Objective: Two Phase 2 studies were conducted to evaluate the safety profile of inhaled CVT-301 administered to Parkinson’s disease (PD) patients with motor fluctuations.

Background: CVT-301, an inhaled levodopa, is under development for rapid relief of OFF time. In Phase 2 studies, CVT-301 reduced UPDRS motor scores over 10-60 minutes post-dose.[1,2]

Methods: Two randomized, double-blind, placebo (PBO)-controlled Phase 2 studies in PD patients experiencing ≥2h/day OFF time were evaluated. In Phase 2a, patients received single doses of oral carbidopa/levodopa (25/100 mg; active control) and each of the following treatments: PBO, 25 mg and 50 mg CVT-301. In Phase 2b, patients received up to 3 daily doses of 35 mg [weeks 1-2] and 50 mg [weeks 3-4] CVT-301 vs PBO. Safety was assessed by incidence of treatment-emergent adverse events (TEAEs), changes in clinical chemistry parameters, ECGs, vital signs, and spirometry. PD diary data were secondary endpoints for evaluating OFF and ON time (with/without dyskinesia).

Results: In Phase 2a (n = 24), the most common TEAE was mild to moderate cough with CVT-301: 25 mg (n = 5, 21.7%); 50 mg (n = 5, 20.8%). There were no SAEs or TEAEs leading to study withdrawal. In Phase 2b, 86 patients were randomized 1:1 to CVT-301 or PBO. Of these, 34 (39.5%) had at least 1 TEAE. Most common TEAEs for CVT-301 combined doses vs PBO were dizziness (7% vs. 5%), acute cough (7% vs. 2%), and nausea (7% vs. 0%). One PBO patient had a serious TEAE (drop attack), and 5 (5.8%) patients withdrew due to TEAEs (PBO [n = 3]: bradykinesia, chest pain, wrist fracture; CVT-301 [n = 2]: sputum discolored, lung discomfort post-inhalation). No serious TEAEs or deaths occurred. Dyskinesia was reported in 1 PBO and 1 CVT-301 patient (50 mg). PD diary data for the CVT-301 35 and 50 mg doses showed no significant increase in ON time with either non-troublesome or troublesome dyskinesia versus PBO. There were no clinically significant changes in clinical chemistry parameters, vital signs, respiratory rate or other spirometry findings in either study.

Conclusions: CVT-301 was generally safe and well tolerated at the tested doses for up to 1 month of repeated use. At the doses tested, CVT-301 did not increase AE reports of dyskinesia. 1. Freed, et al. Neurology. 2014;82(10 suppl):S7.0072. 2. LeWitt, et al. Mov Disord. 2015;30(1 suppl):S99.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/safety-and-tolerability-of-inhaled-levodopa-cvt-301-administered-to-parkinsons-disease-patients-with-motor-fluctuations/