Rotigotine Transdermal Patch for Motor and Non-motor Parkinson's Disease: A Review of 12 Years' Clinical Experience.
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SUBMITTER: Raeder V
PROVIDER: S-EPMC7871129 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:This 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).Patients 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.Of 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.Rotigotine did not improve PD-associated apathy as rated by the patient but provided clinically relevant improvement in motor control and activities of daily living.ClinicalTrials.gov identifier NCT01782222 . Trial registration date: January 30, 2013.
| S-EPMC4895976 | biostudies-literature
Project description:Background and methodsThe efficacy and safety of rotigotine transdermal patch in Parkinson's disease (PD) were studied in some clinical trials. We performed a systematic review and meta-analysis of randomized controlled trials to evaluate the efficacy, tolerability, and safety of rotigotine transdermal patch versus placebo in PD.ResultsSix randomized controlled trials (1789 patients) were included in this meta-analysis. As compared with placebo, the use of rotigotine resulted in greater improvements in Unified Parkinson's Disease Rating Scale activities of daily living score (weighted mean difference [WMD] -1.69, 95% confidence interval [CI] -2.18 to -1.19), motor score (WMD -3.86, 95% CI -4.86 to -2.86), and the activities of daily living and motor subtotal score (WMD -4.52, 95% CI -5.86 to -3.17). Rotigotine was associated with a significantly higher rate of withdrawals due to adverse events (relative risk [RR] 1.82, 95% CI 1.29-2.59), and higher rates of application site reactions (RR 2.92, 95% CI 2.29-3.72), vomiting (RR 5.18, 95% CI 2.25-11.93), and dyskinesia (RR 2.52, 95% CI 1.47-4.32) compared with placebo. No differences were found in the relative risks of headache, constipation, back pain, diarrhea, or serious adverse events.ConclusionsOur meta-analysis showed that the use of rotigotine can reduce the symptoms of PD. However, rotigotine was also associated with a higher incidence of adverse events, especially application site reactions, compared with placebo.
| S-EPMC3720658 | biostudies-literature
Project description: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.
| S-EPMC2895903 | biostudies-literature
Project description:Objective: The effects of rotigotine transdermal patch (RTG) on the neuropsychiatric symptoms of Parkinson's disease (PD) outcomes remain controversial. The aim of this review was to determine the efficacy and safety of RTG on the neuropsychiatric symptoms of PD. Methods: In this systematic review and meta-analysis, PubMed, Cochrane Library, EMBASE, and Web of Science were searched for randomized controlled trials comparing RTG and placebo in PD up to May 10, 2021. We analyzed the data using Review Manager 5.2 software. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation Approach. In order to avoid false-positive results caused by random error, we use TSA software for trial sequential analysis (TSA). Results: We included 10 studies (1,844 patients). The meta-analysis showed that, compared with placebo, RTG can significantly improve the scores for Apathy Scale (MD = -1.68, 95% confidence interval, CI: -2.74 to -0.62, P = 0.002; moderate certainty), Beck Depression Inventory-II (MD = -1.19, 95% CI: -2.26 to -0.11, P = 0.03; moderate certainty), the Non-Motor Symptoms Scale (MD = -3. 66, 95% CI: -4. 30 to -3.01, P < 0.00001; moderate certainty), the sleep/fatigue domains of the Parkinson's Disease Non-motor Symptom Assessment Scale (MD = -2.03, 95% CI: -3.08 to -0.98, P = 0.0001; moderate certainty), the mood/apathy domains of the Non-motor Symptom Scale (MD = -2.48, 95% CI: -4.07 to -0.89, P = 0.002; high certainty), the eight-item Parkinson's Disease Questionnaire (MD = -4. 93, 95% CI: -6.79 to -3.07, P < 0.00001; moderate certainty), and the 39-item Parkinson's Disease Questionnaire (MD = -3.52, 95% CI: -5.25 to -1.79, P < 0.0001; high certainty). However, there was no statistically significant difference on the Snaith-Hamilton Pleasure Scale (MD = -0.12, 95% CI: -0.58 to 0.34, P = 0.61). Our results showed that RTG exerts a positive effect on sleep. According to the TSA, the results implied that, except for the Beck Depression Inventory-II, conclusive evidence have been obtained in the RTG group. It has been proven in our meta-analysis that rotigotine has good safety and tolerability. Conclusions: RTG can effectively improve the neuropsychiatric symptoms, sleep quality, and quality of life in patients with PD.
