The primary study variables were safety and tolerability, including incidence and severity of AEs, safety laboratory abnormalities, ECGs, and vital sign abnormalities. The main PK study variables were area under the plasma concentration‐time curve from time 0 to infinity (AUC0‐∞) and maximum plasma concentration (Cmax) of the active metabolite RO6871765. Other PK variables included the AUC0‐∞ and Cmax of RO6870868 and a minor metabolite RO6872373. Plasma PK parameters were estimated by a standard noncompartmental method using WinNonlin version 6.4 (Pharsight Corporation) and presented with summary statistics. PD variables were regarded as secondary outcomes. In all analyses, placebo subjects from each cohort were pooled into one group. Descriptive statistics were used to summarize PK and PD variables. Detailed methods for determination of PK dose proportionality, PD response, and PK/PD relationships are described in the Supplementary Information S4.

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