Objective: To evaluate the efficacy and safety of tavapadon (formerly known as PF-06649751) in subjects with early stage Parkinson’s disease.

Background: Tavapadon is a potent, highly selective, orally administered, dopamine D1/D5 receptor activator being evaluated for the once-daily symptomatic treatment of Parkinson’s disease.

Method: This phase 2, double-blind, randomized, placebo-controlled, flexible-dose, 15-week study in subjects with early stage Parkinson’s disease was conducted with participants from 23 sites (ClinicalTrials.gov: NCT02847650). The study consisted of a 9 week dose optimization period followed by 6 weeks of dose maintenance. Subjects were randomized to receive either tavapadon or placebo (1:1) orally once daily. Inclusion criteria included: aged 45-80; clinical diagnosis of Parkinson’s disease (Hoehn & Yahr Stage I-III); MDS-UPDRS Part III score ≥10; treatment naïve or history of prior incidental treatment with dopaminergic agents for ≤ 28 days. Exclusion criteria included: atypical Parkinsonian syndrome, significant psychiatric or cardiovascular disease, cognitive impairment, or risk of suicide. The primary endpoint was the change from baseline in the MDS-UPDRS Part III score at week 15, analyzed using a mixed model for repeated measures. Epworth Sleepiness Scale was collected as an exploratory endpoint, and the study included other measures of safety and quality of life.

Results: The study was terminated early for reasons unrelated to safety.  57 subjects received study medication. Treatment compliance was high in both groups and 82% of subjects completed the study. Mean (SE) change in the primary endpoint MDS-UPDRS Part III was –9.0 (1.54) for tavapadon and –4.3 (1.65) for placebo, with an improvement from placebo of 4.8 (2.26) in favor of the tavapadon group (2-sided P = 0.0407). The safety profile of tavapadon was similar to that observed in prior studies, with the majority of adverse events reported as mild or moderate. The most common adverse events in the tavapadon group were nausea, headache, dry mouth, somnolence, and tremor.

Conclusion: Once-daily dosing of oral tavapadon resulted in improvement of motor symptoms and was well tolerated in subjects with early stage Parkinson’s disease.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/efficacy-safety-and-tolerability-of-tavapadon-in-subjects-with-early-stage-parkinsons-disease/