[S7.004] Phase-3 Clinical Trial of the Adenosine 2a Antagonist Preladenant, Given as Monotherapy, in Patients with Parkinson's Disease
Fabrizio Stocchi,1Olivier Rascol,2Robert Hauser,3Susan Huyck,4Anjela Tzontcheva,4Rachel Capece,4Kenneth Wolski,4Tony Ho,4Peter Sklar,4Christopher Lines,4David Michelson,4David Hewitt4
1Rome, Italy, 2Toulouse, France, 3Tampa, FL, USA, 4Whitehouse Station, NJ, USA
BACKGROUND: The adenosine 2a receptor (A2a) has been identified as an important non-dopaminergic target for the treatment of Parkinson's disease (PD). Preladenant is an A2a antagonist that was studied as a potential treatment for PD. On the basis of a positive phase-2b dose-response, adjunctive therapy study, a phase-3 development program was initiated. We report here results from a phase-3 trial which evaluated preladenant given as monotherapy.
DESIGN/METHODS: This was a randomized, 52-week, placebo- and active-controlled, parallel-group, multi-center, double-blind trial conducted in 2 parts of 26-weeks each in adults diagnosed with PD for less than 5 years who were not yet receiving L-Dopa or dopamine agonists. Patients with a Unified PD Rating Scale (UPDRS) Part 3 (motor function) score of at least 10 were randomized 1:1:1:1:1 to preladenant 2mg, 5mg, or 10mg twice-daily, rasagiline 1mg (active-control) once-daily, or placebo. Patients treated with placebo in part-1 were switched to preladenant 5mg twice-daily in part-2. The primary endpoint was the change from baseline at Week-26 in the sum of UPDRS Parts 2 (activities of daily living) and 3 (motor function) scores (UPDRS2+3).
RESULTS: The number of patients treated was 1007. Neither preladenant nor rasagiline was superior to placebo after 26-weeks. The differences versus placebo [95% CI] in UPDRS2+3 scores were: preladenant 2mg = 2.60 [0.86,4.30], preladenant 5mg = 1.30 [-0.41,2.94], preladenant 10mg = 0.40 [-1.29, 2.11], rasagiline 1mg = 0.30 [-1.35,2.03]. Post-hoc analyses did not identify a single causal factor that could explain the finding of a failed trial. Preladenant was generally well-tolerated with few patients discontinuing due to adverse events (preladenant = 7%, rasagiline = 3%, placebo = 4%).
CONCLUSIONS: No evidence supporting the efficacy of preladenant as monotherapy was observed in this phase-3 trial. However, the lack of efficacy of the active-control rasagiline makes it difficult to interpret the results of the trial.
Study Supported by: Merck
Category - Movement Disorders: Parkinson's Disease
Tuesday, April 29, 2014 1:45 PM
S7: Platform Session: Parkinson's Disease: Preclinical and Clinical Therapeutics (1:00 PM-2:45 PM)