Varenicline in Combination With Nicotine Replacement Therapy for Smoking Cessation

This study has been completed.
Sponsor:
Collaborator:
QuitSupport
Information provided by (Responsible Party):
Prof Elvis M Irusen, University of Stellenbosch
ClinicalTrials.gov Identifier:
NCT01444131
First received: September 27, 2011
Last updated: March 25, 2014
Last verified: March 2014
  Purpose

The purpose of this study is to test whether the addition of a nicotine patch to varenicline increases smoking cessation success rate and whether the combination is safe.


Condition Intervention Phase
Tobacco Dependence
Drug: Varenicline, Nicotine Patch
Drug: Varenicline and Placebo Patch
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A 26-Week Phase II, Multicentre, Randomised, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Varenicline in Combination With Nicotine Replacement Therapy for Smoking Cessation

Resource links provided by NLM:


Further study details as provided by University of Stellenbosch:

Primary Outcome Measures:
  • continuous abstinence (CAR) from weeks 9 to 12 of treatment [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
    The primary endpoint is the 4-week continuous abstincence rate for week 9 - 12 of treatment, i.e. the proportion of patients who are able to maintain complete abstinence from cigarette smoking and other nicotine use, with end-expiratory exhaled carbon monoxide (CO) measurements 10 ppm or less, for the planned last 4 weeks of treatment.


Secondary Outcome Measures:
  • CAR from weeks 9 to 24 [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    The secondary endpoint is the 4-week continuous abstincence rate for week 9 - 24 of treatment, i.e. the proportion of patients who are able to maintain complete abstinence from cigarette smoking and other nicotine use, with end-expiratory exhaled carbon monoxide (CO) measurements 10 ppm or less, for the planned last 4 weeks of treatment.


Enrollment: 446
Study Start Date: April 2011
Study Completion Date: June 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Varenicline and Placebo Patch
Varenicline and Nicotine Patch (placebo)
Drug: Varenicline and Placebo Patch
placebo nicotine patches added to varenicline.
Active Comparator: Varenicline and Nicotine Patch
Varenicline and Nicotine Patch 15mg
Drug: Varenicline, Nicotine Patch
active nicotine patches added to varenicline.
Other Names:
  • Champix
  • Nicorette

Detailed Description:

This is a phase-II multicenter study involving 438 smokers, to be conducted at 7 sites in South Africa, over 6 months. In a randomized 1:1 allocation varenicline tartrate 1 mg twice daily, given in an incremental dosage for the first week before target quit date (TQD), will be compared to varenicline tartrate in the same dose combined with a 15mg nicotine patch. The nicotine patch (active and placebo) will be provided by McNeil. The patch will be given 2 weeks prior TQD. Treatment duration from TQD is 12 weeks with varenicline being tapered off during week 13.

A total of 12 clinic visits and 1 telephonic contact is planned for the 6-month study duration. The main efficacy outcome will be the 4-week continuous abstinence rate during the last four weeks of treatment, i.e. weeks 9 - 12. Efficacy assessments will be based on a Nicotine Use Inventory and measurements of end-expiratory exhaled carbon monoxide. Safety assessments will be based on adverse events evaluation, with special attention being given to the occurrence of nausea during the pretreatment period, as well as neuro-psychiatric symptoms such as depression or suicidal ideation. Participants will not be subjected to any invasive procedures.

This protocol is based on current evidence and two further abstracts presented at the European Respiratory Society Conference in Vienna, September 2009, that a combination of varenicline tartrate and nicotine replacement therapy indicate superior efficacy in cessation rate, but also an excellent good safety profile.

This study relates to the area of pharmacotherapy of smoking cessation, and will answer a frequently asked question. Importantly, several leading pulmonologists with experience in smoking cessation in South Africa have expressed their keen interest to participate in this study.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Current cigarette smokers, male and female, aged between 18-75 years (both limits inclusive), and who are motivated to stop smoking.
  2. Have smoked on average at least 10 cigarettes per day during past year and during the month prior to screening, and no period of abstinence greater than 3 months in the past year.
  3. Women of child-bearing potential (WCBP) may be included provided they are not pregnant, not nursing, and meet all of the following criteria:

    • instructed and agree to avoid pregnancy through 30 days after the last dose of study medication
    • negative screening test (beta-HCG) at screening
    • agree to use at least one birth control method (oral contraceptive, IUD, implantable or injectable contraceptive 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 use a barrier method of contraception (p.e.condom, diaphragm with spermicide) while participating in the study through at least 30 days after the last dose of study medication; or abstinence.
  4. Patients must have no serious or unstable disease in the past 6 months.
  5. Patients must be able to be outpatients, to be assessed in a clinical setting, and be able and willing to comply with all study visits during the treatment and non-treatment periods.
  6. Only one subject per household may participate.

Exclusion Criteria:

  1. Patients currently suffering from depression or who have been diagnosed with depression or treated with anti-depressants within the past 12 months.
  2. Patients with a past of present history of psychosis, panic disorder, or bipolar disorder.
  3. Patients with severe chronic obstructive pulmonary disease (COPD).
  4. Patients with clinically significant cardiovascular disease in the past 6 months. such as myocardial infarction, coronary artery bypass graft (CABG), percutaneous transluminal coronary angioplasty (PTCA), severe or unstable angina, serious arrhythmia, and clinically significant ECG conduction abnormalities.
  5. Patients with uncontrolled hypertension or a systolic blood pressure greater than 150mmHg or as diastolic pressure greater than 95mmHg at screening or baseline.
  6. Patients with clinically significant neurological disorders or cerebrovascular diseases (for example, stroke, transient ischemic attack, etc.) in the past 6 months.
  7. Patients with a history of clinically significant endocrine disorders or gastrointestinal diseases, including insulin dependent diabetes mellitus, uncontrolled hyperthyroidism, and active peptic ulcer.
  8. Patients with clinically significant hepatic or renal impairment or other clinically significant abnormal laboratory test values.
  9. Patients with a history of cancer (cured basal cell or squamous cell carcinoma of the skin allowed).
  10. Patients with a history of clinically significant allergic reactions to drugs (for example, severe cutaneous and/or systemic allergic reactions).
  11. Patients with a history of drug (except nicotine) or alcohol abuse or dependence within the past 12 months.
  12. Patients with a body mass index (BMI) less than 15 or greater than 38 when wearing indoor clothing without shoes. No subject will be enrolled with a weight less than 45.5kg (100 pounds).
  13. Patients previously enrolled in a study that included varenicline.
  14. Patients having used nicotine replacement therapy within the last 6 months.
  15. Patients taking another investigational drug within 30 days or 5 half-lives (whichever is longer) before the Baseline visit or within 30 days of study completion.
  16. Use of prohibited medications: any antidepressants, including bupropion; antipsychotic agents; mood stabilizers; naltrexone; steroids (inhaled and topical steroids are permitted); insulin.
  17. Patients who do not agree to completely abstain from using non-cigarette tobacco products (including for example, pipe tobacco, cigars, snuff, chewing tobacco, etc.) or marijuana during study participation.
  18. Patients who intend to donate blood or blood components while receiving study drug or within 1 month of the completion of the study treatment.
  19. Patients unable/or unlikely to comprehend and follow the study protocol, including patients unable and/or unwilling to participate in the non-treatment follow-up. Patients who, in the investigator's opinion, will be unlikely to commit to a 6 month-long study.
  20. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01444131

Locations
South Africa
Synopsis Research
Cape Town, Western Cape, South Africa, 7700
Dr JA O'Brien
Cape Town, Western Cape, South Africa, 8001
Respiratory Research Unit
Cape Town, Western Cape, South Africa, 7505
UCT Lung Institute
Cape Town, Western Cape, South Africa, 8000
Dr AHH Brüning
Gatesville / Cape Town, Western Cape, South Africa, 7764
Dr MS Abdool-Gaffar
Amanzimtoti, South Africa, 4126
Dr C Smith
Sandton, South Africa, 2010
Sponsors and Collaborators
University of Stellenbosch
QuitSupport
Investigators
Principal Investigator: Elvis M Irusen, MBChB, FCP, PhD University of Stellenbosch
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Prof Elvis M Irusen, Clinical Professor, University of Stellenbosch
ClinicalTrials.gov Identifier: NCT01444131     History of Changes
Other Study ID Numbers: VarNic
Study First Received: September 27, 2011
Last Updated: March 25, 2014
Health Authority: South Africa: Medicines Control Council
South Africa: Pharma-Ethics
South Africa: HREC, Faculty of Health Sciences, Stellenbosch University
South Africa: HREC, Faculty of Health Sciences, Cape Town University

Keywords provided by University of Stellenbosch:
Smoking
Smoking cessation
Pharmaceutical aids

Additional relevant MeSH terms:
Nicotine
Varenicline
Ganglionic Stimulants
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 22, 2014