A Pooled Analysis for Eight Randomized Controlled Trials of Istradefylline, an Adenosine A 2A Receptor Antagonist: Efficacy as Adjunct to Levodopa in Parkinson’s Disease (PD) (P3.8-030)
Abstract
Objective: Pooled efficacy analyses of eight randomized, placebo-controlled studies of istradefylline combined with levodopa in patients with PD and motor fluctuations. Background: Istradefylline, a well-tolerated selective adenosine A2A receptor antagonist, acts via the indirect basal ganglia outflow pathway. In 2013, doses of 20 and 40mg/day were approved in Japan as adjunctive treatment to levodopa-containing products in patients with PD experiencing wearing-off phenomena. Design/Methods: Istradefylline was evaluated in patients with PD who concomitantly received levodopa with carbidopa or benserazide and experienced motor-response fluctuations (n=3245 randomized). Eight 12- or 16-week randomized, placebo-controlled, double-blind Phase 2b/3 clinical studies were conducted globally; change in OFF-time in daily, patient-completed 24-hour ON/OFF diaries provided the primary endpoint. Seven of eight studies shared common methodology. Pooled analysis results from once-daily oral istradefylline (20 and 40mg/day) and placebo, evaluated using a mixed-model repeated-measures approach (including study as a variable), are presented. Results: The pooled analysis included 2719 treated patients (placebo, n=992; 20 mg/day, n=848; 40 mg/day, n=879). At week 12, OFF-hours/day with 20 and 40mg istradefylline was reduced (LS mean difference from placebo in reduction from baseline [95%CI], −0.38 [−0.61, −0.15] and −0.45 [−0.68, −0.22], respectively). ON-hours/day without troublesome…
How strong is the evidence?
Evidence Hub reads this as a secondary / pooled analysis, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 3,245 participants or records.
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