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| ID | Type | Description | Link |
|---|---|---|---|
| H9T-MC-NABJ | Other Identifier | Eli Lilly and Company |
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The Primary objective of this study is to test whether LY2196044 can reduce the number of heavy drinking days per month in people with alcohol dependence. Each subject will undergo a screening and assessment period (including medication washout) prior to randomization into a 16 week double blind treatment period.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LY2196044 | Experimental |
| |
| Placebo | Placebo Comparator |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LY2196044 | Drug | 250 milligram (mg) (titrate via 1 week at 50 mg and 1 week at 125 mg), once daily, orally, 16 weeks |
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| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Heavy Drinking Days at Week 16 Endpoint | The Timeline Followback Method assesses the subject's daily drinking by means of a calendar that covers a specific time period and was used to assess the number of heavy drinking days. Heavy drinking is defined as ≥4 drinks/day for women and ≥5 drinks/day for men. Least Squares (LS) Mean value was controlled for treatment, pooled investigator, visit, gender, family history, treatment*visit, gender*family history, baseline, and baseline*visit. An unstructured covariance structure was used. | Week 16 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Drinks Per Day at Week 16 Endpoint | The Timeline Followback Method assesses the subject's daily drinking by means of a calendar that covers a specific time period and was used to assess the number of drinks consumed per day. Least Squares (LS) Mean value was controlled for treatment, pooled investigator, visit, gender, family history, treatment*visit, gender*family history, baseline, and baseline*visit. An unstructured covariance structure was used. |
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Inclusion Criteria:
Have Alcohol Dependence. Subjects must manifest at least the following 3 requirements for their diagnosis of Alcohol Dependence:
Be tolerant, as defined by either of the following:
Consume alcohol, often in larger amounts or over a longer period than was intended.
Have a persistent desire or unsuccessful effort(s) to reduce or control alcohol use.
Drink on average more than 14 drinks (women) or 21 drinks (men) per week with at least 2 heavy drinking days per week (≥4 drinks/day for women and ≥5 drinks/day for men) during the consecutive 30 day period prior to Screening and maintained through Randomization.
Endorse abstinence or reduction in drinking.
Female subjects of childbearing potential must have a negative urine pregnancy test and agree to use a reliable method of birth control during the study and for 2 months following the last dose of study drug.
Exclusion Criteria:
Have experienced an acute alcohol withdrawal syndrome within the past 6 months or are currently at significant risk of suffering an acute alcohol withdrawal syndrome.
Have a history of serious head injury, intracranial neoplasm or hemorrhage, prior seizure (other than remote history of childhood febrile seizure), or other condition that would place the subject at increased risk of seizure.
Have ever taken anticonvulsants for seizure control.
Are diagnosed with substance dependence or abuse (other than alcohol, cannabis, nicotine, or caffeine) within 6 months prior to Screening.
Are receiving intensive behavioral or psychological therapy, delivered by a licensed or certified alcohol treatment specialist, for alcohol dependence.
Meet criteria for a lifetime diagnosis of Schizophrenia, Schizoaffective Disorder, Bipolar I Disorder, or other psychoses.
Have signs and symptoms of an active illness within the past 6 months of Screening for a diagnosis of Major Depressive Disorder (MDD) or Anxiety Disorder, or have a Cognitive Disorder diagnosed by clinical assessment. Subjects who were diagnosed with MDD in the more distant past, but have had a recent diagnosis of an active Major Depressive Episode, will not be eligible.
Are actively suicidal, in the opinion of the investigator.
Have taken any opiate or opioid analgesic (for example, codeine, hydrocodone) or an opiate receptor antagonist (for example, naltrexone) within 14 days prior to Screening.
Are currently taking any medication excluded by the protocol.
Have evidence of significant active cardiac, respiratory, renal, gastrointestinal, or hematologic disease.
Have acute or active hepatitis or hepatic inflammation.
Have a history of cirrhosis or laboratory evidence of significant hepatocellular injury.
Have plasma levels of sodium, potassium, calcium, magnesium, or phosphorous that fall outside of established reference ranges of the central laboratory for those analytes [that is, below lower limit of normal (LLN) or above upper limit of normal (ULN)] unless corrected prior to randomization.
Have electrocardiogram (ECG) abnormalities obtained at Screening that are clinically significant with regard to the subject's participation in the study.
