Randomized Evaluation of the 24-Hour Coverage: Efficacy of Rotigotine (RECOVER)

Phase 3B, Multicenter, Multinational, Double-Blind, Placebo Controlled, 2-Arm Trial to Evaluate the Effect of the 24-Hour Transdermal Delivery of Rotigotine on the Control of Early Morning Motor Function, Sleep Quality, Nocturnal Symptoms, and Non-Motor Symptoms in Subjects With Idiopathic Parkinson's Disease

The objective of this trial is to assess the effects of transdermal rotigotine on the control of early morning motor function and sleep disorders compared to placebo in subjects with idiopathic Parkinsons´s disease. In addition, effects of rotigotine on specific nocturnal and non-motor symptoms of Parkinson´s disease will be evaluated.

The objective of this trial is to assess the effects of rotigotine on the control of early morning motor function and sleep disorders compared to placebo in subjects with idiopathic Parkinsons´s disease. In addition, effects of rotigotine on specific nocturnal and non-motor symptoms of Parkinson´s disease will be evaluated. After a Screening Period of up to 28 days subjects will be hospitalized for two nights. After the second overnight stay, subjects will be randomly assigned either to rotigotine patch or placebo patch. Afterwards patients will be titrated to their optimal dose. After subjects have reached their optimal dose (or the highest dose) they will be maintained on this dose for a certain period. At the end of maintenance the subjects will be hospitalized for two nights. Afterwards the doses will be continuously decreased. Efficacy will be assessed by application of sleep quality scores, motor examination scores, and scores to evaluate non-motor symptoms of Parkinsons. Safety assessments include adverse events, 12-lead electrocardiograms, blood pressure and heart rate assessments, and laboratory checks.

Rotigotine transdermal patches: 10cm2 (2mg/24h); 20cm2 (4mg/24h); 30cm2 (6mg/24h); 40cm2 (8mg/24h) Optimal dosing: The maximum Rotigotine dose allowed is 16mg/24h

The Unified Parkinson´s Disease Rating Scale Part III score is an accepted and validated sumscore of 14 items for the assessment of motor function in Parkinson´s disease. Each of the 14 items in the UPDRS part III is measured on a scale of 0 to 4, where 0 is normal and 4 represents severe abnormalities.

The Parkinson´s Disease Sleep Scale (PDSS) is a questionnaire with 15 questions to assess sleep and nocturnal disability in Parkinson´s disease. The item- scores can range between 0= never and 4= very often. The PDSS score is a sumscore of all 15 questions.

Subjects were asked to assess nocturnal akinesia, dystonia and cramps, using an ordinal severity scale. While a score of 0= normal and 4= maximal severity, subjects could also rate their symptoms with values of 0.5, 1.5, 2.5, 3.5. The nocturnal akinesia score was used to evaluate motor performance while the dystonia and cramps scores were used to evaluate sleep.

Nocturia is the need to get up during the night and interrupt sleep in order to urinate. It is a typical nocturnal symptom of Parkinson´s disease. The change from baseline in number of nocturias was used to evaluate improvements in sleep disorders.

Inclusion Criteria: Early and advanced Idiopathic Parkinson Disease with early morning motor impairment Exclusion Criteria: Atypical Parkinsonian syndromes

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Kassubek J, Chaudhuri KR, Zesiewicz T, Surmann E, Boroojerdi B, Moran K, Ghys L, Trenkwalder C. Rotigotine transdermal system and evaluation of pain in patients with Parkinson's disease: a post hoc analysis of the RECOVER study. BMC Neurol. 2014 Mar 6;14:42. doi: 10.1186/1471-2377-14-42.

Swick TJ, Friedman JH, Chaudhuri KR, Surmann E, Boroojerdi B, Moran K, Ghys L, Trenkwalder C. Associations between severity of motor function and nonmotor symptoms in Parkinson's disease: a post hoc analysis of the RECOVER Study. Eur Neurol. 2014;71(3-4):140-7. doi: 10.1159/000355019. Epub 2014 Jan 21.

Trenkwalder C, Kies B, Rudzinska M, Fine J, Nikl J, Honczarenko K, Dioszeghy P, Hill D, Anderson T, Myllyla V, Kassubek J, Steiger M, Zucconi M, Tolosa E, Poewe W, Surmann E, Whitesides J, Boroojerdi B, Chaudhuri KR; Recover Study Group. Rotigotine effects on early morning motor function and sleep in Parkinson's disease: a double-blind, randomized, placebo-controlled study (RECOVER). Mov Disord. 2011 Jan;26(1):90-9. doi: 10.1002/mds.23441. Epub 2010 Nov 18.