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

Opioid Use Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06441604
• Other study ID #: 2024P001078
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: September 2024
• Est. completion date: July 2026

Study information

• Verified date: June 2024
• Source: Brigham and Women's Hospital
• Contact: Joji Suzuki
• Phone: 6177325752
• Email: jsuzuki2[@]bwh.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: July 2026
• Est. primary completion date: April 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Opioid Use Disorder
• Opioid-Related Disorders

Intervention

Drug:
• Extended-release Buprenorphine
First 10 participants will receive XR-BUP 16mg in single-blind fashion. If at least 90% of the participants who received 16mg successfully complete induction (success defined as experiencing no BPOW),10 additional participants will receive a 24mg dose in a single blind fashion. If at least 90% who received 24mg successfully complete induction (success defined as experiencing no BPOW), 10 additional participants will receive a 32mg dose in a single blind fashion.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Brigham and Women's Hospital	University of Utah

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability of XR-Buprenorphine	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)	For the duration of the inpatient admission, lasting 4 days after receipt of study drug.
Primary	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 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.	Baseline, 0.5, 1, 2, 4, 6, 8, 12, 24, 48 and 72 hours after study drug administration.
Secondary	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, 24, 48 and 72 hours after study drug administration.
Secondary	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, 24, 48 and 72 hours after study drug administration.
Secondary	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, 24, 48 and 72 hours after study drug administration.
Secondary	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, 24, 48 and 72 hours after study drug administration.
Secondary	Buccal Swab	DNA testing to check 3A4 activity levels.	will be done once at the baseline visit.