Safety and Preliminary Efficacy of ANS-6637 to Reduce Drug Craving and Harm in People With Opioid Use Disorder

Safety and Preliminary Efficacy of ANS-6637 to Reduce Drug Craving and Harm in People With Opioid Use Disorder

This is a double blind, placebo controlled, randomized trial to evaluate the safety and preliminary efficacy of ANS-6637 in adults with opioid use disorder with and without opioid agonist therapy. Patients will be randomized to two arms: (1) ANS-6637 for three months vs (2) Placebo for three months. Subjects will subsequently be followed for an additional one month post treatment.

This is a double blind, placebo controlled, randomized trial to evaluate the safety and preliminary efficacy of ANS-6637 in adults with opioid use disorder with and without opioid agonist therapy. At screening, after providing consent, participants will be evaluated to ensure criteria for opioid use disorder by DSM V criteria is met, and whether the subject is receiving opioid agonist therapy will be determined. Participants will undergo a medical evaluation (including medical history, laboratory tests and EKG evaluation) to establish baseline medical and psychiatric diagnosis in order to ensure safety of participation. Once enrollment criteria are met, patients will be randomized in a blinded fashion to ANS-6637 or placebo, stratified by site and form of opioid agonist therapy. On Day 0, patients will be initiated on ANS-6637 vs. placebo according to randomization group. Subjects will be seen twice per week for two weeks, followed by weekly for two weeks, and then monthly for two months.

Inclusion Criteria:

• Must have the ability to understand and must personally sign a written informed consent form, which must be obtained prior to initiation of study procedures.
• Must be between 18 and 65 years of age, inclusive.
• Must have the diagnosis of opioid use disorder by DSM (Diagnostic and Statistical Manual of Mental Disorders) V criteria of at least mild severity
• Must have a total score of 9 or greater (out of a total of 30) on the Opioid Craving Scale at screening
• If on opioid agonist therapy, must be on Opioid Agonist Therapy (OAT) medication for a minimum of six months prior to screening.
• If on medication for depression or anxiety, must be on a stable dose for a minimum of two months prior to screening.
• Must be able to take oral medication and be willing to adhere to the medication regimen
• Must agree to utilize the "AI Cure" platform, either on their personal phone or on a supplied device, for both daily video adherence monitoring as well as daily questionnaires for the entire study duration.
• Male subjects must refrain from sperm donation throughout the study period, and continuing for at least 90 days following the last dose of study drug.
• Subjects must refrain from blood donation throughout the study period, and continuing for at least 30 days following the last dose of study drug.
• Must be willing to comply with contraception guidelines: The fetal risks associated with ANS-6637 are not known, but pre-clinical animal data demonstrate some risk. Subjects must agree not to become pregnant or impregnate a female. Females of childbearing potential must have a pregnancy test at screening and baseline (Day 0). If pregnancy occurs or is suspected to occur, study staff must be notified immediately. For the duration of the study, subjects or female partners of childbearing potential must use one of the following, unless she is surgically sterile, post-menopausal, or partner is surgically sterile: oral contraceptives (OCP), contraceptive sponge, patch double barrier (diaphragm + spermicide or condom + spermicide), intrauterine device (IUD), etonogestrel implant, injection, hormonal vaginal contraceptive ring or complete abstinence
• Must be willing and able to comply with all study requirements and plan to attend all clinic visits.

Exclusion Criteria:

A subject will be ineligible for this study if 1 or more of the following criteria are met:

• Clinically significant AND grade 2 or higher abnormal laboratory values at screening, as determined by principal investigator
• Aspartate transaminase (AST) or Alanine transaminase (ALT) > 2.5 x upper limit of normal or total bilirubin > 1.6 x the upper limit of normal
• Creatinine clearance < 60 mL/min/1.73m2 by Chronic kidney disease (CKD)-Epidemiology Collaboration (EPI) Score.
• Personal or family history of Parkinson's Disease
• Diagnosed major depression AND with current self-reported depression episode
• Diagnosed generalized anxiety disorder AND with current self-reported uncontrolled anxiety
• Current self-reported suicidal ideation
• Diagnosed liver disease, including untreated chronic Hepatitis C (defined as detectable Hepatitis C RNA), Hepatitis B (defined as positive HBsAg), and/or cirrhosis (defined as Fibrosis (FIB)-4 > 3.25 AND confirmed by Fibroscan or Fibrosure)
• Diagnosed Human Immunodeficiency Virus (HIV) AND detectable viral load > 40 copies/mL
• Diagnosed moderate or serious dementia Taking any of the following medications in the last 6 months: dopamine agonist, dopamine antagonist, anti-psychotic, anti-convulsant (except for benzodiazepines and gabapentin) or barbiturate
• Inability to obtain venous access for sample collection.
• Had a prior history of any severe adverse reactions to ethanol [e.g., flushing (noticeable redness of the neck or throat) and/or increased heart rate (subject reports sensation of increased heart rate or palpitations) after drinking alcohol].
• Known hypersensitivity to formulation excipients: microcrystalline cellulose, croscarmellose sodium, magnesium stearate, polyvinyl alcohol, titanium dioxide, polyethylene glycol, and talc.
• Have previously participated in an investigational trial involving administration of any investigational compound within 30 days prior to screening
• Have any unresolved legal issues that could jeopardize continuation or completion of the study, at the discretion of the principal investigator
• Have any serious or active medical, surgical, or psychiatric conditions which, in the opinion of the Investigator, would interfere with subject treatment, assessment, or compliance with the protocol.
• Are unable to comply with study requirements