Nicotine DependencePhase 2NCT00218465
Effectiveness of GW468816, an NMDA Glycine Site Antagonist, for Prevention of Relapse to Smoking
A Phase 2 study testing GW468816 in people with Nicotine Dependence, run by Massachusetts General Hospital at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years, women only
- Conditions the study is for
- Nicotine Dependence
- What is being tested?
- GW468816
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 264 participants
- Where
- 2 sitesUnited States
- Study dates
- Aug 2006to Jun 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
McLean Hospital, Brain Imaging Center
Belmont, Massachusetts, 02478 9106
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
Official title: A Double-Blind, Placebo-Controlled Trial of the NMDA Glycine Site Antagonist, GW468816, for Prevention of Relapse to Smoking
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).
Read the 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.
- Conditions
- Nicotine Dependence
- Being tested
- GW468816, Placebo Comparator: Placebo
- Keywords
- Drugs, Investigational, Therapies for Relapse to Nicotine, Relapse Prevention, Nicotine Cessation Therapies, Smoking Cessation, Nicotine Dependence
- Medical subject headings
- Tobacco Use Disorder, Smoking Cessation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GW468816Drug
Also called GW468816: NMDA glycine-site antagonist
Pharmacotherapies for Relapse Prevention
Placebo Comparator: PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| GW468816 | Experimental | Glycine Antagonist GW468816, 200 mg/day, for a 5-week trial Receives: Drug: GW468816 |
| Placebo | Placebo comparator | Placebo, 200 mg/day, for a 5-week trial Receives: Drug: Placebo Comparator: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Relapse to Smoking in the 5-week Relapse Prevention Phase.
Measured: 5 weeks
Number of Abstinent and Nonabstinent Participants at End of 5 Week Placebo-controlled Relapse Prevention Trial
Measured: 5 weeks
Days to Relapse Within the 60 Days Following Randomization
Measured: 60 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2005 (estimated)
- Study startAug 2006
- Primary completionJun 2009
- Study completionJun 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Nicotine DependenceStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 264 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA), Mclean Hospital, GlaxoSmithKline
- Responsible party
- Principal investigator, Maurizio Fava, MD, Massachusetts General Hospital
- Investigators
- Maurizio Fava, M.D., Principal investigator, Massachusetts General HospitalEden Evins, M.D., M.P.H., Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00218465
- Sponsor's protocol ID
- NIDA-19378-2
- Other IDs
- U01DA019378, IND 74964
- Status last verified
- Mar 2017
- First submitted
- 16 Sep 2005
- Last updated
- 24 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-Blind, Placebo-Controlled Trial of the NMDA Glycine Site Antagonist, GW468816, for Prevention of Relapse to Smoking
- ClinicalTrials.gov ID
- NCT00218465
- Acronym / sponsor ID
- NIDA-19378-2
- Conditions
- Nicotine Dependence
- Keywords
- Drugs, Investigational, Therapies for Relapse to Nicotine, Relapse Prevention, Nicotine Cessation Therapies, Smoking Cessation, Nicotine Dependence
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 264 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA), Mclean Hospital, GlaxoSmithKline
- Study start
- Aug 2006
- Primary completion
- Jun 2009 (actual)
- Study completion
- Jun 2009 (actual)
- First posted
- 22 Sep 2005 (estimated)
- Results
- Posted 20 Dec 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| GW468816 | Experimental | Drug: GW468816Glycine Antagonist GW468816, 200 mg/day, for a 5-week trial |
| Placebo | Placebo comparator | Drug: Placebo Comparator: PlaceboPlacebo, 200 mg/day, for a 5-week trial |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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)
Key exclusion criteria (14 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GW468816Also: GW468816: NMDA glycine-site antagonistPharmacotherapies for Relapse Prevention | Drug | GW468816 |
| Placebo Comparator: Placebo | Drug | Placebo |
Primary outcome
Time to Relapse to Smoking in the 5-week Relapse Prevention Phase.
Time frame: 5 weeks
Number of Abstinent and Nonabstinent Participants at End of 5 Week Placebo-controlled Relapse Prevention Trial
Time frame: 5 weeks
Days to Relapse Within the 60 Days Following Randomization
Time frame: 60 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Maurizio Fava, M.D. principal investigator
Massachusetts General Hospital
Eden Evins, M.D., M.P.H. principal investigator
Massachusetts General Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GW468816 in people with Nicotine Dependence, run by Massachusetts General Hospital at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Dec 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to Relapse to Smoking in the 5-week Relapse Prevention Phase. (time frame: 5 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2017.