The effects of transdermal rotigotine on non-motor symptoms of Parkinson's disease: a multicentre, observational, retrospective, post-marketing study.
Valldeoriola Francesc,Salvador Antonio,Gómez-Arguelles José Maria,Marey José,Moya Miguel,Ayuga Ángel,Ramírez Francisco
The International journal of neuroscience
AIM:This study evaluated the effect of ≥6 months of transdermal rotigotine on non-motor and motor symptoms of patients with advanced Parkinson's disease. MATERIALS AND METHODS:The study was conducted in Spain between September 2011 and December 2012 (ClinicalTrials.gov: NCT01504529). The primary efficacy variable was the change from baseline in non-motor symptoms, as assessed by changes in Parkinson's Disease Non-Motor Symptoms Questionnaire total scores at 6 months. Secondary endpoints included the assessment of motor symptoms by Unified Parkinson's Disease Rating Scale III scores. RESULTS:Data from 378 patients (mean age: 70.2 years; 56.9% male) with Parkinson's disease receiving rotigotine from were collected. Mean disease duration was 6.1 years, and mean rotigotine treatment duration was 45.6 months. Rotigotine reduced non-motor symptoms by 14.6% (mean change from baseline in Parkinson's Disease Non-Motor Symptoms Questionnaire: -1.5 ± 3.4; p < 0.0001). The majority of patients (58.2%) had improved non-motor symptoms at 6 months. Comparing the baseline versus study end, fewer patients experienced events in the urinary (78.6% vs. 73.3%; p = 0.0066), sleep (82.8% vs. 72.8%; p < 0.0001) and mood/cognition (77.3% vs. 66.4%; p < 0.0001) domains of the Parkinson's Disease Non-Motor Symptoms Questionnaire. Mean motor symptoms were reduced from baseline by 8.0% (mean change from baseline in Unified Parkinson's Disease Rating Scale III: -2.6 ± 8.0; p < 0.0001). CONCLUSIONS:In clinical practice in Spain, rotigotine may be an effective treatment to reduce the non-motor and motor symptoms in patients with advanced Parkinson's disease.
Non-ergot dopamine agonist rotigotine as a promising therapeutic tool in atypical parkinsonism syndromes: a 24 months pilot observational open-label study.
Moretti D V,Binetti G,Zanetti O,Frisoni G B
Rotigotine (RTG) is a non-ergot dopamine agonist developed as a new transdermal formulation, indicated for use in early and advanced Parkinson's disease (PD). The potential advantages of the RTG patch include immediacy of effect onset, constant drug delivery, better tolerability avoiding drug peaks and easy of use, helping patient's compliance. So, RTG patch appears to be a suitable candidate in the treatment of patients with atypical parkinsonism. The present is an observational study to evaluate the efficacy and tolerability of RTG in patients affected by atypical parkinsonian disorders. 61 subjects with diagnosis of atypical parkinsonian disorders were treated with transdermal RTG. Diagnosis was: Parkinson disease with dementia, multiple system atrophy parkinsonian type, multiple system atrophy cerebellar type, progressive sopranuclear palsy, cortico-basal degeneration, Lewy body dementia and fronto-temporal dementia with parkinsonism. Patients were evaluated by UPDRS-III, NPI, MMSE and adverse events (AEs) were recorded. Patients treated with RTG show an overall decrease of UPDRS III scores without increasing behavioral disturbances. Main adverse events (AE) were hypotension (14 patients), nausea (13), vomiting (5), drowsiness (5), tachycardia (2) dystonia (3 patients, all treated with concomitant l-dopa). On the whole, 16 patients were affected by AE and 7 patients suspended RTG treatment due to AE (vomiting, tachycardia and sleepiness). In our population transdermal RTG seems to be effective and well tolerated. Due to its system of drug delivery, RTG appears to be a suitable therapy in elderly patients as it has a good tolerability profile, improves patient's compliance and helps management of fragile patients.
Effects of long-term treatment with rotigotine transdermal system on dyskinesia in patients with early-stage Parkinson's disease.
Giladi Nir,Ghys Liesbet,Surmann Erwin,Boroojerdi Babak,Jankovic Joseph
Parkinsonism & related disorders
PURPOSE:In two 6-month, double-blind, placebo-controlled studies, rotigotine transdermal system was well-tolerated and efficacious monotherapy in early-stage PD. This post hoc analysis of the long-term open-label extensions (NCT00594165; NCT00599196) of these studies assessed incidence and severity of dyskinesia in participants treated with rotigotine, with or without concomitant levodopa, for up to 6 years. METHODS:Open-label rotigotine was titrated to optimal dose (≤16 mg/24 h). Concomitant levodopa was permitted. Dyskinesia data, recorded using the Unified Parkinson's Disease Rating Scale Part IV, were pooled from the two open-label studies. RESULTS:Of 596 participants who received open-label rotigotine, 299 (50%) remained at trial closure; no patient discontinued due to dyskinesia. In the two studies, median exposure to rotigotine was 1910 days (∼5 years, 3 months), and 1564.5 days (∼4 years, 3 months). During up to 6 years of open-label rotigotine, 423/596 (71%) received levodopa. Dyskinesias were reported in 115/596 (19%) participants, 90/115 (78%) of who developed dyskinesia after levodopa was added; 25 reported dyskinesia in the absence of levodopa (includes patients who never received open-label levodopa, and those who reported dyskinesia before starting concomitant levodopa). Dyskinesia severity data were available for 107 of the 115 participants. In 56/107 (52%) participants, dyskinesia was considered 'not disabling' for all occurrences; the worst-case severity was 'mildly disabling' for 33/107 (31%), and 'moderately' or 'severely disabling' for 18/107 (17%; 3% of total participants). CONCLUSION:During treatment with rotigotine in patients with PD for up to 6 years the incidence of dyskinesia was low, and the dyskinesia was generally 'not disabling' or 'mildly disabling'.
Rotigotine vs ropinirole in advanced stage Parkinson's disease: a double-blind study.