| S-EPMC8567083 | biostudies-literature
Project description:BackgroundA recent trial involving predominantly Caucasian subjects with Parkinson Disease (PD) showed switching overnight from an oral dopaminergic agonist to the rotigotine patch was well tolerated without loss of efficacy. However, no such data have been generated for Korean patients.MethodsThis open-label multicenter trial investigated PD patients whose symptoms were not satisfactorily controlled by ropinirole, at a total daily dose of 3 mg to 12 mg, taken as monotherapy or as an adjunct to levodopa. Switching treatment from oral ropinirole to transdermal rotigotine was carried out overnight, with a dosage ratio of 1.5:1. After a 28-day treatment period, the safety and tolerability of switching was evaluated. Due to the exploratory nature of this trial, the effects of rotigotine on motor and nonmotor symptoms of PD were analyzed in a descriptive manner.ResultsOf the 116 subjects who received at least one treatment, 99 (85%) completed the 28-day trial period. Dose adjustments were required for 11 subjects who completed the treatment period. A total of 76 treatment-emergent adverse events (AEs) occurred in 45 subjects. No subject experienced a serious AE. Thirteen subjects discontinued rotigotine prematurely due to AEs. Efficacy results suggested improvements in both motor and nonmotor symptoms and quality of life after switching. Fifty-two subjects (46%) agreed that they preferred using the patch over oral medications, while 31 (28%) disagreed.ConclusionsSwitching treatment overnight from oral ropinirole to transdermal rotigotine patch, using a dosage ratio of 1.5:1, was well tolerated in Korean patients with no loss of efficacy.Trial registrationThis trial is registered with the ClincalTrails.gov Registry (NCT00593606).
| S-EPMC3166898 | biostudies-literature
Project description:Background and objectivesRotigotine is a dopamine receptor agonist with activity across the D1 through to D5 receptors as well as select serotonergic and adrenergic sites; continuous transdermal delivery of rotigotine with replacement of the patch once daily maintains stable plasma concentrations over 24 h. Rotigotine is indicated for the treatment of early and advanced-stage Parkinson's disease and moderate-to-severe idiopathic restless legs syndrome. The pharmacokinetics and pharmacodynamics of a drug may vary between subjects of different ethnic origin. This study evaluated the pharmacokinetics, safety, and tolerability of single-dose treatment with rotigotine transdermal patch in Japanese and Caucasian subjects.MethodsIn this open-label, parallel-group study, healthy male and female subjects of Japanese or Caucasian ethnic origin were matched by sex, body mass index, and age. A single transdermal patch delivering 2 mg/24 h rotigotine (patch content 4.5 mg) was applied to the ventral/lateral abdomen for 24 h. The main outcome measures were the plasma concentrations of unconjugated and total rotigotine and its desalkyl metabolites and derived pharmacokinetic parameters (area under the concentration-time curve from time zero to last quantifiable concentration [AUClast], maximum plasma concentration [Cmax], and body weight- and dose-normalized values).ResultsThe pharmacokinetic analysis included 48 subjects (24 Japanese, 24 Caucasian). The mean apparent dose of rotigotine was 2.0±0.5 mg for Japanese subjects and 2.08±0.58 mg for Caucasians. Plasma concentration-time profiles of unconjugated rotigotine and of the main metabolites were similar for both ethnic groups. Parameters of model-independent pharmacokinetics, Cmax, time to Cmax (tmax), and AUClast, for unconjugated rotigotine showed no statistically significant differences between Japanese and Caucasian subjects. Values of concentration-dependent pharmacokinetic parameters were higher in female subjects; this difference was minimized after correction for body weight. A statistically significant difference between ethnic groups was observed for total rotigotine concentrations (total rotigotine=unconjugated rotigotine+conjugated rotigotine), with slightly lower values in Caucasians after correction for body weight and apparent dose. No relevant differences were observed between males and females. Inter-individual variability was high. The terminal half-life for unconjugated rotigotine was 5.3 h in Japanese subjects and 5.7 h in Caucasians; corresponding values for total rotigotine were 8.6 h and 9.6 h. Less than 0.1% of the apparent dose was renally excreted as the parent compound. Renal elimination of total rotigotine covers 11.7% of absorbed dose in Japanese subjects and 10.8% of the absorbed dose in Caucasians, whereas the renal elimination via total despropyl rotigotine was 8.2 and 7.1%, respectively. The corresponding values for total desthienylethyl rotigotine were 3.5% in Japanese subjects and 4.2% Caucasians. Most adverse events were mild in intensity and typical for dopamine agonists or for transdermal therapeutics.ConclusionAdministration of a single patch delivering 2 mg/24 h rotigotine resulted in comparable pharmacokinetic profiles in Japanese and Caucasian subjects. The rotigotine transdermal patch was generally well-tolerated. Our findings suggest similar dose requirements for Japanese and Caucasian populations.
