Phase 2, Randomized, Double-blind, Placebo-controlled, Parallel Group, Multicenter Study to Evaluate the Safety, Tolerability and Efficacy of ADX48621 (dipraglurant). The trial design contained a dose escalation from 50mg once daily up to 100mg three times a day.
The primary outcome measure was the number of participants with abnormal safety and tolerability assessment parameters after 4 weeks. Secondary outcome measures were the severity of dyskinesia as measured by the modified Abnormal Involuntary Movement Scale (mAIMS) after 4 weeks; change in PD severity as measured by participant diary at weeks 1, 2, 3 and 4, UPDRS part III at weeks 2 and 4, UPDRS total score at week 4; and participant and clinician-rated global impression of change in dyskinesia and PD at 4 weeks.
The dipraglurant treatment group of 52 participants had a higher incidence of adverse events (AEs) – 88.5% – than the placebo group of 24 (75%). While most participants completed the dose escalation, 2 participants in the active group discontinued due to AEs. No treatment effects were seen in safety monitoring variables. Dipraglurant had a statistically significant effect against placebo as measured by mAIMS on day 1 (19.9% vs 4.1%). By day 28 a strong placebo response (21.5%) compared to the dipraglurant measure (31.4%) meant that statistical significance was not achieved at the end of the study. The clinician-rated global impression of change showed a statistically significant improvement with dipraglurant (71.2%) versus placebo (49.9%). According to participant diaries, daily on time with dyskinesia reduced and on time without dyskinesia increased. Two pivotal Phase 3 studies are scheduled to start by the end of 2019. Both studies plan the same enrolment (200 participants) split equally between dipraglurant and placebo, with the same primary and secondary outcomes. The first study (#301) will start an open label extension (OLE) after 3 months; the second study (#302) starts the OLE after 6 months. The Phase 3 studies are expected to report results in the third quarter of 2021. As with other experimental therapies for dyskinesia, dipraglurant has been granted orphan drug status by the US FDA, allowing seven years of market exclusivity.