Mizuno Yoshikuni,Nomoto Masahiro,Hasegawa Kazuko,Hattori Nobutaka,Kondo Tomoyoshi,Murata Miho,Takeuchi Masahiro,Takahashi Masayoshi,Tomida Takayuki,
Parkinsonism & related disorders
OBJECTIVE:To confirm the superiority of transdermal rotigotine up to 16 mg/24 h over placebo, and non-inferiority to ropinirole, in Japanese Parkinson's disease (PD) patients on concomitant levodopa therapy. METHODS:This trial was a randomized, double-blind, double-dummy, three-arm parallel group placebo- and ropinirole-controlled trial. Four-hundred and twenty PD patients whose motor symptoms were not well controlled by levodopa treatment were randomized 2:2:1 to receive rotigotine, ropinirole (up to 15 mg/day) or placebo during a 16-week treatment period followed by a 4-week taper period. The primary variable was change in the Unified Parkinson's Disease Rating Scale (UPDRS) Part III (ON state) sum score from baseline to the end of the treatment period. RESULTS:The difference in the change in the UPDRS Part III (ON state) sum score from baseline to the end of treatment between rotigotine and placebo groups was -6.4 ± 1.2 (95% CI: -8.7 to -4.1; p < 0.001), indicating superiority of rotigotine over placebo. The difference between rotigotine and ropinirole groups was -1.4 ± 1.0 (95% CI: -3.2 to 0.5), below the non-inferiority margin, indicating the non-inferiority of rotigotine to ropinirole. Application site reaction was seen in 57.7% of the patients in the rotigotine group and in 18.6% in the ropinirole group (P < 0.001). No other safety issue was noted. CONCLUSIONS:Rotigotine was well tolerated at doses up to 16 mg/24 h and showed similar efficacy to ropinirole except that the application site reaction was much higher in the rotigotine group.
Rotigotine transdermal system for control of early morning motor impairment and sleep disturbances in patients with Parkinson's disease.
Giladi Nir,Fichtner Andreas,Poewe Werner,Boroojerdi Babak
Journal of neural transmission (Vienna, Austria : 1996)
This open-label study (NCT00243945) investigated the efficacy of rotigotine transdermal system in 54 Parkinson's disease (PD) patients with unsatisfactory control of early morning motor impairment and sleep disturbances. Rotigotine dose was up titrated for 8 weeks and maintained for 4 weeks. Mean rotigotine dose at end of maintenance was 11.83 mg/24 h (SD 3.86). Patients had two overnight hospital stays at baseline and end of treatment during which early morning motor performance was assessed, prior to first morning dose of regular oral antiparkinsonian medication. Rotigotine improved mean Unified Parkinson's Disease Rating Scale (UPDRS) part III score by -9.3 points, mean Timed Up and Go test duration by -1.4 s and mean morning finger tapping by 26.5 taps/min; 46% of patients were considered responders (≥30% improvement of UPDRS III). Mean Nocturnal Akinesia, Dystonia and Cramps Sum Score was reduced by 61%; mean number of nocturias decreased by 32%. Rotigotine also improved sleep quality. These results suggest a role for rotigotine in treatment of nocturnal and early morning motor disabilities in PD patients.
Outcomes from switching from rotigotine patch to alternate therapies in Parkinson's disease.
Chitnis Shilpa,Jaffery Manall,Dewey Richard B
The International journal of neuroscience
BACKGROUND:When rotigotine patch was withdrawn from the US market, we prospectively gathered data on efficacy, side effects, and daytime sedation on patients while taking rotigotine and following the switch to alternate therapies. METHODS:Patients rated the efficacy of rotigotine on a scale of 0-5 (ineffective to extremely effective) and completed the Epworth Sleepiness Scale. At a follow-up visit a mean of 3 months later, patients rated their change in efficacy and side effects on a scale of -3 to +3 (much worse to much better) and again completed the Epworth Sleepiness Scale. RESULTS:Thirty-three patients were switched to a single alternate treatment. On rotigotine, the average efficacy score was 3.5, and after switching, the average change in efficacy was -0.67 (worsening). Average change scores for efficacy and adverse effects were 0.25 and 0.38 for levodopa, -0.88 and -0.25 for ropinirole IR, -1.2 and -0.83 for ropinirole XL, -0.80 and 1.0 for pramipexole, and -1.0 and 0.50 for rasagiline, respectively. Average change in Epworth score on each alternate agent was -3.9, -2.3, 1.3, 3.0, and 1. CONCLUSION:Rotigotine was an effective treatment with all groups deteriorating after switch except for the levodopa group. Fifty-eight percent of patients preferred rotigotine versus 36% preferring the alternate treatment.
Steady-state plasma concentration profile of transdermal rotigotine: an integrated analysis of three, open-label, randomized, phase I multiple dose studies.
Elshoff Jan-Peer,Braun Marina,Andreas Jens-Otto,Middle Michelle,Cawello Willi
BACKGROUND:The dopamine agonist rotigotine is formulated in a transdermal delivery system (patch) for once-daily application. It has been reported as efficacious in the treatment of idiopathic Parkinson's disease (PD) and restless legs syndrome. OBJECTIVE:This article summarizes the results of 3 clinical studies conducted to characterize the 24-hour pharmacokinetic profile of rotigotine in steady state and the effect of different patch application sites on this profile. In addition, the relative bioavailability of a single, large patch versus 2 smaller patches was assessed. METHODS:One Phase I study (SP871) assessed the steady-state pharmacokinetic properties at different application sites at a rotigotine maintenance dose of 3 mg/24 hours in healthy participants. Due to tolerability issues, the steady-state pharmacokinetic properties of rotigotine at higher doses (8 mg/24 hours) was assessed in 2 Phase I studies (SP630, SP651) in early-stage PD patients. Relative rotigotine bioavailability from a 40 cm(2) patch versus 2 × 20 cm(2) patches (SP651) and from a 15 cm(2) patch versus 1 × 5 cm(2) + 1 × 10 cm(2) patches (SP871) was also evaluated. Rotigotine concentrations in plasma were analyzed using a validated LC-MS/MS method. The pharmacokinetic variables were calculated using standard noncompartmental analysis. RESULTS:Release of rotigotine to the skin was 31% to 62% of total drug content in the patch. Variability of rotigotine exposure was low within participants (15%) compared with the variability observed between participants (54%). Rotigotine exposure increased proportionally in the therapeutic dose range of 2 mg/24 hours to 8 mg/24 hours. Plasma concentrations at steady state were stable over the 24-hour patch-on period. Delivery via a single, large patch compared with a combination of smaller patches did not appear to influence exposure to rotigotine. Bioavailability showed some variability depending on patch application site (hip, shoulder, abdomen, flank, thigh, upper arm); the respective mean ratios for AUC ranged between 0.87 (abdomen vs flank) and 1.46 (shoulder vs thigh). CONCLUSIONS:Continuous rotigotine delivery via a once-daily transdermal patch generated stable mean steady-state 24-hour plasma concentrations in healthy participants as well as patients with early-stage PD. Doses were achieved either by application of 1 large patch or a combination of smaller patches, resulting in the same total surface area.
Long-term safety and tolerability of rotigotine transdermal system in patients with early-stage idiopathic Parkinson's disease: a prospective, open-label extension study.
Elmer Lawrence W,Surmann Erwin,Boroojerdi Babak,Jankovic Joseph
Parkinsonism & related disorders
PURPOSE:This prospective, open-label extension (SP702; NCT00594165) of a 6-month double-blind, randomized study investigated the long-term safety and tolerability of rotigotine transdermal system in early Parkinson's disease (PD). METHODS:Patients with early-stage idiopathic PD received transdermal rotigotine for up to 6 years at optimal dose (up to 16 mg/24h). Adjunctive levodopa was allowed. Primary outcomes included adverse events (AEs) and extent of rotigotine exposure. Other outcomes included time to levodopa, incidence of dyskinesias, and efficacy using the Unified Parkinson's Disease Rating Scale (UPDRS) II+III total score. RESULTS:Of 217 patients entering the open-label study, 47% were still in the study upon closure; 24% withdrew because of AEs and 6% because of lack of efficacy. The median exposure to rotigotine was 1910 days (≈ 5 years, 3 months; range 1-2188 days). Most common AEs were somnolence (23% per patient-year), falls (17%), peripheral edema (14%), nausea (12%), and application site reactions (ASRs; 12%). 3% withdrew because of ASRs. 26% patients did not initiate levodopa; of those who did, fewer than half started levodopa in the first year. Dyskinesias were reported by 25% patients; the majority (83%) reported their first episode after initiating levodopa. Mean UPDRS II+III total scores remained below double-blind baseline for up to 2 years of open-label treatment. CONCLUSION:This is the longest interventional study of rotigotine conducted to date. Transdermal rotigotine was generally well tolerated for up to 6 years; AEs reported were similar to those observed in shorter studies and led to discontinuation in only 24% patients.
Treatment of patients with early and advanced Parkinson's disease with rotigotine transdermal system: age-relationship to safety and tolerability.
Oertel Wolfgang,LeWitt Peter,Giladi Nir,Ghys Liesbet,Grieger Frank,Boroojerdi Babak
Parkinsonism & related disorders
Although dopamine agonists (DAs) are sometimes perceived as poorly tolerated by the elderly, there is little clinical evidence to support these concerns. Safety and tolerability of rotigotine have been demonstrated in four 6-month randomized placebo-controlled studies: two in early Parkinson's disease (PD) and two in advanced PD. A post hoc analysis of data from these pivotal trials was carried out to compare the adverse event (AE) profiles of younger and older patient populations. Data from early and advanced PD trials were separately pooled and evaluated using two age cut-offs (<65 vs. ≥ 65 years; <75 vs. ≥ 75 years). For most AEs, no age-related differences in incidence were observed. In the early PD pool, nausea (38% vs. 30%) and headache (15% vs. 9%) were more frequent in younger (<65 years) compared with older (≥ 65 years) patients using the 65-year age cut-off. Using the 75-year cut-off, nausea (36% vs. 21%) was more frequent in younger patients (<75 years) and dizziness (15% vs. 28%) was more frequent in older patients (≥ 75 years). In the advanced PD pool, nausea was more frequent in younger patients using the 65-year age cut-off (24% vs. 19%) and falls were more frequent in older patients using the 75-year age cut-off (8% vs. 13%). In this relatively healthy population which included only few patients aged 75 years or older, rotigotine was generally well tolerated regardless of age. Data from more representative PD populations are required to fully assess potential risks of DA therapy in elderly patients.
The effect of dopamine agonists on cognitive functions in non-demented early-mild Parkinson's disease patients.
Brusa Livia,Pavino Valentina,Massimetti Maria Carla,Bove Raffaele,Iani Cesare,Stanzione Paolo
The effect of dopamine agonists (DAs) on cognition in Parkinson's disease (PD) is not yet completely established. Previous papers reported a worsening effect on some cognitive functions with some DAs, but not with others, suggesting that DAs may differently affect cognition in PD patients according to their pharmacological characteristics. We set out to test the effect of rotigotine and cabergoline on cognitive functions in a group of forty non-demented early-mild PD patients (H &Y <2). Subjects were randomly divided into two groups and evaluated in a randomized cross-over study using neuropsychological tests; at the same time, motor function was monitored under three different treatment conditions: DA (rotigotine or cabergoline), L-dopa, and off therapy. Rotigotine and cabergoline were chosen because while they share a mixed D1 and D2 receptor profile, the former is non-ergolinic and the latter ergolinic. No significant differences were found in cognitive function between the basal condition and the DA treatments. On the basis of the present data, which we compare with previous findings regarding pramipexole IR and pergolide, we hypothesize that combined stimulation of both dopamine receptor families, as occurs with rotigotine, cabergoline, L-dopa and pergolide, may preserve cognitive functions more than pure D2 family stimulation.
Randomized, blind, controlled trial of transdermal rotigotine in early Parkinson disease.
Watts R L,Jankovic J,Waters C,Rajput A,Boroojerdi B,Rao J
OBJECTIVE:This multicenter, randomized, double-blind study was performed to compare the safety and efficacy of the once-daily dopamine agonist rotigotine, in a continuous-dosing transdermal-patch formulation, vs placebo in patients with early-stage Parkinson disease (PD). METHODS:Patients were randomized to receive placebo (n = 96) or rotigotine (n = 181), starting at 2 mg/24 h (10-cm(2) patch size; 4.5-mg total drug content), titrated weekly up to 6 mg/24 h (30-cm(2) patch size; 13.5-mg total drug content), and then maintained for 6 months. The primary efficacy measures were 1) the change in the Unified Parkinson's Disease Rating Scale (UPDRS) scores (parts II and III) from baseline to end of treatment and 2) responder rates (patients with > or =20% improvement). RESULTS:Patients receiving rotigotine had a mean absolute difference of 5.28 (+/-1.18) points lower in UPDRS subtotal scores compared with those receiving placebo (p < 0.0001). The mean change in part III motor scores was -3.50 (+/-7.26) (n = 177) and was the greatest contributor to UPDRS improvement. The rotigotine group had more responders (48 vs 19%; p < 0.0001). The most commonly reported adverse events were application site reactions (44% rotigotine vs 12% placebo), nausea (41 vs17%), somnolence (33 vs 20%), and dizziness (19 vs 13%), and most were mild or moderate in intensity. CONCLUSIONS:Transdermal rotigotine, when titrated to a dosage of 6 mg/24 h, was effective for the treatment of early-stage Parkinson disease in this trial. Adverse events were similar to those found with other transdermal systems and dopamine agonists.
