Clinical trial NCT00804570: A Study for the Treatment of Alcohol Dependence
Official title: A Phase 2 Study of LY2196044 Compared With Placebo in the Treatment of Alcohol Dependence
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alcohol Dependence
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2008-12-09
Enrollment: 375
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* Have Alcohol Dependence. Subjects must manifest at least the following 3 requirements for their diagnosis of Alcohol Dependence:

  1. Be tolerant, as defined by either of the following:

     1. A need for markedly increased amounts of alcohol to achieve intoxication or desired effect.
     2. Markedly diminished effect with continued use of the same amount of alcohol.
  2. Consume alcohol, often in larger amounts or over a longer period than was intended.
  3. 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.

  * Note: Subjects who discontinue/washout excluded medications prior to Randomization are not excluded from participation.
* 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.

Primary outcomes:
measure: Percentage of Heavy Drinking Days at Week 16 Endpoint
timeFrame: Week 16
Secondary outcomes:
measure: Change From Baseline in Drinks Per Day at Week 16 Endpoint
timeFrame: Baseline, Week 16
measure: Change From Baseline in Percentage of Days Abstinent at Week 16 Endpoint
timeFrame: Baseline, Week 16
measure: Change From Baseline in Drinks Per Drinking Day at Week 16 Endpoint
timeFrame: Baseline, Week 16
measure: Change From Baseline in Drinks Per Heavy Drinking Day at Week 16 Endpoint
timeFrame: Baseline, Week 16
measure: Change From Baseline in Obsessive Compulsive Drinking Scale (OCDS) Total Score at Week 16 Endpoint
timeFrame: Baseline, Week 16
measure: Change From Baseline in Drinker Inventory of Consequences (DrInC) - Recent Consequences (DrInC-2R) Total Score at Week 16 Endpoint
timeFrame: Baseline, Week 16
measure: Ratio of Geometric Means Over Baseline in Gamma-Glutamyltransferase (GGT) Level at Week 16 Endpoint
timeFrame: Week 16
measure: Ratio of Geometric Means Over Baseline in Percent Carbohydrate-Deficient Transferrin (%CDT) Level at Week 16 Endpoint
timeFrame: Week 16
measure: Ratio of Geometric Means Over Baseline in Aspartate Transaminase (AST) Level at Week 16 Endpoint
timeFrame: Week 16
measure: Change From Baseline in Beck Depression Inventory II (BDI-II) Total Score at Week 16 Endpoint
timeFrame: Baseline, Week 16
measure: Change From Baseline in Beck Anxiety Inventory (BAI) Total Score at Week 16 Endpoint
timeFrame: Baseline, Week 16
measure: Change From Baseline in Barratt Impulsivity Scale-11 (BIS-11) Total Score at Week 16 Endpoint
timeFrame: Baseline, Week 16
measure: Change From Baseline in Thoughts About Abstinence Scale at Week 16 Endpoint
timeFrame: Baseline, Week 16
measure: Change From Baseline in Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) Total Score at Week 16 Endpoint
timeFrame: Baseline, Week 16
measure: Change From Baseline in Endicott Work Productivity Scale (EWPS) Total Score at Week 16 Endpoint
timeFrame: Baseline, Week 16
measure: Population Pharmacokinetic (PK) - Apparent Clearance
timeFrame: Over 16 weeks
measure: Population Pharmacokinetic (PK) - Apparent Volume of Distribution
timeFrame: Over 16 weeks
measure: Change From Baseline in Supine Blood Pressure (BP) at Week 16 Endpoint
timeFrame: Baseline, Week 16
measure: Change From Baseline in Supine Pulse Rate at Week 16 Endpoint
timeFrame: Baseline, Week 16
measure: Change From Baseline in QTc Fridericia's Correction Interval (QTcF) Measured by Electrocardiograms at Week 16 Endpoint
timeFrame: Baseline, Week 16
measure: Percentage of Participants Discontinuation Due to Adverse Events (AEs)
timeFrame: Baseline through Week 16
measure: Percentage of Participants With Treatment-Emergent Adverse Events (TEAE)
timeFrame: Baseline through Week 16
measure: Change From Baseline in Orthostatic Blood Pressure (BP) at Week 16 Endpoint
timeFrame: Baseline, Week 16
measure: Change From Baseline in Orthostatic Pulse Rate at Week 16 Endpoint
timeFrame: Baseline, Week 16
measure: Number of Participants With Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA-Ar)≥10 at Any Time From Baseline Through Week 16 Endpoint
timeFrame: Baseline through Week 16
measure: Change From Baseline in Gastrointestinal Symptom Rating Scale (GSRS) Total Score at Week 16 Endpoint
timeFrame: Baseline, Week 16
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: 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.
state: Indiana
city: Lafayette
country: United States
facility: 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.
state: Indiana
city: Baltimore
country: United States
facility: 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.
state: Maryland
city: Belmont
country: United States
facility: 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.
state: Massachusetts
city: Rochester
country: United States
facility: 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.
state: Minnesota
city: Omaha
country: United States
facility: 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.
state: Nebraska
city: Lebanon
country: United States
facility: 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.
state: New Hampshire
city: New York
country: United States
facility: 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.
state: New York
city: Chapel Hill
country: United States
facility: 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.
state: North Carolina
city: Charlotte
country: United States
facility: 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.
state: North Carolina
city: Cincinnati
country: United States
facility: 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.
state: Ohio
city: Portland
country: United States
facility: 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.
state: Oregon
city: Philadelphia
country: United States
facility: 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.
state: Pennsylvania
city: Providence
country: United States
facility: 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.
state: Rhode Island
city: Charleston
country: United States
facility: 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.
state: South Carolina
city: San Antonio
country: United States
facility: 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.
state: Texas
city: Seattle
country: United States
facility: 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.
state: Washington
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References: