Trial Outcomes & Findings for Buprenorphine Disposition and CYP3A (NCT NCT01576575)

NCT ID: NCT01576575

Last Updated: 2020-01-22

Results Overview

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 21 participants
• Primary outcome timeframe: 96 hr
• Results posted on: 2020-01-22

Participant Flow

Participant milestones

Measure	Healthy Volunteers Healthy males and non-pregnant females
Buprenorphine Control STARTED	21
Buprenorphine Control COMPLETED	18
Buprenorphine Control NOT COMPLETED	3
Buprenorphine + Rifampin STARTED	18
Buprenorphine + Rifampin COMPLETED	15
Buprenorphine + Rifampin NOT COMPLETED	3
Buprenorphine + Grapefruit STARTED	15
Buprenorphine + Grapefruit COMPLETED	14
Buprenorphine + Grapefruit NOT COMPLETED	1
Buprenorphine + Ketoconazole STARTED	14
Buprenorphine + Ketoconazole COMPLETED	14
Buprenorphine + Ketoconazole NOT COMPLETED	0

Reasons for withdrawal

Measure	Healthy Volunteers Healthy males and non-pregnant females
Buprenorphine Control Withdrawal by Subject	3
Buprenorphine + Rifampin Withdrawal by Subject	3
Buprenorphine + Grapefruit Withdrawal by Subject	1

Baseline Characteristics

Buprenorphine Disposition and CYP3A

Baseline characteristics by cohort

Measure	Healthy Volunteers n=21 Participants 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
Age, Continuous	27 years STANDARD_DEVIATION 8 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

Adverse Events

Control (no Pretreatment)

Serious events: 0 serious events

Other events: 21 other events

Deaths: 0 deaths

Liver and Gut CYP3A Induction

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Gut Only CYP3A Inhibition

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Liver and Gut CYP3A Inhibition

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Control (no Pretreatment) n=21 participants at risk Sessions 1\&2: Control (no pretreatment) - intravenous and sublingual buprenorphine. Some subjects will only undergo session 1 (IV)	Liver and Gut CYP3A Induction n=18 participants at risk Sessions 3\&4: Liver and gut CYP3A induction (rifampin 600 mg daily), intravenous and sublingual buprenorphine	Gut Only CYP3A Inhibition n=14 participants at risk Session 5: Gut only CYP3A inhibition (grapefruit juice the night before), sublingual buprenorphine	Liver and Gut CYP3A Inhibition n=13 participants at risk Sessions 6\&7: Liver and gut CYP3A inhibition (ketoconazole 400 mg daily), intravenous and sublingual buprenorphine
Gastrointestinal disorders nausea	57.1% 12/21 • Number of events 40 • Up to 96 hours following dosing	72.2% 13/18 • Number of events 39 • Up to 96 hours following dosing	78.6% 11/14 • Number of events 21 • Up to 96 hours following dosing	92.3% 12/13 • Number of events 30 • Up to 96 hours following dosing
General disorders itch	66.7% 14/21 • Number of events 32 • Up to 96 hours following dosing	55.6% 10/18 • Number of events 32 • Up to 96 hours following dosing	78.6% 11/14 • Number of events 16 • Up to 96 hours following dosing	61.5% 8/13 • Number of events 25 • Up to 96 hours following dosing
Nervous system disorders Headache	19.0% 4/21 • Number of events 6 • Up to 96 hours following dosing	11.1% 2/18 • Number of events 3 • Up to 96 hours following dosing	21.4% 3/14 • Number of events 5 • Up to 96 hours following dosing	38.5% 5/13 • Number of events 15 • Up to 96 hours following dosing
Nervous system disorders Dizzyness	19.0% 4/21 • Number of events 15 • Up to 96 hours following dosing	16.7% 3/18 • Number of events 7 • Up to 96 hours following dosing	7.1% 1/14 • Number of events 2 • Up to 96 hours following dosing	7.7% 1/13 • Number of events 2 • Up to 96 hours following dosing

Additional Information

Evan Kharasch MD PhD

Washington University

Phone: 3143628796

Email: kharasch@wustl.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place