Advanced Parkinson disease treated with rotigotine transdermal system: PREFER Study.
LeWitt Peter A,Lyons Kelly E,Pahwa Rajesh,
BACKGROUND:In patients experiencing motor fluctuations, a major treatment challenge is the reduction of "off" time, particularly upon awakening. Rotigotine (Neupro) is a novel dopaminergic agonist with 24-hour transdermal delivery. METHODS:A randomized, double-blind, placebo-controlled trial (PREFER Study) was performed to assess efficacy and safety with two targeted transdermal doses of rotigotine in subjects with advanced Parkinson disease with > or =2.5 hours of daily "off" time. Subjects were randomized to receive placebo patches (n = 120) or rotigotine up to either 8 mg/24 hours (n = 120) or 12 mg/24 hours (n = 111). The primary efficacy measures compared changes from baseline to the end of week 24 in the number of daily hours "off" and responder rates for subjects achieving > or =30% reduction in "off" time. RESULTS:Compared to placebo, there were significant decreases in mean "off" time of 1.8 hours/day for the rotigotine 8 mg/24 hours group and 1.2 hours/day for the 12 mg/24 hours group. For rotigotine 8 and 12 mg/24 hours groups, > or =30% responder rates were 56.6% and 55.1% compared to the 34.5% placebo response. "On" time without dyskinesia after awakening was more than doubled in both rotigotine treatment groups vs placebo. Drug-related adverse effects included typical dopaminergic side effects, which were generally mild/moderate in intensity. Patch application site reactions including erythema and pruritus were mild to moderate and transient in the majority of instances. CONCLUSIONS:Transdermal rotigotine significantly improved "off" time in subjects with Parkinson disease not optimally controlled with levodopa and was safe and well tolerated, with typical dopaminergic side effects and occasional application site reactions.
Efficacy of pramipexole and transdermal rotigotine in advanced Parkinson's disease: a double-blind, double-dummy, randomised controlled trial.
Poewe Werner H,Rascol Olivier,Quinn Niall,Tolosa Eduardo,Oertel Wolfgang H,Martignoni Emilia,Rupp Markus,Boroojerdi Babak,
The Lancet. Neurology
BACKGROUND:Continuous dopaminergic drug delivery is an unmet medical need in advanced Parkinson's disease. The aim of this trial-Clinical Efficacy of Pramipexole And Transdermal Rotigotine in Advanced PD (CLEOPATRA-PD)-was to assess the efficacy of adjunct treatment with rotigotine in comparison with placebo and with pramipexole in levodopa-treated patients with advanced Parkinson's disease and wearing-off type motor fluctuations. METHODS:In this randomised controlled trial, eligible participants were randomly assigned to receive either rotigotine (up to 16 mg/24 h as a transdermal patch), pramipexole (up to 4.5 mg/day orally), or placebo for 6 months. Primary efficacy variables were absolute change in total hours "off" (assessed by home diaries) from baseline to end of study and responder rate (defined as the proportion of patients with >or=30% reduction in absolute off time per day). Analyses were done by intention to treat. This trial is registered with the US National Institutes of Health clinical trials database (ClinicalTrials.gov), number NCT00244387. FINDINGS:204 patients were randomly assigned to receive rotigotine, 201 to receive pramipexole, and 101 to receive placebo; 427 (84%) completed the trial. The number of discontinuations in each group was similar; most were for adverse events. The mean dose of rotigotine was 12.95 mg/24 h (SD 3.54), the mean dose of pramipexole was 3.1 mg/day (1.24). Mean absolute change in off time from baseline was -2.5 h (SE 0.20) with rotigotine, -2.8 h (0.20) with pramipexole, and -0.9 h (0.29) with placebo. The absolute change in off time from baseline compared with placebo was -1.58 h (95% CI -2.27 to -0.90; p<0.0001) for rotigotine and -1.94 h (-2.63 to -1.25; p<0.0001) for pramipexole. Responder rates were 67% (134 of 200 patients) for pramipexole, 59.7% (120 of 201 patients) for rotigotine, and 35% (35 of 100 patients) for placebo. INTERPRETATION:In terms of change in absolute off time, rotigotine was non-inferior to pramipexole. Continuous delivery of rotigotine as transdermal patches could offer similar efficacy to oral pramipexole in patients with fluctuating Parkinson's disease over 6 months of treatment.
Transdermal rotigotine: double-blind, placebo-controlled trial in Parkinson disease.
Jankovic Joseph,Watts Ray L,Martin Wayne,Boroojerdi Babak
Archives of neurology
OBJECTIVE:To assess the response to the rotigotine transdermal system (Neupro; Schwarz Pharma Ltd, Monheim, Germany), a nonergolinic dopamine agonist, in patients with early Parkinson disease. DESIGN:Randomized, double-blind, multicenter, placebo-controlled study. SETTING:Fifty sites in the United States and Canada. PATIENTS:Two hundred seventy-seven patients with early Parkinson disease. Eligibility was assessed by means of routine clinical and neurological examinations. Patients were randomized 2:1 to receive either rotigotine therapy or placebo. INTERVENTION:Treatment with the rotigotine transdermal system, 2, 4, or 6 mg during 24 hours, for 24 weeks. MAIN OUTCOME MEASURE:Percentage of subjects achieving a 20% response or greater (reduction) as assessed with the Unified Parkinson Disease Rating Scale subtotal (parts II [activities of daily living] and III [motor function]) from baseline to the end of the maintenance phase. RESULTS:Significant differences were observed between the rotigotine-treated and placebo groups for the 20% responder rate (48% for the rotigotine group and 19% for the placebo group; P<.001), least squares mean change in Unified Parkinson Disease Rating Scale subtotal (parts II and III) score (-941 for rotigotine vs -157 for placebo; P<.001), and percentage changes in Unified Parkinson Disease Rating Scale subtotal (parts II and III) score (-15.1% for rotigotine vs 7.3% for placebo; P<.001). Rotigotine treatment significantly increased the patients' Clinical Global Impression Scale scores (57% for rotigotine vs 30% for placebo; P<.001) and had a positive effect on their quality of life. The most common adverse events were application site reactions, nausea, and somnolence. Twenty-five (14%) of 181 patients in the rotigotine group withdrew from the study because of adverse effects. CONCLUSION:The rotigotine transdermal system consistently demonstrated statistically significant and clinically relevant efficacy over placebo in patients with early Parkinson disease and was well tolerated.
Rotigotine transdermal patch in early Parkinson's disease: a randomized, double-blind, controlled study versus placebo and ropinirole.
Giladi Nir,Boroojerdi Babak,Korczyn Amos D,Burn David J,Clarke Carl E,Schapira Anthony H V,
Movement disorders : official journal of the Movement Disorder Society
Rotigotine is a new, non-ergot dopamine agonist formulated in a transdermal delivery system. The present study was to investigate the efficacy and safety of the rotigotine transdermal patch in the treatment of early Parkinson's disease. Patients (n = 561) were randomized to rotigotine, ropinirole, or placebo. The titration period was up to 13 weeks, and there was a minimum dose-maintenance period of 24 weeks for ropinirole and 33 weeks for rotigotine. The primary endpoint was the proportion of patients with a minimum of 20% decrease in the combined Unified Parkinson's Disease Rating Scale Part II and Part III scores. The responder rate in the rotigotine group was significantly higher than in the placebo group (52% vs. 30%, P < 0.0001). Transdermal rotigotine at doses < or =8 mg/24 h did not show noninferiority to ropinirole at doses < or =24 mg/day. In a post-hoc subgroup analysis, rotigotine < or =8 mg/24 hours had a similar efficacy to ropinirole at doses < or =12 mg/day. The rotigotine transdermal patch was well tolerated. The most common adverse events were application-site reactions, nausea, and somnolence. Application-site reactions were predominantly mild or moderate in intensity. In conclusion, the rotigotine transdermal patch represents an effective and safe option for the treatment of patients with early Parkinson's disease.
Thorough QT/QTc study in patients with advanced Parkinson's disease: cardiac safety of rotigotine.
Malik M,Andreas J-O,Hnatkova K,Hoeckendorff J,Cawello W,Middle M,Horstmann R,Braun M
Clinical pharmacology and therapeutics
The potential effects of the dopamine agonist rotigotine on cardiac repolarization were studied in patients with Parkinson's disease, which affects electrocardiogram (ECG) quality. The parallel-group trial was double-blind and placebo- and positive (moxifloxacin 400 mg)-controlled. After two 24-h baseline ECGs, patients were randomized to rotigotine (n = 66) or placebo (n = 64). Twenty four-hour ECGs were recorded on days 14/15, 21/22, 28/29, 35/36, and 42/43 of a regimen involving weekly dose escalations of 4 mg/24 h (4 mg/24 h-24 mg/24 h). In 10-s ECGs (n = 357,948) selected from 24-h records, QT measurements were manually verified and individually rate-corrected (QTc). Assay sensitivity showed maximum mean 13.5 ms QTc prolongation after moxifloxacin with 95% confidence interval (CI) 11.8-15.2 ms. Rotigotine vs. placebo differences in time-matched changes from baseline (54 data points/24 h) showed mean effects close to zero with upper one-sided 95% CI <5 ms. Accurate, thorough QTc studies are possible even in patients with diseases that profoundly affect ECG quality. Rotigotine in supra- and therapeutic doses was shown not to affect cardiac repolarization.
High doses of rotigotine transdermal patch: results of an open-label, dose-escalation trial in patients with advanced-stage, idiopathic Parkinson disease.
Rektor Ivan,Babic Tomislav,Boothmann Bernard,Polivka Jiri,Boroojerdi Babak,Randerath Olaf
OBJECTIVE:The objective of the study was to determine the maximal achievable dose of rotigotine by assessing the tolerability of escalating doses of rotigotine transdermal patch in patients with advanced-stage Parkinson disease. METHODS:Thirty-four patients aged 30 years or older on a stable dose of l-dopa with an off time of at least 2.5 h/d were randomized to 2-titration schemes. The patients started on a dosage of 4 mg/24 h and received an incremental dosage of 4 mg/24 h per week in the fast-titration group and 2 mg/24 h per week in the slow-titration group to the maximal target dosage of 24 mg/24 h (patch size of 120 cm(2)). Thereafter, both groups entered a maintenance period of 42 days or longer for the rapid-titration group and 7 days or longer for the slow titration group followed by a 2-week safety follow-up period with stepwise dosage de-escalation of 4 mg/24 h for 4 days. RESULTS:Twenty-seven patients completed the trial, of whom 24 completed without dose reduction. Twenty-six patients (76%) were titrated to the maximum target dose and thus had a maximal achievable dosage of at least 24 mg/24 h. Adverse events, generally mild or moderate, included application site reaction (12%), nausea, dyskinesia, and visual hallucinations (9% each). The mean time spent off decreased by 2 to 3 h/d. Duration of on without dyskinesia periods increased (2 h/d). The mean total (SD) Unified Parkinson's Disease Rating Score decreased by 18.9 (14.2) in the fast-titration group and 17.8 (14.0) in the slow titration group. A shift from off to on without dyskinesias in status after waking up was observed. CONCLUSIONS:Rotigotine transdermal patch, up to 24 mg/24 h, was effective and well tolerated by patients with advanced-stage Parkinson disease.
Transdermal rotigotine for the perioperative management of Parkinson's disease.
Wüllner Ullrich,Kassubek Jan,Odin Per,Schwarz Michael,Naumann Markus,Häck Hermann-Josef,Boroojerdi Babak,Reichmann Heinz,
Journal of neural transmission (Vienna, Austria : 1996)
Continuous delivery of antiparkinsonian medication during a perioperative period is desirable to avoid 'off'-symptom complications in surgical patients with concomitant Parkinson's disease (PD). Fourteen PD patients undergoing surgery under general anesthesia were switched from oral dopaminergic medication to transdermally delivered 24-h rotigotine (median dose 12 mg/24 h) for the perioperative period. Rotigotine treatment was considered feasible by patients, their anesthesiologists and neurologists with good control of PD symptoms and easy switching and re-switching of PD medication.
A controlled trial of rotigotine monotherapy in early Parkinson's disease.
Archives of neurology
BACKGROUND:Oral dopamine agonists are effective for treating early Parkinson's disease (PD). Rotigotine is a dopamine agonist delivered through a silicone-based transdermal patch that is replaced every 24 hours. OBJECTIVES:To assess the efficacy and safety of rotigotine in patients with PD not receiving dopaminergic medications. DESIGN:Randomized, double-blind, placebo-controlled study. Patients Two hundred forty-two patients with early PD. Intervention Treatment with patches containing either 4.5, 9.0, 13.5, or 18.0 mg of rotigotine or placebo for 11 weeks. Main Outcome Measure The change in the sum of the scores of the activities of daily living and motor components of the Unified Parkinson's Disease Rating Scale from baseline to the end of treatment. RESULTS:There was a significant dose-related improvement in the motor and activities of daily living Unified Parkinson's Disease Rating Scale score between baseline and week 11 for the 13.5- and 18.0-mg groups compared with placebo (placebo, 0.3 +/- 7.7; 13.5-mg group, 5.1 +/- 7.0, P =.001; 18.0-mg group, 5.3 +/- 7.0, P<.001). Adverse experiences that occurred more commonly among subjects randomized to active treatment vs placebo included nausea, application site reactions, dizziness, insomnia, somnolence, vomiting, and fatigue. CONCLUSIONS:Rotigotine can be safely administered once daily transdermally and improves parkinsonian signs in patients with early PD.
Rotigotine transdermal patch in Chinese patients with advanced Parkinson's disease: A randomized, double-blind, placebo-controlled pivotal study.
Zhang Zhen-Xin,Liu Chun-Feng,Tao En-Xiang,Shao Ming,Liu Yi-Ming,Wang Jian,Asgharnejad Mahnaz,Xue Hai-Bo,Surmann Erwin,Bauer Lars
Parkinsonism & related disorders
INTRODUCTION:Rotigotine was demonstrated to be efficacious and well-tolerated in three placebo-controlled studies (CLEOPATRA-PD/PREFER/SP921) of patients with advanced-stage Parkinson's disease (PD), most of whom were Caucasian. This multicenter phase 3 study (SP1037; NCT01646255) was the first to investigate the efficacy and safety of rotigotine in Chinese patients with advanced-stage PD. METHODS:Chinese patients with PD, inadequately controlled on levodopa (stable dose ≥200 mg/day), with ≥2.5 h/day "off" time, and Hoehn & Yahr stage 2-4, were randomized 1:1 to receive transdermal rotigotine or placebo, titrated over ≤7 weeks, maintained at optimal/maximum dose (4-16 mg/24 h) for 12 weeks. Primary efficacy variable: mean change in absolute "off" time (according to patient diaries) from baseline to end of maintenance. Safety variables included adverse events (AEs) and discontinuations due to AEs. RESULTS:346 patients were randomized and 89.9% completed the study (87.8% placebo; 92.0% rotigotine). All were Chinese (58.7% male; mean ± SD age: 62.2 ± 8.9 years; mean ± SD time since PD diagnosis: 6.62 ± 3.70 years). Rotigotine significantly reduced "off" time vs placebo (LS mean [95% CI] treatment difference: -1.20 h/day [-1.83, -0.57]; p = 0.0002), and resulted in more responders (≥30% decrease in "off" time: 36.9% placebo; 48.8% rotigotine; p = 0.0269). AEs were reported for 86 (50.0%) placebo- and 103 (59.2%) rotigotine-treated patients; 15 discontinued due to AEs (placebo 7; rotigotine 8). The most common AEs (≥5%) were dizziness, nausea, pruritus, and dyskinesia. CONCLUSIONS:Rotigotine was efficacious in Chinese patients with advanced-stage PD as add-on therapy to levodopa, significantly reducing "off" time vs placebo; the treatment difference was similar to that observed in previous studies of mainly Caucasian patients. Rotigotine was generally well-tolerated and had a similar AE profile to those observed in previous studies.
Efficacy of Rotigotine at Different Stages of Parkinson's Disease Symptom Severity and Disability: A Post Hoc Analysis According to Baseline Hoehn and Yahr Stage.
Giladi Nir,Nicholas Anthony P,Asgharnejad Mahnaz,Dohin Elisabeth,Woltering Franz,Bauer Lars,Poewe Werner
Journal of Parkinson's disease
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).
Rotigotine Improves Abnormal Circadian Rhythm of Blood Pressure in Parkinson's Disease.
Oka Hisayoshi,Nakahara Atuso,Umehara Tadashi
INTRODUCTION:Cardiovascular autonomic failure is commonly associated with Parkinson's disease (PD), affecting the daily lives of patients. Rotigotine was recently reported not to influence cardiovascular autonomic responses in contrast to other dopaminergic drugs. The effect of rotigotine on daily blood pressure (BP) fluctuations might reflect autonomic failure in patients with PD. METHODS:Twenty-five PD patients who were receiving rotigotine and 12 patients not receiving rotigotine were recruited. Systolic BP during the daytime and nighttime was measured by 24-h BP monitoring at an interval of 2 years. The patients were divided into 3 groups according to the BP fluctuation type: dippers (nocturnal fall in BP ≥10%), non-dippers (0-10%), and risers (< 0%). The time course of BP was compared between the patients given rotigotine and those not given rotigotine. RESULTS:Among the 25 patients who received rotigotine, the BP type worsened in 2 patients, was unchanged in 16 patients, and improved in 7 patients. Among the 12 patients who were not receiving rotigotine, the BP type worsened in 5 patients, was unchanged in 4 patients, and improved only in 3 patients (p = 0.042). CONCLUSION:Rotigotine improves the abnormal circadian rhythm of BP in patients with PD. Rotigotine was suggested to have favorable effects on cardiovascular autonomic responses and circadian rhythm in patients with PD.
Effects of rotigotine transdermal patch in patients with Parkinson's disease presenting with non-motor symptoms - results of a double-blind, randomized, placebo-controlled trial.
