Pharmacokinetic Study of Bupropion Hydrochloride Products With Different Release Patterns

NCT02078180 | Completed Phase 4 Results

• 2 other identifiers: HHSF223201310164CHUM00081894
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

The objectives of this project are to determine if the bioavailability and release pattern of bupropion HCl products differ and if the genotype of the metabolic enzymes affects the saturation of intestinal enzymes with different dose strengths within one product line. Findings from this project will help the FDA Center for Drug Evaluation and Research's (CDER) Office of Generic Drugs improve policy development and review practice in the future for similar products, e.g. extended release oral drug products being metabolized in the gut wall and having multiple strengths. Aim 1: To compare the pharmacokinetics of bupropion and its metabolites in plasma in healthy individuals when they ingest different strengths of bupropion (75-300 mg) with variable release profiles (IR vs XL vs SR) in GI tract. Working hypothesis: Variation in release rate and mechanism of bupropion formulations in gastrointestinal (GI) tract will impact metabolism and saturation of bupropion in GI tract, which will generate different concentration of bupropion and its metabolites in plasma. Aim 2: To investigate pharmacogenomics of CYP 2B6 that influences metabolism, saturation, and pharmacokinetics of bupropion Working hypothesis: The gain of function of CYP2B6 variants (allele \*4 and \*22) in patients will increase the metabolism of bupropion in the GI tract and liver, reduce both local concentration and plasma concentration of bupropion, and thus cause non-bioequivalence when bupropion is released earlier in GI tract

Conditions

Depression

Outcome Measures

Primary Outcomes (1)

• Comparision of the Buproprion Area Under the Concentration Time Curve (AUC) From Time 0 to 96 Hours by Type of Formulation and Dosage

  Each formulation of buproprion has a different rate of release. Some release the drug immediately while others release the drug slowly. We will compare the exposure of buproprion by formulation and dose by looking at the area under the concentration time curve. The area under the concentration time curve is a mathematical way of looking at drug exposure in the body. The reported values are AUC (0-96 hours).

  4 days

Secondary Outcomes (1)

• Comparision of the Buproprion Maximum Concentration (Cmax) by Type of Formulation and Dosage

  4 days

Study Arms (6)

generic bupropion IR75

ACTIVE COMPARATOR

One oral dose of generic bupropion IR75

Drug: generic bupropion

generic bupropion IR100

ACTIVE COMPARATOR

One oral dose of generic bupropion IR100

Drug: generic bupropion

generic bupropion SR100

ACTIVE COMPARATOR

One oral dose of generic bupropion SR100

Drug: generic bupropion

generic bupropion SR150

ACTIVE COMPARATOR

One oral dose of generic bupropion SR150

Drug: generic bupropion

generic bupropion XL150

ACTIVE COMPARATOR

One oral dose of generic bupropion XL150

Drug: generic bupropion

generic bupropion XL300

ACTIVE COMPARATOR

One oral dose of generic bupropion XL300

Drug: generic bupropion

Interventions

generic bupropion DRUG

We are comparing different formulations of bupropion that release this drug at different rates. The abbreviation IR75 means immediate release and the number is the dose in mg. The other abbreviations represent SR for sustained-release and XL for extended release, which release the drug slower than the IR formulation.

Also known as: Wellbutrin

generic bupropion IR100; generic bupropion IR75; generic bupropion SR100; generic bupropion SR150; generic bupropion XL150; generic bupropion XL300

Eligibility Criteria

• Age: 25 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy volunteers 25 to 55 years old.
• Volunteers have a Body Mass Index (BMI), calculated from the ratio of height and weight, within a range of 18.5 to 35.
• Willing to be medication and supplement free 2 weeks prior to beginning study, and throughout the study. All forms of birth control are okay.

You may not qualify if:

• Individuals unwilling or unable to comply with the study protocol (e.g. unable to remain medication or supplement free during the study).
• Individuals unwilling or unable to take bupropion or have an allergy to bupropion
• Any medical or surgical conditions which might significantly alter bupropion absorption (e.g., history of malabsorption, liver disease, gastric bypass surgery )
• Individuals with a history of psychiatric or neurological illness, including seizure disorders
• Nicotine dependence
• Alcohol dependence
• Pregnant or nursing women

Sponsors & Collaborators

• University of Michigan: lead

Study Sites (1)

University of Michigan

Ann Arbor, Michigan, 48109-2700, United States

Location

MeSH Terms

Conditions

Depression

Interventions

Bupropion

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Propiophenones; Ketones; Organic Chemicals

Limitations and Caveats

The small study sample size may have masked the contribution of pharmacogenetics to bupropion metabolism.

Results Point of Contact

• Title: Dr. Duxin Sun
• Organization: University of Michigan

pharmacy.research@umich.edu

734-763-9783

Study Officials

• Duxin Sun, PhD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pharmaceutical Sciences

Study Record Dates

• First Submitted: February 28, 2014
• First Posted: March 5, 2014
• Study Start: April 1, 2014
• Primary Completion: November 1, 2016
• Study Completion: November 1, 2016
• Last Updated: October 6, 2017
• Results First Posted: October 6, 2017

Record last verified: 2017-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)