Winnonlin enterprise version 6

All data analyses were generated using SAS Version 9.2. Unless otherwise stated, all statistical tests were two-tailed at α = 0.05; no adjustments were made for multiple comparisons. Subjects who received placebo in each cohort group were analyzed as one group for safety summaries. Dose proportionality was assessed for HJS (up to 20 mg) and SSS (up to 30 mg and over the entire range) using analysis of variance models for repeated measures. Natural log-transformed, dose-normalized plasma TAK-063 and M-I C_max and AUCs were used as the responses, and treatment group, day, and day-by-treatment group interaction were used as the factors in the models. For SSS, dose proportionality was evaluated for two TAK-063 dose ranges: up to 30 mg, and the entire range, using a power model ln(PK parameter) = β₀ + β₁·ln(Dose) + ε, in which β₀ is the intercept, β₁ is the slope, and ε is the random error term. Dose proportionality was also presented graphically using box plots. PK parameters were determined using non-compartmental analysis with WinNonlin Enterprise Version 6.3 (Pharsight Corp., Mountain View, CA, USA). Plasma and urine PK parameters for TAK-063 and M-I were determined from the concentration–time profiles for all evaluable subjects.