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

Clinical Drug Investigation
Rachel GurrellNicholas DeMartinis

Abstract

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 1 mg to 3 mg over 7 days. 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 3.19 h post-dose on day 1 and day 7. Geometric mean Cmax and area under the plasma concentration-time profile from time 0 to 24 h post-dose on day 7 were 92.51 ng/mL and 1626 ng·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 2550 mg/...Continue Reading

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Citations

Aug 18, 2020·Expert Opinion on Pharmacotherapy·Silvia Cerri, Fabio Blandini
Jan 3, 2021·Brain Research Bulletin·Cheng-Lu ZhangYu-He Yuan
Aug 29, 2021·Pharmaceuticals·E Maruthi Prasad, Shih-Ya Hung

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