Nalmefene in Patients With Alcoholic Compensated Cirrhosis for the Treatment of Alcohol Dependence.

Inclusion Criteria:

• the patient has signed and dated the informed consent form,
• blood alcohol concentration < 0.02% at the screening visit,
• alcohol-dependent patient according to DSM-IV-TR criteria ,
• patient with compensated cirrhosis (cirrhosis demonstrated by clinical and laboratoryand/or morphological examinations and/or by a noninvasive test and/or by liverbiopsy), Child A or B,
• patient with at least a high drinking risk level (a moderate risk level is defined asa consumption ≥ 60 g of alcohol/day for men and ≥ 40 g of alcohol/day for women),
• male or female, over the age of 18 years, excluding protected majors,
• patient with a stable address and telephone number,
• name and address of a family member who will be contacted in the event of loss ofcontact with the patient,
• women of childbearing potential:
• must accept not to become pregnant during the study and,
• must use an effective method of contraception (adequate contraception is definedas oral, systemic contraception, intrauterine device, diaphragm in combinationwith spermicide, or condom for the male partner in combination with spermicide)or,
• must have had their last natural menstruation ≥ 24 months before the screeningvisit or,
• must have been surgically sterilized before the screening visit or,
• must have undergone hysterectomy before the screening visit or,
• must have no sexual activity with a male partner
• patient covered by French national health insurance.

Exclusion Criteria:

• cirrhosis Child Pugh C (decompensated cirrhosis)
• cirrhosis complicated by hepatocellular carcinoma or type I or II hepatorenal syndromeor poorly controlled portal hypertension,
• severe acute alcoholic hepatitis, not responding to corticosteroids by the 7th daydefined by a Lille model > 0.56 (www.lillemodel.com/score.asp)
• hepatic encephalopathy during the 6 months preceding the screening visit,
• patient with fewer than 6 heavy drinking days during the 4 weeks preceding thescreening visit (a heavy drinking day is defined as alcohol consumption of ≥ 60 g/dayfor men, and ≥ 40 g/day for women),
• patient with at least 14 consecutive days of abstinence during the 4 weeks precedingthe screening visit,
• patient with a CIWA-Ar score (Revised Clinical Institute Withdrawal Assessment forAlcohol) ≥ 10,
• patient with:
• a disorder other than alcohol or nicotine dependence, as evaluated on the MINI (Mini-International Neuropsychiatric Interview)
• antisocial personality disorder evaluated with the MINI questionnaire,
• other disorders for which treatment must take priority to the treatment of alcoholdependence, or which are likely to interfere with the study treatment or compromiseadherence to treatment,
• cannabis use does not constitute an exclusion criterion except when it meets thecriterion of cannabis dependence
• patient with a suicide risk evaluated using the suicidal tendency module of the MINI (the patient answers "Yes" to one of questions C2, C3, C4, C5 or C6 of thequestionnaire),
• patient with a history of delirium tremens or alcohol withdrawal seizures,
• ongoing use of addictive substances other than cannabis, nicotine or benzodiazepines,
• presence of a disorder of comprehension, mental retardation or encephalopathy,
• presence of clinically significant unstable disease (e.g.: renal failure,cardiovascular, pulmonary, gastrointestinal, gastrointestinal, endocrine,neurological, infectious, neoplastic disease or metabolic disorders,
• clinically significant ECG abnormalities,
• history of serious drug allergy or hypersensitivity to nalmefene,
• ongoing or recent treatment (during the 3 months preceding the screening visit) withdisulfiram, acamprosate, topiramate, naltrexone, carbimide, or opioid antagonists,
• ongoing or recent treatment (1 week preceding the screening visit) with opioidagonists or partial agonists,
• ongoing or recent treatment (8 weeks preceding the screening visit) withantipsychotics or antidepressants,
• patient taking or who has taken concomitant medications (see supplementary table),
• patient with another disease or taking medications, which, in the investigator'sopinion, could interfere with evaluations of safety, tolerability and efficacy,
• treatment with an investigational medicinal product during the 30 days preceding thescreening visit,
• ongoing or recent participation (during the 4 weeks preceding the screening visit) ina drinking disorders treatment or support programme, including Alcoholics Anonymous,disintoxication treatment and treatment of alcohol withdrawal symptoms,
• pregnancy or breastfeeding,
• patient who, in the investigator's opinion, has little chance of complying with theprotocol or unsuitable for the study for any other reason,
• patient who has already participated in a clinical trial on nalmefene.