E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001594 |
E.1.2 | Term | Alcohol dependence syndrome |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the long term safety and tolerability of as needed use of 20 mg nalmefene versus placebo over a period of 52 weeks in patients with alcohol dependence. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the therapeutic effect of as needed use of 20 mg nalmefene versus placebo over a period of 52 weeks in patients with alcohol dependence, on: - reduction of alcohol consumption - alcohol dependence symptoms and clinical status - liver function and other biological laboratory tests - pharmacoeconomic outcomes |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. The patient is able to read and understand the Subject Information Sheet. 2. The patient has signed the Informed Consent Form. 3. The patient has a BAC of < 0.02% at the screening visit. 4. The patient has a diagnosis of alcohol dependence (diagnostic code 303.90) according to DSM-IV-TR. 5. The patient is a man or a woman, aged 18 years or over. 6. The patient provides a stable address and telephone number. 7. The patient provides an identified locator person that can be contacted during the study in the event of loss of contact. 8. The patient, if female, must: - agree not to try to become pregnant during the study, and - use adequate contraception (adequate contraception is defined as oral/systemic contraception, intrauterine device, diaphragm in combination with spermicide, or condom for male partner in combination with spermicide), or - have had her last natural menstruation at least 24 months prior to baseline, or - have been surgically sterilised prior to baseline, or - have had a hysterectomy prior to baseline, or - not be sexually active with men. |
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E.4 | Principal exclusion criteria |
1. The patient has less than 6 heavy drinking days (HDD) in the 4 weeks preceding the screening visit. A HDD is defined as a day of alcohol consumption with 60 g or more for males and 40 g or more for females. 2. The patient has more than 14 consecutive abstinent days in the 4 weeks preceding the screening visit. 3. The patient has a CIWA-Ar score of 10 or more. 4. The patient has a severe psychiatric disorder (such as psychosis, schizophrenia, severe depression, eating disorders, bipolar disorder), antisocial personality disorder or other disorders for which the treatment takes priority over treatment of the drinking problem, or is likely to interfere with study treatment or impairs treatment compliance. 5. The patient has risk of suicide evaluated by the suicidality module of MINI (the patient answers ‘yes’ to any of the questions C2, C3, C4, C5, or C6). 6. The patient has a history of delirium tremens or alcohol withdrawal seizures. 7. The patient has a cognitive impairment which judged by the investigator is likely to interfere with the patient’s understanding of the study and its procedures. 8. The patient reports or urine drug screen reveals current use of substances of abuse other than alcohol, cannabis, nicotine or benzodiazepines. 9. The patient has seizure disorder, mental retardation, or encephalopathy in the medical history. 10. The patient has a clinically significant unstable illness, for example, hepatic or renal insufficiency, or a cardiovascular, pulmonary, gastrointestinal, endocrine, neurological, infectious, neoplastic or metabolic disturbance. 11. The patient has clinically significant abnormal vital signs. 12. The patient has S-ASAT and/or S-ALAT levels greater than 3 times of upper normal limit, or one or more laboratory values outside the normal range, based on the blood or urine samples taken at the Screening Visit, that are considered by the investigator to be clinically significant. 13. The patient has clinically significant abnormal findings in ECG. 14. The patient has a history of severe drug allergy or hypersensitivity. 15. The patient reports current or recent (within 3 months preceding screening) treatment with disulfiram, acamprosate, topiramate, naltrexone or carbimide, or with any opioid antagonists. 16. The patient reports current or recent (within 1 week preceding screening) treatment with opioid agonists or partial agonists. 17. The patient used/uses disallowed recent or concomitant medication (specified in Appendix II, Recent and Concomitant Medication) or it is anticipated that the patient will require treatment with at least one of the disallowed concomitant medications during the study. 18. The patient has a disease or takes medication that, in the opinion of the investigator, could interfere with the assessments of safety, tolerability, or efficacy. 19. The patient is currently participating or has recently (4 weeks prior to the screening visit) participated in a treatment or support programme for alcohol use disorders, including Alcohol Anonymous, detoxification treatment and treatment of alcohol withdrawal symptoms. 20. The patient has been treated with any investigational medicinal product within 30 days or 5 half lives (whichever is longer) prior to screening. 21. The patient is pregnant or breast-feeding. 22. The patient, in the opinion of the investigator, is unlikely to comply with the clinical study protocol or is unsuitable for any reason. 23. The patient is a member of the site personnel or their immediate families. 24. The patient is under forced treatment. 25. The patient has previously participated in clinical studies with nalmefene. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety will be evaluated by adverse events (AEs), clinical safety laboratory tests, vital signs, weight, electrocardiograms (ECGs), physical examinations and POMS scale. The therapeutic effect on the reduction of alcohol consumption will be evaluated on exploratory basis. It will be evaluated by number of HDD, total consumption, DrInC, CGI-I, CGI-S, GGT, ALAT, CDT and MCV. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 93 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 21 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 21 |
E.8.9.2 | In all countries concerned by the trial days | 0 |