To study the characteristics of OFF time and the impact of solengepras treatment on the patient experience in a Phase 2 study in Parkinson’s Disease (PD).

Solengepras is an oral, once-daily GPR6-inhibitor developed to release inhibition of the indirect (striatopallidal) pathway without directly affecting the dopamine pathway. In a prior study of PD with motor fluctuations, solengepras 150mg daily demonstrated a clinically meaningful -1.3-hour OFF-time reduction versus placebo.  Here, we examine additional characteristics of OFF-time to understand the impact of solengepras treatment on the patient experience.

In this Phase 2 randomized, double-blind, placebo-controlled study, PD patients with ≥2 hours of daily OFF-time based on patient motor diaries were randomized (1:1:1) to receive solengepras (50 mg or 150 mg) daily or placebo for 28 days (NCT04191577).  In this post-hoc exploratory analysis, motor diaries were normalized to a 16-hour day and limited to participants with ≥3 hours of OFF-time at baseline.  Characteristics of OFF-time were analyzed using mixed model for repeated measures (MMRM).  

110 participants (88%) met the criteria for inclusion.  Total daily OFF-time was improved by a mean of -1.78 hours from baseline in the solengepras 150mg group compared to placebo (p=0.0045), equivalent to a 34.7% reduction.  In addition, there was a reduction versus placebo in the mean number of OFF periods per day (-0.98, p=0.0021), mean duration of each OFF period (-26 min, p=0.0887), and mean duration of first morning OFF period (-26 min, p=0.1490).

In this Phase 2 post-hoc analysis of patient motor diaries, solengepras reduced daily OFF-time in PD patients with ≥3 hours of OFF-time at baseline and reduced the mean number of OFF periods per day.  A non-significant reduction was also observed in the duration of OFF periods and morning OFF.  These results help describe the potential of solengepras to reduce patient burden and disability in PD.