Efficacy and Safety Evaluating Study of Odelepran for the Use in Patient With Alcohol Dependence
|ClinicalTrials.gov Identifier: NCT03663374|
Recruitment Status : Completed
First Posted : September 10, 2018
Last Update Posted : May 22, 2019
|Condition or disease||Intervention/treatment||Phase|
|Alcohol Dependence||Drug: Odelepan Drug: Placebo||Phase 3|
Patients for this study were recruited in specialized psychiatric and addictology clinical sites in Russia and Kazakhstan. Eligible patients were randomly allocated in one of the following treatment groups in 1:1 ratio:
- The main group was taking the study drug Odelepran, one 125 mg tablet per day;
- The comparison group was taking the comparison drug (Placebo) orally, one tablet per day.
Duration of the study treatment period was 24 weeks (starting from the Day 1). Patients were keeping a diary to register their drug taking and amount and kind of alcohol beverages consumed.
Patients were not allowed to participate in psychotherapy or take any psychotropic drugs except for short-acting benzodiazepines for insomnia. However benzodiazepines were not allowed for taking less than 24 before any study visit.
Patients visited clinical sites regularly as per the Schedule for visits and procedures. During the visits to the site the patient's mental state examination with the use of psychometric scales was conducted and the study drug was provided.
Starting at randomization and subsequently at all scheduled visits investigators conducted a brief (15 minutes or less) psychotherapeutic intervention (individual counseling) during which patients were asked to provide information on aspects of alcohol consumption and emotional states experienced while abstaining from alcohol. Such individual counseling was aimed to reinforce lifestyle changes, motivate sobriety and enhance protocol adherence. All clinical sites performed such counseling in standardized manner in accordance with protocol-specific Guideline developed at St. Petersburg Psychoneurological Research Institute named after V.M. Bekhterev for the purposes of this study.28 days after the last dose of study drug patients were asked to come for a follow up visit to assess adverse events.
Patients were not paid for participation in the study.
Assessments of efficacy and safety were performed monthly. Assessments of drinking behavior were based on the Time Line Follow-Back (TLFB) method used to provide information of daily number of standard drinks. At every visit patients reported about dynamics of drinking (frequency and amount of consumed alcohol) since the previous visit.
For all assessed variables, the baseline was defined as an assessment at the screening visit.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||644 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||All eligible patients were randomized into two groups to receive investigational drug or placebo at ratio 1:1|
|Masking:||Double (Participant, Investigator)|
|Official Title:||International Multicentre Randomized Double-blind Placebo Controlled Phase III Clinical Study to Assess Efficacy and Safety of Odelepran, 125 mg, for the Use in Patient With Alcohol Dependence|
|Actual Study Start Date :||November 18, 2014|
|Actual Primary Completion Date :||April 16, 2016|
|Actual Study Completion Date :||May 14, 2016|
One tablet once daily
Tablets, 125 mg
Placebo Comparator: Placebo
One tablet once daily
Contains the same excipients as Odelepran but it does not contain the active agent. Placebo is identical to Odelepran in terms of drug form and external characteristics (colour, smell, etc). Doses and route of administration are identical to those for Odelepran.
- Change from baseline in the mean daily alcohol consumption [ Time Frame: Baseline and Week 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, and 24 of treatment ]Calculated as total number of drinks in month divided by number of days in month.
- Change in the number of days of abstinence per month as compared to the baseline [ Time Frame: Baseline and Week 24 of treatment ]
- Change in the percentage of days of heavy drinking per month as compared to the baseline [ Time Frame: Baseline and Week 24 of treatment ]Heavy drinking to be considered as 5 or more drinks per day for men and 4 or more drinks per day for women.
- Time to the first day of drinking [ Time Frame: From baseline till the first day of alcohol consumption ]Full abstinence period duration.
- Time to the first day of heavy drinking [ Time Frame: From baseline till the first day of heavy drinking ]Heavy drinking to be considered as 5 or more drinks per day for men and 4 or more drinks per day for women.
- Change from baseline in alcohol consumption per drinking day [ Time Frame: Baseline and Week Week 1, 2, 3, 4, 6, 8, 10, 12, 16, 20 and 24 of treatment ]Calculated as total number of drinks in month divided by number of drinking days in month.
- Change in alcohol craving from the baseline (based on Obsessive-Compulsive Drinking Scale (OCDS) score) [ Time Frame: Baseline and Week 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, and 24 of treatment ]The OCDS is a validated scale consisted of 14 items for patient self-assessment of alcohol craving. Scoring by simple addition. Higher scores indicate greater level of craving (Anton R.F., Moak D.H., Latham P.K., 1996).
- Change in alcohol craving (based on completed VIsual Analogue Scale) [ Time Frame: Baseline and Week 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, and 24 of treatment ]VIsual Analogue Scale (VAS) ranged from 0 to 100, where 0 corresponds to "no craving at all" and 100 corresponds to "maximal craving"
- Change in patient's self-assessed quality of life (by the SF-36 Questionnaire) as compared to the baseline [ Time Frame: Baseline and Week 8, 24 of treatment ]The Short Form Health Survey (SF-36) is a validated 36 item self-report Quality of Life Questionnaire that measures eight multi-item dimensions of health: physical functioning, social functioning, role limitations due to physical problems, role limitations due to emotional problems, mental health, energy/vitality, pain, and general health perception. Version 2 was used. (Ware J.E., 2000)
- Proportion of patient with clinical improvement as assessed by Clinical Global Impression-improvement (CGI-I) scale [ Time Frame: Week 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, and 24 of treatment ]CGI-I scale is a 7 point scale that requires the investigator to assess how much the patient's illness has improved or worsened relative to a baseline. Rated as: 1 - very much improved, 2 - much improved, 3 - minimally improved, 4 - no change, 5 - minimally worse, 6 - much worse, 7 - very much worse. (Guy W, 1970; 1976)
- Efficacy index of CGI [ Time Frame: Week 12 and 24 of treatment ]Efficacy index is a 4×4 rating scale that assesses the therapeutic effect of treatment with psychiatric medication (with possible considerations: 1 - unchanged or worse; 2 - minimal — slight improvement which doesn't alter status of care of patient; 3 - moderate marked — decided improvement, partial remission of symptoms; 4 - marked - vast improvement, complete or nearly complete remission of all symptoms) and associated side effects (with possible considerations: 1 - none; 2 - do not significantly interfere with patient's functioning; 3 - significantly interfere with patient's functioning; 4 - outweigh therapeutic effect). Derived by dividing therapeutic effect score by side effects score. The lower efficacy index corresponds to the better result (Guy W, 1970; 1976)
- Change from baseline in the Drinker Inventory of Consequences questionnaire (DrInC-2R) total score [ Time Frame: 3 previous months, baseline and Week 4, 8, 12, 16, 20 and 24 of treatment ]DrInC-2R is a validated self-report questionnaire consisted of 50 questions to measure adverse consequences of alcohol abuse in five areas: Interpersonal, Physical, Social, Impulsive, and Intrapersonal as well as frequency of these consequences (answers given on frequency scale grade from 0-3: 0 - never, 1 - once or a few times, 2 - once or twice a week 3 - daily or almost daily). Higher scores indicate greater levels of alcohol-related problems. (Miller W.R., 1995)
- Change in impulsivity (Barratt impulsivity scale by the subscales and by the total score) from the baseline [ Time Frame: Baseline and Week 8, 16 and 24 of treatment ]Barratt impulsivity scale (BIS-11) is a validated self-report questionnaire composed of 30 items describing common impulsive or non-impulsive (for reverse scored items) behaviors and preferences. Items are scored on a 4-point scale: Rarely/Never = 1, Occasionally = 2, Often = 3, Almost Always/Always = 4. Total score is assessed. The higher total score corresponds to the more impulsive behavior (Patton et al., 1995)
- Proportion of patients completed the trial [ Time Frame: Week 24 of treatment ]
- Time to untimely withdrawal from the study [ Time Frame: From baseline to Week 24 of treatment ]
- Number of the early dropouts from the study [ Time Frame: Week 24 of treatment ]Per reasons
- Number of hospitalizations due to alcohol intoxication [ Time Frame: 6 month prior to the baseline and week 28 of treatment ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03663374
|Study Director:||Mikhail Samsonov||R-Pharm|