Bupropion Stereoselective Disposition and CYP2D6-mediated Drug Interactions in Healthy Volunteers

NCT ID: NCT03420469

Last Updated: 2019-12-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-06-05
• Study Completion Date: 2019-05-01

Brief Summary

Primary objectives:

1. To comprehensively characterize steady state stereoselective pharmacokinetics of bupropion and its primary and secondary metabolites in healthy volunteers

2. To prospectively determine the time course (onset), extent and offset of CYP2D6 inhibition in relation to the pharmacokinetic profiles of bupropion and metabolites.

Conditions

Adverse Effect of Drug Therapy Metabolism Medications (Diagnosis)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Baseline CYP2D6 activity

CYP2D6 activity will be determined using a single oral dose of dextromethorphan (30 mg PO) as a probe drug at baseline (control).

Group Type: EXPERIMENTAL

Bupropion

Intervention Type: DRUG

Phase 1: Baseline CYP2D6 activity, using dextromethorphan (30 mg single dose PO) as a probe drug Phase 2: Single dose bupropion pharmacokinetics and its effect on CYP2D6 activity (determined by dextromethorphan 30 mg single dose PO) Phase 3: Steady state disposition of bupropion and its interaction with CYP2D6 activity (30 mg single dose PO)

CYP2D6 activity with single dose of bupropion

The effect of a single dose of bupropion (150 mg PO) on CYP2D6 activity will be determined using a single oral dose of dextromethorphan (30 mg PO) as a probe drug.

Group Type: EXPERIMENTAL

Bupropion

Intervention Type: DRUG

Phase 1: Baseline CYP2D6 activity, using dextromethorphan (30 mg single dose PO) as a probe drug Phase 2: Single dose bupropion pharmacokinetics and its effect on CYP2D6 activity (determined by dextromethorphan 30 mg single dose PO) Phase 3: Steady state disposition of bupropion and its interaction with CYP2D6 activity (30 mg single dose PO)

CYP2D6 activity after treatment with bupropion to steady sate

CYP2D6 activity will be determined using a single oral dose of dextromethorphan (30 mg PO) as a probe drug after 14 days pretreatment with bupropion (150 mg twice daily PO).

Group Type: EXPERIMENTAL

Bupropion

Intervention Type: DRUG

Phase 1: Baseline CYP2D6 activity, using dextromethorphan (30 mg single dose PO) as a probe drug Phase 2: Single dose bupropion pharmacokinetics and its effect on CYP2D6 activity (determined by dextromethorphan 30 mg single dose PO) Phase 3: Steady state disposition of bupropion and its interaction with CYP2D6 activity (30 mg single dose PO)

Interventions

Bupropion

Phase 1: Baseline CYP2D6 activity, using dextromethorphan (30 mg single dose PO) as a probe drug Phase 2: Single dose bupropion pharmacokinetics and its effect on CYP2D6 activity (determined by dextromethorphan 30 mg single dose PO) Phase 3: Steady state disposition of bupropion and its interaction with CYP2D6 activity (30 mg single dose PO)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male and female (approximately 1:1) volunteers between the age of 18 and 55 years old and within 32% of your ideal body weight.
• Judged healthy without any significant medical condition as determined by and decided from a pre-enrollment screening session that include medical history, laboratory tests such as blood and urine tests, and an electrical tracing of the heart beat (electrocardiogram, EKG).
• Individuals who agree to refrain from taking any prescriptions medications, over-the-counter medications, and herbal, dietary, and alternative supplements that may interact with the metabolism of those study drugs at least 2 weeks prior to the start of the study and until study completion.
• Nonsmoker or individuals willing to refrain from smoking or use of tobacco or marijuana for at least two weeks prior to and until the completion of the study (the entire study lasts for approximately 32 days).
• Willing to commit the time requested for this study

Exclusion Criteria

Subjects will be excluded from the study if they:

• Are underweight (weigh less than 52 kg or 114 lb) or overweight [body mass index (BMI) greater than 32].
• Have laboratory results that do not fall in a healthy range (e.g., blood hemoglobin less than 12.0 mg/dl).
• Have baseline EKG readings that are abnormal that could place the patient at the higher risk as decided by the study medical doctor (MD)
• Have history of intolerance, allergic reactions (e.g. rash) or other forms of hypersensitivities to any of the study medications (dextromethorphan and bupropion).
• Have current alcohol (more than 4 alcoholic drinks per day on a regular basis) or drug abuse.
• Have history or current gastrointestinal (digestive) disorders such as persistent diarrhea or malabsorption that would interfere with the absorption of orally administered drugs
• Have history or current seizures, hypertension and heart disease or any other cardiovascular disorders
• Have history or current psychiatric (mental or brain) disorders (e.g., feeling sad or unhappy, loss of interest in normal activities, worried) such as depression, anxiety, or suicidality or suicide attempts.
• Have significantly compromised liver and/or kidney functions.
• Have participated in a research study involving intensive blood sampling or have donated blood within the past two months
• Are unable or unwilling to stop taking other substances that may interfere with the metabolism of the study drugs (bupropion and dextromethorphan) two weeks prior to and during the entire study period, including prescription medications, over-the-counter medications, herbal or dietary supplements, and alternative medicines.
• Are employees or students under supervision of any of the study investigators.
• Cannot state a good understanding of this study including risks and requirements; are unable to follow the rules of this study.
• Cannot commit the time requested for this study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of General Medical Sciences (NIGMS)

NIH

Sponsor Role: collaborator

Indiana University

OTHER

Sponsor Role: lead

Responsible Party

Zeruesenay Desta

Professor of Medicine, Pharmacology and Toxicology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Indiana Clinical Research Center (ICRC)

Indianapolis, Indiana, United States

Countries

United States

Other Identifiers

1R01GM121707-01A1

Identifier Type: NIH

Identifier Source: org_study_id

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