Statistical considerations
tinnitus loudness, tinnitus
TINNITUS
The primary endpoint for this study was the percentage of responders for OTO-313 compared to placebo, where response was defined as achieving at least a 13-point reduction from baseline in the TFI score at both Weeks 4 and 8. It was observed from the Phase 1/2 study that the response rate, using this same definition, was 43% for OTO-313 (0.32 mg) and 13% for placebo [Assuming a 2-sided test and level of significance of 0.05, 60 patients in the placebo group and 60 patients in the OTO-313 group provided approximately 85% power to detect a treatment difference in favor of OTO-313. A discontinuation rate of 15% was projected, hence the total sample size for this 2-arm study was planned to be 140 patients, 70 subjects per arm. These sample size calculations were conducted using EASTv6.5 software with a test for a difference in proportions between two groups.The primary endpoint was analyzed using the Mantel–Haenszel test controlling for duration of tinnitus and baseline TFI score. The change from baseline in tinnitus loudness, tinnitus annoyance, TFI total score, and each TFI subscale score was analyzed using a linear mixed-effects model with treatment, study day, treatment-by-study day interaction, gender, and tinnitus duration as fixed effects. PGIC was analyzed using a Cochrane-Mantel–Haenszel mean score test controlling for baseline TFI score and duration of tinnitus.