[P7.087] Phase-3 Clinical Trials of Adjunctive Therapy with Preladenant, an Adenosine 2a Antagonist, in Patients with Parkinson's Disease
Robert Hauser,1Fabrizio Stocchi,2Olivier Rascol,3Susan Huyck,4Xianwei Ha,4Rachel Capece,4Kenneth Wolski,4Tony Ho,4Peter Sklar,4Christopher Lines,4David Michelson,4David Hewitt4
1Tampa, FL, USA, 2Rome, Italy, 3Toulouse, France, 4Whitehouse Station, NJ, USA
BACKGROUND: The adenosine 2a (A2a) receptor 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 two global phase-3 trials which evaluated preladenant given as adjunctive therapy.
DESIGN/METHODS: Two randomized, 12-week, placebo-controlled, parallel-group, multi-center, double-blind trials in adults with moderate-to-severe PD on a stable L-Dopa regime. Patients had to be experiencing motor fluctuations and a minimum of 2h/day “off” time. In Trial-1 patients were randomized 1:1:1:1:1 to preladenant 2mg, 5mg, or 10mg twice-daily, rasagiline 1mg (active-control) once-daily, or placebo. In Trial-2 patients were randomized 1:1:1 to preladenant 2mg or 5mg twice-daily or placebo. The primary efficacy endpoint was the change from baseline to Week-12 in mean “off” time.
RESULTS: The numbers of patients treated were 769 in Trial-1 and 473 in Trial-2. In Trial-1, neither preladenant nor rasagiline was superior to placebo after 12-weeks. The differences versus placebo [95% CI] in average “off” time were: preladenant 2mg = -0.1h [-0.69, 0.46], preladenant 5mg = -0.2h [-0.75,0.41], preladenant 10mg = -0.0h [-0.62,0.53], rasagiline 1mg= -0.3h [-0.90,0.26]. In Trial-2, preladenant was not superior to placebo after 12-weeks. The differences versus placebo [95% CI] in average “off” time were: preladenant 2mg = -0.2h [-0.72,0.35], preladenant 5mg = -0.3h [-0.86,0.21]). Post-hoc analyses did not explain the observed failed/negative findings. Preladenant was generally well-tolerated in both trials with few patients discontinuing due to adverse events (Trial-1: preladenant = 7%, rasagiline = 12%, placebo = 11%; Trial-2: preladenant = 5%, placebo = 3%).
CONCLUSIONS: No evidence supporting the efficacy of preladenant as adjunctive therapy was observed in two phase-3 trials. However, the lack of efficacy of the active-control included in one of the trials makes it difficult to interpret these results.
Study Supported by: Merck
Category - Movement Disorders: Parkinson's Disease
Thursday, May 1, 2014 3:00 PM
P7: Poster Session VII: Movement Disorders: Parkinson's Disease Therapy (3:00 PM-6:30 PM)