Clinical trial NCT03663374 (phase 3, status: completed)
Conditions: alcohol dependence
ICD codes: F10.20, F10.24, F10.27, F10.280, F10.281, F10.282, F10.288
Drugs: odelepan, placebo
SMILES: NC(=O)C1=CC=C(OC2=C(F)C=C(CNCCC3CCOCC3)C=C2)N=C1, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        Inclusion Criteria:

          -  Signed and dated informed consent.

          -  Outpatients (not hospitalized by the moment of randomization).

          -  Average alcohol consumption during 30 days prior to screening higher than a medium
             drinking risk level (men: > 4 drinks/day or 14 drinks/week; women > 3 drinks/day or 7
             drinks/week) according to the National Institute on Alcohol Abuse and Alcoholism
             (NIAAA) criteria.

          -  Patients diagnosed with alcohol dependence according to the International
             Classification of Diseases (ICD)-10, assessed with the Mini-International
             Neuropsychiatric Interview (MINI).

          -  Abstaining from alcohol during 3 days prior to screening and 3 days before
             randomization confirmed by the test for alcohol in exhaled air (less than 0,02 %).

          -  For women retaining childbearing potential - negative pregnancy test and consent to
             use reliable contraception methods (as well as for men) throughout the study period,
             including the study follow up period.

          -  Patients able to comply with study protocol as per investigator's opinion.

          -  Availability of a patient's trustee who reside with the patient. A trustee is defined
             here as a person who spends with the patient at least 4 hours a day. The trustee must
             give his/her consent for participation in the study as the patient's representative.

          -  Study drug monotherapy must be acceptable for the patient as per investigator's
             opinion.

        Exclusion Criteria:

          -  Hypersensitivity to Odelepran or to any excipient of the study drug (including lactose
             intolerance).

          -  Binge drinking (more than 5 day consecutive days of heavy drinking) during 30 days
             prior to screening. Heavy drinking is considered as 5 or more drinks per day for men
             and 4 or more drinks per day for women.

          -  Ever diagnosed schizophrenia, schizoaffective disorder, bipolar mood disorder or any
             other psychiatric disorder, except for alcohol dependence. History of alcohol induced
             psychosis.

          -  Anxiety or depressive disorder present at enrollment into the study. Montgomery-Asberg
             Depression Rating Scale (MADRS) score higher than 15.

          -  High suicidal risk confirmed by MINI.

          -  Previous use of opioid antagonists implants less than 3 months prior to screening; use
             of long-acting naltrexone injections (e,g, Vivitrol) less than 4 weeks after the first
             injection and 3 months after the second and the following injections; use of cyanamide
             (Kolme) less than 2 weeks prior to screening, use of oral opioid antagonists or
             disulfiram during 2 weeks prior to screening.

          -  Psychotherapeutic "coding" (a method when the patient is induced a misbelief that
             alcohol consumption would lead to death, expected to result from undisclosed
             pharmacological manipulation) that took place during less than 3 months prior to
             screening.

          -  Use of psychotropic medication less than 3 weeks before the screening (for long-acting
             and 'depot' formulations) or 1 week before the screening (for other formulations)
             except for those used to treat alcohol withdrawal syndrome.

          -  Severe alcohol withdrawal syndrome (severity of alcohol withdrawal more than 10 on
             Clinical Institute Withdrawal Assessment of Alcohol (CIWA-Ar) scale).

          -  History of seizures (excepting febrile seizers). Severe brain injury, history of
             intracranial neoplasms and/or intracranial haemorrhages or any conditions that impose
             the risk of seizures. History of anticonvulsive therapy.

          -  Any clinical condition affecting cognitive or other psychoneurological functioning
             (verified for head injury with the loss of consciousness that lasted more than 1 hour,
             or resulted in cognitive or behavioral impairment, stroke, encephalopathy, dementia,
             neurodegenerative disorder, etc). Except for mild cognitive impairment.

          -  Mental retardation of syndromes of severe organic brain injury.

          -  Use of drugs of abuse (opioids, cannabinoids, amphetamines, etc.) or diagnoses of
             substance addiction/dependence at the moment of screening or positive urine drug
             screen test.

          -  Significant liver function impairment (aspartate aminotransferase (AST) and alanine
             aminotransferase (ALT) higher than 3 upper limits of normal range or diagnosis of
             hepatic failure, class B or C by Child Pugh).

          -  Severe renal failure (creatinine clearance calculated at the screening less than 30
             ml/min or renal replacement therapy).

          -  Severe cardiovascular system disorders: unstable angina, poorly controlled arrhythmia,
             cardiac failure of III or IV class by New-York Heart Association (NYHA), acute
             myocardial infarction within the past 6 months.

          -  HIV-infection, hepatitis B or C.

          -  Decompensated diabetes mellitus (determined glycated hemoglobin HbAc1 level more than
             7,5%)

          -  Other concomitant disorders and conditions that, as per investigator's opinion, put
             the patient's safety under risk or that could affect the analysis of safety data.

          -  Any diagnosed or suspected malignancy.

          -  Pregnancy, breast feeding.

          -  Participation in any other clinical study during 30 days or 6 periods of half life
             (depending on what is longer) prior to screening.

          -  Patients that need treatment with drugs prohibited by the study protocol (opioid
             antagonists, psychotropic medications, opioid analgesics, anticonvulsants, central
             muscle relaxants, antineoplastic drugs, glucocorticoids).