| S-EPMC3899448 | biostudies-literature
Project description:AimTo evaluate the influence of different stages of chronic renal insufficiency on the pharmacokinetics and safety/tolerability of the transdermally applied dopamine agonist rotigotine in an open label group comparison including 32 subjects (healthy, mild, moderate or severe impairment of renal function and patients with end-stage renal insufficiency requiring haemodialysis). METHODS All subjects received a single transdermal 10 cm² patch (24 h patch-on period) containing 4.5 mg rotigotine (nominal drug release 2 mg 24 h⁻¹). Main evaluations included relative bioavailability and renal elimination of rotigotine and its metabolites.ResultsPoint estimates for the ratios between the groups with moderate to severe renal impairment and healthy subjects for the pharmacokinetic parameters AUC(0,t(last) ) and C(max) for the active substance unconjugated rotigotine were near 1:0.88 for AUC and 0.93 for C(max) for moderate renal impairment, 1.14 and 1.18 for severe renal impairment and 1.05 and 1.25 for end-stage renal insufficiency requiring haemodialysis. There was no correlation of these parameters with creatinine clearance. The amount of unconjugated rotigotine excreted into urine and renal clearance decreased with increasing severity of renal insufficiency but had no observable effect on total clearance as the amounts excreted were below 1% of the administered dose. Occurrence of adverse events did not increase with the degree of renal insufficiency.ConclusionsThe pharmacokinetic profiles of unconjugated rotigotine were similar in healthy subjects and subjects with impaired renal function indicating that no dose adjustments are required for transdermal rotigotine in patients with different stages of chronic renal insufficiency including patients on haemodialysis.
| S-EPMC3248255 | biostudies-literature
Project description:IntroductionThe rotigotine transdermal patch (RTP) is a dopamine agonist used to treat Parkinson's disease (PD) but is sometimes discontinued because of application site reactions (ASRs). We aimed to investigate the effect of a heparinoid-containing product (HCP) for preventing ASRs due to the RTP by conducting a randomized controlled pilot trial.MethodsTwenty patients with idiopathic non-demented PD were randomized to the skin care group using a HCP (group H) and the non-skin care group (group N). The primary outcome was the change in the baseline Skindex-16 score (ΔSkindex-16) at week 4. In addition, skin symptoms were also evaluated using the Dermatology Life Quality Index (DLQI) and International Contact Dermatitis Research Group (ICDRG) system for clinical scoring allergic patch test reactions up to week 8.ResultsThe ΔSkindex-16 score at week 4 tended to be lower in group H than in group N, although the difference was not statistically significant (-1.5 ± 2.0 vs 1.3 ± 10.9, p = 0.53). When the patients with baseline Skindex-16 scores ≥ 7 were excluded, the ΔSkindex-16 at week 4 was significantly lower in group H (-1.5 ± 2.0 vs 6.1 ± 8.6, p = 0.042). The DLQI also tended to be lower in group H at weeks 4 and 8, but not significantly (p = 0.066 and p = 0.077, respectively). The ICDRG score at week 4 was significantly lower in group H (p = 0.044).ConclusionWe suggest that the HCP has a preventive effect against ASRs cause by the RTP.
| S-EPMC8379504 | biostudies-literature
Project description:Rotigotine 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).Patients 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.Of 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.Transdermal 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.NCT00498186.
| S-EPMC2958158 | biostudies-literature
Project description:Sleep disturbances occur frequently in patients with Parkinson's disease (PD). The aim of this study was to investigate the effects of rotigotine on sleep fluctuations in a sample of PD patients with self-reported complaints of nocturnal awakenings. This prospective, open-label, observational, and multicenter study enrolled consecutive outpatients with PD and administered rotigotine (mean dose 8.9?mg/day) for 3 months. The primary endpoint was the change from baseline in sleep fragmentation, assessed using the sleep maintenance subscale score of the Parkinson's Disease Sleep Scale (PDSS). The newly designed Parkinson's Disease Sleep Fragmentation Questionnaire (PD-SFQ) was used to measure other sleep parameters. A total of 62 patients were enrolled (mean age 70.2 years; 66% male). At 3 months, rotigotine significantly improved sleep fragmentation from baseline on the PDSS-2 sleep maintenance subscale (from 3.4 ± 0.9 to 1.9 ± 1.4; P < 0.0001). Rotigotine also significantly improved nocturnal motor symptoms (P < 0.0001), restless legs-like symptoms (P < 0.005), and nocturia (P = 0.004). Rotigotine significantly improved self-reported complaints of sleep fragmentation in PD patients and could be a useful treatment to improve this specific sleep problem in PD. However, these results are based on a small and clinically heterogeneous sample so they must be taken cautiously.
| S-EPMC4352510 | biostudies-literature