# Brexpiprazole as an adjunctive treatment to buprenorphine to treat Opioid Use Disorder

> **NIH NIH UG3** · OTSUKA PHARMACEUTICAL DEVELOPMENT & COMMERCIALIZATION, INC. · 2020 · $4,023,155

## Abstract

PROJECT SUMMARY/ABSTRACT
 Over 2 million Americans struggle with opioid use disorder (OUD) and the risks associated with misuse
of opioids have prompted a public health crisis. The FDA has approved three medications for the treatment of
OUD that have been grouped under the term Medication Assisted Treatment (MAT), which includes methadone,
naltrexone and buprenorphine-containing products. MATs have demonstrated benefit in the treatment paradigm
for OUD as overall mortality is reduced by as much as fifty percent. However, relapse and treatment
discontinuation are common within the first 5 to 12 weeks of MAT, suggesting an unmet therapeutic need.
Residual psychiatric symptoms such as insomnia, anxiety and depression have been postulated as key risk
factors for relapse and treatment discontinuation in patients on buprenorphine. Since longer treatment retention
is correlated with better long-term outcomes, the development of an adjunctive medication that could be added
to the buprenorphine treatment paradigm to alleviate key residual psychiatric symptoms associated with
treatment failure would address an important unmet need. Therefore, this research proposal seeks to evaluate
the safety and efficacy of brexpiprazole as adjunctive treatment to buprenorphine/naloxone in OUD. Key
milestones for this project include submission and FDA approval of an IND application to conduct first-in-human
studies on the safety and tolerability of adjunctive use of brexpiprazole with buprenorphine/naloxone, followed
by initiation of a 12-week exploratory efficacy study. Under the UG3 program, we have proposed IND-enabling
safety and tolerability studies to evaluate brexpiprazole as adjunctive treatment to buprenorphine/naloxone in
both animals (i.e. nonclinical toxicology) and treatment-seeking patients with moderate to severe OUD (i.e.
Phase 1). Under the UH3 phase we have proposed an exploratory 12-week study to measure key residual
psychiatric symptoms, relapse and treatment retention in treatment-seeking patients with moderate to severe
OUD treated with buprenorphine/naloxone monotherapy vs. adjunctive brexpiprazole plus
buprenorphine/naloxone. The overarching hypothesis is that adjunctive brexpiprazole will attenuate the residual
symptoms that persist on buprenorphine/naloxone monotherapy, resulting in better treatment retention and
potentially improving long-term treatment outcomes.

## Key facts

- **NIH application ID:** 10130067
- **Project number:** 1UG3DA051383-01A1
- **Recipient organization:** OTSUKA PHARMACEUTICAL DEVELOPMENT & COMMERCIALIZATION, INC.
- **Principal Investigator:** Andy Forbes
- **Activity code:** UG3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $4,023,155
- **Award type:** 1
- **Project period:** 2020-09-30 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10130067

## Citation

> US National Institutes of Health, RePORTER application 10130067, Brexpiprazole as an adjunctive treatment to buprenorphine to treat Opioid Use Disorder (1UG3DA051383-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10130067. Licensed CC0.

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