotigotine

Rate Constant of Elimination (λz) of Unconjugated Rotigotine

Terminal Half-Life (t1/2) of Unconjugated Rotigotine

Tmax of Unconjugated Rotigotine

Apparent Dose

AUC(0-∞) of Unconjugated Rotigotine

AUC(0-tz) of Unconjugated Rotigotine

AUC(0-tz)Norm (Apparent Dose) of Unconjugated Rotigotine

AUC(0-tz)Norm (BW) of Unconjugated Rotigotine

CL/f of Unconjugated Rotigotine

Cmax of Unconjugated Rotigotine

Cmax,Norm (Apparent Dose) of Unconjugated Rotigotine

Cmax,Norm (BW) of Unconjugated Rotigotine

MRT of Unconjugated Rotigotine

t1/2 of Unconjugated Rotigotine

Tmax of Unconjugated Rotigotine

λz of Unconjugated Rotigotine

Change From Baseline (Visit 1) in Clinical Global Impression (CGI) (Item 1 - Severity of Illness) to Visit 2

Change From Baseline (Visit 1) in Clinical Global Impression (CGI) (Item 1 - Severity of Illness) to Visit 3

Change From Baseline (Visit 1) in Clinical Global Impression (CGI) (Item 1 - Severity of Illness) to Visit 4

Change From Baseline (Visit 1) in Clinical Global Impression (CGI) (Item 1 - Severity of Illness) to Visit 5

Change From Baseline (Visit 1) in Clinical Global Impression (CGI) (Item 1 - Severity of Illness) to Visit 6

Change From Baseline (Visit 1) in Clinical Global Impression (CGI) (Item 1 - Severity of Illness) to Visit 7

Change in Treatment Regimen Used for Switching to Neupro® up to 28 Days After Entering in the Study

Number of Subjects Who Withdrew From the Trial Due to an Adverse Event During the 5-year Open Label Extension

Number of Subjects With at Least One Adverse Event, as Reported Spontaneously by the Subject or Observed by the Investigator, During the 5-year Open-label Extension.

Reviews

Trials

Other Studies