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

NCT02745912 | Completed Phase 1

• 2 other identifiers: NaltrexBuprop-1004U1111-1166-8630
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Healthy Subjects

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (4)

• Cmax: Maximum Observed Plasma Concentration for Metformin Following a Single Dose of Metformin Administered Alone

  Day 1: predose and at multiple timepoints (up to 48 hours) post-dose

• Cmax: Maximum Observed Plasma Concentration of Metformin Following a Single Dose of Metformin and multiple Doses of naltrexone/bupropion

  Day 14: predose and at multiple timepoints (up to 48 hours) post-dose

• 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

  Day 1: predose and at multiple timepoints (up to 48 hours) post-dose

• 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

  Day 14: predose and at multiple timepoints (up to 48 hours) post-dose

Secondary Outcomes (4)

• Cmax: Maximum Observed Plasma Concentration of bupropion, naltrexone and their metabolites (6beta-naltrexol, Bupropion, Hydroxybupropion, Threohydrobupropion, and Erythrohydrobupropion) following multiple doses of NB alone

  Day 13 predose and at multiple timepoints (up to 12 hours) post-dose

• Cmax: Maximum Observed Plasma Concentration of bupropion, naltrexone and their metabolites following multiple doses of naltrexone/bupropion and a single dose of metformin

  Day 14: predose and at multiple timepoints (up to 12 hours) post-dose

• 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)

  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

• • Percentage of Participants who Experience at Least one Treatment Emergent Adverse Event (TEAE)

  Day 1 upt to Day 45

Study Arms (1)

Metformin + Naltrexone/Bupropion

EXPERIMENTAL

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; Drug: Metformin

Interventions

Naltrexone/Bupropion DRUG

Naltrexone/Bupropion extended-release tablets.

Metformin + Naltrexone/Bupropion

Metformin DRUG

Metformin immediate-release tablet.

Metformin + Naltrexone/Bupropion

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Is a healthy male or female.
• Is aged 18 to 55 years, inclusive, at signing of informed consent and first dose of study drug.
• 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.
• Has normal renal function (defined as CrCl \>=90 mL/min/1.73 m\^2) at Screening and Check-in (Day -1).
• 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.

You may not qualify if:

• Has known hypersensitivity to metformin, bupropion, naltrexone, or any component of the formulations.
• Has history of seizure of any etiology, or of predisposition to seizures.
• Has history of bulimia.
• Has history of anorexia nervosa.
• 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.
• 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.
• 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.

Sponsors & Collaborators

• Orexigen Therapeutics, Inc: lead

MeSH Terms

Interventions

Naltrexone; Bupropion; Metformin

Intervention Hierarchy (Ancestors)

Naloxone; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Propiophenones; Ketones; Organic Chemicals; Biguanides; Guanidines; Amidines

Study Officials

• Medical Director

  Takeda

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2016
• First Posted: April 20, 2016
• Study Start: April 1, 2016
• Primary Completion: June 1, 2016
• Study Completion: August 1, 2016
• Last Updated: September 29, 2016

Record last verified: 2016-09