E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10037175 |
E.1.2 | Term | Psychiatric disorders |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001594 |
E.1.2 | Term | Alcohol dependence syndrome |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
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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 determine the reduction in alcohol consumption in patients with alcohol dependence treated with 18 mg
Selincro® as-needed use, in conjunction with continuous psychosocial support in primary care (Cohort A). |
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E.2.2 | Secondary objectives of the trial |
-To evaluate the change in patients treated with 18 mg Selincro®, as-needed use, on clinical status, liver function, quality of life.
-To determine the reduction in alcohol consumption in patients with alcohol dependence who reduce their
alcohol consumption to below a high drinking risk level (according to WHO) in the screening period (and are therefore not eligible for Selincro® (nalmefene) treatment according to the Summary of Product Characteristics (SmPC)) (Cohort B).
-To evaluate the psychometric properties of the Alcohol Quality of Life Scale (AQoLS).
-To evaluate the safety and tolerability of 18 mg Selincro®, as-needed use, in primary care. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• The patient has alcohol dependence diagnosed according to ICD-10.
• The patient has had a high DRL in the 4 weeks preceding the Screening Visit.
• The patient is a man or woman, aged ≥18 years.
• The patient provides a stable address and telephone number. |
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E.4 | Principal exclusion criteria |
• The patient has one or more contraindications to the prescription of Selincro®:
a. hypersensitivity to the active substance or to any of the excipients,
b. taking opioid analgesics,
c. current or recent opioid addiction,
d. acute symptoms of opioid withdrawal,
e. recent use of opioids suspected,
f. severe hepatic impairment (Child-Pugh classification),
g. severe renal impairment (eGFR <30 ml/min per 1.73 m2),
h. a recent history of acute alcohol withdrawal syndrome (including hallucinations, seizures, or delirium tremens).
• The patient has had <6 HDDs (defined by the European Medicines Agency as a day with an alcohol consumption >60g for men or >40g for women) in the 4 weeks preceding the Screening Visit.
• The patient has physical alcohol withdrawal symptoms and requires immediate detoxification for which inpatient treatment is required.
• The patient is currently participating or has recently (in the 4 weeks preceding 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, or the patient is already taking nalmefene or has taken nalmefene in the 6 months preceding the Screening Visit. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Outcome Measure:
• Change in the number of Heavy Drinking Days (HDDs) (days/month) [Cohort A] |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary Outcome Measure:
• Change in the number of Heavy Drinking Days (HDDs) (days/month) [Cohort A] Time Frame: Baseline to Month 3 |
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E.5.2 | Secondary end point(s) |
Secondary Outcome Measures:
• Change in Total Alcohol Consumption (TAC) (g/day) [Cohort A]
• Drinking Risk Level response (RSDRL); defined as a downward shift in Drinking Risk Level (DRL); for patients with a very high DRL at baseline, a shift to medium DRL or below; for patients with a high DRL at baseline, a shift to low DRL or below [Cohort A]
• RLDRL response; defined as a downward shift in DRL to low DRL or below [Cohort A]
• Response defined as ≥70% reduction in TAC Month 3 [Cohort A]
• Response defined as 0 to 4 HDDs (days/month) [Cohort A]
• Change in Clinical Global Impression - Severity of Illness (CGI-S) score [Cohort A]
• Clinical Global Impression - Global Improvement (CGI-I) [Cohort A]
• y-glutamyl transferase (y-GT) [Cohort A]
• Alanine aminotransferase (ALT) [Cohort A]
• Aspartate aminotransferase (AST) [Cohort A]
• Change in 36-item Short-form Health Survey version 2 (SF-36) (only for patients in France and the United Kingdom) [Cohort A]
• Change in Alcohol Quality of Life Scale (AQoLS) (only for patients in France and the United Kingdom) [Cohort A]
• Change in the number of HDDs (days/month) [Cohort B]
• Change in TAC (g/day) [Cohort B]
• Adverse events [Cohorts A and B] |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary Outcome Measures:
• Change in TAC [Cohort A] - Baseline to Month 3
• RSDRL [Cohort A] - Baseline to Month 3
• RLDRL [Cohort A] - Baseline to Month 3]
• Response: ≥70% reduction in TAC [Cohort A] - Baseline to Month 3
• Response: 0 to 4 HDDs (days/month) [Cohort A] - Month 3
• CGI-S score [Cohort A] - Baseline to Week 12
• CGI-I [Cohort A] - Week 12
• y-GT [Cohort A] - Week 12
• ALT [Cohort A] - Week 12
• AST [Cohort A] - Week 12
• Change in SF-36 (France, UK) [Cohort A] - Baseline to Week 12
• Change in AQoLS (France, UK) [Cohort A] - Baseline to Week 12
• Change in the number of HDDs (days/month) [Cohort B] - Baseline to Month 3
• Change in TAC [Cohort B] - Baseline to Month 3
• Adverse events [Cohorts A and B] - Up to Week 12 |
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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 | Yes |
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 | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 55 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |