Mesdopetam for the Treatment of Levodopa Induced Dyskinesia in Parkinson's Disease: A Randomized Phase 2b Trial

Background: The treatment of levodopa-induced dyskinesia in Parkinson's disease (PD) is a largely unmet need. Objectives: Mesdopetam is a novel small molecule dopamine D3 receptor antagonist aimed for the treatment of levodopa-induced dyskinesia. This was a phase 2b study dose finding study to investigate efficacy and safety of 2.5 mg, 5 mg and 7,5 mg b.i.d. in a randomized controlled trial. Methods: PD patients with ≥2 hours of troublesome dyskinesia were randomized to placebo or mesdopetam twice daily for 12 weeks. The primary efficacy endpoint was change from baseline to week 12 in ON time without troublesome dyskinesia (Good ON-time) as recorded with home diaries. Secondary efficacy endpoints assessing ON phase dyskinesia were the modified UDysRS (sum of parts 1, 3 and 4) and MDS-UPDRS part 4.2. Results: Groups did not differ in change from baseline to end of study in Good ON-time. Several secondary assessments for ON phase dyskinesia such as the modified UDysRS showed clinically relevant and statistically significant improvements for the 2.5 and 7.5 mg doses. OFF time showed dose dependent decrease with highest efficacy for the 7.5 mg dose. The adverse event profile was similar to placebo. Conclusions: In this study mesdopetam failed to increase Good ON-time as compared to placebo. However, a statistically significant and clinically meaningful improvement in the prespecified secondary efficacy endpoint UDysRS warrants further investigation. Results from this dose finding study suggest 7.5 mg b.i.d. to be the preferred dose for further study.