NCT01576575

Brief Summary

To evaluate role of CYP3A in buprenorphine disposition and effect

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
21

participants targeted

Target at P25-P50 for not_applicable healthy

Timeline
Completed

Started Jun 2010

Longer than P75 for not_applicable healthy

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2010

Completed
1.9 years until next milestone

First Submitted

Initial submission to the registry

April 10, 2012

Completed
2 days until next milestone

First Posted

Study publicly available on registry

April 12, 2012

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 29, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 29, 2014

Completed
5.8 years until next milestone

Results Posted

Study results publicly available

January 22, 2020

Completed
Last Updated

January 22, 2020

Status Verified

January 1, 2020

Enrollment Period

3.8 years

First QC Date

April 10, 2012

Results QC Date

June 20, 2018

Last Update Submit

January 8, 2020

Conditions

Healthy

Keywords

buprenorphine CYP3A

Outcome Measures

Primary Outcomes (1)

  • Plasma Cmax of Buprenorphine

    96 hr

Study Arms (1)

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

Drug: Buprenorphine ControlDrug: Buprenorphine + RifampinDrug: Buprenorphine + Grapefruit juiceDrug: Buprenorphine + Ketoconazole

Interventions

Buprenorphine ControlDRUG

Control (no pretreatment) - intravenous and sublingual buprenorphine. Some subjects will only undergo session 1 (IV)

Healthy males and non-pregnant females
Buprenorphine + RifampinDRUG

Liver and gut CYP3A induction (rifampin 600 mg daily), intravenous and sublingual buprenorphine

Healthy males and non-pregnant females
Buprenorphine + Grapefruit juiceDRUG

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

Healthy males and non-pregnant females
Buprenorphine + KetoconazoleDRUG

Liver and gut CYP3A inhibition (ketoconazole 400 mg daily), intravenous and sublingual buprenorphine

Healthy males and non-pregnant females

Eligibility Criteria

Age18 Years - 50 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (3)

  • 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.

    PMID: 378645BACKGROUND

  • 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.

    PMID: 8491067BACKGROUND

  • 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.

    PMID: 7542336BACKGROUND

MeSH Terms

Interventions

BuprenorphineRifampinKetoconazole

Intervention Hierarchy (Ancestors)

MorphinansOpiate AlkaloidsAlkaloidsHeterocyclic CompoundsHeterocyclic Compounds, Bridged-RingHeterocyclic Compounds, 4 or More RingsHeterocyclic Compounds, Fused-RingPhenanthrenesPolycyclic Aromatic HydrocarbonsPolycyclic CompoundsRifamycinsLactams, MacrocyclicMacrocyclic CompoundsPiperazinesHeterocyclic Compounds, 1-Ring

Results Point of Contact

Title
Evan Kharasch MD PhD
Organization
Washington University
kharasch@wustl.edu
3143628796

Study Officials

  • Evan Kharasch, MD, PhD

    Washington University School of Medicine

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
not applicable
Masking
NONE
Purpose
OTHER
Intervention Model
SEQUENTIAL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 10, 2012

First Posted

April 12, 2012

Study Start

June 1, 2010

Primary Completion

March 29, 2014

Study Completion

March 29, 2014

Last Updated

January 22, 2020

Results First Posted

January 22, 2020

Record last verified: 2020-01

Locations

US(1)