Trial record 2 of 11 for:    contrave

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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Orexigen Therapeutics, Inc
ClinicalTrials.gov Identifier:
NCT02735603
First received: April 5, 2016
Last updated: April 28, 2016
Last verified: April 2016
  Purpose
The purpose of this study is to evaluate the potential effect of naltrexone and bupropion extended-release combination on cardiac repolarization in healthy participants.

Condition Intervention Phase
Heart Repolarization
Drug: Naltrexone HCl/bupropion HCl
Other: Placebo
Drug: Moxifloxacin
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
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

Resource links provided by NLM:


Further study details as provided by Orexigen Therapeutics, Inc:

Primary Outcome Measures:
  • The time-matched change from Baseline in QT interval with Fridericia correction method (QTcF) [ Time Frame: Time matched Baseline and Day 11 within 30 minutes predose and up to 23.5 hours postdose ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Time-Matched Change From Baseline in QT Interval With Bazett Correction Method (QTcB) at Day 11 [ Time Frame: Time matched baseline and at multiple time-points (up to 23.5 hours) postdose on Day 11 ] [ Designated as safety issue: No ]
    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-Matched Change From Baseline in QT Interval With Individual Correction Method (QTcI) at Day 11 [ Time Frame: Time matched baseline and at multiple time-points (up to 23.5 hours) postdose on Day 11 ] [ Designated as safety issue: Yes ]
    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-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 ] [ Designated as safety issue: Yes ]
  • Time-Matched Increases From Baseline in QTcF, QTcB, QTcI, and QT > 30 msec and > 60 msec at Day 11 [ Time Frame: Baseline and Day 11 ] [ Designated as safety issue: Yes ]
    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

  • QTcF, QTcB, QTcI, and QT intervals >450 msec, >480 msec or >500 msec at Day 11 [ Time Frame: Day 11 ] [ Designated as safety issue: Yes ]
    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 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.

  • T-U wave complex morphology on Day 11 [ Time Frame: Day 11 ] [ Designated as safety issue: No ]
  • Cmax- Maximum Observed Plasma Concentration for Naltrexone, Bupropion, and their Metabolites [ Time Frame: Day 11: predose and at multiple time points (up to 23.5 hours) postdose ] [ Designated as safety issue: No ]
  • Tmax- Time to Reach the Maximum Plasma Concentration (Cmax) for Naltrexone, Bupropion, and their Metabolites [ Time Frame: Day 11: predose and at multiple time points (up to 23.5 hours) postdose ] [ Designated as safety issue: No ]
  • 9. Percentage of Participants Reporting at least one Treatment-Emergent Adverse Event (TEAE) [ Time Frame: Baseline up to 30 days after the last dose of study drug ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 84
Study Start Date: April 2016
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Nalterxone/Bupropion + Placebo + Moxifloxacin
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.
Drug: Naltrexone HCl/bupropion HCl
Naltrexone HCl/bupropion HCl extended-release tablet.
Other: Placebo
Naltrexone/bupropion placebo-matching tablets.
Drug: Moxifloxacin
Moxifloxacin tablet.
Experimental: Placebo + Moxifloxacin + Naltrexone/Bupropion
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.
Drug: Naltrexone HCl/bupropion HCl
Naltrexone HCl/bupropion HCl extended-release tablet.
Other: Placebo
Naltrexone/bupropion placebo-matching tablets.
Drug: Moxifloxacin
Moxifloxacin tablet.
Experimental: Moxifloxacin + Naltrexone/Bupropion + Placebo
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.
Drug: Naltrexone HCl/bupropion HCl
Naltrexone HCl/bupropion HCl extended-release tablet.
Other: Placebo
Naltrexone/bupropion placebo-matching tablets.
Drug: Moxifloxacin
Moxifloxacin tablet.
Experimental: Naltrexone/Bupropion + Moxifloxacin + Placebo
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.
Drug: Naltrexone HCl/bupropion HCl
Naltrexone HCl/bupropion HCl extended-release tablet.
Other: Placebo
Naltrexone/bupropion placebo-matching tablets.
Drug: Moxifloxacin
Moxifloxacin tablet.
Experimental: Placebo + Naltrexone/Bupropion + Moxifloxacin
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.
Drug: Naltrexone HCl/bupropion HCl
Naltrexone HCl/bupropion HCl extended-release tablet.
Other: Placebo
Naltrexone/bupropion placebo-matching tablets.
Drug: Moxifloxacin
Moxifloxacin tablet.
Experimental: Moxifloxacin + Placebo + Naltrexone/Bupropion
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.
Drug: Naltrexone HCl/bupropion HCl
Naltrexone HCl/bupropion HCl extended-release tablet.
Other: Placebo
Naltrexone/bupropion placebo-matching tablets.
Drug: Moxifloxacin
Moxifloxacin tablet.

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

Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02735603

Locations
United States, Texas
Austin, Texas, United States
Sponsors and Collaborators
Orexigen Therapeutics, Inc
Investigators
Study Director: Medical Director Takeda
  More Information

Responsible Party: Orexigen Therapeutics, Inc
ClinicalTrials.gov Identifier: NCT02735603     History of Changes
Other Study ID Numbers: NaltrexBuprop-1001  U1111-1171-3290 
Study First Received: April 5, 2016
Last Updated: April 28, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Bupropion
Moxifloxacin
Fluoroquinolones
Norgestimate, ethinyl estradiol drug combination
Naltrexone
Bupropion hydrochloride, naltrexone hydrochoride drug combination
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Dopamine Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Dopamine Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Cytochrome P-450 CYP2D6 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Anti-Bacterial Agents
Anti-Infective Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Antineoplastic Agents
Contraceptives, Oral, Combined
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on July 28, 2016