A Phase I Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Novel Dopamine D1 Receptor Partial Agonist, PF-06669571, in Subjects with Idiopathic Parkinson's Disease.

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There is an unmet medical need for additional treatment options for Parkinson's disease. This was a Phase I, double-blind clinical trial assessing safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple doses of the novel dopamine D1 receptor partial agonist, PF-06669571, in subjects with idiopathic Parkinson's disease on a stable dose of L-DOPA. Subjects received PF-06669571 (or matching placebo) titrated from 1mg to 3mg over 7days. The primary pharmacodynamic endpoint was the change from baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III total motor score at the pharmacodynamic time of maximum change from baseline on day 7. Twenty subjects were randomized and 19 completed the study. Maximum plasma concentrations (Cmax) of PF-06669571 were reached 3.35 and 3.19h post-dose on day 1 and day 7. Geometric mean Cmax and area under the plasma concentration-time profile from time 0 to 24h post-dose on day 7 were 92.51ng/mL and 1626ng·h/mL, respectively. The primary pharmacodynamic endpoint did not meet the pre-specified criteria for significant improvement; however, the criteria were met in a sensitivity analysis excluding data from a L-DOPA outlier (L-DOPA dose of 2550mg/d). The most common adverse events (AEs) were nausea (experienced by 2 subjects each in the PF-06669571 and placebo groups). There were no permanent discontinuations or dose reductions due to AEs. Multiple daily doses of PF-06669571 were safe and well tolerated with no notable safety concerns. The pharmacodynamic endpoint did not meet the pre-specified criteria for significant improvement. CLINICALTRIALS. NCT02565628.