2.9.3. Sample size estimation.
coronavirus disease
Referring to the Kaplan–Meier curve of the time to resolution of the 5 COVID-19 symptoms in a patient group with <72 hours from the onset of COVID-19 to randomization in the phase 2b study, we assumed a Weibull distribution as shown in Figure Weibull distribution (A) and corresponding hazard ratio curve (B) assumed when calculating the required number of patients for the phase 3 study for the time to resolution of the 5 symptoms of COVID-19. COVID-19 = coronavirus disease 2019.As described above, phase 3 consisted of 3 arms: the ensitrelvir 125 mg, ensitrelvir 250 mg, and placebo arms. The analysis population and the primary endpoint were changed based on the phase 2b outcomes as well as the sample size estimation. The original sample size estimation was as follows: in the phase 2b study, the median time to resolution for each ensitrelvir arm was conservatively assumed to be 8 days, while that for the placebo arm was assumed to be 10 days. The original primary comparisons were pairwise comparisons between each ensitrelvir group and the placebo group, which required multiplicity adjustment. Using the Bonferroni method