Clinical trial NCT02735603: Study to Evaluate the Effect of Naltrexone and Bupropion Extended-Release Combination on Cardiac Repolarization in Healthy Participants
Official title: A Randomized, Double-Blind, Placebo- and Moxifloxacin Positive-Controlled (Open-Label), Cross-Over Study to Evaluate the Potential Effect of Naltrexone and Bupropion Extended-Release Combination on Cardiac Repolarization in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Heart Repolarization
Lead sponsor: Orexigen Therapeutics, Inc
Sponsor class: INDUSTRY
First posted: 2016-04-12
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

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

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: The time-matched change from Baseline in QT interval with Fridericia correction method (QTcF)
timeFrame: Time matched Baseline and Day 11 within 30 minutes predose and up to 23.5 hours postdose
Secondary outcomes:
measure: Time-Matched Change From Baseline in QT Interval With Bazett Correction Method (QTcB) at Day 11
timeFrame: Time matched baseline and at multiple time-points (up to 23.5 hours) postdose on Day 11
measure: Time-Matched Change From Baseline in QT Interval With Individual Correction Method (QTcI) at Day 11
timeFrame: Time matched baseline and at multiple time-points (up to 23.5 hours) postdose on Day 11
measure: Time-Matched Change From Baseline in Uncorrected QT at Day 11
timeFrame: Time matched baseline and at multiple time-points (up to 23.5 hours) postdose on Day 11
measure: Time-Matched Increases From Baseline in QTcF, QTcB, QTcI, and QT > 30 msec and > 60 msec at Day 11
timeFrame: Baseline and Day 11
measure: QTcF, QTcB, QTcI, and QT intervals >450 msec, >480 msec or >500 msec at Day 11
timeFrame: Day 11
measure: T-U wave complex morphology on Day 11
timeFrame: Day 11
measure: Cmax- Maximum Observed Plasma Concentration for Naltrexone, Bupropion, and their Metabolites
timeFrame: Day 11: predose and at multiple time points (up to 23.5 hours) postdose
measure: Tmax- Time to Reach the Maximum Plasma Concentration (Cmax) for Naltrexone, Bupropion, and their Metabolites
timeFrame: Day 11: predose and at multiple time points (up to 23.5 hours) postdose
measure: 9. Percentage of Participants Reporting at least one Treatment-Emergent Adverse Event (TEAE)
timeFrame: Baseline up to 30 days after the last dose of study drug
Other outcomes:
Locations:
city: Austin
country: United States
state: Texas
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_DIRECTOR
References: