A futility study of minocycline in Huntington's disease.
This study assessed the futility of proceeding with a Phase 3 clinical trial of minocycline as a disease-modifying treatment for Huntington's disease (HD). One hundred fourteen research participants with HD were randomized, 87 to minocycline (200 mg/d) and 27 to placebo. The change in Total Functional Capacity (TFC) score from baseline to Mo 18 was prespecified as the primary measure of HD progression. By using a futility design, we tested the null hypothesis that minocycline would reduce the mean decline in TFC score by at least 25% compared to a fixed value obtained from a historical database, with a one-tailed significance level of 10%. The placebo group was included to facilitate blinding. Rejection of the null hypothesis would discourage a major definitive trial of minocycline in HD. For the primary analysis, missing data were handled by carrying forward the last available observation; a secondary analysis used multiple imputations. The mean TFC decline in the minocycline group was 1.55 (SD 1.85), and futility was not declared (P = 0.12) for the primary analysis. When multiple imputation was used to handle missing data, the mean TFC decline in the minocycline group of 1.71 (SD 1.96, P = 0.07) suggested futility, as was the case for prespecified secondary outcome measures. There were no safety abnormalities attributable to minocycline. Based on the threshold of 25% improvement in TFC, further study of minocycline 200 mg/d in HD was not warranted. Futility designs aid in screening potential therapies for HD.
D000203:Activities of Daily Living; D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006816:Huntington Disease / Q000188:drug therapy*; D008297:Male; D018447:Medical Futility; D008875:Middle Aged; D008911:Minocycline / Q000627:therapeutic use*; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D008911:Minocycline