ANS-6637 is a new chemical entity (a selective ALDH2 Inhibitor) with a mechanism of action expected to prevent craving and relapse for patients being treated for substance use disorders.
SAN FRANCISCO /PRNewswire/ -- Amygdala Neurosciences (a private company) announced today the start of dosing in a NIH/NIAID Phase 1b study to test the safety of ANS-6637, and how it effects the processing of drugs such buprenorphine that are processed by the same liver enzyme pathway. Results from this study will inform dosing of ANS-6637 and buprenorphine in subsequent studies of ANS-6637 for opioid use disorder.
ANS-6637 has an anti-craving mechanism of action that reduces dopamine surge associated with craving without changes in basal dopamine. ANS-6637 has been shown to reduce craving and drug seeking behavior in preclinical studies and has the potential for use as pharmacotherapy for substance and behavior-based addictions.
"NIH has been a great collaborator. They understand the unmet need for treating addiction and preventing relapse. Their financial, operational and intellectual support for ANS-6637 development has been very productive. NIH is generating data and proactively planning for the next Phase 2 studies to be conducted with funding from their HEAL Initiative," said Ivan Diamond MD, PhD, Amygdala co-founder and Chief Scientific Officer.
In addition to the NIH HEAL Initiative funded SEARCH program of clinical studies, planning is underway for a National Institute on Alcohol Abuse and Alcoholism (NIAAA, a division of NIH) funded Phase 2 proof of concept study with ANS-6637 for Alcohol Use Disorder. Separately, Amygdala is planning for 3 additional Phase 2 proof of concept studies with ANS-6637 as an aide to Smoking Cessation, as monotherapy treatment for Opioid Use Disorder and as a prophylaxis for Opioid Use Disorder.
About the NIH HEAL Initiative
The NIH HEAL (Helping to End Addiction Long-term) Initiative is an ambitious, trans-agency effort to speed scientific solutions to stem the national opioid public health crisis.
About the SEARCH Program of Phase 2 clinical Studies
The SEARCH (Safety and Efficacy of ANS-6637 to Reduce Drug Craving and Harm in People with Opioid Use Disorder) program of Phase 2 clinical studies are sponsored by the NIH HEAL Initiative, National Institute of Allergy and Infectious Diseases (NIAID, a division of NIH) and the NIH Clinical Center in collaboration with the Institute of Human Virology (IHV) at the University of Maryland School of Medicine. The project is led by Dr. Henry Masur, Chief of the NIH Critical Care Medicine Department and Dr. Shyam Kottilil, Professor of Medicine, Director Division of Clinical Care & Research, Institute of Human Virology, University of Maryland School of Medicine. The SEARCH program of clinical studies will receive up to $12.4 million of funding from the NIH HEAL Initiative. These Phase 2 clinical studies will test the safety, efficacy, and underlying mechanisms of craving reduction as a strategy to prevent opioid misuse, dependence, and relapse while improving morbidity and mortality in patients with opioid use disorder.
ANS-6637 is a selective and reversible ALDH2 inhibitor, a new chemical entity with a novel mechanism of action for treating substance use disorder. Based on its mechanism of action in the brain to prevent pathophysiologic dopamine surge without changes to basal dopamine (Nature Medicine 16:1024, 2010), ANS-6637 has the potential to prevent drug seeking behavior, craving and relapse. In preclinical studies, ALDH2 inhibition reduced self-administration, cue- and drug-primed relapse in nicotine, alcohol, cocaine, heroin, methamphetamine and binge eating models and also demonstrated anti-anxiety properties in models of stress. Amygdala acquired the asset ANS-6637 from Gilead Sciences in 2017. ANS-6637 has completed extensive Phase 1 studies in over 135 human subjects. Amygdala is preparing to start 5 Phase 2 proof of concept studies with ANS-6637.
About the Clinical Study
The study will enroll 12 healthy volunteers. This open label, fixed sequence intra-subject drug-drug interaction study is designed to evaluate the effect of CYP3A4 inhibition by ANS-6637 and GS-548351 (active metabolite) on midazolam and pharmacokinetics. Over the 10-day study, subjects will receive midazolam only, ANS-6637 only and midazolam with ANS-6637. Midazolam was chosen because its processing by the body is well understood, acting as a template for liver metabolism. Additional details about the study, Influence of ANS-6637 on Midazolam Pharmacokinetics in Healthy Volunteers, are available on clinicaltrials.gov using the identifier NCT03831971.
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