Does Adjunctive Preladenant Reduce “Off” Time in Parkinson Disease?

Effective treatment of motor symptoms in patients with Parkinson disease becomes more difficult with disease progression, and physicians often struggle to balance multiple medications to limit motor fluctuations without causing or exacerbating dyskinesias. Adenosine 2A (A_2A) receptor antagonists such as preladenant and istradefylline are a novel class of agents being developed as adjuncts to dopaminergic therapy, with the goal of shortening daily “off” time (periods during which Parkinson symptoms return as medication wears off) without worsening dyskinesias. In a manufacturer-funded and designed, phase II, double-blind, dose-finding trial involving 253 patients, researchers evaluated the efficacy and safety of adjunctive preladenant at doses of 1, 2, 5, or 10 mg twice daily compared with placebo; randomization was performed based on an adaptive protocol. The primary outcome measure was change in mean daily “off” time from baseline to 12 weeks, as reported in diaries maintained by participants.

At 12 weeks, adjusted mean total daily “off” time was reduced from baseline by 1.0 hour in the 5-mg group (P=0.049) and by 1.2 hours in the 10-mg group (P=0.019). In addition, dyskinesias did not seem to increase in association with reductions in “off” time (although the study was not adequately powered for such analysis). Preladenant was well tolerated at all doses.