Oral Buprenorphine as a Novel Low-dose Induction Strategy for Opioid Use Disorder

Sponsor

Brigham and Women's Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06086275

Collaborator

University of Utah (Other)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

This is a human laboratory-based, randomized, cross-over study in which buprenorphine will be administered to healthy volunteers (n=22) in 3 separate inpatient 2-night visits, at least 1 week apart. At each visit, the participant will receive a single dose buprenorphine, either 0.15mg IV, 8mg PO, or 16mg PO. The order for the first dose administered will be fixed to the IV dose, and the subsequent doses will be randomized and counterbalanced to 8mg or 16mg PO. Participants will be given naltrexone to produce opioid blockade to eliminate the risk for opioid dependence in individuals without OUD. Timed blood samples will be collected up to 24 hours.

Condition or Disease	Intervention/Treatment	Phase
Opioid Use Disorder	Drug: Buprenorphine	Phase 1

Detailed Description

The approach is to conduct a randomized, cross-over trial in a controlled human laboratory setting with healthy volunteers (n=22). After obtaining informed consent, eligible participants will be scheduled for 3 separate two-night test days to receive 0.15mg IV, 8mg PO, or 16mg PO of buprenorphine. The first dose administered will be fixed to an open-label IV dose, and the subsequent doses will be randomized and counterbalanced to 8mg or 16mg PO. Visits will be scheduled at least 1 week apart to allow for washout of drug. One hour prior to receipt of the buprenorphine dose, all participants will be fed a standardized light breakfast. The IV dose will be given after establishing IV access, while the PO doses will be swallowed whole. Participants will also receive oral naltrexone 100mg 24 hours prior to each dosing to provide blockade at the mu-receptor, as well as 50mg PO at the study visit itself prior to receipt of buprenorphine. Timed blood samples will be collected in heparinized Vacutainer tubes via a catheter in the antecubital vein at baseline, and at 0.5, 1, 2, 4, 8, and 24 hours. Samples will be centrifuged and frozen until analysis.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

22 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

All participants will first receive the IV arm in fixed order, in an open-label fashion. Subsequently, participants will be randomized to the two PO.All participants will first receive the IV arm in fixed order, in an open-label fashion. Subsequently, participants will be randomized to the two PO.

Masking:

None (Open Label)

Masking Description:

All portions will be open label

Primary Purpose:

Other

Official Title:

Oral Buprenorphine as a Novel Low-Dose Induction Strategy for Individuals With Opioid Use Disorder

Anticipated Study Start Date :

Jan 1, 2024

Anticipated Primary Completion Date :

Jan 1, 2026

Anticipated Study Completion Date :

Mar 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 8mg PO buprenorphine After the open-label period, the participant will receive 8mg PO, then 16mg PO will be administered in the following visit.	Drug: Buprenorphine At each visit, the participant will receive a single dose of buprenorphine, either 0.15mg IV, 8mg PO, or 16mg PO. The order for the first dose administered will be fixed to the IV dose, and the subsequent doses will be randomized and counterbalanced to 8mg or 16mg PO.
Experimental: 16mg PO buprenorphine After the open-label period, the participant will receive 16mg PO, then 8mg PO will be administered in the following visit.	Drug: Buprenorphine At each visit, the participant will receive a single dose of buprenorphine, either 0.15mg IV, 8mg PO, or 16mg PO. The order for the first dose administered will be fixed to the IV dose, and the subsequent doses will be randomized and counterbalanced to 8mg or 16mg PO.
Experimental: 0.15mg IV Dose The first dose administered will be fixed to an open-label 0.15mg IV dose.	Drug: Buprenorphine At each visit, the participant will receive a single dose of buprenorphine, either 0.15mg IV, 8mg PO, or 16mg PO. The order for the first dose administered will be fixed to the IV dose, and the subsequent doses will be randomized and counterbalanced to 8mg or 16mg PO.

Arm

Intervention/Treatment

Experimental: 8mg PO buprenorphine

After the open-label period, the participant will receive 8mg PO, then 16mg PO will be administered in the following visit.

Drug: Buprenorphine

At each visit, the participant will receive a single dose of buprenorphine, either 0.15mg IV, 8mg PO, or 16mg PO. The order for the first dose administered will be fixed to the IV dose, and the subsequent doses will be randomized and counterbalanced to 8mg or 16mg PO.

