SP512 Rotigotine
(2007)Objective
To evaluate the efficacy and safety of rotigotine transdermal system in patients with early Parkinson's disease compared to placebo.
Study Summary
• Mean UPDRS II+III score decreased by 15.1%
• Adverse events included skin reactions (44%), nausea (41%), and somnolence (33%)
Intervention
Randomized, double-blind, multicenter, placebo-controlled trial at 50 sites in the US and Canada. 277 early PD patients received rotigotine (2–6 mg/24h) or placebo for 24 weeks. Dose titrated weekly, followed by maintenance phase.
Inclusion Criteria
• Idiopathic PD for ≤5 years
• ≥2 of bradykinesia, tremor, rigidity, postural instability
• UPDRS III ≥10
• Hoehn and Yahr ≤ III
• MMSE ≥25
Study Design
Arms: Rotigotine transdermal patch, Placebo patch
Patients per Arm: Rotigotine: 181, Placebo: 96
Outcome
• UPDRS II+III: −941 vs −157 (P<0.001)
• Clinical Global Impression improvement in 57% (rotigotine) vs 30% (placebo)
Bottom Line
Transdermal rotigotine (2-8 mg/24h) significantly improved UPDRS II+III vs placebo in early PD: -3.98 points difference at optimal dose (P<0.001). Dose-dependent response. 277 patients, 12-week, 39 European centers. Published Lancet Neurology 2007.
Major Points
- UPDRS II+III improvement: rotigotine 6mg -5.14 vs placebo -1.31 (diff -3.98; P<0.001).
- Dose-response: 2mg -1.84, 4mg -3.44, 6mg -3.98, 8mg -4.42 difference from placebo.
- Responder rate (≥20% UPDRS improvement): 48-52% (rotigotine) vs 30% (placebo).
- 277 early PD patients (Hoehn & Yahr ≤3). Double-blind, placebo-controlled, 12-week.
- Transdermal patch: once-daily application, continuous drug delivery.
- AEs: application site reactions (39-44%), nausea (16-32%), dizziness (10-14%), somnolence (8-17%).
- 39 European centers. Schwarz Pharma sponsored.
- Established rotigotine patch as viable monotherapy for early PD.
- Advantage: transdermal route avoids GI absorption issues and first-pass metabolism.
- Published Lancet Neurology 2007 (Giladi et al.).
Study Design
- Study Type
- Randomized, double-blind, placebo-controlled trial
- Randomization
- Yes
- Blinding
- Patients and investigators were blinded
- Sample Size
- 277
- Follow-up
- 24 weeks
- Centers
- 50
- Countries
- USA, Canada
Primary Outcome
Definition: ≥20% reduction in UPDRS II + III score at 24 weeks
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 19% | 48% | - | <0.001 |
Limitations & Criticisms
- Study duration (24 weeks) too short to assess long-term complications like dyskinesia
- QOL effects modest and largely exploratory
- High rate of application site reactions may limit tolerability
- No active comparator (e.g., oral dopamine agonist)
Citation
Arch Neurol. 2007;64:676–682