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Study to Evaluate the Effect of Naltrexone and Bupropion Combination on the Pharmacokinetics of Metformin in Healthy Participants

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Orexigen Therapeutics, Inc
ClinicalTrials.gov Identifier:
NCT02745912
First received: April 18, 2016
Last updated: September 27, 2016
Last verified: September 2016
  Purpose
The purpose of this study is to determine the effect of multiple oral doses of naltrexone/bupropion on the pharmacokinetics (PK) of a single oral dose of metformin.

Condition Intervention Phase
Healthy Subjects
Drug: Naltrexone/Bupropion
Drug: Metformin
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: A Phase 1, Open-Label, Sequential Design Study to Evaluate the Potential Effect of Multiple Oral Doses of Extended-Release Combination of Naltrexone and Bupropion on the Pharmacokinetics of a Single Oral Dose of Metformin in Healthy Subjects

Resource links provided by NLM:


Further study details as provided by Orexigen Therapeutics, Inc:

Primary Outcome Measures:
  • Cmax: Maximum Observed Plasma Concentration for Metformin Following a Single Dose of Metformin Administered Alone [ Time Frame: Day 1: predose and at multiple timepoints (up to 48 hours) post-dose ] [ Designated as safety issue: No ]
  • Cmax: Maximum Observed Plasma Concentration of Metformin Following a Single Dose of Metformin and multiple Doses of naltrexone/bupropion [ Time Frame: Day 14: predose and at multiple timepoints (up to 48 hours) post-dose ] [ Designated as safety issue: No ]
  • AUC(0-inf): Area Under the Plasma Concentration-time Curve from Time 0 to Infinity of Metformin Following a Single Dose of Metformin Administered Alone [ Time Frame: Day 1: predose and at multiple timepoints (up to 48 hours) post-dose ] [ Designated as safety issue: No ]
  • AUC(0-inf): Area Under the Plasma Concentration-time Curve from Time 0 to Infinity of Metformin Following a Single Dose of Metformin and Multiple Doses of naltrexone/bupropion [ Time Frame: Day 14: predose and at multiple timepoints (up to 48 hours) post-dose ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Cmax: Maximum Observed Plasma Concentration of bupropion, naltrexone and their metabolites (6beta-naltrexol, Bupropion, Hydroxybupropion, Threohydrobupropion, and Erythrohydrobupropion) following multiple doses of NB alone [ Time Frame: Day 13 predose and at multiple timepoints (up to 12 hours) post-dose ] [ Designated as safety issue: No ]
  • Cmax: Maximum Observed Plasma Concentration of bupropion, naltrexone and their metabolites following multiple doses of naltrexone/bupropion and a single dose of metformin [ Time Frame: Day 14: predose and at multiple timepoints (up to 12 hours) post-dose ] [ Designated as safety issue: No ]
  • AUC(0-tau): Area Under the Plasma Concentration-time Curve during a dosing interval for upropion, naltrexone and their metabolites (6beta-naltrexol, Bupropion, Hydroxybupropion, Threohydrobupropion, and Erythrohydrobupropion) [ Time Frame: Day 13: predose and at multiple timepoints (up to 12 hours) post-dose for naltrexone/buprop alone, Day 14: predose and at multiple timepoints (up to 12 hours) post-dose, Day 14: predose and at multiple timepoints (up to 48 hours) post-dose ] [ Designated as safety issue: Yes ]
  • • Percentage of Participants who Experience at Least one Treatment Emergent Adverse Event (TEAE) [ Time Frame: Day 1 upt to Day 45 ] [ Designated as safety issue: Yes ]

Enrollment: 30
Study Start Date: April 2016
Study Completion Date: August 2016
Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Metformin + Naltrexone/Bupropion
Metformin (850 mg, immediate release tablet, orally, once on Day 1 and Day 14) naltrexone/bupropion (8/90 mg/mg, extended-release tablets, orally, twice daily from Day 3 through Day 5 and 16/180 mg/mg, twice daily from Day 6 through Day 15.
Drug: Naltrexone/Bupropion
Naltrexone/Bupropion extended-release tablets.
Drug: Metformin
Metformin immediate-release tablet.

