Effectiveness of GSK598809, a Selective D3 Antagonist, Added to CBT and NRT for Smoking Cessation and Relapse Prevention
Condition: Nicotine Dependence
MeSH terms: Recurrence; Tobacco Use Disorder
Intervention: GSK598809; Placebo
Intervention description: Oral dose of 60 mg/day for a treatment period six weeks; Placebo
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 84.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Drugs, Investigational; Nicotine Dependence; Therapies for Relapse to Nicotine; Relapse Prevention; Smoking Cessation; Nicotine Cessation Therapies

Summary:

      The purpose of this research study is to find out if an investigational drug, GSK598809 can
      help people who have very recently quit smoking; the investigators want to find out if
      continuing to take GSK598809 over six weeks can help prevent smokers from relapsing. To
      relapse means you "fall back" into smoking again after quitting. The investigators also want
      to find out if GSK598809 is safe to take without causing too many side effects.
    

Eligibility criteria:

        Exclusion criteria:

          1. Pregnant or able to become pregnant and not willing to use approved contraception.

          2. Breastfeeding or planning to breastfeed during the study or lactating within the month
             prior to enrollment.

          3. Has any of the following medical conditions/situations:

             Severe or unstable COPD or Asthma Bundle branch block Evidence of active neurological
             disease, including current migraine headaches requiring chronic treatment.

             Clinically significant renal dysfunction eGFR <60 History of any tissue/organ
             transplant Total fasting cholesterol or triglycerides greater than 2 times the upper
             limit of normal Previous or current history of cancer, including skin cancer Serum
             Prolactin > 25 ng/mL at the time of screening or randomization Evidence of chronic
             liver disease or ALT, AST, or alkaline phosphatase values >1.5 times the upper limit
             of normal, total bilirubin values > the upper limit of normal, or history of severe
             hepatobiliary disease (e.g. hepatitis B or C, or cirrhosis, Child-Pugh Class B/C)
             Positive screening Hepatitis B surface antigen or Hepatitis C antibody, or positive
             result within 3 months of screening A positive test for HIV antibody Any other
             unstable cardiovascular or pulmonary disease, or medication for said diseases has been
             changed in the past 3 months, or the medication is listed on the excluded medications
             list.

          4. Is unlikely to cooperate or unable to follow all of the procedures outlined in the
             protocol

          5. Use of tobacco-containing products other than cigarettes (e.g., cigar, pipe) and
             unwilling to discontinue use of these on the quit date.

          6. Abuse or dependence of any substance other than nicotine or caffeine in the past 6
             months.

          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 as determined by SCID.

          9. History of multiple adverse drug reactions.

         10. Has participated in a clinical trial and has received an investigational product
             within the following time period prior to the first dosing day in the current study:
             30 days, 5 half-lives or twice the duration of the biological effect of the
             investigational product (whichever is longer).

         11. Urine positive for drugs of abuse at screening and any pre-randomization visit.

         12. Alcohol abuse, defined as self-report of an average weekly intake of > 21 standard
             drinks or an average daily intake of >3 standard drinks (males) or an average weekly
             intake of >14 standard drinks or an average daily intake of >2 standard drinks
             (females) in the past 6 months. One unit is equivalent to a half-pint (220mL) of beer
             or one (25mL) measure of spirits or one glass (125mL) of wine. Participants will be
             advised to minimize alcohol consumption during the study, as there may be the
             potential for additive effects of study medication and alcohol, potentially causing
             greater sedation and feeling of intoxication than alcohol alone.

         13. Has been exposed to more than four new chemical entities within 12 months prior to the
             first day of the double-blind treatment phase.

         14. Has used non-prescription drugs or herbal medicines that are centrally active within
             14 days prior to the first dosing day, with the exception of non-daily PRN use of
             acetaminophen or ibuprofen and daily use of vitamins.

         15. Has ever used chronic antipsychotic, anti-epileptic, or mood stabilizing medication;
             has used anti-anxiety medication, antidepressant medication, or prescription sedatives
             or hypnotics within 5 half lives or two weeks of randomization, whichever is greater.

         16. Has a history of sensitivity to any of the study medications, or components thereof or
             a history of drug or other allergy that, in the opinion of the investigator makes
             participation contraindicated.

         17. Has donated blood such that participation in the study would result in donation of
             blood or blood products in excess of 500 ml within a 56-day period.

         18. Has a failed smoking cessation attempt using adequate smoking cessation
             pharmacotherapy within the last month.

         19. Current Axis II DSM-IV diagnosis that may interfere with the conduct of the study.

         20. Personal or family history of long QT syndrome, personal or family history of
             unexplained syncope, or family history of unexplained sudden death.

         21. Currently using, or have used within the month prior to study start, any drug that can
             cause prolongation of the QT interval.

         22. Currently using any HMG CoA Reductase Inhibitor.