A Study in the Treatment of Alcohol Dependence.

Study Overview
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Brief Summary
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H8R-MC-HJAQ is a Phase 2, parallel, double-blind, randomized study comparing LY686017 with placebo in a 12-week trial that includes Medical Management. This study is an outpatient study in which approximately 180 alcohol dependent subjects will be enrolled. Subjects will be randomized in a 1:1 fashion to LY686017 or placebo, and will receive once daily dosing for twelve weeks.

Official Title
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A Phase 2 Study of LY686017 Compared With Placebo for the Treatment of Alcohol Dependence

Conditions
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Alcohol Dependence

Intervention / Treatment
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* Drug: LY686017
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have Alcohol Dependence. Are men or women who are ambulatory outpatients between 21 to 65 years of age (inclusive) showing evidence of living in a non-custodial stable residence and with no plans to move during the next 5 months. Females of childbearing potential (not surgically sterilized and between menopause) must test negative for pregnancy at the time of enrollment based on a pregnancy test. They must agree to use a reliable method of birth control during the study and for 2 months following the last dose of study drug. Drink on average more than 14 drinks (women) or 21 drinks (men) per week with at least 2 heavy drinking days per week. Endorse abstinence or reduction in drinking as an interim goal toward abstinence. Exclusion Criteria: Are investigator site personnel directly affiliated with this study and/or their immediate families. Are Lilly employees. Are currently enrolled in or discontinued within the last 30 days from a clinical trial. Have experienced an acute alcohol withdrawal syndrome within the past 6 months or are currently or during this study at significant risk of suffering an acute alcohol withdrawal syndrome. Have a history of serious head injury, neoplasm or hemorrhage, prior seizure (other than a history of childhood febrile seizure), or other condition that would place the subject at increased risk for seizures. Are taking or have taken anticonvulsant medications for seizures. Are diagnosed with substance dependence or substance abuse other than alcohol, cannabis, nicotine, or caffeine within 12 months prior to first visit. Are receiving medications or intensive behavioral or psychological therapy delivered by a licensed or certified alcohol treatment specialist for alcohol dependence. Have signs and symptoms or an active illness within the past 2 weeks of first visit that meet criteria diagnosis of Major Depressive Disorder. In addition, meet criteria as diagnosis for any comorbid Axis I disorders (such as anxiety disorders, obsessive compulsive disorder (OCD), Posttraumatic stress disorder (PTSD), panic disorder, or dysthymia). Have a positive urine drug screen for any non-prescribed substances of abuse. Have a serious medical illness including but not limited to any cardiovascular, hepatic, respiratory, hematological, endocrine, or neurological disease, or any clinically significant laboratory abnormality. Ever had electroconvulsive therapy (ECT). Have abnormal thyroid stimulating hormone (TSH) concentrations or are taking thyroid supplements. Have a history of cirrhosis or laboratory evidence of hepatocellular injury. An abnormality in serum Prothrombin time. Are unable to make themselves available for the duration of the study or abide by study procedures and restrictions.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Daily by oral route for 12 weeks<br>|
| Experimental: LY686017<br> | Drug: LY686017<br>* 50 milligrams (mg) daily by oral route for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Heavy Drinking Days | The Alcohol Timeline Followback (TLFB) is used in calculating the percent reduction in heavy drinking days. The TLFB is a method for assessing the quantity of alcohol consumption on a daily basis. With a calendar as a guide, the interviewee provides a retrospective estimate of daily habits over a specified period of as long as the previous year. The goal is to provide a detailed record of patterns of use that can be used to guide treatment and to assess treatment outcome. Recorded is the number of standard drinks that have been consumed each day during last 4 weeks. One standard drink on the TLFB was defined as: 12 ounce (oz) beer [5% alcohol by volume (abv)], 5 oz of wine (10-12% abv), 3 oz of fortified wine (16-18% abv), or 1-1.2 oz of hard liquor (86-100 proof; 43-50% abv). Heavy drinking is defined as ≥4 drinks per day for women and ≥5 drinks per day for men. | Baseline, Weeks 4 and 8 and 12 and 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Days Abstinent Per Month | The Alcohol Timeline Followback (TLFB) is used in calculating the percentage of days abstinent (days where no alcoholic drinks were consumed). The TLFB is a method for assessing the quantity of alcohol consumption on a daily basis. With a calendar as a guide, the interviewee provides a retrospective estimate of daily habits over a specified period of as long as the previous year. The goal is to provide a detailed record of patterns of use that can be used to guide treatment and to assess treatment outcome. Recorded is the number of standard drinks that have been consumed each day. One standard drink on the TLFB was defined as: 12 ounce (oz) beer [5% alcohol by volume (abv)], 5 oz of wine (10-12% abv), 3 oz of fortified wine (16-18% abv), or 1-1.2 oz of hard liquor (86-100 proof; 43-50% abv). Percentage days per month= (number of days where no alcoholic beverages were consumed/number of days in a month)*100. | Baseline and Weeks 4 and 8 and 12 and 16. | 
| Number of Drinks Per Drinking Day During a Month | The Alcohol Timeline Followback (TLFB) is used in calculating the number of drinks per drinking day. The TLFB is a method for assessing the quantity of alcohol consumption on a daily basis. With a calendar as a guide, the interviewee provides a retrospective estimate of daily habits over a specified period of as long as the previous year. The goal is to provide a detailed record of patterns of use that can be used to guide treatment and to assess treatment outcome. Recorded is the number of standard drinks that have been consumed each day. One standard drink on the TLFB was defined as: 12 ounce (oz) beer [5% alcohol by volume (abv)], 5 oz of wine (10-12% abv), 3 oz of fortified wine (16-18% abv), or 1-1.2 oz of hard liquor (86-100 proof; 43-50% abv). | Baseline and Weeks 4 and 8 and12 and 16 | 
| Time to First Heavy Drinking Day | The Alcohol Timeline Followback (TLFB) is used to assess the time to first heavy drinking day. The TLFB is a method for assessing the quantity of alcohol consumption on a daily basis. With a calendar as a guide, the interviewee provides a retrospective estimate of daily habits over a specified period of as long as the previous year. The goal is to provide a detailed record of patterns of use that can be used to guide treatment and to assess treatment outcome. Recorded is the number of standard drinks that have been consumed each day. One standard drink on the TLFB was defined as: 12 ounce (oz) beer [5% alcohol by volume (abv)], 5 oz of wine (10-12% abv), 3 oz of fortified wine (16-18% abv), or 1-1.2 oz of hard liquor (86-100 proof; 43-50% abv). Heavy drinking is defined as ≥4 drinks per day for women and ≥5 drinks per day for men. Those who did not drink are considered to be censored. | Baseline up to Week 12 | 
| Change From Baseline in Drinker Inventory of Consequences (DrInC) Subscale and Total Scale | DrInC is a self-administered, 50-item questionnaire designed to measure adverse consequences of alcohol abuse in 5 areas: Interpersonal, Physical, Social, Impulsive, and Intrapersonal. All items for the DrInC are scored from 0-3 with higher scores indicating worse adverse consequences. Interpersonal subscale (10 items: scores range from 0-30) measures the impact of drinking on the participants' relationships. Physical subscale (8 items: scores range from 0-24) measures adverse physical states resulting from excessive drinking. Social subscale (7 items: scores range from 0-21) measures role fulfillment. Impulsive subscale (12 items: scores range from 0-36) measures sequelae of over drinking. Intrapersonal subscale (8 items: scores range from 0-24) measures subjective perceptions that may not be readily observable by others. Total scores range from 0-150, with higher scores indicating greater severity of symptoms. | Baseline, Week 12 | 
| Change From Baseline in Alcohol Urge Questionnaire (AUQ) | AUQ measures participant's feeling and thoughts about drinking, and uses a 7 point (1-7) Likert scale for each of 8 items (questions). Scores range from 8 (less urge to drink) to 56 (more urge to drink). | Baseline, Weeks 1 and 2 and 3 and 4 and 6 and 8 and 10 and 12 | 
| Change From Baseline in Penn Alcohol Craving Scale (PACS) | PACS is a 5-item self-administered instrument that measures frequency, intensity, and duration of thoughts about drinking, ability to resist drinking and craving. Each item ranges from 0-6 with 6 indicating worse symptoms. | Baseline, Weeks 1 and 2 and 3 and 4 and 6 and 8 and 10 and 12 | 
| Change From Baseline in Beck Depression Inventory II (BDI-II) Total Score | BDI-II is a 21-item, participant-completed questionnaire to assess characteristics of depression. There is a 4-point scale for each item ranging from 0 (no depression) to 3 (very depressed). Total scores range from 0-63. Higher scores indicate greater severity of depression. | Baseline, Weeks 1 and 2 and 3 and 4 and 6 and 8 and 10 and 12 | 
| Change From Baseline Beck Anxiety Index (BAI) Total Score | BAI is a 21-item participant-completed questionnaire designed to assess the characteristics of anxiety. Each item is rated on a 4-point scale (0= not present; 3= present in the extreme). Total scores range from 0 to 63. Higher total scores indicate greater severity of anxiety symptoms. | Baseline, Weeks 6 and 12 | 
| Change From Baseline in Plasma Gamma-Glutamyl Transferase (GGT) |  | Baseline, Weeks 1 and 2 and 3 and 4 and 6 and 8 and 10 and 12 | 
| Change From Baseline in Plasma Carbohydrate Deficient Transferrin (CDT) | Carbohydrate Deficient Transferrin is a laboratory test that measures alcohol consumption. Greater levels suggest recent alcohol consumption. | Baseline, Weeks 1 and 2 and 3 and 4 and 6 and 8 and 10 and 12 | 
| 12 -Item Short-Form Health Survey (SF-12) Scores: Physical Component Summary (PCS) | Short Form 12 (SF-12) is a 12-item assessment used to measure participant's physical wellbeing [physical component score (PCS)] and mental wellbeing [mental component score (MCS)]. The PCS score ranges from 0 (lowest wellbeing) to 100 (highest wellbeing) and is designed to have a mean of 50 and standard deviation (SD) of 10 in the general population. | Baseline and Week 12 | 
| 12-Item Short-Form Health Survey (SF-12) Scores: Mental Component Summary (MCS) | Short Form 12 (SF-12) is a 12-item assessment used to measure participant's physical wellbeing [physical component score (PCS)] and mental wellbeing [mental component score (MCS)]. The MCS score ranges from 0 (lowest wellbeing) to 100 (highest wellbeing) and is designed to have a mean of 50 and standard deviation (SD) of 10 in the general population. | Baseline and Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alcoholic