ASP8062 / Astellas - LARVOL DELTA

Effects of a novel GABA-B positive allosteric modulator, ASP8062, on alcohol cue-elicited craving and naturalistic alcohol consumption in a multisite randomized, double-blind, placebo-controlled trial. (PubMed, Alcohol Clin Exp Res (Hoboken)) - "Although ASP8062 was well tolerated with no serious AEs, the novel compound did not significantly dampen alcohol cue-elicited craving or improve other AUD-related outcome measures. These data indicate positive allosteric modulation of the GABAB receptor at the dose evaluated here may not blunt alcohol cue-elicited craving, and preliminary drinking outcome data suggest it may not be an efficacious treatment strategy for AUD."

Clinical • Journal • Addiction (Opioid and Alcohol) • Anesthesia

A Study to Assess the Analgesic Efficacy and Safety of ASP8062 in Subjects With Fibromyalgia (clinicaltrials.gov) - P2 | N=183 | Completed | Sponsor: Astellas Pharma Global Development, Inc. | Phase classification: P2a ➔ P2

Phase classification • Fibromyalgia • Musculoskeletal Pain • Pain • Rheumatology

A Study to Assess the Effect of a Single Dose of ASP8062 on the Multiple Dose Safety, Tolerability and Pharmacokinetics of Buprenorphine/Naloxone in Participants With Opioid Use Disorder (clinicaltrials.gov) - P1 | N=23 | Completed | Sponsor: Astellas Pharma Global Development, Inc. | Phase classification: P1b ➔ P1

Phase classification • Substance Abuse

Positive allosteric modulators of the GABAB receptor: a new class of ligands with therapeutic potential for alcohol use disorder. (PubMed, Alcohol Alcohol) - "These effects closely mirrored those of baclofen; notably, they were associated to remarkably lower levels of tolerance and toxicity. The recent transition of ASP8062 to clinical testing will soon prove whether these highly consistent preclinical data translate to AUD patients."

Journal • Addiction (Opioid and Alcohol)

Human Laboratory Study of ASP8062 for Alcohol Use Disorder (clinicaltrials.gov) - P2 | N=60 | Completed | Sponsor: National Institute on Alcohol Abuse and Alcoholism (NIAAA) | Active, not recruiting ➔ Completed

Trial completion • Addiction (Opioid and Alcohol)

Successes in Translation: Rapid Medication Development for PTSD, Alcohol and Opioid Use Disorders (ASCP 2023) - P2 | "These examples will include: 1) CERC-501, a kappa antagonist owned by the pharmaceutical company Cerecor, was assessed in predator odor-induced place aversion (POIPA) an animal model of PTSD; 2) the impact of ASP8062, a GABAb allosteric modulator was assessed using operant alcohol self-administration (model of alcohol use disorder); and 3) the effects of an anti-fentanyl vaccine (FEN-CRM) formulated with components contained in vaccines presently on the market was assessed in analgesic tests (e.g. tail flick, hotplate), schedule-controlled responding, FEN-induced overdose and brain distribution. Learning Objectives At the conclusion of the presentation, the learner will know more about promising novel treatments for ASUDs . At the conclusion of the presentation, the learner will have a better understanding of pre-clinical studies critical to establishing potential efficacy prior to assessing these treatments in human clinical trials."

Addiction (Opioid and Alcohol) • CNS Disorders • Pain • Post-traumatic Stress Disorder • Substance Abuse

A phase 1 randomized, placebo-controlled study to investigate potential interactions between ASP8062, a positive allosteric modulator of the GABA receptor, and morphine in recreational opioid users. (PubMed, J Psychopharmacol) - "In this phase 1 study, we did not observe any unexpected safety signals or notable PK interactions with concomitant morphine administration. These data suggest a potentially low risk for an increase in drug abuse- or withdrawal-related adverse events or respiratory distress in participants exposed to ASP8062 and morphine."

Journal • P1 data • CNS Disorders • Depression • Psychiatry • Substance Abuse

Effect of ASP8062 on morphine self-administration and morphine-induced respiratory suppression in monkeys. (PubMed, J Pharmacol Sci) - "Further, ASP8062 did not potentiate morphine-induced respiratory suppression up to exposure levels higher than the clinically relevant dose. ASP8062 may reduce opioid use in OUD patients without affecting respiratory system, providing justification for further ASP8062 development as a potential treatment option for OUD."

Journal • Substance Abuse

A phase 1b study to investigate the potential interactions between ASP8062 and buprenorphine/naloxone in patients with opioid use disorder. (PubMed, J Psychopharmacol) - P1b | "To investigate the safety, tolerability, interaction potential, and pharmacokinetics (PK) of ASP8062 in combination with buprenorphine/naloxone (B/N; Suboxone). In this phase 1 study, ASP8062 was safe, well tolerated, and did not enhance respiratory suppression induced by buprenorphine. Clinicaltrials.gov identifier: NCT04447287."

