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

Orexigen

Status and phase: Completed; Phase 1

Conditions: Heart Repolarization

Treatments: Drug: Moxifloxacin; Drug: Naltrexone HCl/bupropion HCl; Other: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02735603

NaltrexBuprop-1001

U1111-1171-3290 (Registry Identifier)

Details and patient eligibility

About

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

Full 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.

Enrollment: 84 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

84 participants in 6 patient groups

Nalterxone/Bupropion + Placebo + Moxifloxacin

Experimental group

Description:

Naltrexone hydrochloride (HCl) 8 milligram (mg)/bupropion HCl 90 mg (NB) placebo-matching 2 tablets, orally, once in the morning on Day -1, NB, 1 extended-release tablet, orally, twice daily and NB placebo-matching 1 tablet, orally, twice daily from Days 1 to 3, NB, 2 extended-release tablets, orally, twice daily from Days 4 to 10 and once in the morning on Day 11 in treatment period 1, followed by 14 days washout period, followed by NB placebo-matching 2 tablets, orally, once in the morning on Day -1, twice daily from Days 1 to 10, and once in the morning on Day 11 in treatment period 2, followed by 14 days washout period, followed by NB placebo-matching 2 tablets, orally, once in the morning on Day -1, twice daily from Days 1 to 10, moxifloxacin 400 mg, tablet, orally, once in the morning on Day 11 in treatment period 3.

Treatment:

Drug: Naltrexone HCl/bupropion HCl

Other: Placebo

Drug: Moxifloxacin

Placebo + Moxifloxacin + Naltrexone/Bupropion

Experimental group

Description:

NB placebo-matching 2 tablets, orally, once in the morning on Day -1, twice daily from Days 1 to 10 and once in the morning on Day 11 in treatment period 1, followed by 14 days washout period, followed by NB placebo-matching 2 tablets, orally, once in the morning on Day -1, twice daily from Days 1 to 10, moxifloxacin 400 mg, tablet, orally, once in the morning on Day 11 in treatment period 2, followed by 14 days washout period, followed by NB placebo-matching 2 tablets, orally, once in the morning on Day -1, NB, 1 extended-release tablet, orally, twice daily and NB placebo-matching 1 tablet, orally, twice daily from Days 1 to 3, NB, 2 extended-release tablets, orally, twice daily from Days 4 to 10 and once in the morning on Day 11 in treatment period 3.

Treatment:

Drug: Naltrexone HCl/bupropion HCl

Other: Placebo

Drug: Moxifloxacin

Moxifloxacin + Naltrexone/Bupropion + Placebo

Experimental group

Description:

NB placebo-matching 2 tablets, orally, once in the morning on Day -1, twice daily from Days 1 to 10, moxifloxacin 400 mg, tablet, orally, once in the morning on Day 11 in treatment period 1, followed by 14 days washout period, followed by NB placebo-matching 2 tablets, orally, once in the morning on Day -1, NB, 1 extended-release tablet, orally, twice daily and NB placebo-matching 1 tablet, orally, twice daily from Days 1 to 3, NB, 2 extended-release tablets, orally, twice daily from Day 4 to 10, and once in the morning on Day 11 in treatment period 2, followed by 14 days washout period, followed by NB placebo-matching 2 tablets, orally, once in the morning on Day -1, twice daily from Days 1 to 10 and once in the morning on Day 11 in the treatment period 3.

Treatment:

Drug: Naltrexone HCl/bupropion HCl

Other: Placebo

Drug: Moxifloxacin

Naltrexone/Bupropion + Moxifloxacin + Placebo

Experimental group

Description:

NB placebo-matching 2 tablets, orally, once in the morning on Day -1, NB, 1 extended-release tablet, orally, twice daily and NB placebo-matching 1 tablet, orally, twice daily from Days 1 to 3, NB, 2 extended-release tablets, orally, twice daily from Days 4 to 10 and once in the morning on Day 11 in treatment period 1, followed by 14 days washout period, followed by NB placebo-matching 2 tablets, orally, once in the morning on Day -1, twice daily from Days 1 to 10, moxifloxacin 400 mg, tablet, orally, once in the morning on Day 11 in treatment period 2 followed by 14 days washout period, followed by NB placebo-matching 2 tablets, orally, once in the morning on Day -1, twice daily from Days 1 to 10 and once in the morning on Day 11 in treatment period 3.

Treatment:

Drug: Naltrexone HCl/bupropion HCl

Other: Placebo

Drug: Moxifloxacin

Placebo + Naltrexone/Bupropion + Moxifloxacin

Experimental group

Description:

NB placebo-matching 2 tablets, orally, once in the morning on Day -1, twice daily from Days 1 to 10 and once in the morning on Day 11 in treatment period 1, followed by 14 days washout period, followed by NB placebo-matching 2 tablets, orally, once in the morning on Day -1, NB, 1 extended-release tablet, orally, twice daily and NB placebo-matching 1 tablet, orally, twice daily from Days 1 to 3, NB, 2 extended-release tablets, orally, twice daily from Days 4 to 10 and once in the morning on Day 11 in treatment period 2 followed by 14 days washout period, followed by NB placebo-matching 2 tablets, orally, once in the morning on Day -1, twice daily from Days 1 to 10, moxifloxacin 400 mg, tablet, orally, once in the morning on Day 11 in treatment period 3.

Treatment:

Drug: Naltrexone HCl/bupropion HCl

Other: Placebo

Drug: Moxifloxacin

Moxifloxacin + Placebo + Naltrexone/Bupropion

Experimental group

Description:

NB placebo-matching 2 tablets, orally, once in the morning on Day -1, twice daily from Days 1 to 10, moxifloxacin 400 mg, tablet, orally, once in the morning on Day 11 in treatment period 1 followed by 14 days washout period, followed by NB placebo-matching 2 tablets, orally, once in the morning on Day -1, twice daily from Days 1 to 10 and once in the morning on Day 11 in treatment period 2 followed by 14 days washout period, followed by NB placebo-matching 2 tablets, orally, once in the morning on Day -1, NB, 1 extended-release tablet, orally, twice daily and NB placebo-matching 1 tablet, orally, twice daily from Days 1 to 3, NB, 2 extended-release tablets, orally, twice daily from Days 4 to 10 and once in the morning on Day 11 in treatment period 3.

Treatment:

Drug: Naltrexone HCl/bupropion HCl

Other: Placebo

Drug: Moxifloxacin