Varenicline Treatment of Alcohol Dependence in Smokers

• Percentage of heavy drinking days during the last 8 weeks of treatment [ Time Frame: week 11 ] [ Designated as safety issue: No ]
  The percentage of days of heavy drinking will be examined over the final 8 weeks of the study averaged by month (weeks 9-12 and weeks 13-16). A heavy drinking day is defined as 5 or more standard drinks for men and 4 or more standard drinks for women. A standard drink contains approximately 0.6 fluid ounces of pure alcohol.
• Percentage of heavy drinking days during the last 8 weeks of treatment [ Time Frame: week 13 ] [ Designated as safety issue: No ]
  The percentage of days of heavy drinking will be examined over the final 8 weeks of the study averaged by month (weeks 9-12 and weeks 13-16). A heavy drinking day is defined as 5 or more standard drinks for men and 4 or more standard drinks for women. A standard drink contains approximately 0.6 fluid ounces of pure alcohol.
• Percentage of heavy drinking days during the last 8 weeks of treatment [ Time Frame: Week 15 ] [ Designated as safety issue: No ]
  The percentage of days of heavy drinking will be examined over the final 8 weeks of the study averaged by month (weeks 9-12 and weeks 13-16). A heavy drinking day is defined as 5 or more standard drinks for men and 4 or more standard drinks for women. A standard drink contains approximately 0.6 fluid ounces of pure alcohol.
• Percentage of heavy drinking days during the last 8 weeks of treatment [ Time Frame: Week 17 ] [ Designated as safety issue: No ]
  The percentage of days of heavy drinking will be examined over the final 8 weeks of the study averaged by month (weeks 9-12 and weeks 13-16). A heavy drinking day is defined as 5 or more standard drinks for men and 4 or more standard drinks for women. A standard drink contains approximately 0.6 fluid ounces of pure alcohol.

• Percentage of heavy drinking days during the last 8 weeks of treatment [ Time Frame: week 10 ] [ Designated as safety issue: No ]
  The percentage of days of heavy drinking will be examined over the final 8 weeks of the study averaged by month (weeks 9-12 and weeks 13-16). A heavy drinking day is defined as 5 or more standard drinks for men and 4 or more standard drinks for women. A standard drink contains approximately 0.6 fluid ounces of pure alcohol.
• Percentage of heavy drinking days during the last 8 weeks of treatment [ Time Frame: week 12 ] [ Designated as safety issue: No ]
  The percentage of days of heavy drinking will be examined over the final 8 weeks of the study averaged by month (weeks 9-12 and weeks 13-16). A heavy drinking day is defined as 5 or more standard drinks for men and 4 or more standard drinks for women. A standard drink contains approximately 0.6 fluid ounces of pure alcohol.
• Percentage of heavy drinking days during the last 8 weeks of treatment [ Time Frame: Week 14 ] [ Designated as safety issue: No ]
  The percentage of days of heavy drinking will be examined over the final 8 weeks of the study averaged by month (weeks 9-12 and weeks 13-16). A heavy drinking day is defined as 5 or more standard drinks for men and 4 or more standard drinks for women. A standard drink contains approximately 0.6 fluid ounces of pure alcohol.
• Percentage of heavy drinking days during the last 8 weeks of treatment [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
  The percentage of days of heavy drinking will be examined over the final 8 weeks of the study averaged by month (weeks 9-12 and weeks 13-16). A heavy drinking day is defined as 5 or more standard drinks for men and 4 or more standard drinks for women. A standard drink contains approximately 0.6 fluid ounces of pure alcohol.

• Smoking abstinence [ Time Frame: abstinence over the last month of treatment is based on data obtained at weeks 15 and 17 ] [ Designated as safety issue: No ]
  Smoking abstinence is defined by self-reported abstinence from smoking for the last four weeks of treatment (weeks 13-16) and a urine cotinine level less than 15ng/mL measured at week 17.
• Drinking related consequences [ Time Frame: End of treatment (Week 17) ] [ Designated as safety issue: No ]
  A self-report measure of negative consequences from drinking will be administered and the total score will be analyzed.

• Smoking abstinence [ Time Frame: abstinence over the last month of treatment is based on data obtained at weeks 14 and 16 ] [ Designated as safety issue: No ]
  Smoking abstinence is defined by self-reported abstinence from smoking for the last four weeks of treatment (weeks 13-16) and a urine cotinine level less than 15ng/mL measured at week 16.
• Drinking related consequences [ Time Frame: End of treatment (Week 16) ] [ Designated as safety issue: No ]
  A self-report measure of negative consequences from drinking will be administered and the total score will be analyzed.

The purpose of this study is to determine whether varenicline is effective in the treatment of alcohol dependence in smokers.

Building upon knowledge about the role of nicotinic acetylcholine receptors in alcohol drinking and smoking, varenicline, a smoking cessation treatment that targets these receptors, will be tested as a potential treatment for alcohol dependent smokers seeking alcohol treatment.

• Alcoholism
• Alcohol Abuse
• Smoking
• Alcohol Drinking

• Placebo Comparator: Sugar pill
  Intervention: Drug: Varenicline
• Active Comparator: Varenicline
  Intervention: Drug: Varenicline

Inclusion Criteria:

• are 18 - 70 years of age and seeking treatment of alcohol drinking;
• meet DSM-IV TR Criteria for Alcohol Dependence
• smoke ≥ 5 cigarettes/day for ≥ 6 months and have a CO > 10ppm;
• report heavy drinking on at least 2 days on average per week (i.e., ≥ 4 drinks on an occasion for women and ≥ 5 drinks for men) for the past 90 days and no more than 7 consecutive days of abstinence at intake.

Exclusion Criteria:

• exhibit current, clinically significant physical disease or abnormality based on medical history, physical examination, or routine laboratory evaluation including:

  • any unexplained elevations in liver enzymes (i.e., transaminases, bilirubin)
  • clinically significant, unstable cardiovascular disease/uncontrolled hypertension
  • hepatic or renal impairment
  • severe obstructive pulmonary disease
  • diabetes mellitus requiring insulin or certain oral medications (i.e., sulfonylureas) and an A1C hemoglobin test score of > 7 for participants not prescribed these medications
  • baseline systolic blood pressure higher than 150 mm Hg or diastolic blood pressure higher than 95 mm Hg
• have a history of cancer (except treated basal cell or squamous cell carcinoma of the skin)
• have a history of clinically significant allergic reactions
• exhibit serious psychiatric illness (i.e., schizophrenia, bipolar disorder, severe major depression, panic disorder, borderline personality disorder, organic mood or mental disorders by history or psychological examination
• report current suicidal ideation (past 6 months) or lifetime hx of suicidal behavior assessed with the Columbia Suicide Severity Rating Scale 60; or risk for aggression using a cut-off of 15 or more on the Overt Aggression Scale - Modified Aggression Scale or 6 or more on the OAS-M Irritability Subscale 61.
• have used any psychotropic drug in the past month, except individuals who are on a stable dose of a Selective Serotonin Reuptake Inhibitor for at least two months
• have a current DSM-IV diagnosis of drug dependence other than nicotine or alcohol

• are at risk for an alcohol withdrawal syndrome as evidenced by:

  • a history of seizures, delirium, or hallucinations during alcohol withdrawal
  • a Clinical Institute Withdrawal Assessment scale 62 score of > 8,
  • report drinking to avoid withdrawal symptoms
  • have required medical treatment of alcohol withdrawal within the past 6 months
• have used another investigational drug within 30 days or have used medications to treat alcohol (e.g., naltrexone, topiramate, acamprosate, disulfiram) or nicotine use (e.g., clonidine, varenicline, bupropion, nicotine replacement) in the past 3 months or intend to use these medications;prior use of nicotine replacement in situations where smoking is not permitted (e.g., planes) without the intention to quit smoking is not exclusionary;
• intend to donate blood or blood products during the treatment phase of the study
• have a Body Mass Index (calculated as weight in kilograms divided by the square of height in meters) less than 15 or greater than 38 or weight less than 45 kg
• are a female of childbearing potential who is pregnant, nursing, or not practicing effective contraception (oral, injectable, or implantable contraceptives, intrauterine device, or barrier method with spermicide).