A 12-week, double-blind, placebo-controlled, multicenter study with a 40 week follow-up evaluating the safety and efficacy of Varenicline tartrate 1 mg BID for smoking cessation in subjects with cardiovascular disease - Not available

• Conditions: Smoking Cessation; MedDRA version: 9.1Level: LLTClassification code 10053325Term: Smoking cessation therapy

• Registration Number: EUCTR2005-004411-29-CZ
• Lead Sponsor: Pfizer Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2005-11-23
• Last Update Posted: 18 April 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 700

Inclusion Criteria

Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the trial:
1. Subjects must be able to be outpatients, to be assessed in a clinic setting, and be able and willing to comply with all study visits for 52 weeks during the treatment and
non-treatment phases
2. Participating subjects must be able to provide written informed consent
3. Only one subject per household may participate
4. Subjects must be current cigarette smokers, male or female, who are between the ages of 35 and 75 years, inclusive, and who are motivated to stop smoking
5. Subjects must have smoked an average of at least 10 cigarettes per day during the past 12 months and during the month prior to the Screening visit
6. Subjects must have stable, documented cardiovascular disease other than hypertension diagnosed >2 months prior to the Screening visit. Examples include:
• Coronary Artery Disease demonstrated by:
Angina pectoris and evidence of abnormal myocardial perfusion or myocardial
ischemia by stress testing or myocardial perfusion imaging or angina pectoris with
positive coronary angiography. Test results or physician report must be provided.
Myocardial infarction documented by hospital summaries, procedure reports,
laboratory reports, etc.
Coronary revascularization documented by physician or procedure report
• Peripheral Vascular Disease demonstrated by:
Stable peripheral vascular disease (arterial) documented by history and physical exam
(ankle-brachial index-ABI <0.9 but > 0.5), ultrasonography, arteriography. Subjects
with asymptomatic carotid disease documented by imaging studies may be included
Peripheral revascularization documented by procedure report
• Cerebrovascular Disease. For example, TIA or stroke without significant
neurological impairment documented by neurological evaluation, procedure
report.
7. Females who are not of childbearing potential (eg, 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 serum pregnancy test (ß-hCG) at screening
• Agree to use at least one of the birth control methods listed below:
• An oral contraceptive agent, an intrauterine device (IUD), an implantable
contraceptive (for example, Norplant), or an injectable contraceptive (for
example, 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
• A barrier method of contraception, for example, condom and/or diaphragm with
spermicide while participating in the study through at least 30 days after the last
dose of study medication
• Abstinence
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

1. Subjects who have made a serious attempt to quit smoking in the past 3 months but have failed
2. Subjects currently suffering with depression, or who have been diagnosed with
depression or treated with an anti-depressant for depression within the past 12 months
3. Subjects with a past or present history of psychosis, anxiety disorder, panic disorder, or bipolar disorder
4. Subjects who, in the judgment of the investigator, have moderate or severe chronic obstructive pulmonary disease (COPD) (see Appendix 1 of the protocol for definitions of severity based on spirometry; however a study specific spirometry is not required. Subjects who have had a previous hospitalization for COPD should be excluded
5. Subjects with NYHA Class III or IV congestive heart failure (see Appendix 2 of the protocol for NYHA Classification)
6. Subjects with unstable cardiovascular disease or cardiovascular events in the past 2 months. Examples include, coronary artery bypass graft (CABG), percutaneous
transluminal coronary angioplasty (PTCA), severe or unstable angina, serious (life
threatening) arrhythmia, and clinically significant cardiac conduction abnormalities
(>10 AV block)
7. Subjects with uncontrolled hypertension or a systolic blood pressure greater than
160 mmHg or a diastolic blood pressure greater than 95 mmHg at the Screening or
Baseline visit
8. Subjects with clinically significant neurological deficits related to cerebrovascular or
other diseases, for example, stroke, etc.
9. Subjects with peripheral vascular disease (PVD) which has resulted in amputation or where the ankle-brachial index is =0.5.
10. Subjects with a history of clinically significant endocrine disorders or gastrointestinal diseases that are uncontrolled, including uncontrolled hyperthyroidism, and active peptic ulcer diseaseSubjects with clinically significant hepatic or renal impairment or other clinically
significant abnormal laboratory test values:
Subjects with an SGOT (AST) or SGPT (ALT) greater than 1.5 times the upper limit
of normal (ULN) or total bilirubin greater than 1.1 times the ULN
Subjects with severe abnormalities of renal function (estimated creatinine clearance
by Cockcroft-Gault equation <30 mL/min) (Appendix 3)
12. Subjects with a history of cancer (cured basal cell or squamous cell carcinoma of the skin allowed)
13. Subjects with a history of drug (except nicotine) or alcohol abuse or dependence
within the past 12 months
14. Subjects with a positive urine drug screen for drugs of potential abuse and no medical indication for use of the drug.
15. Subjects with a body mass index (BMI) less than 15 or greater than 38 when wearing indoor clothing without shoes (see Appendix 5 of the protocol). No subject will be enrolled with a weight less than 45.5 kg (100 pounds)
16. Subjects previously enrolled in a study that included varenicline (CP-526,555)
17. Subjects taking another investigational drug within 30 days or 5 half-lives (whichever is longer) before the Baseline visit or within 30 days of completion of another study
18. Subjects taking a concomitant medication that is prohibited by this protocol (see
Section 5.5 of the protocol)
19. Subjects requiring other medications during the study that might interfere with the evaluation of the study drug (for example, nicotine replacement therapy, bupropion, clonidine, nortriptyline, or other medications used for smoking cessation including over the counter herbal remedies)

Exclusion criteria 20 to 26 has been left

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Main objective: The primary efficacy objective of this protocol is a comparison of 12 weeks of treatment with varenicline 1 mg BID to placebo for smoking cessation in subjects with cardiovascular disease and to evaluate continuous abstinence from smoking 40 weeks after the treatment period.<br><br>;Secondary Objective: Secondary objectives: The safety objective is to gather safety data in subjects with cardiovascular disease for 12 weeks of treatment with varenicline 1 mg BID or placebo followed by a 40 week nontreatment follow-up period.;Primary end point(s): The primary endpoint is the 4-week Continuous Quit Rate (CQR) for Weeks 9-12, i.e., the proportion of subjects who are able to maintain complete abstinence from cigarette smoking and other nicotine use, with end-expiratory exhaled CO measurements =10 ppm, for the planned last 4 weeks of treatment.