Clinical trial NCT02197598: Treatment of Patients Suffering of Alcohol Dependence and Impaired Liver Function With Selincro® As-needed Use
Official title: Exploratory, Interventional, Open-label, Fixed-dose Study With Selincro® As-needed Use, in Alcohol Dependent Patients With Liver Impairment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Alcohol Dependence
Keywords: nalmefene, alcohol consumption, liver effects
Lead sponsor: H. Lundbeck A/S
Sponsor class: INDUSTRY
First posted: 2014-07-22
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to explore the treatment effects of Selincro in alcohol dependent patients with liver impairment.


Eligibility criteria: Inclusion Criteria:

* The patient has alcohol dependence, diagnosed at screening according to DSM-IV-TR™
* The patient has had an average alcohol consumption at, at least, a high drinking risk level (that is \>60 g of alcohol/day for men and \>40 g of alcohol/day for women) in the 4 weeks preceding the Screening Visit and in the period between the Screening and Inclusion Visits (that is, in the Screening Period)
* The patient has liver impairment defined by elevated liver stiffness and elevated liver enzymes at the Screening Visit (both criteria have to be fulfilled): liver stiffness (LS) as measured by Fibroscan \>6 kPa, elevated transaminases (AST or ALT). Transaminase levels up to 5 times the upper limit of the reference range and γGT levels up to 10 times the upper limit of the reference range are allowed. At the discretion of the investigator, transaminase levels \>5 times the upper limit of the reference range and γGT \>10 times the upper limit of the reference range can be allowed if considered habitual for the patient, either confirmed by patient records or a repeat measurement during the Screening Period
* The patient has a breath alcohol concentration (BrAC) \<0.02% at the Screening Visit.
* The patient provides a stable address and telephone number
* The patient is a man or woman, aged ≥ 18 years
* The patient has BMI≤30 kg/m2

Exclusion Criteria:

* The patient has any psychiatric disorder or Axis I disorder (DSM-IV-TR™ criteria), established as the primary diagnosis, other than alcohol dependence assessed using the Mini International Neuropsychiatric Interview (MINI) or another diagnostic interview , that in any way will interfere with the ability of the patient to take part in the study
* The patient has reported current use of, or has been tested positive for, drugs of abuse (opiates, methadone, cocaine, amphetamines \[including ecstasy\], barbiturates)
* The patient has severe liver impairment classified with a Child-Pugh Score C
* The patient has one or more clinical laboratory test values outside the reference range, based on the blood and urine samples taken at the Screening Visit, that are of potential risk to the patient's safety, or the patient has: Severe renal impairment (eGFR \<30 mL/min per 1.73 m2), and/or Hypercholesterolemia with serum cholesterol levels \> 300 mg/dL, (\>7,758 mmol/L), and/or bilirubin \> 3 mg/dL (50 μmol/L)
* The patient has had \<6 heavy drinking days (HDDs, defined by the European Medicines Agency as a day with an alcohol consumption \>60 g for men or \>40 g for women) in the 4 weeks preceding the Screening Visit
* The patient has \>5 consecutive abstinence days in the 4 weeks preceding the Screening Visit
* The patient has a recent history of acute alcohol withdrawal syndrome (including hallucinations, seizures, or delirium tremens)

Other protocol-defined inclusion and exclusion criteria may apply.

Primary outcomes:
measure: Change from baseline in the number of heavy drinking days per month (HDDs) (days/month)
timeFrame: Baseline to months 1, 2 and 3
measure: Change from baseline in the number of HDDs per week (days/week)
timeFrame: Baseline to weeks 1 and 2
measure: Change from baseline in total alcohol consumption (TAC) (g alcohol/day)
timeFrame: Baseline to months 1, 2 and 3
measure: Change from baseline in TAC (g alcohol/day)
timeFrame: Baseline to weeks 1 and 2
measure: Response Shift Drinking Risk Level (RSDRL)
timeFrame: Baseline to month 3
measure: Response Low Drinking Risk Level (RLDRL)
timeFrame: Baseline to month 3
measure: Response defined as ≥70% reduction in TAC
timeFrame: Baseline to month 3
measure: Response defined as 0 to 4 HDDs (days/month)
timeFrame: Month 3
measure: Clinical Global Impression, global improvement (CGI-I).
timeFrame: Weeks 4 and 12
measure: Change from baseline in Clinical Global Impression, Severity of illness (CGI-S)
timeFrame: Baseline to weeks 4 and 12
measure: Change in the Short-Form 36-Item Health Survey (SF-36)
timeFrame: Baseline to week 12
measure: Change in liver stiffness
timeFrame: Baseline to weeks 1,2 4 and 12
measure: Category shift in fibrosis stage
timeFrame: Baseline to weeks 1,2 4, and 12
measure: Change in transaminases and γ-glutamyl transferase (γGT)
timeFrame: Baseline to weeks 1,2,4,8, and 12
measure: Change in bilirubin, albumin, and International Normalized Ratio (INR)
timeFrame: Baseline to weeks 1,2,4,8, and 12
measure: Number of adverse events
timeFrame: Screening to week 14
Secondary outcomes:
Other outcomes:
Locations:
city: Heidelberg
country: Germany
facility: DE001
city: Mannheim
country: Germany
facility: DE002
city: München
country: Germany
facility: Optuminisight
Study officials:
affiliation: LundbeckClinicalTrials@lundbeck.com
name: Email contact via H.Lundbeck A/S
role: STUDY_DIRECTOR
References: