MOST-ABLE Trial

The three-group design allows dose-response characterisation, and plasma semaglutide concentration measurements at week 36 will provide direct exposure–response data. The total trial period is 48 weeks: a 36-week treatment phase followed by a 12-week washout phase during which no study drug is taken. The MOST-ABLE study is the world's first phase 2 randomised controlled trial of oral semaglutide tablets in Parkinson's disease. Acknowledged limitations include the small sample size of 99 participants and the short 36-week active treatment period, which may limit detection of slowly developing disease-modifying effects. The trial uses a three-group, double-blind, placebo-controlled design with 1:1:1 allocation to semaglutide 7 mg, 14 mg, or placebo, stratified by Hoehn and Yahr stage. The trial is conducted across eight sites in Japan, with recruitment running from November 2023 to September 2024 and a total enrolment target of 99 participants.