Phase 1 Parkinson's Disease Studies Show the Dopamine D1/D5 Agonist PF-06649751 is Safe and Well Tolerated.

ABSTRACT:

Introduction

There is a need for new therapies in Parkinson's disease that may help to address known limitations of current options. PF-06649751 is a novel, highly selective dopamine D1/D5 agonist targeted for Parkinson's disease treatment.

Methods

The safety, pharmacokinetics, and pharmacodynamics of PF-06649751 were assessed in single ascending dose and multiple ascending dose clinical trials in patients with Parkinson's disease. The single ascending dose study (N = 18) was a double-blind, placebo-controlled study with a three-way crossover design consisting of three treatment periods separated by 7-day study drug washout periods. PF-06649751 doses were 0.75 mg, 1.5 mg, 3 mg, 6 mg, and 9 mg. In the open-label multiple ascending dose study, eligible subjects received once-daily doses of PF-06649751 (N = 45) over 21 days, with up-titration to 5 mg, 15 mg, and 25 mg once daily. Pharmacodynamics were assessed by measuring change from baseline in the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III at different time points post dose.

Results

PF-06649751 was safe and well tolerated across studies and in all cohorts. Peak plasma concentrations were attained 1-4 h post dose across both studies, and exposure increased with increasing dose. PF-06649751 demonstrated sustained pharmacodynamic effects compared with placebo, with mean reductions from baseline in the MDS-UPDRS Part III up to 12 h post dose at 9 mg single dose. MDS-UPDRS Part III changes in the open-label multiple dose study on day 22 also demonstrated sustained pharmacodynamic activity.

Conclusions

PF-06649751 represents a novel therapeutic candidate for Parkinson's disease with an initial safety, tolerability, and pharmacokinetic profile and potential for efficacy that merits further study in larger clinical trials.

Trial registration

These studies are registered at www.clinicaltrials.gov as NCT02373072, NCT02224664.

Funding

Pfizer.

SUBMITTER: Sohur US 

PROVIDER: S-EPMC6283789 | biostudies-literature |

REPOSITORIES: biostudies-literature