Background:

Current drug treatments have little efficacy in advanced-to-end-stage Parkinson’s disease (advPD), yet there are no reports of interventional trials in advPD. D₁ dopamine agonists have the potential to provide benefit.

Objective:

To determine the feasibility and safety of the selective D₁/D₅ dopamine partial agonist PF 06412562 in advPD.

Methods:

A two-week, randomized, double blind, crossover phase Ib study in advPD patients compared standard-of-care (SoC) carbidopa/levodopa with PF 06412562. Each week, there was a Day 1 baseline evaluation with overnight levodopa washout, then treatment on Days 2 and 3 with either SoC or PF-06412562 (split dose 25 + 20 mg), followed by discharge on Day 4. Primary endpoints were safety and tolerability. Secondary endpoints were global clinical impression of change (GCI-C) rated by clinicians and caregivers.

Results:

Eight advPD patients and their caregivers consented to participate and six were randomized (average disease duration: 22 y). None withdrew voluntarily. One participant with baseline Day 1 dehydration, pre-renal kidney injury, and autonomic dysfunction experienced symptomatic and serious hypotension after receiving PF-06412562 in Week 1 and was discontinued from the study. All other adverse events were rated mild (PF-06412562: n = 1, SoC: n = 0), moderate (PF-06412562: n = 1, SoC: n = 1), or severe but non-serious (PF-06412562: n = 3, SoC: n = 2). No clinically meaningful laboratory changes were observed. Among the five participants who completed the study, GCI-C favored PF-06412562 in two per clinicians’ and four participants per caregivers’ rating.

Conclusion:

PF-06412562 was tolerated in advPD patients. This study provides the feasibility for future safety and efficacy studies in this population with unmet needs.

Search results

The D 1 /D 5 Dopamine Partial Agonist PF-06412562 in Advanced-Stage Parkinson’s Disease: A Feasibility Study