Are women who are either pregnant or breast feeding.
Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.
Have previously completed or withdrawn from this study or any other study investigating LY2196044.
Are unable, unreliable, and/or unwilling to provide informed consent, make themselves available for the duration of the study or abide by study procedures and restrictions.
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| Name | Affiliation | Role |
|---|---|---|
| Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) | Eli Lilly and Company | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Indianapolis | Indiana | 46260 |
Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
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| ID | Title | Description |
|---|---|---|
| FG000 | LY2196044 | 250 milligram (mg) (titrate via 1 week at 50 mg and 1 week at 125 mg), once daily, orally, 16 weeks |
| FG001 | Placebo | once daily, orally, 16 weeks |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| placebo | Drug | once daily, orally, 16 weeks |
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| Baseline, Week 16 |
| Change From Baseline in Percentage of Days Abstinent at Week 16 Endpoint | The Timeline Followback Method assesses the subject's daily drinking by means of a calendar that covers a specific time period and was used to assess the percentage of days abstinent. Least Squares (LS) Mean value was controlled for treatment, pooled investigator, visit, gender, family history, treatment*visit, gender*family history, baseline, and baseline*visit. An unstructured covariance structure was used. | Baseline, Week 16 |
| Change From Baseline in Drinks Per Drinking Day at Week 16 Endpoint | The Timeline Followback Method assesses the subject's daily drinking by means of a calendar that covers a specific time period and was used to assess the number of drinks consumed on the days the participant drank. Least Squares (LS) Mean value was controlled for treatment, pooled investigator, visit, gender, family history, treatment*visit, gender*family history, baseline, and baseline*visit. An unstructured covariance structure was used. | Baseline, Week 16 |
| Change From Baseline in Drinks Per Heavy Drinking Day at Week 16 Endpoint | The Timeline Followback Method assesses the subject's daily drinking by means of a calendar that covers a specific time period and was used to assess the number of drinks consumed on heavy drinking days. Heavy drinking is defined as ≥4 drinks/day for women and ≥5 drinks/day for men. Least Squares (LS) Mean value was controlled for treatment, pooled investigator, visit, gender, family history, treatment*visit, gender*family history, baseline, and baseline*visit. An unstructured covariance structure was used. | Baseline, Week 16 |
| Change From Baseline in Obsessive Compulsive Drinking Scale (OCDS) Total Score at Week 16 Endpoint | Cravings will be assessed using the OCDS. The OCDS is a 14-item self-rating instrument. Total scores range from 0-40. Higher scores indicate more obsessive and craving. Least Squares (LS) Mean value was controlled for treatment, site, visit, gender, history, baseline, gender*history, treatment*visit, baseline*visit, gender*treatment, gender*treatment*visit. Subject was treated as a random effect. An unstructured covariance structure was used. | Baseline, Week 16 |
| Change From Baseline in Drinker Inventory of Consequences (DrInC) - Recent Consequences (DrInC-2R) Total Score at Week 16 Endpoint | 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. DrInC-2R provides a measurement since the last interview. Total scores range from 0-150, and higher scores indicate greater severity of symptoms. Least Squares (LS) Mean value was controlled for treatment, pooled investigator, visit, gender, family history, baseline, gender*family history, treatment*visit, baseline*visit. Subject was treated as a random effect. An unstructured covariance structure was used. | Baseline, Week 16 |
| Ratio of Geometric Means Over Baseline in Gamma-Glutamyltransferase (GGT) Level at Week 16 Endpoint | GGT and carbohydrate-deficient transferrin (%CDT) will be used as biochemical markers of alcohol consumption. A combination of GGT and %CDT improves the sensitivity of detecting excessive alcohol consumption as compared to either marker alone, or other traditional markers. Elevated levels indicate heavy alcoholism. Least Squares (LS) Mean value was controlled for treatment, pooled investigator, visit, gender, family history, baseline, gender*family history, treatment*visit, baseline*visit. An unstructured covariance structure was used. | Week 16 |
| Ratio of Geometric Means Over Baseline in Percent Carbohydrate-Deficient Transferrin (%CDT) Level at Week 16 Endpoint | Gamma-Glutamyltransferase (GGT) and %CDT will be used as biochemical markers of alcohol consumption. A combination of GGT and %CDT improves the sensitivity of detecting excessive alcohol consumption as compared to either marker alone, or other traditional markers. Elevated levels indicate heavy alcoholism. Least Squares (LS) Mean value was controlled for treatment, pooled investigator, visit, gender, family history, baseline, gender*family history, treatment*visit, baseline*visit. An unstructured covariance structure was used. | Week 16 |
| Ratio of Geometric Means Over Baseline in Aspartate Transaminase (AST) Level at Week 16 Endpoint | AST is a potential biomarker for LY2196044 efficacy as decreases reflect decreased alcohol consumption. Least Squares (LS) Mean value was controlled for treatment, pooled investigator, visit, gender, family history, baseline, gender*family history, treatment*visit, baseline*visit. An unstructured covariance structure was used. | Week 16 |
| Change From Baseline in Beck Depression Inventory II (BDI-II) Total Score at Week 16 Endpoint | The BDI-II contains 21 items that characterize how the subject was feeling in the past 2 weeks. There is a 4-point scale for each item ranging from 0 to 3 (0=no depression; 3=very depressed). Total scores range from 0-63. Higher scores indicate greater severity of depression. Least Squares (LS) Mean value was controlled for treatment, pooled investigator, gender, family history, baseline, gender*family history, treatment*visit, baseline*visit. An unstructured covariance structure was used. | Baseline, Week 16 |
| Change From Baseline in Beck Anxiety Inventory (BAI) Total Score at Week 16 Endpoint | BAI is a 21-item patient-completed questionnaire designed to assess the characteristics of anxiety. Participant was asked to rate how much he or she has been bothered by each symptom over the past week. Each item is rated on a 4-point scale (0=not present; 3=present in the extreme). Total scores range from 0 to 63. The higher the score, the more severe the anxiety symptoms. LS Mean value was controlled for treatment, pooled investigator, gender, family history, visit, baseline, gender*family history, treatment*visit, baseline*visit. An unstructured covariance structure was used. | Baseline, Week 16 |
| Change From Baseline in Barratt Impulsivity Scale-11 (BIS-11) Total Score at Week 16 Endpoint | The BIS-11 is a 30-item, self-administered impulsivity scale. Motor, cognitive, and non-planning domains are assessed and a total score is computed. This scale has previously been used in substance-abusing populations. Total scores range from 30-120. Higher scores indicate greater severity of symptoms. Least Squares (LS) Mean value was controlled for treatment, pooled investigator, gender, family history, baseline, gender*family history. | Baseline, Week 16 |
| Change From Baseline in Thoughts About Abstinence Scale at Week 16 Endpoint | Thoughts About Abstinence Scale was to measure participant's commitment to abstinence. It includes 3 items on a scale of 1-10: own desire to stop drinking (1=no desire to quit); own expectation of success in quitting (1=lowest expectation of success); how difficult to quit and remain abstinent (1=lowest amount of difficulty); and their goal related to alcohol use (scale of 1-7: 1=having no goal, up to total abstinence at 6 [7 was none of 6 above]). Least Squares (LS) Mean value was controlled for treatment, pooled investigator, gender, family history, baseline, gender*family history. | Baseline, Week 16 |
| Change From Baseline in Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) Total Score at Week 16 Endpoint | Q-LES-Q-SF is a self-report instrument that assesses the degree of enjoyment and satisfaction in daily life activities. The domains include: social relationships, living or house situation, and physical health. Total scores range from 14-70. Higher scores indicate better quality of life. Least Squares (LS) Mean value was controlled for treatment, pooled investigator, gender, family history, visit, baseline, gender*family history, treatment*visit, baseline*visit. An unstructured covariance structure was used. | Baseline, Week 16 |
| Change From Baseline in Endicott Work Productivity Scale (EWPS) Total Score at Week 16 Endpoint | EWPS is a self-rated work productivity scale that assesses such topics as work hours, work missed, and behaviors and feelings related to the workplace. The EWPS will be completed only by subjects who work outside the home. There are 25 items and total scores range from 0-100. Higher scores indicate poorer productivity. Least Squares (LS) Mean value was controlled for treatment, pooled investigator, gender, family history, visit, baseline, gender*family history, treatment*visit, baseline*visit. An unstructured covariance structure was used. | Baseline, Week 16 |
| Population Pharmacokinetic (PK) - Apparent Clearance | Plasma concentrations were analyzed using population PK methodology with non-linear mixed effect modeling (NONMEM) software. | Over 16 weeks |
| Population Pharmacokinetic (PK) - Apparent Volume of Distribution | Plasma concentrations were analyzed using population PK methodology with non-linear mixed effect modeling (NONMEM) software. | Over 16 weeks |
| Change From Baseline in Supine Blood Pressure (BP) at Week 16 Endpoint | Least Squares (LS) Mean value was controlled for treatment, pooled investigator, visit, baseline, treatment*visit. An unstructured covariance structure was used. | Baseline, Week 16 |
| Change From Baseline in Supine Pulse Rate at Week 16 Endpoint | Least Squares (LS) Mean value was controlled for treatment, pooled investigator, visit, baseline, treatment*visit. An unstructured covariance structure was used. | Baseline, Week 16 |
| Change From Baseline in QTc Fridericia's Correction Interval (QTcF) Measured by Electrocardiograms at Week 16 Endpoint | Least Squares (LS) Mean value was controlled for treatment, pooled investigator, visit, baseline, treatment*visit. An unstructured covariance structure was used. | Baseline, Week 16 |
| Percentage of Participants Discontinuation Due to Adverse Events (AEs) | Percentage of participants discontinued study due to one or more AEs. | Baseline through Week 16 |
| Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) | Percentage of participants had one or more TEAEs during treatment period. TEAE is a worsening or new occurrence of adverse event during treatment compared to baseline. | Baseline through Week 16 |
| Change From Baseline in Orthostatic Blood Pressure (BP) at Week 16 Endpoint | Orthostatic BP is the BP measured within 3 minutes of standing. Least Squares (LS) Mean value was controlled for treatment, pooled investigator, visit, baseline, treatment*visit. An unstructured covariance structure was used. | Baseline, Week 16 |
| Change From Baseline in Orthostatic Pulse Rate at Week 16 Endpoint | Orthostatic pulse rate is the pulse rate measured within 3 minutes of standing. Least Squares (LS) Mean value was controlled for treatment, pooled investigator, visit, baseline, treatment*visit. An unstructured covariance structure was used. | Baseline, Week 16 |
| Number of Participants With Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA-Ar)≥10 at Any Time From Baseline Through Week 16 Endpoint | The revised CIWA-Ar scale measured the severity of alcohol withdrawal by rating 10 signs and symptoms: nausea; tremor; autonomic hyperactivity; anxiety; agitation; tactile, visual, and auditory disturbances; headache; and disorientation. Total scores range from 0-67. Higher scores indicate greater severity of withdrawal. | Baseline through Week 16 |
| Change From Baseline in Gastrointestinal Symptom Rating Scale (GSRS) Total Score at Week 16 Endpoint | The GSRS is a clinician-administered scale used to assess upper and lower gastrointestinal physical symptoms. 15 items covering domains of abdominal pain, reflux syndrome, indigestion syndrome, diarrhea syndrome, and constipation syndrome were assessed with a 1-week recall period. Total scores range from 0-45. Higher scores indicate greater severity of symptoms. Least Squares (LS) Mean value was controlled for treatment, pooled investigator, gender, family history, visit, baseline, gender*family history, treatment*visit, baseline*visit. An unstructured covariance structure was used. | Baseline, Week 16 |
| United States |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Lafayette | Indiana | 47905 | United States |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Baltimore | Maryland | 21205 | United States |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Belmont | Massachusetts | 02478 | United States |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Rochester | Minnesota | 55905 | United States |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Omaha | Nebraska | 68133 | United States |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Lebanon | New Hampshire | 03756 | United States |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | New York | New York | 10016 | United States |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Chapel Hill | North Carolina | 27599 | United States |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Charlotte | North Carolina | 28211 | United States |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Cincinnati | Ohio | 45237 | United States |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Portland | Oregon | 97210 | United States |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Philadelphia | Pennsylvania | 19104 | United States |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Providence | Rhode Island | 02908 | United States |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Charleston | South Carolina | 29425 | United States |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | San Antonio | Texas | 78229 | United States |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Seattle | Washington | 98104 | United States |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | LY2196044 | 250 milligram (mg) (titrate via 1 week at 50 mg and 1 week at 125 mg), once daily, orally, 16 weeks |
| BG001 | Placebo | once daily, orally, 16 weeks |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Number | participants |
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| Region of Enrollment | Number | participants |
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| Years of Alcohol Use | Mean | Standard Deviation | years |
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| Years of Heavy Drinking | Heavy drinking is defined as ≥4 drinks/day for women and ≥5 drinks/day for men. | Mean | Standard Deviation | years |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Percentage of Heavy Drinking Days at Week 16 Endpoint | The Timeline Followback Method assesses the subject's daily drinking by means of a calendar that covers a specific time period and was used to assess the number of heavy drinking days. Heavy drinking is defined as ≥4 drinks/day for women and ≥5 drinks/day for men. Least Squares (LS) Mean value was controlled for treatment, pooled investigator, visit, gender, family history, treatment*visit, gender*family history, baseline, and baseline*visit. An unstructured covariance structure was used. | Participants with a baseline and post-baseline value. | Posted | Least Squares Mean | Standard Error | percentage of days | Week 16 |
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| Secondary | Change From Baseline in Drinks Per Day at Week 16 Endpoint | The Timeline Followback Method assesses the subject's daily drinking by means of a calendar that covers a specific time period and was used to assess the number of drinks consumed per day. Least Squares (LS) Mean value was controlled for treatment, pooled investigator, visit, gender, family history, treatment*visit, gender*family history, baseline, and baseline*visit. An unstructured covariance structure was used. | Participants with a baseline and post-baseline value. | Posted | Least Squares Mean | Standard Error | number of drinks/day | Baseline, Week 16 |
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| Secondary | Change From Baseline in Percentage of Days Abstinent at Week 16 Endpoint | The Timeline Followback Method assesses the subject's daily drinking by means of a calendar that covers a specific time period and was used to assess the percentage of days abstinent. Least Squares (LS) Mean value was controlled for treatment, pooled investigator, visit, gender, family history, treatment*visit, gender*family history, baseline, and baseline*visit. An unstructured covariance structure was used. | Participants with a baseline and post-baseline value. | Posted | Least Squares Mean | Standard Error | percentage of days | Baseline, Week 16 |
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| Secondary | Change From Baseline in Drinks Per Drinking Day at Week 16 Endpoint | The Timeline Followback Method assesses the subject's daily drinking by means of a calendar that covers a specific time period and was used to assess the number of drinks consumed on the days the participant drank. Least Squares (LS) Mean value was controlled for treatment, pooled investigator, visit, gender, family history, treatment*visit, gender*family history, baseline, and baseline*visit. An unstructured covariance structure was used. | Participants with a baseline and post-baseline value. | Posted | Least Squares Mean | Standard Error | number of drinks/drinking day | Baseline, Week 16 |
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| Secondary | Change From Baseline in Drinks Per Heavy Drinking Day at Week 16 Endpoint | The Timeline Followback Method assesses the subject's daily drinking by means of a calendar that covers a specific time period and was used to assess the number of drinks consumed on heavy drinking days. Heavy drinking is defined as ≥4 drinks/day for women and ≥5 drinks/day for men. Least Squares (LS) Mean value was controlled for treatment, pooled investigator, visit, gender, family history, treatment*visit, gender*family history, baseline, and baseline*visit. An unstructured covariance structure was used. | Participants with a baseline and post-baseline value. | Posted | Least Squares Mean | Standard Error | number of drinks/heavy drinking day | Baseline, Week 16 |
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| Secondary | Change From Baseline in Obsessive Compulsive Drinking Scale (OCDS) Total Score at Week 16 Endpoint | Cravings will be assessed using the OCDS. The OCDS is a 14-item self-rating instrument. Total scores range from 0-40. Higher scores indicate more obsessive and craving. Least Squares (LS) Mean value was controlled for treatment, site, visit, gender, history, baseline, gender*history, treatment*visit, baseline*visit, gender*treatment, gender*treatment*visit. Subject was treated as a random effect. An unstructured covariance structure was used. | Participants with a baseline and post-baseline value. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline, Week 16 |
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| Secondary | Change From Baseline in Drinker Inventory of Consequences (DrInC) - Recent Consequences (DrInC-2R) Total Score at Week 16 Endpoint | 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. DrInC-2R provides a measurement since the last interview. Total scores range from 0-150, and higher scores indicate greater severity of symptoms. Least Squares (LS) Mean value was controlled for treatment, pooled investigator, visit, gender, family history, baseline, gender*family history, treatment*visit, baseline*visit. Subject was treated as a random effect. An unstructured covariance structure was used. | Participants with a baseline and post-baseline value. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline, Week 16 |
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| Secondary | Ratio of Geometric Means Over Baseline in Gamma-Glutamyltransferase (GGT) Level at Week 16 Endpoint | GGT and carbohydrate-deficient transferrin (%CDT) will be used as biochemical markers of alcohol consumption. A combination of GGT and %CDT improves the sensitivity of detecting excessive alcohol consumption as compared to either marker alone, or other traditional markers. Elevated levels indicate heavy alcoholism. Least Squares (LS) Mean value was controlled for treatment, pooled investigator, visit, gender, family history, baseline, gender*family history, treatment*visit, baseline*visit. An unstructured covariance structure was used. | Participants with a baseline and post-baseline value. | Posted | Geometric Mean | Standard Error | ratio | Week 16 |
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| Secondary | Ratio of Geometric Means Over Baseline in Percent Carbohydrate-Deficient Transferrin (%CDT) Level at Week 16 Endpoint | Gamma-Glutamyltransferase (GGT) and %CDT will be used as biochemical markers of alcohol consumption. A combination of GGT and %CDT improves the sensitivity of detecting excessive alcohol consumption as compared to either marker alone, or other traditional markers. Elevated levels indicate heavy alcoholism. Least Squares (LS) Mean value was controlled for treatment, pooled investigator, visit, gender, family history, baseline, gender*family history, treatment*visit, baseline*visit. An unstructured covariance structure was used. | Participants with a baseline and post-baseline value. | Posted | Geometric Mean | Standard Error | ratio | Week 16 |
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| Secondary | Ratio of Geometric Means Over Baseline in Aspartate Transaminase (AST) Level at Week 16 Endpoint | AST is a potential biomarker for LY2196044 efficacy as decreases reflect decreased alcohol consumption. Least Squares (LS) Mean value was controlled for treatment, pooled investigator, visit, gender, family history, baseline, gender*family history, treatment*visit, baseline*visit. An unstructured covariance structure was used. | Participants with a baseline and post-baseline value. | Posted | Geometric Mean | Standard Error | ratio | Week 16 |
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| Secondary | Change From Baseline in Beck Depression Inventory II (BDI-II) Total Score at Week 16 Endpoint | The BDI-II contains 21 items that characterize how the subject was feeling in the past 2 weeks. There is a 4-point scale for each item ranging from 0 to 3 (0=no depression; 3=very depressed). Total scores range from 0-63. Higher scores indicate greater severity of depression. Least Squares (LS) Mean value was controlled for treatment, pooled investigator, gender, family history, baseline, gender*family history, treatment*visit, baseline*visit. An unstructured covariance structure was used. | Participants with a baseline and post-baseline value. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline, Week 16 |
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| Secondary | Change From Baseline in Beck Anxiety Inventory (BAI) Total Score at Week 16 Endpoint | BAI is a 21-item patient-completed questionnaire designed to assess the characteristics of anxiety. Participant was asked to rate how much he or she has been bothered by each symptom over the past week. Each item is rated on a 4-point scale (0=not present; 3=present in the extreme). Total scores range from 0 to 63. The higher the score, the more severe the anxiety symptoms. LS Mean value was controlled for treatment, pooled investigator, gender, family history, visit, baseline, gender*family history, treatment*visit, baseline*visit. An unstructured covariance structure was used. | Participants with a baseline and post-baseline value. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline, Week 16 |
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| Secondary | Change From Baseline in Barratt Impulsivity Scale-11 (BIS-11) Total Score at Week 16 Endpoint | The BIS-11 is a 30-item, self-administered impulsivity scale. Motor, cognitive, and non-planning domains are assessed and a total score is computed. This scale has previously been used in substance-abusing populations. Total scores range from 30-120. Higher scores indicate greater severity of symptoms. Least Squares (LS) Mean value was controlled for treatment, pooled investigator, gender, family history, baseline, gender*family history. | Participants with a baseline and post-baseline value. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline, Week 16 |
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| Secondary | Change From Baseline in Thoughts About Abstinence Scale at Week 16 Endpoint | Thoughts About Abstinence Scale was to measure participant's commitment to abstinence. It includes 3 items on a scale of 1-10: own desire to stop drinking (1=no desire to quit); own expectation of success in quitting (1=lowest expectation of success); how difficult to quit and remain abstinent (1=lowest amount of difficulty); and their goal related to alcohol use (scale of 1-7: 1=having no goal, up to total abstinence at 6 [7 was none of 6 above]). Least Squares (LS) Mean value was controlled for treatment, pooled investigator, gender, family history, baseline, gender*family history. | Participants with a baseline and post-baseline value. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline, Week 16 |
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| Secondary | Change From Baseline in Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) Total Score at Week 16 Endpoint | Q-LES-Q-SF is a self-report instrument that assesses the degree of enjoyment and satisfaction in daily life activities. The domains include: social relationships, living or house situation, and physical health. Total scores range from 14-70. Higher scores indicate better quality of life. Least Squares (LS) Mean value was controlled for treatment, pooled investigator, gender, family history, visit, baseline, gender*family history, treatment*visit, baseline*visit. An unstructured covariance structure was used. | Participants with a baseline and post-baseline value. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline, Week 16 |
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| Secondary | Change From Baseline in Endicott Work Productivity Scale (EWPS) Total Score at Week 16 Endpoint | EWPS is a self-rated work productivity scale that assesses such topics as work hours, work missed, and behaviors and feelings related to the workplace. The EWPS will be completed only by subjects who work outside the home. There are 25 items and total scores range from 0-100. Higher scores indicate poorer productivity. Least Squares (LS) Mean value was controlled for treatment, pooled investigator, gender, family history, visit, baseline, gender*family history, treatment*visit, baseline*visit. An unstructured covariance structure was used. | Participants with a baseline and post-baseline value. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline, Week 16 |
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| Secondary | Population Pharmacokinetic (PK) - Apparent Clearance | Plasma concentrations were analyzed using population PK methodology with non-linear mixed effect modeling (NONMEM) software. | Participants who took study drug and contributed PK sample. | Posted | Mean | Standard Error | Liter/hour (L/hr) | Over 16 weeks |
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| Secondary | Population Pharmacokinetic (PK) - Apparent Volume of Distribution | Plasma concentrations were analyzed using population PK methodology with non-linear mixed effect modeling (NONMEM) software. | Participants who took study drug and contributed PK sample. | Posted | Mean | Standard Error | Liter (L) | Over 16 weeks |
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| Secondary | Change From Baseline in Supine Blood Pressure (BP) at Week 16 Endpoint | Least Squares (LS) Mean value was controlled for treatment, pooled investigator, visit, baseline, treatment*visit. An unstructured covariance structure was used. | Participants who took at least one dose of study drug. | Posted | Least Squares Mean | Standard Error | millimeters of mercury (mmHg) | Baseline, Week 16 |
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| Secondary | Change From Baseline in Supine Pulse Rate at Week 16 Endpoint | Least Squares (LS) Mean value was controlled for treatment, pooled investigator, visit, baseline, treatment*visit. An unstructured covariance structure was used. | Participants who took at least one dose of study drug. | Posted | Least Squares Mean | Standard Error | beats per minute (bpm) | Baseline, Week 16 |
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| Secondary | Change From Baseline in QTc Fridericia's Correction Interval (QTcF) Measured by Electrocardiograms at Week 16 Endpoint | Least Squares (LS) Mean value was controlled for treatment, pooled investigator, visit, baseline, treatment*visit. An unstructured covariance structure was used. | Participants who took at least one dose of study drug. | Posted | Least Squares Mean | Standard Error | milliseconds | Baseline, Week 16 |
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| Secondary | Percentage of Participants Discontinuation Due to Adverse Events (AEs) | Percentage of participants discontinued study due to one or more AEs. | Participants who took at least one dose of study drug. | Posted | Number | percentage of participants | Baseline through Week 16 |
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| Secondary | Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) | Percentage of participants had one or more TEAEs during treatment period. TEAE is a worsening or new occurrence of adverse event during treatment compared to baseline. | Participants who took at least one dose of study drug. | Posted | Number | percentage of participants | Baseline through Week 16 |
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| Secondary | Change From Baseline in Orthostatic Blood Pressure (BP) at Week 16 Endpoint | Orthostatic BP is the BP measured within 3 minutes of standing. Least Squares (LS) Mean value was controlled for treatment, pooled investigator, visit, baseline, treatment*visit. An unstructured covariance structure was used. | Posted | Least Squares Mean | Standard Error | mmHg | Baseline, Week 16 |
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| Secondary | Change From Baseline in Orthostatic Pulse Rate at Week 16 Endpoint | Orthostatic pulse rate is the pulse rate measured within 3 minutes of standing. Least Squares (LS) Mean value was controlled for treatment, pooled investigator, visit, baseline, treatment*visit. An unstructured covariance structure was used. | Participants who took at least one dose of study drug. | Posted | Least Squares Mean | Standard Error | beats per minute | Baseline, Week 16 |
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| Secondary | Number of Participants With Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA-Ar)≥10 at Any Time From Baseline Through Week 16 Endpoint | The revised CIWA-Ar scale measured the severity of alcohol withdrawal by rating 10 signs and symptoms: nausea; tremor; autonomic hyperactivity; anxiety; agitation; tactile, visual, and auditory disturbances; headache; and disorientation. Total scores range from 0-67. Higher scores indicate greater severity of withdrawal. | Participants who took at least one dose of study drug. | Posted | Number | participants | Baseline through Week 16 |
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| Secondary | Change From Baseline in Gastrointestinal Symptom Rating Scale (GSRS) Total Score at Week 16 Endpoint | The GSRS is a clinician-administered scale used to assess upper and lower gastrointestinal physical symptoms. 15 items covering domains of abdominal pain, reflux syndrome, indigestion syndrome, diarrhea syndrome, and constipation syndrome were assessed with a 1-week recall period. Total scores range from 0-45. Higher scores indicate greater severity of symptoms. Least Squares (LS) Mean value was controlled for treatment, pooled investigator, gender, family history, visit, baseline, gender*family history, treatment*visit, baseline*visit. An unstructured covariance structure was used. | Participants with a baseline and post-baseline value. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline, Week 16 |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | LY2196044 | 250 milligram (mg) (titrate via 1 week at 50 mg and 1 week at 125 mg), once daily (QD), orally (PO), 16 weeks | 4 | 187 | 143 | 187 | ||
| EG001 | Placebo | once daily (QD), orally (PO), 16 weeks | 5 | 188 | 116 | 188 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
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| Biliary colic | Hepatobiliary disorders | MedDRA 13.0 | Systematic Assessment |
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| Cholecystitis | Hepatobiliary disorders | MedDRA 13.0 | Systematic Assessment |
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| Appendicitis | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
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| Muscle strain | Injury, poisoning and procedural complications | MedDRA 13.0 | Systematic Assessment |
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| Blood creatine phosphokinase increased | Investigations | MedDRA 13.0 | Systematic Assessment |
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| Blood creatine phosphokinase mb increased | Investigations | MedDRA 13.0 | Systematic Assessment |
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| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
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| Alcoholism | Psychiatric disorders | MedDRA 13.0 | Systematic Assessment |
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| Depression | Psychiatric disorders | MedDRA 13.0 | Systematic Assessment |
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| Alcohol detoxification | Surgical and medical procedures | MedDRA 13.0 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal distension | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
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| Flatulence | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
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| Frequent bowel movements | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
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| Gastrointestinal sounds abnormal | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 13.0 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
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| Blood creatine phosphokinase increased | Investigations | MedDRA 13.0 | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA 13.0 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA 13.0 | Systematic Assessment |
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| Libido decreased | Psychiatric disorders | MedDRA 13.0 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 13.0 | Systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA 13.0 | Systematic Assessment |
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Based on exposure data from an Alcohol Interaction study, H9T-MC-NABL (unregistered Phase 1 trial), the maximum dose in this study was reduced from 250 mg to 125 mg of LY2196044 after about 2/3 into the conduct of the trial.
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Eli Lilly and Company | 800-545-5979 |
| ID | Term |
|---|---|
| D000437 | Alcoholism |
| ID | Term |
|---|---|
| D019973 | Alcohol-Related Disorders |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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Not provided
| ID | Term |
|---|---|
| C586667 | LY2196044 |
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| American Indian or Alaska Native |
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| Unknown/Missing |
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