Detailed Description:

The drug being tested in this study is naltrexone HCl and bupropion HCl Extended- Release fixed dose combination (NB) . This study will evaluate the potential effect of multiple oral doses of extended-release combination of naltrexone/bupropion on the PK of a single oral dose of metformin in healthy participants with normal renal function (defined as creatinine clearance [CrCl] greater than equal to [>=] 90 milliliter per minute [mL/min]/1.73 meter square [m^2]).

The study will enroll approximately 30 participants. Participants will receive:

Metformin 850 mg as a single dose alone and in combination with multiple doses of Naltrexone/Bupropion Naltrexone 8 mg/Bupropion 90 mg + Naltrexone 16 mg/Bupropion 180 mg as multiple doses alone and in combination with a single dose of metformin

All participants will be asked to take 1 tablet of metformin in the morning on Day 1 and Day 14, 1 tablet of naltrexone/bupropion twice daily from Day 3 through Day 5, and 2 tablets of naltrexone/bupropion twice daily from Day 6 through Day 15.

This single center trial will be conducted in the United States. The overall time to participate in this study is 73 days. Participants will be admitted on Day -1 (check in) and remain confined to the clinic until Day 16 and will be contacted by telephone 30 (±2) days after last dose of study drug for a follow-up assessment. Serial blood samples will be collected for PK assessments. Safety will be monitored throughout the study.

  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 40.0 kilogram per square meter (kg/m^2), inclusive, at Screening.
  4. Has normal renal function (defined as CrCl >=90 mL/min/1.73 m^2) at Screening and Check-in (Day -1).
  5. A female subject of childbearing potential* who is sexually active with a nonsterilized* male partner agrees to use adequate contraception* from signing of informed consent throughout the duration of the study and for 12 weeks after the last dose of study drug.

Exclusion Criteria:

  1. Has known hypersensitivity to metformin, bupropion, naltrexone, or any component of the formulations.
  2. Has history of seizure of any etiology, or of predisposition to seizures.
  3. Has history of bulimia.
  4. Has history of anorexia nervosa.
  5. Has resting heart rate outside the normal range of 45 to 100 beats per minutes at Screening or Check-in (Day -1) and confirmed by a repeat measurement approximately 30 minutes following the initial measurement.
  6. Has orthostatic blood pressure >=25 millimeter of mercury (mm Hg) at Screening or Check-in (Day -1) and confirmed by a repeat measurement approximately 30 minutes following the initial measurement.
  7. Has sustained supine systolic blood pressure >=140 mm Hg or less than equal to (<=) 90 mm Hg or a diastolic blood pressure >=90 mm Hg or <=50 mm Hg at Screening or Check-in (Day -1) and confirmed by a repeat measurement approximately 30 minutes following the initial measurement.
  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: NCT02745912

Sponsors and Collaborators
Orexigen Therapeutics, Inc
Investigators
Study Director: Medical Director Takeda
  More Information

Responsible Party: Orexigen Therapeutics, Inc
ClinicalTrials.gov Identifier: NCT02745912     History of Changes
Other Study ID Numbers: NaltrexBuprop-1004  U1111-1166-8630 
Study First Received: April 18, 2016
Last Updated: September 27, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Orexigen Therapeutics, Inc:
Drug Therapy

Additional relevant MeSH terms:
Metformin
Naltrexone
Bupropion
Bupropion hydrochloride, naltrexone hydrochoride drug combination
Hypoglycemic Agents
Physiological Effects of Drugs
Narcotic Antagonists
Sensory System Agents
Peripheral Nervous System Agents
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
Cytochrome P-450 CYP2D6 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Anti-Obesity Agents

ClinicalTrials.gov processed this record on December 02, 2016