Efficacy Of Rotigotine Transdermal Patch Research Articles

Rotigotine for nocturnal hypokinesia in Parkinson's disease: Quantitative analysis of efficacy from a randomized, placebo-controlled trial using an axial inertial sensor

BackgroundNocturnal hypokinesia is a common symptom in Parkinson's disease (PD), negatively affecting quality of life of both patients and caregivers. However, evidence-based treatment strategies are limited. ObjectiveTo evaluate the efficacy of rotigotine transdermal patch, using a wearable sensor, in the management of nocturnal immobility. Methods34 PD subjects with nocturnal immobility were randomized to receive rotigotine transdermal patch (mean ± SD of 10.46 ± 4.63 mg/24 h, n = 17) or placebo patch (n = 17). Treatment was titrated to an optimal dose over 1–8 weeks, then maintained for 4 weeks. Primary endpoints were objective parameters assessing axial rotation measured using an axial inertial sensor (the NIGHT-Recorder) over two nights at the patients' home. Scale-based assessments were also performed. ResultsThere was a significant difference, in favor of rotigotine, in change from baseline score in the number of turns in bed (ANCOVA, p = 0.001), and degree of axial turn (p = 0.042). These objective improvements were mirrored by significantly greater improvements in clinical scale-based assessments, including the Unified Parkinson's Disease Rating Scale (UPDRS) total scores (p = 0.009), UPDRS-motor scores (p < 0.001), UPDRS-axial scores (p = 0.01), the Modified Parkinson's Disease Sleep Scale (p < 0.001), the Nocturnal Akinesia Dystonia and Cramp Scale (p = 0.003) and the eight-item PD Questionnaire (PDQ-8) scores (p = 0.01) from baseline to end of treatment in patients given rotigotine compared to placebo. ConclusionWe show that the rotigotine patch provides a significant improvement in nocturnal symptoms as assessed using both objective measures and clinical rating scales. The study demonstrates the feasibility of using wearable sensors to record objective outcomes in PD-related clinical trials.

Efficacy of Rotigotine at Different Stages ofParkinson's Disease Symptom Severity and Disability: A Post Hoc Analysis According to Baseline Hoehn and Yahr Stage.

Background: The efficacy of rotigotine has been demonstrated in studies of patients with early (i.e. not receiving levodopa) and advanced (i.e. not adequately controlled on levodopa; average 2.5 h/day in ‘off’ state) Parkinson’s disease (PD).Objective: To further investigate the efficacy of rotigotine transdermal patch across different stages of PD symptom severity and functional disability, according to baseline Hoehn and Yahr (HY) staging.Methods: Post hoc analysis of six placebo-controlled studies of rotigotine in patients with early PD (SP506, SP512, SP513; rotigotine ≤8 mg/24 h) or advanced-PD (CLEOPATRA-PD, PREFER, SP921; rotigotine ≤16 mg/24 h). Data were pooled and analyzed according to baseline HY stage (1, 2, 3 or 4) for change from baseline to end of maintenance in Unified Parkinson’s Disease Rating Scale (UPDRS) II (activities of daily living), UPDRS III (motor) and UPDRS II+III; statistical tests are exploratory.Results: Data were available for 2057 patients (HY 1 : 262; HY 2 : 1230; HY 3 : 524; HY 4 : 41). Patients at higher HY stages were older, had a longer time since PD diagnosis and higher baseline UPDRS II+III scores vs patients at lower HY stages. Rotigotine improved UPDRS II+III versus placebo for each individual HY stage (p < 0.05 for each HY stage), with treatment differences increasing with increasing HY stages. Similar results were observed for UPDRS II and UPDRS III.Conclusions: This post hoc analysis suggests that rotigotine may be efficacious across a broad range of progressive stages of PD symptom severity and functional disability (HY stages 1–4).

Evaluation of rotigotine transdermal patch for the treatment of apathy and motor symptoms in Parkinson's disease.

BackgroundThis multicenter, double-blind, placebo-controlled study assessed the efficacy of rotigotine transdermal patch on apathy and motor symptoms in patients with Parkinson’s disease (PD).MethodsPatients with PD-associated apathy (Unified Parkinson's Disease Rating Scale [UPDRS] I item 4 [motivation] ≥2 and patient-rated Apathy Scale [AS] ≥14) were randomized 1:1:1 to “low-dose” rotigotine (≤6 mg/24 h for early PD [those not receiving levodopa] or ≤8 mg/24 h for advanced PD [those receiving levodopa]), “high-dose” rotigotine (≤8 mg/24 h for early PD or ≤16 mg/24 h for advanced PD), or placebo, and maintained at optimal/maximal dose for 12 weeks. Coprimary efficacy variables were: change from baseline to End of Maintenance in patient-rated AS and UPDRS II + III total score. Recruitment was stopped after an interim futility analysis; therefore, all p values are exploratory.ResultsOf 122 patients randomized, 81.1 % completed the study (placebo, n = 32/40 [80.0 %]; low-dose rotigotine, n = 30/41 [73.2 %]; high-dose rotigotine, n = 37/41 [90.2 %]). No treatment difference was observed in the change in patient-rated AS (least squares mean [95 % confidence interval (CI)] difference: low-dose, 0.04 [−2.42, 2.50], p =0.977; high-dose, −0.22 [−2.61, 2.18], p = 0.859). Rotigotine improved UPDRS II + III total scores versus placebo (least squares mean [95 % CI] treatment difference: low-dose, −7.29 [−12.30, −2.28], p = 0.005; high-dose, −6.06 [−10.90, −1.21], p = 0.015), and the “mood/apathy” domain of the Non-Motor Symptom Scale as rated by the investigator (secondary outcome). The most frequent adverse events in rotigotine-treated patients were application site reactions, somnolence, and nausea.ConclusionsRotigotine did not improve PD-associated apathy as rated by the patient but provided clinically relevant improvement in motor control and activities of daily living.Trial registrationClinicalTrials.gov identifier NCT01782222. Trial registration date: January 30, 2013.Electronic supplementary materialThe online version of this article (doi:10.1186/s12883-016-0610-7) contains supplementary material, which is available to authorized users.

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

Objective: This post-hoc analysis of a prospective open-label study investigated patients with restless legs syndrome (RLS) taking approved dosages (1, 2 or 3 mg/24 h) of rotigotine transdermal patch for up to 5 years.Research design and methods: Following 6 weeks' double-blind treatment, patients with moderate-to-severe RLS received open-label rotigotine titrated to optimal dosage.Main outcome measures: Safety was assessed by adverse events (AEs) and efficacy was assessed by the International Restless Legs Syndrome Study Group Rating Scale (IRLS).Results: Of 295 patients who entered the open-label study, 198 (67%) began the maintenance period taking rotigotine dosages of 1 – 3 mg/24 h, or increased their dosage from 0.5 mg in the first 3 months of the maintenance period. Of the 198 patients, 45 patients (23%) completed 5 years of follow-up within this dosage range, 79 patients (40%) had their dosage adjusted outside this range during follow-up and 74 patients (37%) withdrew (including 49 [25%] due to AEs and 6 [3%)] for lack of efficacy). Application site reactions were the most common AEs (102 of 198 patients [52%]), with an incidence of 35% (69 of 198) in year 1, 19% (19 of 102) in year 2, and 4 – 6% during each of years 3 – 5. Mean IRLS total score decreased from 27.1 ± 6.0 at double-blind baseline to 6.5 ± 6.5 at the beginning of maintenance, and to 7.4 ± 8.4 after 5 years' treatment on 1 – 3 mg/24 h (n = 45); 21 patients (47%) were classified as symptom-free (IRLS = 0).Conclusions: Consistent with the results for the overall population, rotigotine transdermal patch at approved dosages of 1 – 3 mg/24 h was generally well tolerated after the first year, with sustained efficacy in patients who completed 5 years of treatment at dosages of 1 – 3 mg/24 h.

Long-term safety and efficacy of rotigotine transdermal patch for moderate-to-severe idiopathic restless legs syndrome: a 5-year open-label extension study

Safety and efficacy of non-ergot dopamine agonists for the treatment of idiopathic restless legs syndrome have been shown in short-term trials. We did a prospective open-label extension of a 6-week, double-blind randomised trial to assess the safety, tolerability, and efficacy of rotigotine transdermal patch for up to 5 years in patients with restless legs syndrome. Patients (aged 18-75 years) with moderate-to-severe idiopathic restless legs syndrome were treated with once-daily rotigotine transdermal patch in 33 centres in Austria, Germany, and Spain between July 31, 2003, and April 15, 2009. The dose was titrated in weekly increments (up to 4 weeks) from 0·5 mg/24 h to a maximum of 4 mg/24 h, and was followed by up to 5 years of maintenance at the optimum dose. Primary safety outcomes included occurrence of adverse events and dropouts. Efficacy assessments were secondary and included the International Restless Legs Syndrome study group severity rating scale (IRLS). Augmentation of symptoms was assessed by means of standard diagnostic criteria and was confirmed by an international expert panel. All patients who received at least one dose of study drug were included in assessments. This study is registered with ClinicalTrials.gov, number NCT00498186. 295 patients entered the open-label study, of whom 126 (43%) completed 5 years of follow-up. 169 (57%) patients discontinued treatment, 89 (30%) because of adverse events and 31 (11%) because of lack of efficacy. 70 patients (24%) discontinued during year 1 of maintenance. The most common adverse events were application site reactions, which occurred in 37% (106/290) of patients in year 1, 17% (38/220) of patients in year 2, 14% (27/191) of patients in year 3, and in less than 6% of patients during year 4 (8/159) and year 5 (8/147). 56 patients (19%) discontinued because of application site reactions. Mean rotigotine dose was 2·43 mg/24 h (SD 1·21) after initial titration and 3·09 mg/24 h (1·07) at the end of maintenance. Of 89 patients who discontinued because of adverse events, 28 (31%) were on 4 mg/24 h rotigotine. Mean IRLS score of patients entering the open-label study was 27·8 (SD 5·9) at baseline of the double-blind trial. In patients who completed the maintenance period, mean IRLS score was reduced from a baseline score of 27·7 (SD 6·0) by a mean of 18·7 points (SD 9·5) to a score of 9·0 (SD 9·2) at the end of maintenance. 39% (48/123) of patients who completed the trial were classified as symptom free according to the IRLS. Clinically significant augmentation was recorded in 39 patients (13%), of whom 15 (5%) were receiving a dose of rotigotine within the range approved by the European Medicines Agency (EMA; 1-3 mg/24 h) and 24 (8%) were receiving 4 mg/24 h rotigotine. Rotigotine transdermal patch is generally well tolerated after 1 year and provides sustained efficacy for patients with moderate-to-severe restless legs syndrome at a stable dose for up to 5 years. Thus, rotigotine transdermal patch is an appropriate long-term treatment option for moderate-to-severe restless legs syndrome, a disorder that often requires lifelong treatment. UCB BioSciences, on behalf of Schwarz Pharma, Ireland.

Treatment of moderate to severe restless legs syndrome: 2-year safety and efficacy of rotigotine transdermal patch

BackgroundRotigotine is a unique dopamine agonist with activity across D1 through D5 receptors as well as select adrenergic and serotonergic sites. This study reports the 2-year follow-up safety and efficacy data of an ongoing open-label multicenter extension study (NCT00498186) of transdermal rotigotine in patients with moderate to severe restless legs syndrome (RLS).MethodsPatients received a once-daily patch application of an individually optimized dose of rotigotine between 0.5 mg/24 h to 4 mg/24 h. 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). Quality of life (QoL) was measured by QoL-RLS.ResultsOf 310 patients who completed a 6-week placebo-controlled trial (SP709), 295 (mean age 58 ± 10 years, 66% females) were included in the open-label trial SP710. 64.7% (190/295 patients) completed the 2-year follow-up; 29 patients discontinued during the second year. Mean daily rotigotine dose after 2 years was 2.93 ± 1.14 mg/24 h with a 2.9% dose increase from year 1. Rotigotine was generally well tolerated. The rate of typical dopaminergic side effects, nausea and fatigue, was low (0.9% and 2.3%, respectively) during the second year; application site reactions were frequent but lower than in year 1 (16.4% vs. 34.5%). The IRLS total score improved from baseline of SP709 (27.8 ± 5.9) by 17.2 ± 9.2 in year 2 completers. Similar improvements were observed in RLS-6 scales, CGI scores and QoL-RLS. The responder rate in the CGI change item 2 ("much" and "very much" improved) was 95% after year 2.ConclusionsTransdermal rotigotine is an efficacious and well-tolerated long-term treatment option for patients with moderate to severe RLS with a high retention rate during 2 years of therapy.Trial registrationNCT00498186

Rotigotine transdermal patch in moderate to severe idiopathic restless legs syndrome: A randomized, placebo-controlled polysomnographic study

Objective To assess the efficacy of rotigotine transdermal patch in subjects with moderate to severe idiopathic restless legs syndrome (RLS) and periodic limb movement (PLM) in sleep in a double-blind, randomized, placebo-controlled, multicenter study ( NCT00275236). Methods Sixty-seven (46 rotigotine, 21 placebo) subjects applied rotigotine (maximum 3 mg/24 h) or placebo patches once-daily during a 4-week maintenance period; efficacy evaluations used polysomnographic measures and clinician/patient ratings. Results Mean PLM index (PLMI; PLM/h time in bed) decreased more with rotigotine (50.9/h to 8.1/h) than with placebo (37.4/h to 27.1/h; adjusted treatment ratio 4.25 (95% CI [2.48, 7.28], p < 0.0001). PLM during sleep with arousal index (PLMSAI; 8.57/h to 2.47/h under rotigotine, 6.5/h to 4.95/h under placebo; adjusted treatment difference: −3.12 (95% CI [−5.36, −0.88], p = 0.0072) also improved more under rotigotine. At end of maintenance, 39% of rotigotine subjects had PLMI levels <5/h and 26% showed no RLS symptoms (IRLS = 0), whereas no placebo subject met these criteria. Common drug-related adverse events for rotigotine and placebo included nausea (21.7%/4.8%), headache (17.4%/14.3%), application site reactions (17.4%/4.8%), and somnolence (10.9%/9.5%); most were mild to moderate in intensity. Conclusions Rotigotine transdermal patch was efficacious and well tolerated in the short-term treatment of RLS motor symptoms and associated sleep disturbances.

2.245 Long-term safety and efficacy of rotigotine transdermal patch in early-stage Parkinson's disease

2.245 Long-term safety and efficacy of rotigotine transdermal patch in early-stage Parkinson's disease

2.244 Efficacy of rotigotine transdermal patch as adjunct to levodopa in subgroups of advanced-stage Parkinson's patients

Objective: To investigate efficacy and safety of adjunctive rotigotine (Neupro®), a D3/D2/D1 dopaminergic receptor agonist formulated as a transdermal patch, in advanced Parkinson’s disease (PD). Method: PD subjects inadequately controlled with levodopa alone were randomized to placebo or one of two doses of rotigotine (either 8mg/24 hr or 12mg/24 hr). The primary efficacy measurement was reduced “off” time in all-day patient diary home motor function assessments. Results: Of 351 randomized subjects (111 to rotigotine 12mg/24 hr and 120 to rotigotine 8mg/24 hr; 120 to placebo), 260 (74%) completed the maintenance phase. Rotigotine-treated subjects receiving 12mg/24 hr had an adjusted mean decrease of −2.1 hrs in “off” time; and the group receiving 8mg/24 hr had “off” time reduction by −2.7 hrs compared to their baseline vs. −0.9 hrs in the placebo group (p-values of 0.003 and <0.001, respectively). Neither rotigotine group experienced an increase in the time “on with troublesome dyskinesias”. Both doses of rotigotine resulted in decreased absolute “off” time regardless of subject’s gender, age, severity and duration of PD, or absolute “off” time at baseline. However, subjects whose baseline “off” time was 6 hrs showed greater improvement at the end of treatment. The most common adverse effects with rotigotine were application site reactions, somnolence, nausea, and dizziness; all were usually mild to moderate in intensity. Conclusion: Rotigotine transdermal system as adjunctive therapy to levodopa showed clinically relevant and statistically significant reductions in “off” time using doses of 8−12mg/24 hr. Subgroup analysis did not reveal differences in efficacy. There was no increase in “on time with troublesome dyskinesias”. Rotigotine transdermal patch was well-tolerated for the majority of subjects in this trial.