Healthy
Conditions
Keywords
buprenorphine CYP3A
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
Interventions
DRUGBuprenorphine Control
Control (no pretreatment) - intravenous and sublingual buprenorphine. Some subjects will only undergo session 1 (IV)
DRUGBuprenorphine + Rifampin
Liver and gut CYP3A induction (rifampin 600 mg daily), intravenous and sublingual buprenorphine
DRUGBuprenorphine + Grapefruit juice
Gut only CYP3A inhibition (grapefruit juice the night before), sublingual buprenorphine
DRUGBuprenorphine + Ketoconazole
Liver and gut CYP3A inhibition (ketoconazole 400 mg daily), intravenous and sublingual buprenorphine
Sponsors
Washington University School of Medicine
Study design
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
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
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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Plasma Cmax of Buprenorphine | 96 hr |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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 | 21 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Buprenorphine Control | Withdrawal by Subject | 3 |
| Buprenorphine + Grapefruit | Withdrawal by Subject | 1 |
| Buprenorphine + Rifampin | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Healthy Volunteers |
|---|---|
| Age, Continuous | 27 years STANDARD_DEVIATION 8 |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 18 | 0 / 14 | 0 / 13 |
| other Total, other adverse events | 21 / 21 | 15 / 18 | 14 / 14 | 13 / 13 |
| serious Total, serious adverse events | 0 / 21 | 0 / 18 | 0 / 14 | 0 / 13 |
Outcome results
Primary
Plasma Cmax of Buprenorphine
Time frame: 96 hr
Population: 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.