Pharmacogenetics of Bupropion Metabolism

• ClinicalTrials.gov Identifier: NCT00791869
• Recruitment Status: Completed
• First Posted: November 17, 2008
• Last Update Posted: May 22, 2013
• Sponsor: University of California, San Francisco
• Information provided by (Responsible Party): University of California, San Francisco

Tracking Information

• First Submitted Date: November 14, 2008
• First Posted Date: November 17, 2008
• Last Update Posted Date: May 22, 2013
• Study Start Date: June 2008
• Actual Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 20, 2013)

Area under the plasma concentration versus time curve (AUC) for bupropion [ Time Frame: 0, 4, 8, 12, 16,24 hours from steady state ]

Subjects took bupropion daily for 7 days as outpatients prior to the study day to allow them to reach steady state concentrations of bupropion and its metabolites. The time frame shown is measured from 08:00 on the morning of inpatient admission.

• Original Primary Outcome Measures: Not Provided
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Pharmacogenetics of Bupropion Metabolism
• Official Title: Pharmacogenetics of Bupropion Metabolism
• Brief Summary: The aim of the investigators research is to see if variants in a particular gene (named CYP2B6) affect how the body metabolizes (breaks down) certain medications, including the drug bupropion. Bupropion is widely used in the treatment of depression and for helping people quit smoking. Genes are portions of DNA that code for particular proteins in the body. The investigators are studying the gene that codes for a protein called CYP2B6. Differences in the structure of the gene are called variants and may mean that a person metabolizes a drug faster or slower than a person with a different variant.

Detailed Description

Bupropion is widely used in the treatment of depression and for smoking cessation. It's most abundant metabolite, hydroxybupropion, may be responsible for most of the therapeutic effect of bupropion under conditions of long term dosing. Because the primary enzyme involved in metabolism of bupropion to hydroxybupropion is the liver enzyme CYP2B6, we propose to study the effect of different CYP2B6 genotypes on the metabolism of bupropion. These data will guide the use of genotypes as a surrogate for measuring drug blood levels in studying genetic determinants of outcomes for bupropion treatment.

A minimum of Forty-four subjects with 4 different CYP2B6 genotypes will participate in a 7-day study in which they take bupropion as outpatients for 6 days (to achieve steady state drug levels) and then come to the San Francisco General Hospital (SFGH) Clinical Research Center for a 1-day admission during which multiple blood and urine samples will be collected for pharmacokinetic analysis.

• Study Type: Observational
• Study Design: Observational Model: Case-Only; Time Perspective: Cross-Sectional
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: Healthy subjects with selected CYP2B6 genotypes.

Condition

• Metabolism
• Pharmacokinetics

• Intervention: Not Provided
• Study Groups/Cohorts: Not Provided
• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 20, 2013): 43
• Original Estimated Enrollment (submitted: November 14, 2008): 59
• Actual Study Completion Date: November 2010
• Actual Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Age: 18 - 65 years
• Gender: Either
• Ethnic/Racial Group: Any
• Smoking Status: Both smokers and non-smokers are eligible
• CYP2B6 genotype: CYP2B6 *1/*1 (11 subjects); *4, *5 and *6 alleles (11 each) [44 subjects total] Up to 15 additional subjects may be studied with genotypes that do not fall into one of the primary groups.

Exclusion Criteria:

• Medical: Exclude most any chronic illness requiring regular medication.
• Cardiac: History of angina or other serious heart disease; ECG abnormalities on screening.
• Hypertension: screening visit BP of 150/95 or more after 5 min rest
• Respiratory: Asthma - acceptable if in remission, otherwise exclude.
• Systemic: "Morbidly Obese" Exclude if BMI > 35
• Diabetes: By history
• Chronic Active Hepatitis: By history; elevated Liver Function Tests
• Cancers: By history
• Pregnancy/breastfeeding: By history; positive urine pregnancy test
• Seizures: individuals with a history of seizures will be excluded (risk factor for bupropion-induced seizures)
• Eating Disorders: individuals with a history of eating disorders will be excluded (risk factor for bupropion-induced seizures)
• Head Trauma: individuals with a history of head trauma will be excluded (risk factor for bupropion-induced seizures)
• Other tobacco users (pipe, cigar, chewing tobacco, snuff users
• Medications/Supplements: General Exclusion = "any regular oral and/or prescription drug use"; current use of oral contraceptives or other female hormones.
• Drug/alcohol use: no alcohol abuse by history, no regular recreational drug use, any intravenous drug abuse, recent history of Treatment program

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00791869
• Other Study ID Numbers: H133-31868; U01DA020830 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: University of California, San Francisco
• Study Sponsor: University of California, San Francisco
• Collaborators: Not Provided

Investigators

• Principal Investigator: Neal L Benowitz, MD; University of California, San Francisco

• PRS Account: University of California, San Francisco
• Verification Date: May 2013