Extended-release Buprenorphine as a Novel Low-dose Induction Strategy
- Conditions
- Opioid Use Disorder
- Interventions
- Registration Number
- NCT06441604
- Lead Sponsor
- Brigham and Women's Hospital
- Brief Summary
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 DSM-5 diagnosis of OUD (n=30) will be admitted to an inpatient unit to complete study procedures over the course of 5 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.
- Detailed Description
The approach is to conduct a single ascending dose trial in a controlled human laboratory setting with individuals with a DSM-5 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 5 days-4 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, 24, 48 and 72 hours after the XR-BUP injection.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 30
- English speaking adults aged 18 and above.
- DSM-5 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.
- Seeking medication treatment for opioid use disorder with sublingual buprenorphine or methadone.
- Received buprenorphine or methadone treatment in prior 30 days.
- Current DSM-5 diagnosis of alcohol or sedative/hypnotic use disorder.
- Physical dependence on alcohol or sedative/hypnotics.
- Psychotic disorder, active suicidality or homicidally or any psychiatric condition that impair ability to provide informed Consent.
- Requiring treatment with opioids for acute or chronic pain.
- History of hypersensitivity or allergy to buprenorphine or fentanyl.
- Pregnant or breastfeeding.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description 16mg Extended-Release Buprenorphine Extended-release Buprenorphine The first 10 participants will receive XR-BUP 16mg in single-blind fashion. 24mg Buprenorphine Extended-release Buprenorphine After first 10 participants have been completed, the next 10 participants will receive 24mg in a single-blind fashion. 32mg Buprenorphine Extended-release Buprenorphine After the 20 participants have been completed, the next 10 participants will receive 32mg in a single-blind fashion.
- Primary Outcome Measures
Name Time Method Plasma-concentration curves (AUC) of buprenorphine. Baseline, 0.5, 1, 2, 4, 6, 8, 12, 24, 48 and 72 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 EDTA anticoagulant Vacutainer tubes via venipuncture at baseline, 0.5, 1, 2, 4, 6, 8, 12, 24, 48 and 72 hours after the XR-BUP injection. Samples will be centrifuged and frozen until analysis.Safety and tolerability of XR-Buprenorphine For the duration of the inpatient admission, lasting 4 days after receipt of study drug. The primary outcome is the proportion of participants who successfully complete induction, defined as experiencing no BPOW. BPOW is a score of 5 or more on the Clinical Opiate Withdrawal Scale (COWS)
- Secondary Outcome Measures
Name Time Method Time to Maximum Plasma Concentration Baseline, 0.5, 1, 2, 4, 6, 8, 12, 24, 48 and 72 hours after study drug administration. Plasma data will be used to calculate time to maximum plasma concentration (Tmax) for buprenorphine, norbuprenorphine, and their glucuronides.
Elimination half-life Baseline, 0.5, 1, 2, 4, 6, 8, 12, 24, 48 and 72 hours after study drug administration. Plasma data will be used to calculate elimination half-life (t1/2) for buprenorphine, norbuprenorphine, and their glucuronides.
Maximum Plasma Concentration Baseline, 0.5, 1, 2, 4, 6, 8, 12, 24, 48 and 72 hours after study drug administration. Plasma data will be used to calculate maximum plasma concentration (Cmax) for buprenorphine, norbuprenorphine, and their glucuronides.
Minimum Plasma Concentration (Cmin), Baseline, 0.5, 1, 2, 4, 6, 8, 12, 24, 48 and 72 hours after study drug administration. Plasma data will be used to calculate minimum plasma concentration (Cmin) for buprenorphine, norbuprenorphine, and their glucuronides.
Buccal Swab will be done once at the baseline visit. DNA testing to check 3A4 activity levels.