HealthyNCT01576575

Buprenorphine Disposition and CYP3A

A study testing Buprenorphine + Rifampin, Buprenorphine + Grapefruit juice and Buprenorphine + Ketoconazole in people with Healthy, run by Washington University School of Medicine at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

To evaluate role of CYP3A in buprenorphine disposition and effect Read more about this study

Who is it for?: Ages 18 to 50 yearsHealthy volunteers can take part
Conditions the study is for: Healthy
What is being tested?: Buprenorphine + Rifampin, Buprenorphine + Grapefruit juice and Buprenorphine + Ketoconazole
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 21 participants
Where: 1 siteUnited States
Study dates: Jun 2010to 29 Mar 2014
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 50 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Each subject must meet all of the following criteria:
Male or non-pregnant female volunteer, 18-50 yr old
Good general health with no known major medical conditions
BMI < 33
Provide informed consent

Who cannot join

Subjects will not be enrolled if any of the following criteria exist:
Known history of liver or kidney disease
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).
Females who are pregnant or nursing
Known history of drug or alcohol addiction (prior or present addiction or addiction treatment)
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)

Trial locations and contacts

1 site in 1 country.

United States1 site

Washington University School of Medicine
St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: Influence of CYP3A Modulation on Buprenorphine Disposition and Clinical Effects

To evaluate role of CYP3A in buprenorphine disposition and effect

Read the 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

Conditions: Healthy
Being tested: Buprenorphine Control, Buprenorphine + Rifampin, Buprenorphine + Grapefruit juice, Buprenorphine + Ketoconazole
Keywords: buprenorphine CYP3A

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Buprenorphine ControlDrug
Control (no pretreatment) - intravenous and sublingual buprenorphine. Some subjects will only undergo session 1 (IV)
Buprenorphine + RifampinDrug
Liver and gut CYP3A induction (rifampin 600 mg daily), intravenous and sublingual buprenorphine
Buprenorphine + Grapefruit juiceDrug
Gut only CYP3A inhibition (grapefruit juice the night before), sublingual buprenorphine
Buprenorphine + KetoconazoleDrug
Liver and gut CYP3A inhibition (ketoconazole 400 mg daily), intravenous and sublingual buprenorphine

Study groups in NCT01576575
Study group	Role	What they receive
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 Receives: Drug: Buprenorphine Control; Drug: Buprenorphine + Rifampin; Drug: Buprenorphine + Grapefruit juice; Drug: Buprenorphine + Ketoconazole

What is being measured

The primary outcome is the main question the study is designed to answer.

Plasma Cmax of Buprenorphine
Measured: 96 hr

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 201029 Mar 2014

First posted12 Apr 2012 (estimated)
Study startJun 2010
Primary completion29 Mar 2014
Study completion29 Mar 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for HealthyStudies of the same condition, open and under way.
More trials run by Washington University School of MedicineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Other
Intervention model: Sequential
Masking: None (open label)
Enrolment: 21 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01576575
Sponsor's protocol ID: 201104146
Status last verified: Jan 2020
First submitted: 10 Apr 2012
Last updated: 22 Jan 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

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.
PubMed 378645
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.
PubMed 8491067
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.
PubMed 7542336

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 22 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Influence of CYP3A Modulation on Buprenorphine Disposition and Clinical Effects
ClinicalTrials.gov ID: NCT01576575
Acronym / sponsor ID: 201104146
Conditions: Healthy
Keywords: buprenorphine CYP3A
Study type: Interventional
Recruitment status: Completed
Enrolment: 21 participants (actual)
Lead sponsor: Washington University School of MedicineUniversity, hospital or other
Study start: Jun 2010
Primary completion: 29 Mar 2014 (actual)
Study completion: 29 Mar 2014 (actual)
First posted: 12 Apr 2012 (estimated)
Results: Posted 22 Jan 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Other
Intervention model: Sequential
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Healthy males and non-pregnant females	Experimental	Drug: Buprenorphine Control, Drug: Buprenorphine + Rifampin, Drug: Buprenorphine + Grapefruit juice, Drug: Buprenorphine + KetoconazoleSubjects 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

Who may qualify

Ages: 18 to 50 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (5 listed)

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

Key exclusion criteria (6 listed)

Known history of liver or kidney disease
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).
Females who are pregnant or nursing
Known history of drug or alcohol addiction (prior or present addiction or addiction treatment)
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)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Buprenorphine ControlControl (no pretreatment) - intravenous and sublingual buprenorphine. Some subjects will only undergo session 1 (IV)	Drug	Healthy males and non-pregnant females
Buprenorphine + RifampinLiver and gut CYP3A induction (rifampin 600 mg daily), intravenous and sublingual buprenorphine	Drug	Healthy males and non-pregnant females
Buprenorphine + Grapefruit juiceGut only CYP3A inhibition (grapefruit juice the night before), sublingual buprenorphine	Drug	Healthy males and non-pregnant females
Buprenorphine + KetoconazoleLiver and gut CYP3A inhibition (ketoconazole 400 mg daily), intravenous and sublingual buprenorphine	Drug	Healthy males and non-pregnant females

Primary outcome

Plasma Cmax of Buprenorphine
Time frame: 96 hr

Results and safety

Results posted to the registry on 22 Jan 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Healthy Volunteers	21	18

Primary outcome: Plasma Cmax of Buprenorphine

Time frame: 96 hr

Population analysed: 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.

Adverse events

Time frame: Up to 96 hours following dosing. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Control (no Pretreatment)	0 of 21 (0%)	21 of 21 (100%)	0 of 21
Liver and Gut CYP3A Induction	0 of 18 (0%)	15 of 18 (83.3%)	0 of 18
Gut Only CYP3A Inhibition	0 of 14 (0%)	14 of 14 (100%)	0 of 14
Liver and Gut CYP3A Inhibition	0 of 13 (0%)	13 of 13 (100%)	0 of 13

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 378645Heel 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.
Background: PubMed 8491067Pickworth 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.
Background: PubMed 7542336Walsh 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Evan Kharasch, MD, PhD principal investigator

Washington University School of Medicine

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Plasma Cmax of Buprenorphine (time frame: 96 hr). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01576575, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2020.