Pharmacokinetics, Tolerability, and Bioequivalence of Two Formulations of Rotigotine in Healthy Chinese Subjects.

Purpose: The pharmacokinetic (PK) profile of the rotigotine transdermal patch is well characterized in Caucasian patients with Parkinson's disease (PD) but not in Chinese subjects. This article reports the PK variables, safety, and tolerability of the rotigotine transdermal patch (2 mg/24 hours and 4 mg/24 hours cold-chain PR2.1.

Rotigotine transdermal patch in Chinese patients with advanced Parkinson's disease: A randomized, double-blind, placebo-controlled pivotal study.

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.

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

Background: 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).

Methods: 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.

Rotigotine transdermal patch in Chinese patients with early Parkinson's disease: A randomized, double-blind, placebo-controlled pivotal study.

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.

A Randomized Controlled Exploratory Pilot Study to Evaluate the Effect of Rotigotine Transdermal Patch on Parkinson's Disease-Associated Chronic Pain.

Pain is a troublesome nonmotor symptom of Parkinson's disease (PD). This double-blind exploratory pilot study (NCT01744496) was the first to specifically investigate the effect of a dopamine agonist on PD-associated pain as primary outcome. Patients with advanced PD (ie, receiving levodopa) and at least moderate PD-associated chronic pain (≥3 months, ≥4 points on 11-point Likert pain scale) were randomized to rotigotine (optimal/maximum dose ≤16 mg/24h) or placebo and maintained for 12 weeks.

Effects of long-term treatment with rotigotine transdermal system on dyskinesia in patients with early-stage Parkinson's disease.

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).

A randomized study of rotigotine dose response on 'off' time in advanced Parkinson's disease.

Background: Previous phase III studies in patients with advanced Parkinson's disease (PD) not adequately controlled on levodopa demonstrated significant reduction of 'off' time with rotigotine transdermal system up to 16 mg/24 h. However, the minimal effective dose has not been established.

Objective: This international, randomized, double-blind, placebo-controlled study (SP921; NCT00522379) investigated rotigotine dose response up to 8 mg/24 h.

Rotigotine transdermal system and evaluation of pain in patients with Parkinson's disease: a post hoc analysis of the RECOVER study.

Background: Pain is a troublesome non-motor symptom of Parkinson's disease (PD). The RECOVER (Randomized Evaluation of the 24-hour Coverage: Efficacy of Rotigotine; Clintrials.gov: NCT00474058) study demonstrated significant improvements in early-morning motor function (UPDRS III) and sleep disturbances (PDSS-2) with rotigotine transdermal system.

Associations between severity of motor function and nonmotor symptoms in Parkinson's disease: a post hoc analysis of the RECOVER Study.

Background: RECOVER (NCT00474058), a double-blind, placebo-controlled trial in patients with Parkinson's disease (PD) and unsatisfactory early-morning motor symptom control, demonstrated significant improvements with rotigotine in early-morning motor function (Unified Parkinson's Disease Rating Scale [UPDRS] III), and nocturnal sleep disturbances (modified Parkinson's Disease Sleep Scale [PDSS-2]), and improvements in nonmotor symptoms (NMS; Non-Motor Symptom Scale [NMSS]).

Methods: Post hoc analyses investigated the correlation between motor symptom and NMS severity in PD by evaluating associations between UPDRS III and both NMSS and PDSS-2 scores. Categories were defined for UPDRS III, NMSS, and PDSS-2 total scores; analyses were conducted for the full analysis set (n = 267).

Rotigotine and specific non-motor symptoms of Parkinson's disease: post hoc analysis of RECOVER.

Background: Non-motor symptoms of Parkinson's disease (PD) represent major causes of morbidity. RECOVER, a randomized controlled trial of rotigotine transdermal system, was the first prospective controlled trial to use the Non-Motor Symptoms Scale (NMSS) as an exploratory outcome for assessment of treatment effects on non-motor symptoms in PD. Rotigotine improved NMSS total score compared with placebo, and the "Sleep/fatigue" and "Mood/apathy" domains.

The safety and tolerability of rotigotine transdermal system over a 6-year period in patients with early-stage Parkinson's disease.

This open-label extension (SP716; NCT00599196) of a 6-month, double-blind, randomized study (SP513) investigated the safety and tolerability of rotigotine transdermal system over up to ~6 years in patients with Parkinson's disease (PD; early-stage PD at double-blind enrollment). Eligible patients completing the 6-month study received optimal dose open-label rotigotine (≤ 16 mg/24 h) for up to ~6 years. Adjunctive levodopa was permitted.

Rotigotine transdermal system for long-term treatment of patients with advanced Parkinson's disease: results of two open-label extension studies, CLEOPATRA-PD and PREFER.

Open-label extensions [studies SP516 (NCT00501969) and SP715 (NCT00594386)] of the CLEOPATRA-PD and PREFER studies were conducted to evaluate the safety, tolerability and efficacy of the dopaminergic agonist, rotigotine, over several years of follow-up in patients with advanced Parkinson's disease (PD). Eligible subjects completing the double-blind trials received open-label adjunctive rotigotine (≤16 mg/24 h) for up to 4 and 6 years in Studies SP516 and SP715, respectively. Safety and tolerability were assessed using adverse events, vital signs and laboratory parameters, and efficacy assessed using the unified Parkinson's disease rating scale (UPDRS).

Long-term safety and tolerability of rotigotine transdermal system in patients with early-stage idiopathic Parkinson's disease: a prospective, open-label extension study.

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.

Effect of rotigotine on sleep and quality of life in Parkinson's disease patients: post hoc analysis of RECOVER patients who were symptomatic at baseline.

Objective: The aim of this research is to characterize further the potential motor and non-motor benefits of rotigotine reported in the double-blind, placebo-controlled RECOVER trial primary publication, by performing a post hoc exploratory analysis of patient status (symptom improvement/worsening).

Methods: Full RECOVER trial methodological details have already been reported. The post hoc analyses presented here are done on individual items of the PDSS-2 and PDQ-8 for all patients and two subgroups (baseline symptomatic and highly symptomatic patients).

Rotigotine effects on early morning motor function and sleep in Parkinson's disease: a double-blind, randomized, placebo-controlled study (RECOVER).

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).