Extended-release Buprenorphine as a Novel Low-dose Induction Strategy

This is a clinical trial to characterize the safety and pharmacokinetics of using extended-release buprenorphine (XR-BUP) as a novel low-dose buprenorphine induction strategy. Individuals with a diagnosis of Opioid Use Disorder (OUD) (n=30) will be admitted to an inpatient unit to complete study procedures over the course of 3 days. Participants will receive fentanyl to prevent the emergence of withdrawal. Each participant will then receive a single injection of XR-BUP after which study staff will monitor for any precipitated withdrawal.

Study Overview

• Status: Recruiting
• Conditions: Opioid Use Disorder
• Intervention / Treatment: Drug: Extended-release Buprenorphine

Detailed Description

The approach is to conduct a single ascending dose trial in a controlled human laboratory setting with individuals with a diagnosis of OUD (n=30) actively using illicit fentanyl. After obtaining informed consent and establishing eligibility, 10 participants will be scheduled for an inpatient visit lasting 3 days, 2 nights and receive XR-BUP when not yet experiencing any opioid withdrawal. Participants will receive fentanyl to prevent the emergence of withdrawal, and on the following morning, receive XR-BUP 16mg in single-blind fashion. If at least 90% successfully complete induction (success defined as experiencing no precipitated withdrawal) with the 16mg dose, then we will proceed with 10 more participants to receive the 24mg dose. If at least 90% successfully complete induction the 24mg dose, then we will proceed with 10 more participants to the 32mg dose. 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, 6, 8, 12, and 24 hours after the XR-BUP injection.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Joji Suzuki; Phone Number: 6177325752; Email: jsuzuki2@bwh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02118-5605
      • Recruiting
      • Brigham and Women's Hospital
      • Contact: Anika Clinical Research Coordinator; Phone Number: 617-525-0676; Email: akopczynski@bwh.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• English speaking adults aged 18 and above.
• diagnosis of opioid use disorder.
• Self-reporting use of illicit opioids in >21 days in the prior 30 days.
• Provide urine toxicology testing positive for fentanyl at baseline.

Exclusion Criteria:

• Seeking medication treatment for opioid use disorder with sublingual buprenorphine or methadone.
• Received buprenorphine or methadone treatment in prior 30 days.
• Current diagnosis of alcohol or sedative/hypnotic use disorder.
• Positive urine drug screen for benzodiazepines, alcohol and or methadone.
• Physical dependence on alcohol or sedative/hypnotics.
• Psychotic disorder, active suicidality or homicidally or any psychiatric condition that impair ability to provide informed consent.
• Have a history or diagnosis of Intracranial mass/bleed, seizure disorder, liver cirrhosis, renal failure, obstructive lung disease, hyperthyroidism, narrow-angle glaucoma, valvular heart disease, cardiac arrhythmias, heart failure.
• Recent (within 6 months) head trauma, stroke, or myocardial infarction
• Requiring treatment with opioids for acute or chronic pain.
• History of hypersensitivity or allergy to buprenorphine or fentanyl.
• Pregnant or breastfeeding.
• Liver function test greater than 3 times upper normal limit.
• Receiving medications that are strong or moderate CYP34A inducers or inhibitors (including but not limited to ketoconazole, itraconazole, clarithromycin, fluconazole, erythromycin), in the past 30 days.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 16mg Extended-Release Buprenorphine; The first 10 participants will receive XR-BUP 16mg in single-blind fashion.	Drug: Extended-release Buprenorphine; The study is a single-blind, fixed-order, dose-escalation designed trial in an inpatient setting with individuals with a DSM-5 diagnosis of OUD (n=30). The first 10 participants will receive XR-BUP 16mg in single-blind fashion. We will then proceed with 10 more participants to the 24mg dose, and finally proceed with 10 more participants to the 32mg dose. All participants will receive fentanyl to prevent withdrawal symptoms. (Figure 2). Symptomatic treatments will be provided at any sign of worsening withdrawal including evidence of precipitated withdrawal.
Experimental: 24mg Buprenorphine; After first 10 participants have been completed, the next 10 participants will receive 24mg in a single-blind fashion.	Drug: Extended-release Buprenorphine; The study is a single-blind, fixed-order, dose-escalation designed trial in an inpatient setting with individuals with a DSM-5 diagnosis of OUD (n=30). The first 10 participants will receive XR-BUP 16mg in single-blind fashion. We will then proceed with 10 more participants to the 24mg dose, and finally proceed with 10 more participants to the 32mg dose. All participants will receive fentanyl to prevent withdrawal symptoms. (Figure 2). Symptomatic treatments will be provided at any sign of worsening withdrawal including evidence of precipitated withdrawal.
Experimental: 32mg Buprenorphine; After the 20 participants have been completed, the next 10 participants will receive 32mg in a single-blind fashion.	Drug: Extended-release Buprenorphine; The study is a single-blind, fixed-order, dose-escalation designed trial in an inpatient setting with individuals with a DSM-5 diagnosis of OUD (n=30). The first 10 participants will receive XR-BUP 16mg in single-blind fashion. We will then proceed with 10 more participants to the 24mg dose, and finally proceed with 10 more participants to the 32mg dose. All participants will receive fentanyl to prevent withdrawal symptoms. (Figure 2). Symptomatic treatments will be provided at any sign of worsening withdrawal including evidence of precipitated withdrawal.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma-concentration curves (AUC) of buprenorphine.	The area under the plasma concentration curves (AUC) of buprenorphine will be determined. Timed blood samples will be collected in anticoagulant Vacutainer tubes via venipuncture at baseline, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours after the XR-BUP injection. Samples will be centrifuged and frozen until analysis.	Baseline, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours after study drug administration.
Safety and tolerability of XR-Buprenorphine	The primary outcome is the proportion of participants who successfully complete induction, defined as experiencing no BPOW, which will be assessed using the COWS. An increase in the COWS score by 8 or more with the total score exceeding 13, within 4 hours will be considered BPOW.	For the duration of the inpatient admission, lasting 24 hours after receipt of study drug.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Buccal Swab	DNA testing to check 3A4 activity levels.	will be done once at the baseline visit.
Maximum Plasma Concentration	Plasma data will be used to calculate maximum plasma concentration (Cmax) for buprenorphine, norbuprenorphine, and their glucuronides.	Baseline, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours after study drug administration.
Minimum Plasma Concentration (Cmin),	Plasma data will be used to calculate minimum plasma concentration (Cmin) for buprenorphine, norbuprenorphine, and their glucuronides.	Baseline, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours after study drug administration.
Time to Maximum Plasma Concentration	Plasma data will be used to calculate time to maximum plasma concentration (Tmax) for buprenorphine, norbuprenorphine, and their glucuronides.	Baseline, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours after study drug administration.
Elimination half-life	Plasma data will be used to calculate elimination half-life (t1/2) for buprenorphine, norbuprenorphine, and their glucuronides.	Baseline, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours after study drug administration.

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: University of Utah

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2025
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2026

Study Registration Dates

• First Submitted: May 8, 2024
• First Submitted That Met QC Criteria: June 1, 2024
• First Posted (Actual): June 4, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2026
• Last Update Submitted That Met QC Criteria: March 23, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Opioid Use Disorder; Buprenorphine
• Additional Relevant MeSH Terms: Narcotic-Related Disorders; Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Opioid-Related Disorders; Physiological Effects of Drugs; Peripheral Nervous System Agents; Central Nervous System Depressants; Sensory System Agents; Analgesics; Analgesics, Opioid; Narcotics; Narcotic Antagonists; Buprenorphine
• Other Study ID Numbers: 2024P001078

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No