Antonini A,Bauer L,Dohin E,Oertel W H,Rascol O,Reichmann H,Schmid M,Singh P,Tolosa E,Chaudhuri K Ray
European journal of neurology
BACKGROUND AND PURPOSE:Non-motor symptoms (NMS) of Parkinson's disease (PD) have a major impact on health-related quality of life. This is the first randomized controlled trial to use the NMS Scale (NMSS) as a primary outcome to assess treatment effects on NMS in PD. METHODS:In this double-blind trial (NCT01300819), patients with PD and a total NMSS score ≥40 were randomized (2:1) to rotigotine or placebo, titrated over 1-7 weeks to optimal dose (≤8 mg/24 h for patients not receiving levodopa, ≤16 mg/24 h for patients receiving levodopa), maintained for 12 weeks. The primary outcome was change in NMSS total score from baseline to end of maintenance. Secondary outcomes were the nine NMSS domains, Unified Parkinson's Disease Rating Scale (UPDRS) III (motor) and the 39-item Parkinson's Disease Questionnaire (PDQ-39). RESULTS:In total, 283/349 (81.1%) randomized patients completed the trial; 211 rotigotine and 122 placebo were included in the full analysis set. The NMSS total score decreased by 23 (rotigotine) and 19 (placebo) points; the treatment difference was not statistically significant (-3.58; 95% confidence interval -8.43, 1.26; P = 0.147). Numerically greater than placebo improvements were detected in the 'mood/apathy' and 'miscellaneous' NMSS domains (P < 0.05). Treatment differences in UPDRS III (-2.60; -4.27, -0.92; P = 0.002) and PDQ-39 (-2.79; -5.21, -0.37; P = 0.024) favoured rotigotine. Adverse events reported more frequently with rotigotine were nausea, application site reactions, somnolence and headache. CONCLUSIONS:Rotigotine improvement in the multi-domain NMSS total score was not superior to placebo. A different sensitivity of individual NMSS domains to dopaminergic therapy and a large placebo effect may have contributed to these findings.
Rotigotine transdermal patch in Chinese patients with early Parkinson's disease: A randomized, double-blind, placebo-controlled pivotal study.
Zhang Zhen-Xin,Shang Hui-Fang,Hu Xingyue,Chen Shengdi,Zhao Zhongxin,Du Xinlu,Surmann Erwin,Bauer Lars,Asgharnejad Mahnaz
Parkinsonism & related disorders
INTRODUCTION:Two phase3 studies (SP512; SP513) involving mostly Caucasian patients showed that rotigotine (≤8 mg/24 h) was efficacious and welltolerated in early-stage Parkinson's disease (PD). We report results from a phase 3 study (SP0914/NCT01646268) investigating rotigotine in Chinese patients with early-stage PD. METHODS:Patients were randomized 1:1 to rotigotine or placebo, titrated over 1-4 weeks, maintained at optimal/maximum dose (≤8 mg/24 h) for 24 weeks. Primary efficacy variable: change in Unified Parkinson's Disease Rating Scale (UPDRS) II + III total score from Baseline to End-of-Maintenance. Secondary variables: UPDRS II + III responders (≥20% decrease in UPDRS II + III) and changes in UPDRS II (activities of daily living [ADL]) and III (motor examination) subscores. RESULTS:Of 247 patients randomized, 113/124 (91.1%) rotigotine- and 107/123 (87.0%) placebo-treated patients completed the study. PATIENTS:mean (SD) age: 59.4 (10.2) years; time since PD diagnosis: 1.01 (1.22) years, 60.7% male. Rotigotine significantly improved UPDRS II + III total score (change from Baseline LSmean [95%CI] treatment difference, -4.82 [-7.18 to -2.45]; P < 0.0001). UPDRS II + III responder rates were higher with rotigotine (42.3% vs 22.3%; P = 0.0006). UPDRS II and III subscores improved with rotigotine (both subscores: P < 0.0005 vs. placebo). Most frequent adverse events (AEs): nausea (8.9% rotigotine, 3.3% placebo), dizziness (8.1%, 5.7%), pruritus (8.1%, 4.1%), somnolence (8.1%, 3.3%), erythema (6.5%, 1.6%), and vomiting (5.6%, 1.6%). Thirteen (5.3%) patients discontinued due to AEs (6 rotigotine, 7 placebo). CONCLUSIONS:Rotigotine was efficacious in Chinese patients with early-stage PD, providing benefits to control of ADL and motor function. Rotigotine was generally welltolerated, with similar AEs to those observed in Caucasian patients.
Rotigotine effects on early morning motor function and sleep in Parkinson's disease: a double-blind, randomized, placebo-controlled study (RECOVER).
Trenkwalder Claudia,Kies Bryan,Rudzinska Monika,Fine Jennifer,Nikl Janos,Honczarenko Krystyna,Dioszeghy Peter,Hill Dennis,Anderson Tim,Myllyla Vilho,Kassubek Jan,Steiger Malcolm,Zucconi Marco,Tolosa Eduardo,Poewe Werner,Surmann Erwin,Whitesides John,Boroojerdi Babak,Chaudhuri Kallol Ray,
Movement disorders : official journal of the Movement Disorder Society
In a multinational, double-blind, placebo-controlled trial (NCT00474058), 287 subjects with Parkinson's disease (PD) and unsatisfactory early-morning motor symptom control were randomized 2:1 to receive rotigotine (2-16 mg/24 hr [n = 190]) or placebo (n = 97). Treatment was titrated to optimal dose over 1-8 weeks with subsequent dose maintenance for 4 weeks. Early-morning motor function and nocturnal sleep disturbance were assessed as coprimary efficacy endpoints using the Unified Parkinson's Disease Rating Scale (UPDRS) Part III (Motor Examination) measured in the early morning prior to any medication intake and the modified Parkinson's Disease Sleep Scale (PDSS-2) (mean change from baseline to end of maintenance [EOM], last observation carried forward). At EOM, mean UPDRS Part III score had decreased by -7.0 points with rotigotine (from a baseline of 29.6 [standard deviation (SD) 12.3] and by -3.9 points with placebo (baseline 32.0 [13.3]). Mean PDSS-2 total score had decreased by -5.9 points with rotigotine (from a baseline of 19.3 [SD 9.3]) and by -1.9 points with placebo (baseline 20.5 [10.4]). This represented a significantly greater improvement with rotigotine compared with placebo on both the UPDRS Part III (treatment difference: -3.55 [95% confidence interval (CI) -5.37, -1.73]; P = 0.0002) and PDSS-2 (treatment difference: -4.26 [95% CI -6.08, -2.45]; P < 0.0001). The most frequently reported adverse events were nausea (placebo, 9%; rotigotine, 21%), application site reactions (placebo, 4%; rotigotine, 15%), and dizziness (placebo, 6%; rotigotine 10%). Twenty-four-hour transdermal delivery of rotigotine to PD patients with early-morning motor dysfunction resulted in significant benefits in control of both motor function and nocturnal sleep disturbances.
