Anthony P Nicholas1, Rupam Borgohain2, Pedro Chaná3, Erwin Surmann4, Emily L Thompson5, Lars Bauer4, John Whitesides6, Lawrence W Elmer7. 1. Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, USA. 2. Department of Neurology, Nizam's Institute of Medical Sciences, Andhra Pradesh, India. 3. Department of Neurology, Universidad de Santiago de Chile, Santiago, Chile. 4. UCB Pharma, Monheim am Rhein, Germany. 5. Evidence Scientific Solutions Ltd, London, UK. 6. UCB Pharma, Raleigh, NC, USA. 7. Department of Neurology, University of Toledo, Toledo, OH, USA.
Abstract
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. METHODS:Patients with advanced idiopathic PD (≥2.5 h of daily 'off' time on stable doses oflevodopa) were randomized 1:1:1:1:1 to receive rotigotine 2, 4, 6, or 8 mg/24 h or placebo, titrated over 4 weeks and maintained for 12 weeks. The primary efficacy variable was change from baseline to end of maintenance in absolute time spent 'off'. RESULTS: 409/514 (80%) randomized patients completed maintenance. Mean (±SD) baseline daily 'off' times (h/day) were placebo: 6.4 (±2.5), rotigotine 2-8 mg/24 h: 6.4 (±2.6). Rotigotine 8 mg/24 h was the minimal dose to significantly reduce 'off' time versus placebo. LS mean (±SE) absolute change in daily 'off' time (h/day) from baseline was -2.4 (±0.28) with rotigotine 8 mg/24 h, and -1.5 (±0.26) with placebo; absolute change in 'off' time in the 8 mg/24 h group compared with placebo was -0.85 h/day (95% CI -1.59, -0.11; p = 0.024). There was an apparent dose-dependent trend. Adverse events (AEs) reported at a higher incidence in the rotigotine 8 mg/24 h group versus placebo included application site reactions, nausea, dry mouth, and dyskinesia; there was no worsening of insomnia, somnolence, orthostatic hypotension, confusional state or hallucinations, even in patients ≥75 years of age. CONCLUSIONS: The minimal statistically significant effective dose of rotigotine to reduce absolute 'off' time was 8 mg/24 h. The AE profile was similar to previous studies.
RCT Entities:
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. METHODS:Patients with advanced idiopathic PD (≥2.5 h of daily 'off' time on stable doses of levodopa) were randomized 1:1:1:1:1 to receive rotigotine 2, 4, 6, or 8 mg/24 h or placebo, titrated over 4 weeks and maintained for 12 weeks. The primary efficacy variable was change from baseline to end of maintenance in absolute time spent 'off'. RESULTS: 409/514 (80%) randomized patients completed maintenance. Mean (±SD) baseline daily 'off' times (h/day) were placebo: 6.4 (±2.5), rotigotine 2-8 mg/24 h: 6.4 (±2.6). Rotigotine 8 mg/24 h was the minimal dose to significantly reduce 'off' time versus placebo. LS mean (±SE) absolute change in daily 'off' time (h/day) from baseline was -2.4 (±0.28) with rotigotine 8 mg/24 h, and -1.5 (±0.26) with placebo; absolute change in 'off' time in the 8 mg/24 h group compared with placebo was -0.85 h/day (95% CI -1.59, -0.11; p = 0.024). There was an apparent dose-dependent trend. Adverse events (AEs) reported at a higher incidence in the rotigotine 8 mg/24 h group versus placebo included application site reactions, nausea, dry mouth, and dyskinesia; there was no worsening of insomnia, somnolence, orthostatic hypotension, confusional state or hallucinations, even in patients ≥75 years of age. CONCLUSIONS: The minimal statistically significant effective dose of rotigotine to reduce absolute 'off' time was 8 mg/24 h. The AE profile was similar to previous studies.
Authors: Nir Giladi; Anthony P Nicholas; Mahnaz Asgharnejad; Elisabeth Dohin; Franz Woltering; Lars Bauer; Werner Poewe Journal: J Parkinsons Dis Date: 2016-10-19 Impact factor: 5.568
Authors: Peter A LeWitt; Werner Poewe; Lawrence W Elmer; Mahnaz Asgharnejad; Babak Boroojerdi; Frank Grieger; Lars Bauer Journal: Clin Neuropharmacol Date: 2016 Mar-Apr Impact factor: 1.592