A Study of the Effect of RO4917838 on the QTcF Interval in Healthy Volunteers

Study Overview
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Brief Summary
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This multiple-center, multiple-dose, randomized, double-blind, double-dummy, placebo-controlled, positive-controlled, parallel group study will investigate the effect of RO4917838 on the QTc interval in healthy volunteers. Healthy volunteers will be randomized to one of 4 treatment arms; Arm A: low dose of RO4917838, Arm B: high dose of RO4917838, Arm C: placebo to RO4917838 and moxifloxacin on Day 1, Arm D: placebo to RO4917838 and moxifloxacin on Day 11. The anticipated time on study treatment is 11 days.

Official Title
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A Multiple-center, Multiple-dose, Randomized, Double-blind, Double-dummy, Placebo-controlled, Positive-controlled, Parallel Group Study to Investigate the Effect of RO4917838 on the QTc Interval in Healthy Subjects.

Conditions
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Healthy Volunteer

Intervention / Treatment
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* Drug: Moxifloxacin
* Drug: Moxifloxacin
* Drug: RO4917838
* Drug: RO4917838
* Drug: RO4917838 placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male volunteers aged 18 to 65 years inclusive Body mass index (BMI) between 18 and 30 kg/m2 inclusive. Have no contraindications from the following: a detailed medical and surgical history, and a complete physical examination Able to participate, and willing to give written informed consent and to comply with the study restrictions Exclusion Criteria: History of any clinically significant gastrointestinal, renal, hepatic, broncho-pulmonary, neurological, mental, cardiac, vascular, endocrinological, hematological or allergic disease, metabolic disorder, cancer or cirrhosis. History of alcohol and/or drug abuse or addiction within the last 2 years prior to Day 1 of the study. Consumption of nicotine and/or tobacco containing products within the last 3 months prior to Day 1 of the study. Infection with human immunodeficiency virus, hepatitis B and/or hepatitis C Any condition or disease detected during the medical interview / physical examination that would render the subject unsuitable for the study, place the subject at undue risk or interfere with the ability of the subject to complete the study in the opinion of the Investigator. Positive drug screen or alcohol test at screening or prior to enrollment. Coffee or tea consumption > 10 cups per day or methylxanthine containing drinks >1.5 liter/day or more than 250 g/day of chocolate. Alcohol consumption averaging > 3 drinks daily

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A<br> | Drug: RO4917838<br>* Multiple daily low doses of RO4917838 for 10 days<br>|
| Experimental: Treatment B<br> | Drug: RO4917838<br>* Multiple daily oral high doses of RO4917838 for 10 days<br>|
| Placebo Comparator: Treatment C<br> | Drug: Moxifloxacin<br>* Single oral dose on Day 1<br>Drug: RO4917838 placebo<br>* Oral daily doses of placebo to RO4917838 for 10 days<br>|
| Placebo Comparator: Treatment D<br> | Drug: Moxifloxacin<br>* Single oral dose on Day 11<br>Drug: RO4917838 placebo<br>* Oral daily doses of placebo to RO4917838 for 10 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in QTcF interval at steady state |  | Baseline and Day 10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of electrocardiogram |  | Baseline and Day 10 | 
| Correlation of RO4917838 plasma concentration and the electrocardiogram |  | Day 10 | 
| Change in the QTc interval, using moxifloxacin as an active control |  | Days 1 and 11 | 
| Safety: incidence of adverse events |  | 8 weeks | 
| Pharmacokinetics: area under the concentration time curve of RO4917838 |  | Up to Day 19 | 
| Pharmacokinetics: Maximum plasma concentration of RO4917838 |  | Up to Day 19 |