Effectiveness of GW468816, an NMDA Glycine Site Antagonist, for Prevention of Relapse to Smoking
Condition: Nicotine Dependence
MeSH terms: Recurrence; Tobacco Use Disorder
Intervention: GW468816; Placebo Comparator: Placebo
Intervention description: Pharmacotherapies for Relapse Prevention
Intervention MeSH terms: Glycine
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 264.0
Sex: Female
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Drugs, Investigational; Therapies for Relapse to Nicotine; Relapse Prevention; Nicotine Cessation Therapies; Smoking Cessation; Nicotine Dependence

Summary:

      The purpose of this study is to evaluate the efficacy of the glycine antagonist, GW468816,
      compared with placebo on duration of abstinence and rates of relapse in recently quit female
      smokers in a randomized, double-blind, five-week clinical trial.

      According to the investigators, the new medication, GW468816, is thought to send certain
      signals in the brain that may be effective in helping people stay abstinent after they have
      recently quit smoking. GW468816 is a non-nicotine drug.

      The investigators of this study hypothesize that subjects receiving GW468816 will demonstrate
      a significantly longer time to relapse to smoking than those in the placebo group, as
      measured by the primary outcome measure (see below).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Written informed consent

          2. WOMEN aged 18-65 years, inclusive

          3. Self-report of smoking 10 or more cigarettes per day in the past 6 months and expired
             air CO >10 ppm at the time of enrollment

          4. DSM-IV criteria for current Nicotine Dependence satisfied

          5. Subjects must be willing to take the study medication and be motivated to quit smoking
             (willing to set a quit date within 2 weeks of entry into the protocol)

          6. Women of childbearing potential must have a negative urine pregnancy test
             (quantitative HCG) at baseline and at week 8, prior to receiving the first dose of
             study medication and females must agree to use an approved form of contraception from
             the day of the first dose of study medication for 90 days after the last dose of study
             medication. Approved forms of contraception include any of the following:

               -  Complete abstinence from intercourse from 2 weeks prior to administration of the
                  study drug, through the treatment phase and for 90 days after discontinuation of
                  study medication.

               -  Sterilization of male partner

               -  Implant of levonorgestrel

               -  Injectable progesterone

               -  Intrauterine device (IUD) with <1 percent rate of failure per year

               -  Any other method with published rate of failure of <1 percent per year Due to
                  induction of cytochrome p450 3A4, oral contraceptives may be continued during the
                  study but cannot be relied upon as a sole means of contraception, and a second
                  method of contraception such as a barrier method will be required and reimbursed
                  by the study.

        Exclusion Criteria:

          1. Pregnant or able to become pregnant and not willing to use approved contraception

          2. Severe unstable medical illness including cardiovascular, hepatic, renal, respiratory,
             metabolic, neurological, or hematological disease by history, physical examination or
             clinical laboratory test results such that hospitalization for treatment of that
             illness is likely within the next two months

          3. Life-threatening arrhythmia, cerebro-vascular or cardiovascular event within six
             months of enrollment

          4. Elevation over 1.5 times upper limit of normal value (ULN) of any of the following
             laboratory results: Total, conjugated, or unconjugated bilirubin; alkaline
             phosphatase, alanine transferase (ALT), aspartate aminotransferase (AST), creatine
             phosphokinase (CPK), or lactate dehydrogenase (LDH).

          5. Use of tobacco-containing products other than cigarettes (e.g., cigar, pipe)

          6. Abuse or dependence of any substance other than nicotine or caffeine in the past 6
             months. Abuse of alcohol is here defined as an average weekly intake of greater than
             21 units or an average daily intake of greater than three units (males) or defined as
             an average weekly intake of greater than 14 units or an average daily intake of
             greater than two units (females). One unit is equivalent to a half-pint (220mL) of
             beer or one (25mL) measure of spirits or one glass (125mL) of wine.

          7. Diagnosis of major depressive disorder in the past 6 months

          8. Lifetime DSM-IV diagnosis of organic mental disorder, schizophrenia, schizoaffective
             disorder, bipolar disorder, delusional disorder or psychotic disorders not elsewhere
             classified

          9. History of non-response in the past month to an adequate trial of nicotine re
             placement therapy, defined as nicotine replacement > 21 mg per day patch (or
             equivalent dose of gum, inhaler, nasal spray, or lozenge) for at least 4 weeks.

         10. History of multiple adverse drug reactions

         11. Use of an investigational drug or device within 4 weeks of enrollment

         12. Concurrently enrolled in a study that involves exposure to a drug or device.

         13. Urine positive for drugs of abuse at screening visit.

         14. Use of statins during the period of the investigation.