This is a two-part study to evaluate the safety and tolerability of supratherapeutic doses of RO7033877 (Part 1) and to investigate the effect of RO7033877 on the QTc interval in healthy volunteers (Part 2). Part 1 is a single ascending dose, randomized, observer-blind, placebo-controlled study to determine the safety tolerability and pharmacokinetics of a supratherapeutic dose to be used in Part 2. Participants will be randomized in up to 8 cohorts to receive a single dose of either RO7033877 or placebo. Part 2 will be a single dose, randomized, double-blind, double dummy, placebo-controlled, positive control, 4-way crossover study. Part 2 will evaluate whether a single therapeutic or supratherapeutic dose of RO7033877 has a threshold pharmacologic effect on cardiac repolarization, as detected by changes in the QT/QTc interval measured by electrocardiogram (ECG). Pharmacokinetic parameters will be assessed for Parts 1 and 2, continuous ECG recordings will be evaluated in Part 2.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Masking
DOUBLE
Enrollment
64
Single dose
Single dose
Single dose RO7033877 and moxifloxacin placebo
Single dose RO7033877 and moxifloxacin placebo
Single dose moxifloxacin and RO7033877 placebo
Single dose moxifloxacin placebo and RO7033877 placebo
Unnamed facility
Lenexa, Kansas, United States
Part 1: Incidence of adverse events (AEs) after single, supratherapeutic dose of RO7033877
Time frame: Up to 30 days
Part 1: Pharmacokinetic parameters derived from plasma and urine concentrations, single dose of RO7033877: Area under the curve (AUC)
Time frame: Day 1
Part 2: Continuous, 12-lead Holter electrocardiogram (ECG) recordings
Time frame: Day -1 and 1 of each Period
Incidence of AEs after single IV infusion of RO7033877
Time frame: Up to 9 weeks
Part 2 only: Changes in other ECG parameters, descriptive analysis
Time frame: Up to 9 weeks
Part 2 only: Changes in PK/PD relationships between any effect on ECG and RO7033877 plasma concentrations, descriptive analysis
Time frame: Up to 9 weeks
Part 2: Area under the concentration-time curve (AUC) of RO7033877
Time frame: Day 1 of each Period
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