Experimental: 16mg PO buprenorphine

After the open-label period, the participant will receive 16mg PO, then 8mg PO will be administered in the following visit.

Drug: Buprenorphine

Experimental: 0.15mg IV Dose

The first dose administered will be fixed to an open-label 0.15mg IV dose.

Drug: Buprenorphine

Outcome Measures

Primary Outcome Measures

Plasma-Concentration Curves (AUC) of Buprenorphine [Baseline, 0.5, 1, 2, 4, 8, and 24 hours after study drug administration.]
The area under the plasma concentration curves (AUC) of buprenorphine will be determined. Timed blood samples will be collected in heparinized Vacutainer tubes via a catheter in the antecubital vein at baseline, and at 0.5, 1, 2, 4, 8, and 24 hours. Samples will be centrifuged and frozen until analysis.

Secondary Outcome Measures

Maximum Plasma Concentration [Baseline, 0.5, 1, 2, 4, 8, and 24 hours after study drug administration.]
Plasma data will be used to calculate maximum plasma concentration (Cmax) for buprenorphine, norbuprenorphine, and their glucuronides.
Time to Maximum Plasma Concentration [Baseline, 0.5, 1, 2, 4, 8, and 24 hours after study drug administration.]
Plasma data will be used to calculate time to maximum plasma concentration (Tmax) for buprenorphine, norbuprenorphine, and their glucuronides.
Volume of Distribution [Baseline, 0.5, 1, 2, 4, 8, and 24 hours after study drug administration.]
Plasma data will be used to calculate volume of distribution (Vd) for buprenorphine, norbuprenorphine, and their glucuronides.
Elimination half-life [Baseline, 0.5, 1, 2, 4, 8, and 24 hours after study drug administration.]
Plasma data will be used to calculate elimination half-life (t1/2) for buprenorphine, norbuprenorphine, and their glucuronides.
Total Clearance [Baseline, 0.5, 1, 2, 4, 8, and 24 hours after study drug administration.]
Plasma data will be used to calculate total clearance (CL) for buprenorphine, norbuprenorphine, and their glucuronides.
Pupil Size [Baseline, 0.5, 1, 2, 4, 8, and 24 hours after study drug administration.]
Pupil size will be measured through visual inspection both before and after buprenorphine dosing to confirm opioid blockade.
The Drug Effects Questionnaire [Baseline, 0.5, 1, 2, 4, 8, and 24 hours after study drug administration.]
To confirm opioid blockade, subjective and objective opioid effects will be measured using previously validated Drug Evaluation Questionnaire (DEQ). The DEQ is a 5-item questionnaire where participants answer questions on a sliding scale from 0-100, where 0 indicates lower levels drug effects and 100 indicates higher levels of drug effects.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

English speaking adults aged 18 years and above
In good physical health as determined by routine medical screening
Prior personal history of opioid use, therapeutic or non-therapeutic

Exclusion Criteria:

DSM-5 diagnosis of any substance use disorder excluding tobacco
Presence of any alcohol, cannabis, or illicit substances on urine toxicology at any study visit
Receiving treatment with opioid analgesic in last 60 days, or anticipate to require opioids during the proposed trial
History of chronic pain
Psychotic disorder, active suicidality or homicidality or any psychiatric condition that impair ability to provide informed consent
History of hypersensitivity or allergy to buprenorphine or naltrexone
Pregnant or breastfeeding
Liver function test greater than 3 times upper normal limit
Receiving medications that are strong or moderate CYP3A4 inducers or inhibitors in the past 30 days

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Brigham and Women's Hospital
University of Utah

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Joji Suzuki, MD, Associate Professor, Brigham and Women's Hospital

ClinicalTrials.gov Identifier:

NCT06086275

Other Study ID Numbers:

2023P002634

First Posted:

Oct 17, 2023

Last Update Posted:

Oct 17, 2023

Last Verified:

Oct 1, 2023

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Keywords provided by Joji Suzuki, MD, Associate Professor, Brigham and Women's Hospital

opioid use disorder

buprenorphine

Additional relevant MeSH terms:

Opioid-Related Disorders

Substance-Related Disorders

Buprenorphine

Study Results

No Results Posted as of Oct 17, 2023