Objective: The objective of the Phase 2b-trial was to investigate efficacy and safety of three doses of Mesdopetam as adjunct treatment in patients with PD experiencing troublesome dyskinesia.

Background: Mesdopetam, a dopamine D3-receptor antagonist with antidyskinetic and antipsychotic properties in preclinical models, displayed antidyskinetic effects and an acceptable safety profile in two previous 4-week Phase1b/2a-studies in PD.

Method: This was a double-blind, placebo-controlled, study conducted in US/Europe/Israel. Patients on stable regimen of antiparkinson medication, experiencing troublesome dyskinesia, were randomized to placebo, Mesdopetam 2.5, 5, or 7.5 mg bid for 12 weeks. The primary endpoint was daily ON-time without troublesome dyskinesia (“good ON”) measured by Hauser-diaries. Secondary endpoints included UDysRS (parts 1,3,4), time in different motor-states, MDS-UPDRS, CGI, MMSE, along with adverse events, safety and pharmacokinetics.

Results: Of 156 patients randomized, 125 patients completed the treatment period. The primary endpoint did not reach statistical significance vs. placebo. Separate analysis of the secondary efficacy endpoint UDysRS showed significant anti-dyskinetic effects vs. placebo (nominal p-value = 0.045, 0.004, 0.026 at 4, 8, and 12 weeks, respectively, at 7.5 mg bid, FAS). This was corroborated by numerical improvement in MDS-UPDRS-4.2. Further, daily OFF-time showed a numerical decrease vs. placebo favoring the 7.5 mg bid dose. The secondary endpoint MDS-UPDRS-part II was unchanged by Mesdopetam. 

The adverse event profile of Mesdopetam was similar to placebo. The most common adverse events reported were nervous system disorders reported by 20% of Mesdopetam-treated subjects and 23% of placebo-treated subjects. Parkinsonism was reported by 4% of Mesdopetam-treated subjects and 10% of placebo-treated subjects.

Conclusion: Mesdopetam demonstrated significant antidyskinetic effects as measured by UDysRS. These antidyskinetic properties were obtained without impairing normal motor function and are further strengthened by an apparent reduction in OFF-time. Full analyses are in progress and detailed results will be presented during the meeting.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/results-from-irl790c005-a-randomized-double-blind-placebo-controlled-phase-iib-study-evaluating-the-efficacy-of-mesdopetam-on-daily-on-time-without-troublesome-dyskinesia-in-patients-with-parkinso/