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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1: Placebo | Placebo Comparator | Saline solution, given as a minimum of a 2 hour infusion |
|
| Part 1: RO7033877 | Experimental | Single ascending dose |
|
| Part 2: RO7033877 | Experimental | Single-dose 4-way crossover |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Part 1: SAD RO7033877 | Drug | Single dose |
| |
| Part 1: SAD placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Part 1: Incidence of adverse events (AEs) after single, supratherapeutic dose of RO7033877 | Up to 30 days | |
| Part 1: Pharmacokinetic parameters derived from plasma and urine concentrations, single dose of RO7033877: Area under the curve (AUC) | Day 1 | |
| Part 2: Continuous, 12-lead Holter electrocardiogram (ECG) recordings | Day -1 and 1 of each Period |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of AEs after single IV infusion of RO7033877 | Up to 9 weeks | |
| Part 2 only: Changes in other ECG parameters, descriptive analysis | Up to 9 weeks | |
| Part 2 only: Changes in PK/PD relationships between any effect on ECG and RO7033877 plasma concentrations, descriptive analysis |
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Inclusion Criteria:
Exclusion Criteria:
Exclusion criteria for Part 2 only:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Lenexa | Kansas | 66219 | United States |
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| Drug |
Single dose |
|
| Part 2: Treatment A, RO7033877 | Drug | Single dose RO7033877 and moxifloxacin placebo |
|
| Part 2: Treatment B, RO7033877 | Drug | Single dose RO7033877 and moxifloxacin placebo |
|
| Part 2: Treatment C, moxifloxacin | Drug | Single dose moxifloxacin and RO7033877 placebo |
|
| Part 2: Treatment D, RO7033877 and moxifloxacin placebo | Drug | Single dose moxifloxacin placebo and RO7033877 placebo |
|
| Up to 9 weeks |
| Part 2: Area under the concentration-time curve (AUC) of RO7033877 | Day 1 of each Period |
| ID | Term |
|---|---|
| D000077266 | Moxifloxacin |
| ID | Term |
|---|---|
| D024841 | Fluoroquinolones |
| D042462 | 4-Quinolones |
| D015363 | Quinolones |
| D011804 | Quinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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