Buprenorphine Disposition and CYP3A

Not Applicable

Completed

• Conditions: Healthy
• Interventions: Drug: Buprenorphine Control; Drug: Buprenorphine + Rifampin; Drug: Buprenorphine + Grapefruit juice; Drug: Buprenorphine + Ketoconazole

• Registration Number: NCT01576575
• Lead Sponsor: Washington University School of Medicine

Brief Summary

To evaluate role of CYP3A in buprenorphine disposition and effect

Detailed Description

Subjects will be studied during a maximum of seven occasions.

Study drugs are intravenous buprenorphine (0.025-0.2 mg infused over 1 hr) and sublingual buprenorphine (2-4 mg), with 1-3 week washout between sessions.

Sessions 1\&2: Control (no pretreatment) - intravenous and sublingual buprenorphine. Some subjects will only undergo session 1 (IV)

Sessions 3\&4: Liver and gut CYP3A induction (rifampin 600 mg daily), intravenous and sublingual buprenorphine

Session 5: Gut only CYP3A inhibition (grapefruit juice the night before), sublingual buprenorphine

Sessions 6\&7: Liver and gut CYP3A inhibition (ketoconazole 400 mg daily), intravenous and sublingual buprenorphine

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2010-06
• Study First Submitted: 2012-04-10
• Study First Submitted QC: 2012-04-11
• Study First Posted: 2012-04-12
• Primary Completion: 2014-03-29
• Study Completion: 2014-03-29
• Results First Submitted: 2018-06-20
• Status Verified: 2020-01
• Results First Submitted QC: 2020-01-08
• Last Update Submitted: 2020-01-08
• Results First Posted: 2020-01-22
• Last Update Posted: 2020-01-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 21

Inclusion Criteria

Each subject must meet all of the following criteria:

1. Male or non-pregnant female volunteer, 18-50 yr old
2. Good general health with no known major medical conditions
3. BMI < 33
4. Provide informed consent

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Exclusion Criteria

Subjects will not be enrolled if any of the following criteria exist:

1. Known history of liver or kidney disease
2. Use of prescription or non-prescription medications, herbals or foods known to be metabolized by or affect CYP3A activity (this includes the use of oral contraceptives).
3. Females who are pregnant or nursing
4. Known history of drug or alcohol addiction (prior or present addiction or addiction treatment)
5. Direct physical access to and routine handling of addicting drugs in the regular course of duty (this is a routine exclusion from studies of drugs with addiction potential)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Healthy males and non-pregnant females	Buprenorphine + Ketoconazole	Subjects will be studied during a maximum of seven occasions. Study drugs are intravenous buprenorphine (0.025-0.2 mg infused over 1 hr) and sublingual buprenorphine (2-4 mg), with 1-3 week washout between sessions. Sessions 1\&2: Control (no pretreatment) - intravenous and sublingual buprenorphine. Some subjects will only undergo session 1 (IV) Sessions 3\&4: Liver and gut CYP3A induction (rifampin 600 mg daily), intravenous and sublingual buprenorphine Session 5: Gut only CYP3A inhibition (grapefruit juice the night before), sublingual buprenorphine Sessions 6\&7: Liver and gut CYP3A inhibition (ketoconazole 400 mg daily), intravenous and sublingual buprenorphine
Healthy males and non-pregnant females	Buprenorphine Control	Subjects will be studied during a maximum of seven occasions. Study drugs are intravenous buprenorphine (0.025-0.2 mg infused over 1 hr) and sublingual buprenorphine (2-4 mg), with 1-3 week washout between sessions. Sessions 1\&2: Control (no pretreatment) - intravenous and sublingual buprenorphine. Some subjects will only undergo session 1 (IV) Sessions 3\&4: Liver and gut CYP3A induction (rifampin 600 mg daily), intravenous and sublingual buprenorphine Session 5: Gut only CYP3A inhibition (grapefruit juice the night before), sublingual buprenorphine Sessions 6\&7: Liver and gut CYP3A inhibition (ketoconazole 400 mg daily), intravenous and sublingual buprenorphine
Healthy males and non-pregnant females	Buprenorphine + Rifampin	Subjects will be studied during a maximum of seven occasions. Study drugs are intravenous buprenorphine (0.025-0.2 mg infused over 1 hr) and sublingual buprenorphine (2-4 mg), with 1-3 week washout between sessions. Sessions 1\&2: Control (no pretreatment) - intravenous and sublingual buprenorphine. Some subjects will only undergo session 1 (IV) Sessions 3\&4: Liver and gut CYP3A induction (rifampin 600 mg daily), intravenous and sublingual buprenorphine Session 5: Gut only CYP3A inhibition (grapefruit juice the night before), sublingual buprenorphine Sessions 6\&7: Liver and gut CYP3A inhibition (ketoconazole 400 mg daily), intravenous and sublingual buprenorphine
Healthy males and non-pregnant females	Buprenorphine + Grapefruit juice	Subjects will be studied during a maximum of seven occasions. Study drugs are intravenous buprenorphine (0.025-0.2 mg infused over 1 hr) and sublingual buprenorphine (2-4 mg), with 1-3 week washout between sessions. Sessions 1\&2: Control (no pretreatment) - intravenous and sublingual buprenorphine. Some subjects will only undergo session 1 (IV) Sessions 3\&4: Liver and gut CYP3A induction (rifampin 600 mg daily), intravenous and sublingual buprenorphine Session 5: Gut only CYP3A inhibition (grapefruit juice the night before), sublingual buprenorphine Sessions 6\&7: Liver and gut CYP3A inhibition (ketoconazole 400 mg daily), intravenous and sublingual buprenorphine

Primary Outcome Measures

Name	Time	Method
Plasma Cmax of Buprenorphine	96 hr

Trial Locations

Locations (1)

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States