A PHASE 4 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY EVALUATING THE EFFICACY AND SAFETY OF RE-TREATMENT WITH VARENICLINE IN SUBJECTS WHO ARE CURRENTLY SMOKING, AND WHO HAVE PREVIOUSLY TAKEN VARENICLINE

• Register: EUCTR
• Last refreshed on: 19 May 2014
• Main ID: EUCTR2010-021789-31-CZ
• Date of registration: 20/09/2010
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc.
• Public title: A PHASE 4 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY EVALUATING THE EFFICACY AND SAFETY OF RE-TREATMENT WITH VARENICLINE IN SUBJECTS WHO ARE CURRENTLY SMOKING, AND WHO HAVE PREVIOUSLY TAKEN VARENICLINE
• Scientific title: A PHASE 4 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY EVALUATING THE EFFICACY AND SAFETY OF RE-TREATMENT WITH VARENICLINE IN SUBJECTS WHO ARE CURRENTLY SMOKING, AND WHO HAVE PREVIOUSLY TAKEN VARENICLINE
• Date of first enrolment: 10/11/2010
• Target sample size: 490
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-021789-31
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Czech Republic, Germany, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Subject eligibility should be reviewed and documented by an appropriately qualified member of the investigator’s study team before subjects are included in the study. Subjects must meet all of the following inclusion criteria at screening and baseline to be eligible for randomization into the study:
1. Male or female cigarette smokers, aged 18 years or above, motivated to stop smoking and considered suitable for a smoking cessation attempt.
2. Subjects must have smoked an average of at least 10 cigarettes (cigarettes only) per day during the past 4 weeks, with an exhaled carbon monoxide (CO) > 10ppm at screening.
3. Subjects who have previously attempted to stop smoking on at least one occasion with varenicline for a treatment duration of two weeks, with the last varenicline dose taken at least 3 months prior to screening. Subjects may be enrolled irrespective of whether they failed to stop smoking during the previous attempt(s) supported by varenicline, or whether they succeeded but subsequently relapsed.
4. At least 3 months must have elapsed since the subject's last quit attempt, irrespective of whether the last attempt was pharmacologically supported or not.
5. Females who are not of childbearing potential (ie, who are surgically sterilized or at least 2 years postmenopausal) and who are not nursing may be included. Females who are of childbearing potential may be included provided that they are not pregnant, not nursing, and meet all of the following criteria:
• Are instructed and agree to avoid pregnancy through 30 days after the last dose of study medication;
• Have a negative pregnancy test (ß -hCG) at Screening and Baseline and;
• Agree to use at least one of the birth control methods listed below:- an oral contraceptive agent, an intrauterine device (IUD), an implantable contraceptive (eg, Norplant), or an injectable contraceptive (eg, Depo Provera) for at least 1 month prior to entering the study and will continue its use through at least 30 days after the last dose of study medication or:- a barrier method of contraception, eg, condom and/or diaphragm with spermicide while participating in the study through at least 30 days after the last dose of study medication or abstinence.
6. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study.
7. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Subjects presenting with any of the following will not be included in the study:
1. Subjects who have previously experienced an adverse drug reaction that the investigator considers potentially due to varenicline treatment, and of sufficient concern that further exposure to varenicline would be inadvisable.
2. Subjects with severe chronic obstructive pulmonary disease (COPD), defined as any subject who fulfills any of the following criteria:
• History of repeated exacerbations of COPD (greater than or equal to 3 in 3 years);
• Requires systemic corticosteroid maintenance (eg, oral prednisolone) for management of chronic symptoms;
• Is maintained on oxygen therapy for management of chronic symptoms.
3. Subjects with a recent (less than 5 years) history of cancer. Subjects with a remote (>5 years) history of cancer may be considered pending discussion with the study clinician. Subjects with cured basal cell or squamous cell carcinoma of the skin are allowed.
4. Subjects with clinically significant cardiovascular disease in the past 2 months. Examples of clinically significant cardiovascular disease include:
•Myocardial infarction;
•Coronary artery bypass graft (CABG);
•Percutaneous transluminal coronary angioplasty (PTCA);
•Severe or unstable angina;
•A serious arrhythmia;
•Clinically significant ECG conduction abnormalities;
•Heart failure.
5.Subjects with clinically significant cerebrovascular disease in the past 2 months. Examples of clinically significant cerebrovascular disease include:
•Cerebrovascular accident (CVA), stroke;
•Documented transient ischaemic attack.
6.Subjects with a history of a suicide attempt or any suicidal behaviour in the past 2 years.
7.Subjects with suicidal ideation identified by the C-SSRS at the screening or baseline visit.
8.Subjects with current depression, or who have been diagnosed or treated with antidepressants during the past 12 months.
9.Subjects with a lifetime diagnosis of psychosis, panic disorder, other anxiety disorders or bipolar disorder.
10.Subjects with alcohol or substance abuse or dependence (except nicotine) unless in full remission for at least 12 months.
11.Subjects with a positive urine drug screen (at screening or baseline) for drugs of abuse/potential abuse not prescribed for the treatment of a medical condition.
12.Any subject at screening or baseline with an AST (SGOT) or ALT (SGPT) greater than 3 times the upper limit of normal (ULN), or total bilirubin greater than 2 times the ULN.
13.Subjects with evidence or history of clinically significant allergic reactions to drugs (eg, severe cutaneous and/or systemic allergic reactions).
14.Subjects with a clinically significant ECG at the screening visit (as determined by the Principal Investigator or medically appropriate designee).
15.Subjects taking a concomitant medication that is prohibited by this protocol.
16. Subjects who intend to donate blood or blood components while receiving study drug or within one month of the completion of the treatment phase of the study.
17. Subjects who do not agree to abstain from using non-cigarette tobacco products (including eg, pipe tobacco, cigars, snuff, chewing tobacco etc) or marijuana during study participation.
18. Subjects who do not agree to abstain from using nicotine replacement therapy, bupropion, varenicline and other aids to smoking cessation during the treatment period of the study.
19. Participation in other studies within 30 days before the current study begins and/or during stu

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Smoking Cessation
MedDRA version: 12.1 Level: LLT Classification code 10053325 Term: Smoking cessation therapy

Intervention(s)

Trade Name: CHAMPIX
Pharmaceutical Form: Film-coated tablet
CAS Number: 375815-87-5
Other descriptive name: VARENICLINE TARTRATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.5-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: The primary objective of this study is to compare the efficacy and safety of the re-treatment with varenicline with placebo for smoking cessation for the last 4 weeks of a 12 week treatment period (Continuous Abstinence Rate; CAR 9-12).

Primary end point(s): Primary efficacy endpoint:
Continuous Abstinence Rate for Weeks 9-12 (CAR 9-12), confirmed by exhaled carbon monoxide (CO) of less than or equal to 10ppm.

Secondary Objective: The key secondary objective is to compare the efficacy of varenicline with placebo from Week 9 to the end of the long term non-treatment follow up period to 52 weeks (CAR 9-52). Additional secondary efficacy objectives include:
• Comparing smoking abstinence at the 24 week timepoint (CAR 9-24) between the varenicline and placebo treatment groups;
• Comparing the 7-day point prevalence of smoking abstinence at specific timepoints (Weeks 12, 24 and 52) between the varenicline and placebo treatment groups.

Secondary ID(s)

2010-021789-31-DE

A3051139