Journal • P1 data • Addiction (Opioid and Alcohol) • CNS Disorders • Depression • Psychiatry • Substance Abuse • Suicidal Ideation

Human Laboratory Study of ASP8062 for Alcohol Use Disorder (clinicaltrials.gov) - P2 | N=60 | Active, not recruiting | Sponsor: National Institute on Alcohol Abuse and Alcoholism (NIAAA) | Recruiting ➔ Active, not recruiting

Enrollment closed • Addiction (Opioid and Alcohol)

Human Laboratory Study of ASP8062 for Alcohol Use Disorder (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: National Institute on Alcohol Abuse and Alcoholism (NIAAA) | Trial completion date: Jan 2023 ➔ May 2023 | Trial primary completion date: Nov 2022 ➔ May 2023

Trial completion date • Trial primary completion date • Addiction (Opioid and Alcohol)

A Study to Assess the Safety and Efficacy of ASP8062 as an Add-on Therapy to Buprenorphine/Naloxone in Participants With Opioid Use Disorder (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Astellas Pharma Global Development, Inc. | N=252 ➔ 0 | Suspended ➔ Withdrawn

Enrollment change • Trial withdrawal • Substance Abuse

A Study to Assess the Safety and Efficacy of ASP8062 as an Add-on Therapy to Buprenorphine/Naloxone in Participants With Opioid Use Disorder (clinicaltrials.gov) - P2 | N=252 | Suspended | Sponsor: Astellas Pharma Global Development, Inc. | Recruiting ➔ Suspended

Trial suspension • Substance Abuse

Novel Agents for the Pharmacological Treatment of Alcohol Use Disorder. (PubMed, Drugs) - "Pharmacotherapies discussed include: disulfiram, acamprosate, naltrexone, nalmefene, topiramate, gabapentin, varenicline, baclofen, sodium oxybate, aripiprazole, ondansetron, mifepristone, ibudilast, suvorexant, prazosin, doxazosin, N-acetylcysteine, GET73, ASP8062, ABT-436, PF-5190457, and cannabidiol. Importantly, these medications also offer potential improvements towards the advancement of precision medicine and personalized treatment for the heterogeneous AUD population. However, there remains a great need to improve access to treatment, increase the menu of approved pharmacological treatments, and de-stigmatize and increase treatment-seeking for AUD."

Journal • Review • Addiction (Opioid and Alcohol)

Human Laboratory Study of ASP8062 for Alcohol Use Disorder (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: National Institute on Alcohol Abuse and Alcoholism (NIAAA) | Not yet recruiting ➔ Recruiting

Enrollment open • Addiction (Opioid and Alcohol)

A phase 1 study to assess potential interaction between ASP8062 and alcohol in healthy adult subjects. (PubMed, J Psychopharmacol) - "ASP8062 administered alone was safe and well-tolerated and safety findings in subjects administered alcohol alone were not augmented when ASP8062 was administered in combination with alcohol. The data support further clinical studies investigating ASP8062 in patients with AUD."

Clinical • Journal • P1 data • Addiction (Opioid and Alcohol) • Substance Abuse

A Study to Assess the Safety and Efficacy of ASP8062 as an Add-on Therapy to Buprenorphine/Naloxone in Participants With Opioid Use Disorder (clinicaltrials.gov) - P2; N=252; Recruiting; Sponsor: Astellas Pharma Global Development, Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Substance Abuse

Human Laboratory Study of ASP8062 for Alcohol Use Disorder (clinicaltrials.gov) - P2; N=60; Not yet recruiting; Sponsor: National Institute on Alcohol Abuse and Alcoholism (NIAAA)

New P2 trial • Addiction (Opioid and Alcohol)

A Study to Assess the Safety and Efficacy of ASP8062 as an Add-on Therapy to Buprenorphine/Naloxone in Participants With Opioid Use Disorder (clinicaltrials.gov) - P2; N=252; Not yet recruiting; Sponsor: Astellas Pharma Global Development, Inc.

Clinical • New P2 trial • Substance Abuse

The GABA receptor positive allosteric modulator ASP8062 reduces operant alcohol self-administration in male and female Sprague Dawley rats. (PubMed, Psychopharmacology (Berl)) - "ASP8062 decreases alcohol reinforcement like baclofen but without non-specific effects which are influenced by sex. Results support further development of ASP8062 as a potential treatment for AUD in humans."

Journal • Preclinical • Addiction (Opioid and Alcohol)

A randomized phase 1 single-dose polysomnography study of ASP8062, a GABA receptor positive allosteric modulator. (PubMed, Psychopharmacology (Berl)) - "Single-dose ASP8062 (35 and 70 mg) appeared to result in CNS penetration and enhanced GABAergic activity as measured by increases in slow-wave sleep and growth hormone release."

Clinical • Journal • P1 data • CNS Disorders • Pain • Sleep Disorder

A Study to Assess the Effect of a Single Dose of ASP8062 on the Multiple Dose Safety, Tolerability and Pharmacokinetics of Buprenorphine/Naloxone in Participants With Opioid Use Disorder (clinicaltrials.gov) - P1b; N=23; Completed; Sponsor: Astellas Pharma Global Development, Inc.; Recruiting ➔ Completed

Clinical • Trial completion

A Study to Assess the Safety, Tolerability and Pharmacokinetics of Multiple Doses of ASP8062 With a Single Dose of Morphine in Recreational Opioid Using Participants (clinicaltrials.gov) - P1; N=24; Completed; Sponsor: Astellas Pharma Global Development, Inc.; Recruiting ➔ Completed

Clinical • Trial completion

A Study to Assess the Effect of a Single Dose of ASP8062 on the Multiple Dose Safety, Tolerability and Pharmacokinetics of Buprenorphine/Naloxone in Participants With Opioid Use Disorder (clinicaltrials.gov) - P1b; N=30; Recruiting; Sponsor: Astellas Pharma Global Development, Inc.

Clinical • New P1 trial

A Study to Assess the Safety, Tolerability and Pharmacokinetics of Multiple Doses of ASP8062 With a Single Dose of Morphine in Recreational Opioid Using Participants (clinicaltrials.gov) - P1; N=24; Recruiting; Sponsor: Astellas Pharma Global Development, Inc.

Clinical • New P1 trial