Effect of Patient Characteristics on Motor Function in Response to 35-50 mg of Inhaled Levodopa (CVT-301) in Patients with Parkinson’s Disease: Results from a Phase 2b Study (P5.372)

Objective: To examine whether the response to an inhaled levodopa formulation (CVT-301; 35 and 50 mg) is dependent on baseline patient characteristics. Background: Many patients with Parkinson’s disease (PD) treated with levodopa experience motor fluctuations (OFF episodes) after a period of good motor control. CVT-301, levodopa inhalation powder formulation, is under development for rapid relief of OFF episodes. In a phase 2b study, oral levodopa dosage at baseline ranged from 250-1800 mg/day. CVT-301 significantly improved UPDRS (Unified Parkinson’s Disease Rating Scale) Part 3 relative to placebo; treatment effect was evident at 10 minutes, the earliest time point assessed. Design/Methods: Data were derived from a phase 2b study (CVT-301-003; NCT01777555). CVT-301 and placebo were self-administered up to 3 times/day. Dose was escalated from 35 mg (weeks 1 and 2) to 50 mg (weeks 3 and 4). Baseline characteristics, including gender, PD stage (Hoehn & Yahr; H&Y), dyskinesia, and daily OFF time, were examined for possible influence on UPDRS Part 3 changes in CVT-301 versus placebo (end of week 4). Tolerability was assessed. Additional analyses will be performed. Results: Eighty-six patients were randomized 1:1 to CVT-301 or placebo; 66.3[percnt] male, 33.7[percnt] female, mean age 62.4 years (range 37-79). At week 4, the mean change in UPDRS Part 3 was -10.02 (CVT-301) versus -3.07 (placebo), treatment effect of -6.95; P<0.001. The difference in UPDRS Part 3 score between CVT-301 and placebo was independent of gender (male, P=0.03; female, P<0.001), H&Y (<2.5, P=0.04; ≥2.5, P<0.001), daily OFF time (<4 hours, P=0.04; ≥4 hours, P<0.001), and presence of dyskinesia (YES, P=0.004; NO, trend with P=0.07). CVT-301 was tolerated during the 4-week study. Conclusions: Antiparkinsonian efficacy, defined by change in motor function, did not vary as a function of the demographic and clinical characteristics tested.