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EFFECT OF ISTRADEFYLLINE DOSAGE ON UNIFIED PARKISONS’ DISEASE RATING SCALE (UPDRS) III-ON SCORES: RESULTS FROM FOUR RANDOMIZED CLINICAL TRIALS
Abstract
Aims
Istradefylline, a selective adenosine A2A receptor antagonist, is indicated in the US and Japan as adjunctive treatment to levodopa-containing medication in adults with Parkinson’s disease (PD) experiencing OFF-time. This four-trial analysis evaluated impact of istradefylline dosage on UPDRS-III-ON score.
Methods
Data from four randomized, phase 2b/3 trials (6002-US-018, 6002-009, 6002-0608, and 6002-014) were analyzed to determine the difference in impact of 20 vs 40mg/day istradefylline on UPDRS-III-ON scores in patients with PD experiencing OFF-time. For each study, difference in least-squares (LS) mean change from baseline in UPDRS-III-ON scores for the two dosages was assessed by mixed-model repeated-measures analyses; results were combined using a random-effect meta-analysis.
Results
The LS mean change from baseline to week 12 in UPDRS-III-ON score was greater with istradefylline than placebo; in three studies, this effect was greater at the 40mg/day dose vs 20mg/day (Figure). In the random-effect meta-analysis, there was a significant difference in LS mean change from baseline between 20 and 40mg/day treatment arms (-0.80 [95%CI, -1.55, -0.04], nominal p=0.038). The rates of treatment-emergent adverse events (TEAEs) from each of the four studies were comparable between the 20 (59-82%) and 40mg/day (59-84%) dosages; the most common TEAE was dyskinesia in three studies (20mg/day, 11-17% vs 40mg/day, 12-26%) and nasopharyngitis in one (6% vs 9%). Impact of baseline UPDRS-III-ON score on improvements at both dosages will be presented.
Conclusions
Regarding motor improvement, these data suggest that 40mg/day istradefylline has greater benefit than 20mg/day. Safety was comparable between the two istradefylline treatment groups.