Pharmacokinetic Study of Bupropion Hydrochloride Products With Different Release Patterns

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

Study Overview

• Status: Completed
• Conditions: Depression
• Intervention / Treatment: Drug: generic bupropion

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-2700
      • University of Michigan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: generic bupropion IR75; One oral dose of generic bupropion IR75	Drug: generic bupropion; 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.; Other Names: Wellbutrin
Active Comparator: generic bupropion IR100; One oral dose of generic bupropion IR100	Drug: generic bupropion; 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.; Other Names: Wellbutrin
Active Comparator: generic bupropion SR100; One oral dose of generic bupropion SR100	Drug: generic bupropion; 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.; Other Names: Wellbutrin
Active Comparator: generic bupropion SR150; One oral dose of generic bupropion SR150	Drug: generic bupropion; 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.; Other Names: Wellbutrin
Active Comparator: generic bupropion XL150; One oral dose of generic bupropion XL150	Drug: generic bupropion; 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.; Other Names: Wellbutrin
Active Comparator: generic bupropion XL300; One oral dose of generic bupropion XL300	Drug: generic bupropion; 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.; Other Names: Wellbutrin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparision of the Buproprion Maximum Concentration (Cmax) 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 maximum concentration. The maximum concentration depends on the rate of drug release and so looking at this value can help us compare differences between formulation.	4 days

Collaborators and Investigators

• Sponsor: University of Michigan
• Investigators: Principal Investigator: Duxin Sun, PhD, University of Michigan

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): November 1, 2016
• Study Completion (Actual): November 1, 2016

Study Registration Dates

• First Submitted: February 28, 2014
• First Submitted That Met QC Criteria: March 4, 2014
• First Posted (Estimate): March 5, 2014

Study Record Updates

• Last Update Posted (Actual): October 6, 2017
• Last Update Submitted That Met QC Criteria: September 1, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Depression; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Dopamine Agents; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Dopamine Uptake Inhibitors; Bupropion
• Other Study ID Numbers: HHSF223201310164C; HUM00081894 (Other Identifier: UM IRBMED)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO