# Evaluation of the Safety and Efficacy of a New Oral Small Molecule GABA-B Receptor Positive Allosteric Modulator (PAM) as an Add-on Maintenance Therapy for Opioid Use Disorder (OUD)

> **NIH NIH UG3** · ASTELLAS PHARMA GLOBAL DEVELOPMENT, INC. · 2020 · $6,000,000

## Abstract

The opioid crisis in America is real and increasing. In 2017, over 47,600 American lives were lost due to an
overdose of an opioid. The recent rise in illegally manufactured fentanyl shipped to the United States from
sources around the globe have only increased the opioid epidemic and further accelerated a critical need to find
and develop new therapies to address this scourge. This UG3/UH3 grant seeks funding to test a γ-aminobutyric
acid subtype B positive allosteric modulator (GABAB PAM) compound, ASP8062, in 3 separate clinical studies.
This target is one of the prioritized research approaches for NIDA to evaluate in trying to address the opioid
crisis. This grant application will include two phase 1 studies to evaluate the impact of ASP8062 on side effects
including respiratory depression when administered in combination with a) buprenorphine/naloxone and b)
morphine. The third clinical study included in the grant is a phase 2 study in opioid use disorder (OUD)
subjects testing ASP8062 or placebo in addition to an ongoing medication assisted treatment (MAT) program
that includes buprenorphine-based therapy as cornerstone treatment.
Studies have shown that the GABAB receptor is involved with reducing self-administration and drug-seeking
behavior across several substances of abuse (i.e., opioids, alcohol, cocaine, nicotine) by suppressing dopamine
release from key areas of the brain, including the prefrontal cortex, ventral tegmental area and the striatum.
Baclofen, a GABAB receptor agonist, has yielded positive findings in nonclinical studies such as suppression of
opioid, ethanol, cocaine or nicotine self-administration in rats. However, activation of GABAB receptors by
direct-acting agonists induces side effects including sedation or somnolence, excessive weakness, vertigo and
psychological disturbances. Centrally penetrant GABAB PAMs amplify the signaling of endogenous GABA to its
receptor within the central nervous system and preserve the spatiotemporal nature of GABA
neurotransmission, thus resulting in a lower incidence of undesirable side effects compared to orthosteric
GABAB agonist drugs and optimizing compliance and prolonged, tolerable craving suppression.
The sponsor will conduct these studies under a company IND. A pre-IND meeting with FDA is planned for Q4
2019 to confirm adequacy of the current nonclinical pharmacology and toxicology data package, clinical study
subject populations, endpoints and safety monitoring. Upon execution of the studies included in this grant
application, the sponsor will evaluate the data together with input from NIDA, and make a go/no-go decision
for further internal investment for future development of ASP8062 in the management of OUD.

## Key facts

- **NIH application ID:** 10026953
- **Project number:** 1UG3DA051392-01
- **Recipient organization:** ASTELLAS PHARMA GLOBAL DEVELOPMENT, INC.
- **Principal Investigator:** Jay Erdman
- **Activity code:** UG3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $6,000,000
- **Award type:** 1
- **Project period:** 2020-04-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10026953

## Citation

> US National Institutes of Health, RePORTER application 10026953, Evaluation of the Safety and Efficacy of a New Oral Small Molecule GABA-B Receptor Positive Allosteric Modulator (PAM) as an Add-on Maintenance Therapy for Opioid Use Disorder (OUD) (1UG3DA051392-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10026953. Licensed CC0.

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