Effectiveness of GW468816, an NMDA Glycine Site Antagonist, for Prevention of Relapse to Smoking

NCT00218465 | Completed Phase 2 Results DMC

• 3 other identifiers: NIDA-19378-2U01DA019378IND 74964
• Study Type: interventional
• Target: 264
• Locations: 1 country
• Sites: 2

Brief 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).

Conditions

Nicotine Dependence

Keywords

Drugs, Investigational; Therapies for Relapse to Nicotine; Relapse Prevention; Nicotine Cessation Therapies; Smoking Cessation; Nicotine Dependence

Outcome Measures

Primary Outcomes (3)

• Time to Relapse to Smoking in the 5-week Relapse Prevention Phase.

  5 weeks

• Number of Abstinent and Nonabstinent Participants at End of 5 Week Placebo-controlled Relapse Prevention Trial

  5 weeks

• Days to Relapse Within the 60 Days Following Randomization

  60 days

Study Arms (2)

GW468816

EXPERIMENTAL

Glycine Antagonist GW468816, 200 mg/day, for a 5-week trial

Drug: GW468816

Placebo

PLACEBO COMPARATOR

Placebo, 200 mg/day, for a 5-week trial

Drug: Placebo Comparator: Placebo

Interventions

GW468816 DRUG

Pharmacotherapies for Relapse Prevention

Also known as: GW468816: NMDA glycine-site antagonist

GW468816

Placebo Comparator: Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent
• WOMEN aged 18-65 years, inclusive
• 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
• DSM-IV criteria for current Nicotine Dependence satisfied
• 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)
• 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.

You may not qualify if:

• Pregnant or able to become pregnant and not willing to use approved contraception
• 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
• Life-threatening arrhythmia, cerebro-vascular or cardiovascular event within six months of enrollment
• 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).
• Use of tobacco-containing products other than cigarettes (e.g., cigar, pipe)
• 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.
• Diagnosis of major depressive disorder in the past 6 months
• Lifetime DSM-IV diagnosis of organic mental disorder, schizophrenia, schizoaffective disorder, bipolar disorder, delusional disorder or psychotic disorders not elsewhere classified
• 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.
• History of multiple adverse drug reactions
• Use of an investigational drug or device within 4 weeks of enrollment
• Concurrently enrolled in a study that involves exposure to a drug or device.
• Urine positive for drugs of abuse at screening visit.
• Use of statins during the period of the investigation.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Institute on Drug Abuse (NIDA): collaborator
• Mclean Hospital: collaborator
• GlaxoSmithKline: collaborator

Study Sites (2)

McLean Hospital, Brain Imaging Center

Belmont, Massachusetts, 02478 9106, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Tobacco Use Disorder; Smoking Cessation

Interventions

GW 468816

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Health Behavior; Behavior

Results Point of Contact

• Title: Sara Carlini
• Organization: Center for Addiction Medicine

scarlini@partners.org

617-643-1990

Study Officials

• Maurizio Fava, M.D.

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

• Eden Evins, M.D., M.P.H.

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Maurizio Fava, M.D.

Study Record Dates

• First Submitted: September 16, 2005
• First Posted: September 22, 2005
• Study Start: August 1, 2006
• Primary Completion: June 1, 2009
• Study Completion: June 1, 2009
• Last Updated: March 24, 2017
• Results First Posted: December 20, 2010

Record last verified: 2017-03

Locations

US (2)