Effectiveness of GW468816, an NMDA Glycine Site Antagonist, for Prevention of Relapse to Smoking
Condition: Nicotine Dependence
MeSH terms: Recurrence; Tobacco Use Disorder
Study type: Interventional
Phase: Phase 2

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).
    

Detailed description: 
      Smoking is the leading cause of preventable mortality in developed countries.
      Pharmacotherapy, including bupropion and nicotine replacement therapy (NRT), is universally
      recommended for smoking cessation treatment; however, even with treatment, the majority of
      smokers either fail to quit in the short term or relapse in the first year. The high failure
      rate reported for smoking cessation, then, presents a challenge to explore innovative
      approaches to treating relapse to smoking.

      The purpose of this study, then, is to evaluate the efficacy of the glycine antagonist,
      GW468816, compared with placebo on duration of abstinence and rates of relapse in female
      outpatient smokers during a randomized, double-blind, five-week clinical trial.

      To do this, the investigators will conduct a two-phase study, in which 300 adult, female
      outpatient smokers will be enrolled.

      Phase I will consist of an 8-week smoking cessation study in which nicotine replacement
      therapy (NRT) and a behavioral intervention are openly administered on a tapered schedule.
      Participants who are able to quit smoking after 7 weeks in this preliminary study will then
      be eligible to enter Phase II.

      Phase II is a 5-week, double-blind, placebo-controlled, relapse prevention trial with the
      investigational medication, GW468816.

      Participants in the Phase I smoking cessation study will begin by receiving nicotine
      replacement therapy in the form of the patch and brief support to stop smoking. Participants
      will be required to schedule office visits every 1-2 weeks throughout Phase I.

      Subjects who are abstinent at the end of Phase I will be eligible to continue Phase II, in
      which they will be randomly assigned by chance to receive the investigational medication,
      GW468816, at 200 mg or placebo (a pill that looks exactly like the study drug but contains no
      active drug). Participants will be required to schedule weekly office visits throughout Phase
      II.

      Subjects who complete the 15-week trial (both Phases I and II) will enter the 6-Month
      Follow-Up to evaluate rates of long term abstinence from nicotine. They will have office
      visits at Weeks 20, 24, 28, 32, 36, and 40 after discontinuation of study medications.

      Participants who enter the study will be offered the opportunity to participate in an
      ancillary neuroimaging study of mechanisms and surrogate markers of relapse that includes
      BOLD fMRI and MR spectroscopy, to be carried out at the McLean Brain Imaging Center.
    

Intervention name(s): GW468816; Placebo Comparator: Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Pharmacotherapies for Relapse Prevention
Other intervention name(s): GW468816: NMDA glycine-site antagonist
Intervention MeSH terms: Glycine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Drugs, Investigational; Therapies for Relapse to Nicotine; Relapse Prevention; Nicotine Cessation Therapies; Smoking Cessation; Nicotine Dependence