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To evaluate role of CYP3A in buprenorphine disposition and effect
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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Healthy males and non-pregnant females | Experimental | 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Buprenorphine Control | Drug | Control (no pretreatment) - intravenous and sublingual buprenorphine. Some subjects will only undergo session 1 (IV) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Plasma Cmax of Buprenorphine | 96 hr |
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Inclusion Criteria:
Each subject must meet all of the following criteria:
Exclusion Criteria:
Subjects will not be enrolled if any of the following criteria exist:
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| Name | Affiliation | Role |
|---|---|---|
| Evan Kharasch, MD, PhD | Washington University School of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Washington University School of Medicine | St Louis | Missouri | 63110 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 378645 | Background | Heel RC, Brogden RN, Speight TM, Avery GS. Buprenorphine: a review of its pharmacological properties and therapeutic efficacy. Drugs. 1979 Feb;17(2):81-110. doi: 10.2165/00003495-197917020-00001. | |
| 8491067 | Background | Pickworth WB, Johnson RE, Holicky BA, Cone EJ. Subjective and physiologic effects of intravenous buprenorphine in humans. Clin Pharmacol Ther. 1993 May;53(5):570-6. doi: 10.1038/clpt.1993.72. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Healthy Volunteers | Healthy males and non-pregnant females |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Buprenorphine Control |
|
| ||||||||||||||||||
| Buprenorphine + Rifampin |
| |||||||||||||||||||
| Buprenorphine + Grapefruit |
| |||||||||||||||||||
| Buprenorphine + Ketoconazole |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Healthy Volunteers | 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Plasma Cmax of Buprenorphine | 0 participants analyzed. The PI has left the institution. Sincere efforts were made to contact the PI but were unsuccessful. No study data are available. | Posted | 96 hr |
|
Up to 96 hours following dosing
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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 | Control (no Pretreatment) | Sessions 1&2: Control (no pretreatment) - intravenous and sublingual buprenorphine. Some subjects will only undergo session 1 (IV) |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| nausea | Gastrointestinal disorders | Systematic Assessment | Adverse Event Reporting Description by Arms/Groups are combined as individual results not available. Adverse events all due to buprenorphine not pretreatments |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Evan Kharasch MD PhD | Washington University | 3143628796 | kharasch@wustl.edu |
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| ID | Term |
|---|---|
| D002047 | Buprenorphine |
| D012293 | Rifampin |
| D007654 | Ketoconazole |
| ID | Term |
|---|---|
| D009019 | Morphinans |
| D053610 | Opiate Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
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| Buprenorphine + Rifampin | Drug | Liver and gut CYP3A induction (rifampin 600 mg daily), intravenous and sublingual buprenorphine |
|
| Buprenorphine + Grapefruit juice | Drug | Gut only CYP3A inhibition (grapefruit juice the night before), sublingual buprenorphine |
|
| Buprenorphine + Ketoconazole | Drug | Liver and gut CYP3A inhibition (ketoconazole 400 mg daily), intravenous and sublingual buprenorphine |
|
| 7542336 | Background | Walsh SL, Preston KL, Bigelow GE, Stitzer ML. Acute administration of buprenorphine in humans: partial agonist and blockade effects. J Pharmacol Exp Ther. 1995 Jul;274(1):361-72. |
|
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
Session 5: Gut only CYP3A inhibition (grapefruit juice the night before), sublingual buprenorphine |
| OG003 | Ketoconazole | Sessions 6&7: Liver and gut CYP3A inhibition (ketoconazole 400 mg daily), intravenous and sublingual buprenorphine |
|
| 0 |
| 21 |
| 0 |
| 21 |
| 21 |
| 21 |
| EG001 | Liver and Gut CYP3A Induction | Sessions 3&4: Liver and gut CYP3A induction (rifampin 600 mg daily), intravenous and sublingual buprenorphine | 0 | 18 | 0 | 18 | 15 | 18 |
| EG002 | Gut Only CYP3A Inhibition | Session 5: Gut only CYP3A inhibition (grapefruit juice the night before), sublingual buprenorphine | 0 | 14 | 0 | 14 | 14 | 14 |
| EG003 | Liver and Gut CYP3A Inhibition | Sessions 6&7: Liver and gut CYP3A inhibition (ketoconazole 400 mg daily), intravenous and sublingual buprenorphine | 0 | 13 | 0 | 13 | 13 | 13 |
|
| itch | General disorders | Systematic Assessment | Adverse Event Reporting Description by Arms/Groups are combined as individual results not available. Adverse events all due to buprenorphine not pretreatments |
|
| Headache | Nervous system disorders | Systematic Assessment |
|
| Dizzyness | Nervous system disorders | Systematic Assessment |
|
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| D006572 |
| Heterocyclic Compounds, Bridged-Ring |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D010616 | Phenanthrenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D012294 | Rifamycins |
| D047029 | Lactams, Macrocyclic |
| D047028 | Macrocyclic Compounds |
| D010879 | Piperazines |
| D006573 | Heterocyclic Compounds, 1-Ring |