Ropinirole hydrochloride for amyotrophic lateral sclerosis: A single-center, randomized feasibility, double-blind, placebo-controlled trial

Abstract: Background: We previously used an induced pluripotent stem cell-based drug repurposing approach to demonstrate that ropinirole hydrochloride (ropinirole) attenuated amyotrophic lateral sclerosis (ALS)-specific pathological phenotypes. Here, we assessed the safety and feasibility of ropinirole in ALS patients to verify its efficacy.Methods: We conducted a randomized feasibility trial of ALS. Twenty participants with ALSFRS-R scores greater than 2 points were randomly assigned using dynamic allocation to receive ropinirole or placebo for 24 weeks in the double-blind period. Upon completion, participants could choose to participate in the following 24-week open-label active extension period. The primary outcomes were safety and tolerability. The secondary outcomes for the feasibility trial objective were the change in the ALS Functional Rating Scale-Revised (ALSFRS-R) score, composite functional endpoint, combined assessment of function and survival, event-free survival, and time to ≤50% forced vital capacity (blinded outcome assessment). This study is registered with the UMIN Clinical Trials Registry, UMIN000034954.Findings: Twenty-one participants were randomized into two groups (ropinirole group; n=14) and received ropinirole (n=13) or placebo (n=7) and the data of all participants were analysed using mixed-effects models for repeated measures together. Overall, the incidences of adverse events, most of which had been reported previously, were similar within both groups. Notably, the incidence of gastrointestinal disorders (mainly, temporary mild nausea and diarrhoea) was high at 76·9% in the ropinirole group (14·3% in the placebo group). Regarding the feasibility of verifying efficacy, there were no significant differences in the ALSFRS-R score and combined assessment of function and survival scores during the double-blind period for 6 months, while the participants in the ropinirole group had lived an additional 27·9 weeks without disease progression events compared with the placebo group (log-rank test, 95% confidence interval, 4·3–37·4) at 12 months (secondary outcome).Interpretation: Ropinirole is safe and tolerable for patients with ALS and this trial indicates feasibility for a subsequent large-scale trial.Funding: This study was funded by The Japan Agency for Medical Research and Development and K Pharma Inc.