Transdermal rotigotine in early stage Parkinson's disease: a randomized, double-blind, placebo-controlled trial.
Mizuno Yoshikuni,Nomoto Masahiro,Kondo Tomoyoshi,Hasegawa Kazuko,Murata Miho,Takeuchi Masahiro,Ikeda Junji,Tomida Takayuki,Hattori Nobutaka,
Movement disorders : official journal of the Movement Disorder Society
BACKGROUND:We conducted a randomized, double-blind, placebo-controlled trial to determine the safety and efficacy of transdermal rotigotine at doses up to 16 mg/24 hours in patients with early stage Parkinson's disease (PD) in Japan. METHODS:Patients received once-daily rotigotine 2 to 16 mg/24 hours (mean dose, 12.8 mg/24 hours; n = 82) or placebo (n = 90) for 12 weeks. The primary endpoint was the change in Unified Parkinson's Disease Rating Scale (UPDRS) part II (activities of daily living) and part III (motor function) scores from baseline to the end of treatment. RESULTS:The mean (± standard deviation) changes in UPDRS part II and III scores were -8.4 ± 9.7 in the rotigotine group and -4.1 ± 8.2 in the placebo group and were significantly different (P = 0.002). More patients in the rotigotine group than in the placebo group had a ≥ 20% score reduction. No serious drug-related adverse events were reported. CONCLUSIONS:Rotigotine at doses up to 16 mg/24 hours was well tolerated and improved function in patients with early stage PD.
Transdermal rotigotine in advanced Parkinson's disease: a randomized, double-blind, placebo-controlled trial.
Nomoto Masahiro,Mizuno Yoshikuni,Kondo Tomoyoshi,Hasegawa Kazuko,Murata Miho,Takeuchi Masahiro,Ikeda Junji,Tomida Takayuki,Hattori Nobutaka
Journal of neurology
Rotigotine, a non-ergot dopamine receptor agonist, offers potential for continuous dopaminergic stimulation that could avoid the fluctuations observed with traditional treatments. We conducted a randomized, double-blind, placebo-controlled trial in Japanese patients with advanced Parkinson's disease (PD) to investigate the efficacy and safety of rotigotine. Inclusion criteria included the presence of motor complications, such as wearing off, on-off, delayed-on/no-on, any circumstances that could interfere with levodopa dose escalation because of side effects, or declining levodopa efficacy. The enrolled patients received once-daily applications of rotigotine transdermal patches or matched placebo patches. A total of 174 patients were randomly assigned to rotigotine (87 patients) or placebo (87 patients). The full analysis set included 172 patients (86 for the rotigotine group and 86 for the placebo group). The maximum maintenance dose of rotigotine was set at 16 mg/24 h. The changes in unified PD rating scale Part III scores from baseline to the end of the trial were -10.1 ± 9.0 (mean ± standard deviation) in the rotigotine group and -4.4 ± 7.4 in the placebo group (p < 0.001). There was a significantly greater reduction in the off-time (p = 0.014) in the rotigotine group. Rotigotine was well tolerated, with serious adverse events being reported in only three patients in each group. Rotigotine at doses of up to 16 mg/24 h is efficacious and safe in Japanese patients with advanced PD.
Rotigotine, a dopamine receptor agonist, increased BDNF protein levels in the rat cortex and hippocampus.
Adachi Naoki,Yoshimura Aya,Chiba Shuichi,Ogawa Shintaro,Kunugi Hiroshi
Brain-derived neurotrophic factor (BDNF) critically controls the fate and function of the neuronal network and has received much attention as a target of many brain diseases. Dopaminergic system dysfunction has also been implicated in a variety of neuropsychiatric diseases. Rotigotine, a non-ergot dopamine receptor agonist, is used in the treatment of Parkinson's disease and restless legs syndrome. To investigate the effects of rotigotine on neuronal functions both in vivo and in vitro, rats and primary cortical neurons were administered rotigotine, and the mRNA and protein expression levels of BDNF, its receptor TrkB and downstream signaling molecules, and synaptic proteins were determined. We found that BDNF protein was increased in the cortex and hippocampus of rats after 7days of rotigotine treatment. In contrast, BDNF mRNAs were reduced 6h after rotigotine treatment in cultured neurons presumably through the transient suppression of neuronal activity. We identified differential expression of D1, D2, and D3 receptors in the rat brain and cultured neurons. The observed increase in the expression of BDNF protein in the cortex and hippocampus after subchronic administration of rotigotine suggests that it may exert its medical effect in part through improving BDNF function in the brain. In addition, our results highlight the complex relationships between rotigotine and BDNF expression, which depend on the brain region, time course, and dose of the drug.
Efficacy and safety of rotigotine in elderly patients with Parkinson's disease in comparison with the non-elderly: a post hoc analysis of randomized, double-blind, placebo-controlled trials.
Nomoto Masahiro,Iwaki Hirotaka,Kondo Hiroyuki,Sakurai Masaya
Journal of neurology
Rotigotine-a non-ergot dopamine agonist-has two advantages; it can stimulate all dopamine receptors (D1-D5) like innate dopamine, and its transdermal administration provides continuous dopaminergic stimulation. The age of the patient impacts the effect and adverse events of anti-parkinsonian treatment. We conducted a post hoc analysis on three randomized, double-blind, placebo-controlled trials performed in Japan to clarify the difference of anti-parkinsonian treatment in elderly and non-elderly patients. Data from two combination therapy trials (with levodopa) in advanced stage Parkinson's disease patients and one monotherapy trial in early stage patients were pooled and grouped by age (non-elderly aged < 70, elderly aged 70 +). In each age group, efficacy of rotigotine was compared to placebo. In the combination therapy, total Unified Parkinson's Disease Rating Scale Part III scores and some subtotal scores, including those for tremor, akinesia and gait disturbance, significantly improved in both elderly and non-elderly patients. Regarding safety, the incidence of total adverse event tended to be lower in elderly patients than non-elderly patients, although it was not significant. No difference was observed in maintenance dosage of rotigotine between the two groups. In conclusion, the improvement in motor symptoms and frequency of adverse events were shown to be similar in elderly and non-elderly patients with rotigotine-levodopa combination therapy. Further, there was no major difference in maintenance dosage of rotigotine between the age groups. These results suggest good tolerability of rotigotine among elderly patients.