PF-06649751 efficacy and safety in early Parkinson's disease: a randomized, placebo-controlled trial.

BACKGROUND

PF-06649751 is a novel, oral, non-catechol-based, D1/D5 dopamine receptor partial agonist under investigation for the treatment of motor symptoms associated with Parkinson's disease.

METHODS

A 15-week, phase II, double-blind, placebo-controlled clinical trial was conducted to assess the efficacy and safety of flexible-dose PF-06649751 in subjects with early stage Parkinson's disease (ClinicalTrials.gov identifier: NCT02847650).

RESULTS

Enrollment was terminated early for reasons unrelated to the trial. Overall, 57 subjects received study medication (PF-06649751 = 29; placebo = 28) and 47 completed the study (PF-06649751 = 25; placebo = 22). Despite early termination, the study met its primary endpoint with the PF-06649751 group showing statistically significant improvement from baseline in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III score at week 15 compared with placebo. Mean (SE) change in MDS-UPDRS Part III score was -9.0 (1.54) for PF-06649751 and -4.3 (1.65) for placebo. This corresponds to an improvement placebo of 4.8 for the PF-06649751 group (two-sided  = 0.0407; 90% CI = 1.0, 8.6). Statistically significant improvement in MDS-UPDRS-III score was also observed at all assessment time points prior to week 15. The safety profile of PF-06649751 was similar to that observed in prior studies, with the majority of adverse events (AEs) reported as mild or moderate. The most common AEs in the PF-06649751 group were nausea, headache, dry mouth, somnolence, and tremor.

CONCLUSIONS

Once-daily dosing of oral PF-06649751 resulted in significant improvement of motor symptoms and was generally well tolerated in subjects with early stage Parkinson's disease.