Study to Evaluate the Effect of Naltrexone and Bupropion Extended-Release Combination on Cardiac Repolarization in Healthy Participants

Orexigen Therapeutics, Inc84 enrolled

Overview

The purpose of this study is to evaluate the potential effect of naltrexone and bupropion extended-release combination on cardiac repolarization in healthy participants.

The drug being tested in this study is called naltrexone HCl/bupropion HCl (NB). NB is approved by the U.S. Food and Drug Administration (FDA) in addition to a reduced-calorie diet and increased physical activity for chronic weight management in adults who are obese or who are overweight and have at least one additional weight-related condition such as high blood pressure, diabetes or high cholesterol. This study is conducted to determine the potential effect of NB relative to placebo on cardiac repolarization. The study will enroll approximately 84 participants. Participants will be randomly assigned (by chance, like flipping a coin) to 1 of 6 treatment sequences, which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need): * Naltrexone/Bupropion + Placebo + Moxifloxacin * Placebo + Moxifloxacin + Naltrexone/Bupropion * Moxifloxacin + Naltrexone/Bupropion + Placebo * Naltrexone/Bupropion + Moxifloxacin + Placebo * Placebo + Naltrexone/Bupropion + Moxifloxacin * Moxifloxacin + Placebo + Naltrexone/Bupropion This study is consisted of 3 periods separated by a washout period (Days 11 through 25). Participants will be admitted to the clinic on Day -2 (Check-in) of each study period and will remain confined to the clinic until the morning of Day 12 of each study period. On Day -1 and Day 11 of each period, participants will undergo 24 hour Holter recordings using an ambulatory electrocardiograph recorder. This single center trial will be conducted in the United States. The overall time to participate in this study is approximately 96 days.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Masking

QUADRUPLE

Enrollment

Conditions

Heart Repolarization

Interventions

Naltrexone HCl/bupropion HClDRUG

Naltrexone HCl/bupropion HCl extended-release tablet.

PlaceboOTHER

Naltrexone/bupropion placebo-matching tablets.

MoxifloxacinDRUG

Moxifloxacin tablet.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: 1. Is a healthy male or female. 2. Is aged 18 to 55 years, inclusive, at signing of informed consent and first dose of study drug. 3. Weighs at least 50 kilogram (kg) and has a body mass index (BMI) of 18.0 to 35.0 kilogram per square meter (kg/m\^2), inclusive, at screening. Exclusion Criteria: 1. Has known hypersensitivity to moxifloxacin or other quinolone antibiotics or any component of the formulation of naltrexone/bupropion. 2. Has a history of seizure of any etiology, or of predisposition to seizures. 3. Has a history of significant cardiac disease. 4. Has a history of bulimia. 5. Has a history of anorexia nervosa. 6. Has a hemoglobin concentration less than (\<) 12 gram per deciliter (g/dL) at screening or check-in (day -2) of period 1. 7. Has resting heart rate outside the normal range of 45 to 100 beats per minute at screening or check-in (day -2) of period 1. 8. Has orthostatic blood pressure greater than or equal to (\>=) 25 millimeters of mercury (mm Hg) at screening or check-in (day -2) of period 1. 9. Has sustained supine systolic blood pressure \>=140 mm Hg or \<=90 mm Hg or a diastolic blood pressure \>=90 mm Hg or \<=50 mm Hg at screening or check-in (day -2) of period 1. 10. Has abnormal screening or check-in (day -2) of period 1 ECG indicating a second- or third-degree atrioventricular block, or 1 or more of the following: PR \>220 msec, QRS \>120 msec, and QTcF \>450 msec, or any rhythm other than sinus rhythm that is interpreted by the investigator to be clinically significant or could interfere with an accurate measurement of the QT interval. 11. Has family history of long QT syndrome. 12. Had extensive exercising in normal life, for example, marathon running, triathlon, physical sports at a contest level.

Locations (1)

Unnamed facility

Austin, Texas, United States

Outcomes

Primary Outcomes

The time-matched change from Baseline in QT interval with Fridericia correction method (QTcF)

QT and RR intervals will be recorded using ECG machines. Fridericia correction method is calculated by dividing QT interval by the cube root of the RR interval: QTcF = QT/RR\^1/3.

Time frame: Time matched Baseline and Day 11 within 30 minutes predose and up to 23.5 hours postdose

Secondary Outcomes

Time-Matched Change From Baseline in QT Interval With Bazett Correction Method (QTcB) at Day 11

QT and RR intervals will be recorded using ECG machines. QTcB will be calculated by dividing QT interval by the square root of the RR interval: QTcB = QT/RR\^1/2.

Time frame: Time matched baseline and at multiple time-points (up to 23.5 hours) postdose on Day 11

Time-Matched Change From Baseline in QT Interval With Individual Correction Method (QTcI) at Day 11

QT and RR intervals will be recorded using ECG machines. QTcI will be calculated as QT/RR\^beta, where the value of beta will be calculated using linear regression modeling for each subject on all baseline QT - RR interval pairs.

Time frame: Time matched baseline and at multiple time-points (up to 23.5 hours) postdose on Day 11

Time-Matched Change From Baseline in Uncorrected QT at Day 11

Time frame: Time matched baseline and at multiple time-points (up to 23.5 hours) postdose on Day 11

Time-Matched Increases From Baseline in QTcF, QTcB, QTcI, and QT > 30 msec and > 60 msec at Day 11

QTcF will be calculated by dividing QT interval by the cube root of the RR interval: QTcF= QT/RR\^1/3. QTcB will be calculated by dividing QT interval by the square root of the RR interval: QTcB = QT/RR\^1/2. QTcI will be calculated as as QT/RR\^beta, where the value of beta will be calculated using linear regression modeling for each subject on all baseline QT - RR interval pairs

Data from ClinicalTrials.gov

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