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| ID | Type | Description | Link |
|---|---|---|---|
| HUM00081894 | Other Identifier | UM IRBMED |
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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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| generic bupropion IR75 | Active Comparator | One oral dose of generic bupropion IR75 |
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| generic bupropion IR100 | Active Comparator | One oral dose of generic bupropion IR100 |
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| generic bupropion SR100 | Active Comparator | One oral dose of generic bupropion SR100 |
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| generic bupropion SR150 | Active Comparator | One oral dose of generic bupropion SR150 |
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| generic bupropion XL150 | Active Comparator | One oral dose of generic bupropion XL150 |
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| generic bupropion XL300 | Active Comparator | One oral dose of generic bupropion XL300 |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| 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 |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Duxin Sun, PhD | University of Michigan | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Michigan | Ann Arbor | Michigan | 48109-2700 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | IR75, IR200, SR100, SR150, XL150, XL300 | Participants were randomized to receive one pill each of IR 75, IR 100, SR 100, SR 150, XL 150 and XL 300,in randomized order at six time points. Given the large number of possible sequence combinations, participants are reported as a single Participant Flow Arm with Milestones used to indicate how many participants received each intervention |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | IR 75, IR 100, SR 100, SR 150, XL 150 and XL 300 | Participants were randomized to receive one pill each of IR 75, IR 100, SR 100, SR 150, XL 150 and XL 300,in randomized order at six time points. Given the large number of possible sequence combinations, participants are reported as a single Participant Flow Arm with Milestones used to indicate how many participants received each intervention |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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). | Posted | Mean | Standard Deviation | h*nanogram/milliliter | 4 days |
|
Varied per person from 3 months to 10 months based on their randomization sequence and the time that it took to complete all phases of the study with washout between each formulation.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | IR 75, IR 100, SR 100, SR 150, XL 150 and XL 300 | Participants were randomized to receive one pill each of IR 75, IR 100, SR 100, SR 150, XL 150 and XL 300,in randomized order at six time points. Given the large number of possible sequence combinations, participants are reported as a single Participant Flow Arm with Milestones used to indicate how many participants received each intervention |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | Systematic Assessment |
The small study sample size may have masked the contribution of pharmacogenetics to bupropion metabolism.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Duxin Sun | University of Michigan | 734-763-9783 | pharmacy.research@umich.edu |
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| ID | Term |
|---|---|
| D003863 | Depression |
| ID | Term |
|---|---|
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
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| ID | Term |
|---|---|
| D016642 | Bupropion |
| ID | Term |
|---|---|
| D011427 | Propiophenones |
| D007659 | Ketones |
| D009930 | Organic Chemicals |
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| 4 days |
| Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| OG001 | Generic Bupropion IR100 | One oral dose of generic bupropion IR100 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. |
| OG002 | Generic Bupropion SR100 | One oral dose of generic bupropion SR100 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. |
| OG003 | Generic Bupropion SR150 | One oral dose of generic bupropion SR150 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. |
| OG004 | Generic Bupropion XL150 | One oral dose of generic bupropion XL150 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. |
| OG005 | Generic Bupropion XL300 | One oral dose of generic bupropion XL300 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. |
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| Secondary | 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. | Posted | Mean | Standard Error | nanogram/milliliter | 4 days |
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| 0 |
| 34 |
| 0 |
| 34 |
| 10 |
| 34 |
| Peripheral vision loss | Eye disorders | Systematic Assessment | Briefly experienced loss of peripheral vision in right eye for approximately 30 minutes 6 days after dose. Full vision came back and participant did not experience anything out of the ordinary before or since resolution of vision loss. |
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| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Dizzyness | Nervous system disorders | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | Systematic Assessment | Rash on both arms following completion of phase six of the study. Rash was located near site of blood draws on arms. |
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