# Randomized controlled trial of extended-release buprenorphine vs. sublingual buprenorphine for the treatment opioid use disorder patients using fentanyl analogues

> **NIH NIH R21** · NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC · 2021 · $198,875

## Abstract

Project Summary
 The US opioid epidemic continues to evolve with highly potent synthetic opioids (HPSO) now driving higher
overdose fatality rates. There has been a five-fold increase in US synthetic opioid overdose rate from 2013
(3,105) to 2016 (approximately 20,000) out of the approximately 42,000 overdose deaths due to opioids.
Fentanyl analogs and other HPSO are now commonly found in heroin and counterfeit prescription painkiller
pills. Due to the rapidly changing nature of the illicit drug supply, the efficacy of commonly used
pharmacotherapies for opioid use disorder (OUD) (e.g., buprenorphine, methadone, naltrexone) in treating
users of HPSO is unknown. The increasing number of overdose deaths combined with possible lower efficacy
of standard therapies creates an urgent need to develop new strategies for the HPSO-using patient.
 Despite the known effectiveness of buprenorphine sublingual (BSL) maintenance treatment, retention and
continued non-prescribed opioid use remain significant limitations, with approximately 50% or more of patients
treated with BSL dropping out of treatment by 3 to 6 months. The first extended-release injectable
buprenorphine (Sublocade™) became commercially available in 2018 after FDA Fast Track and Priority
Review designation. This monthly buprenorphine formulation, which is available in two doses (100 mg and 300
mg), can achieve serum buprenorphine concentrations in excess of that achieved by BSL 24 mg per day.
Moreover, if an unexpected drug holiday is experienced, at two weeks past the injection due date, µ-opioid
receptor remains above 70%, providing extended protection against opioid withdrawal and relapse. While this
buprenorphine extended-release (BXR) injection formulation has not yet been compared to BSL treatment, the
pharmacologic advantages of an extended-release injection can be expected to improve treatment retention
and outcomes. The extended-release injection aspect should improve compliance and reduce relapse by
providing more continuous buprenorphine serum levels as compared to the sublingual formulation. We
hypothesize that BXR injection will have particular benefit for individuals using fentanyl analogues because by
providing continuous therapeutic serum buprenorphine levels there will be substantially less opportunity for
non-compliance and relapse. Individuals who discontinue BSL and use HPSO containing opioids may have
more difficulty restarting sublingual treatment, leading to treatment failure.
 We propose an early Phase II clinical trial, in which patients seeking treatment for OUD who are positive for
HPSO at screening (N = 40) will be inducted onto BSL and then randomly assigned to receive either standard
therapy (BSL maintenance) or BXR injection, under open label conditions, with a primary outcome measure of
days of opioid use per week as measured by the timeline followback method confirmed by urine toxicology. To
our knowledge, this would be the first trial testing a treatment for i...

## Key facts

- **NIH application ID:** 10158460
- **Project number:** 5R21DA049037-02
- **Recipient organization:** NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
- **Principal Investigator:** Frances Rudnick Levin
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $198,875
- **Award type:** 5
- **Project period:** 2020-05-15 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10158460

## Citation

> US National Institutes of Health, RePORTER application 10158460, Randomized controlled trial of extended-release buprenorphine vs. sublingual buprenorphine for the treatment opioid use disorder patients using fentanyl analogues (5R21DA049037-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10158460. Licensed CC0.

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