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Phase 2 N=375 Randomized Triple-blind Treatment

A Study for the Treatment of Alcohol Dependence

Alcohol Dependence

Enrolled (actual)
375
Serious AEs
2.4%
Results posted
Feb 2017
Primary outcome: Primary: Percentage of Heavy Drinking Days at Week 16 Endpoint — -43.02; -38.72 percentage of days — p=0.120

Study Design & Population

Study type
Interventional
Phase
Phase 2
Interventions
LY2196044 (Drug); placebo (Drug)
Age
Adult, Older Adult · 21+ yrs
Sex
All
Sponsor
Eli Lilly and Company
Primary completion
Feb 2010

Outcome Measures

OutcomeResultp-value
PRIMARY
Percentage of Heavy Drinking Days at Week 16 Endpoint
-43.02; -38.72 0.120
SECONDARY
Change From Baseline in Drinks Per Day at Week 16 Endpoint
-5.37; -4.66 0.013 sig
SECONDARY
Change From Baseline in Percentage of Days Abstinent at Week 16 Endpoint
33.49; 28.12 0.051
SECONDARY
Change From Baseline in Drinks Per Drinking Day at Week 16 Endpoint
-3.77; -3.38 0.249
SECONDARY
Change From Baseline in Drinks Per Heavy Drinking Day at Week 16 Endpoint
-2.61; -2.17 0.199
SECONDARY
Change From Baseline in Obsessive Compulsive Drinking Scale (OCDS) Total Score at Week 16 Endpoint
-8.64; -7.96 0.318
SECONDARY
Change From Baseline in Drinker Inventory of Consequences (DrInC) - Recent Consequences (DrInC-2R) Total Score at Week 16 Endpoint
-16.54; -13.53 0.034 sig
SECONDARY
Ratio of Geometric Means Over Baseline in Gamma-Glutamyltransferase (GGT) Level at Week 16 Endpoint
0.85; 0.94 0.001 sig
SECONDARY
Ratio of Geometric Means Over Baseline in Percent Carbohydrate-Deficient Transferrin (%CDT) Level at Week 16 Endpoint
0.90; 0.94 0.103
SECONDARY
Ratio of Geometric Means Over Baseline in Aspartate Transaminase (AST) Level at Week 16 Endpoint
0.88; 0.94 0.012 sig
SECONDARY
Change From Baseline in Beck Depression Inventory II (BDI-II) Total Score at Week 16 Endpoint
-3.10; -2.78 0.392
SECONDARY
Change From Baseline in Beck Anxiety Inventory (BAI) Total Score at Week 16 Endpoint
-1.98; -1.54 0.185
SECONDARY
Change From Baseline in Barratt Impulsivity Scale-11 (BIS-11) Total Score at Week 16 Endpoint
-1.70; -2.95 0.142
SECONDARY
Change From Baseline in Thoughts About Abstinence Scale at Week 16 Endpoint
-0.60; -0.11; -0.20; -0.00; -1.11; -0.63 0.69
SECONDARY
Change From Baseline in Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) Total Score at Week 16 Endpoint
2.85; 2.08 0.297
SECONDARY
Change From Baseline in Endicott Work Productivity Scale (EWPS) Total Score at Week 16 Endpoint
-5.67; -6.13 0.633
SECONDARY
Population Pharmacokinetic (PK) - Apparent Clearance
36.5
SECONDARY
Population Pharmacokinetic (PK) - Apparent Volume of Distribution
587
SECONDARY
Change From Baseline in Supine Blood Pressure (BP) at Week 16 Endpoint
-1.22; -0.45; -1.53; -1.08 0.409
SECONDARY
Change From Baseline in Supine Pulse Rate at Week 16 Endpoint
-0.16; 0.37 0.456
SECONDARY
Change From Baseline in QTc Fridericia's Correction Interval (QTcF) Measured by Electrocardiograms at Week 16 Endpoint
-1.90; 0.18 0.081
SECONDARY
Percentage of Participants Discontinuation Due to Adverse Events (AEs)
7.5; 3.7 0.122
SECONDARY
Percentage of Participants With Treatment-Emergent Adverse Events (TEAE)
76.5; 61.7 0.002 sig
SECONDARY
Change From Baseline in Orthostatic Blood Pressure (BP) at Week 16 Endpoint
-1.23; -0.55; -0.07; 0.25 0.235
SECONDARY
Change From Baseline in Orthostatic Pulse Rate at Week 16 Endpoint
0.65; -0.09 0.077
SECONDARY
Number of Participants With Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA-Ar)≥10 at Any Time From Baseline Through Week 16 Endpoint
0; 0
SECONDARY
Change From Baseline in Gastrointestinal Symptom Rating Scale (GSRS) Total Score at Week 16 Endpoint
0.03; -0.54 <0.001 sig

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:
  • Be tolerant, as defined by either of the following:
  • A need for markedly increased amounts of alcohol to achieve intoxication or desired effect.
  • Markedly diminished effect with continued use of the same amount of alcohol.
  • 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.
  • 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.
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00804570). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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