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

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.

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer
• Intervention / Treatment: Drug: RO4917838; Drug: RO4917838; Drug: Moxifloxacin; Drug: Moxifloxacin; Drug: RO4917838 placebo

• Study Type: Interventional
• Enrollment (Actual): 169
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Strasbourg, France, 67064
• United States
  • Arizona
    • Tempe, Arizona, United States, 85283

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Hofmann C, Banken L, Hahn M, Swearingen D, Nagel S, Martin-Facklam M. Evaluation of the effects of bitopertin (RG1678) on cardiac repolarization: a thorough corrected QT study in healthy male volunteers. Clin Ther. 2012 Oct;34(10):2061-71. doi: 10.1016/j.clinthera.2012.08.010. Epub 2012 Sep 12.

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (Actual): July 1, 2009
• Study Completion (Actual): July 1, 2009

Study Registration Dates

• First Submitted: May 23, 2012
• First Submitted That Met QC Criteria: June 4, 2012
• First Posted (Estimate): June 6, 2012

Study Record Updates

• Last Update Posted (Estimate): November 2, 2016
• Last Update Submitted That Met QC Criteria: November 1, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral, Combined; Contraceptives, Oral; Contraceptive Agents, Female; Moxifloxacin; Norgestimate, ethinyl estradiol drug combination
• Other Study ID Numbers: BP21705; 2008-001127-57 (EudraCT Number)