Varenicline in Combination With Nicotine Replacement Therapy for Smoking Cessation

NCT01444131 | Completed Phase 2 DMC

• 1 other identifier: VarNic
• Study Type: interventional
• Target: 446
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Tobacco Dependence

Keywords

Smoking; Smoking cessation; Pharmaceutical aids

Outcome Measures

Primary Outcomes (1)

• continuous abstinence (CAR) from weeks 9 to 12 of treatment

  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.

  3 months

Secondary Outcomes (1)

• CAR from weeks 9 to 24

  6 months

Study Arms (2)

Varenicline and Placebo Patch

PLACEBO COMPARATOR

Varenicline and Nicotine Patch (placebo)

Drug: Varenicline and Placebo Patch

Varenicline and Nicotine Patch

ACTIVE COMPARATOR

Varenicline and Nicotine Patch 15mg

Drug: Varenicline, Nicotine Patch

Interventions

Varenicline, Nicotine Patch DRUG

active nicotine patches added to varenicline.

Also known as: Champix, Nicorette

Varenicline and Nicotine Patch

Varenicline and Placebo Patch DRUG

placebo nicotine patches added to varenicline.

Varenicline and Placebo Patch

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Current cigarette smokers, male and female, aged between 18-75 years (both limits inclusive), and who are motivated to stop smoking.
• 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.
• 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.
• Patients must have no serious or unstable disease in the past 6 months.
• 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.
• Only one subject per household may participate.

You may not qualify if:

• Patients currently suffering from depression or who have been diagnosed with depression or treated with anti-depressants within the past 12 months.
• Patients with a past of present history of psychosis, panic disorder, or bipolar disorder.
• Patients with severe chronic obstructive pulmonary disease (COPD).
• 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.
• Patients with uncontrolled hypertension or a systolic blood pressure greater than 150mmHg or as diastolic pressure greater than 95mmHg at screening or baseline.
• Patients with clinically significant neurological disorders or cerebrovascular diseases (for example, stroke, transient ischemic attack, etc.) in the past 6 months.
• Patients with a history of clinically significant endocrine disorders or gastrointestinal diseases, including insulin dependent diabetes mellitus, uncontrolled hyperthyroidism, and active peptic ulcer.
• Patients with clinically significant hepatic or renal impairment or other clinically significant abnormal laboratory test values.
• Patients with a history of cancer (cured basal cell or squamous cell carcinoma of the skin allowed).
• Patients with a history of clinically significant allergic reactions to drugs (for example, severe cutaneous and/or systemic allergic reactions).
• Patients with a history of drug (except nicotine) or alcohol abuse or dependence within the past 12 months.
• 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).
• Patients previously enrolled in a study that included varenicline.
• Patients having used nicotine replacement therapy within the last 6 months.
• 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.

Sponsors & Collaborators

• University of Stellenbosch: lead
• QuitSupport: collaborator

Study Sites (7)

Respiratory Research Unit

Cape Town, Western Cape, 7505, South Africa

Location

Synopsis Research

Cape Town, Western Cape, 7700, South Africa

Location

UCT Lung Institute

Cape Town, Western Cape, 8000, South Africa

Location

Dr JA O'Brien

Cape Town, Western Cape, 8001, South Africa

Location

Dr AHH Brüning

Gatesville / Cape Town, Western Cape, 7764, South Africa

Location

Dr MS Abdool-Gaffar

eManzimtoti, 4126, South Africa

Location

Dr C Smith

Sandton, 2010, South Africa

Location

Related Publications (11)

• Gonzales D, Rennard SI, Nides M, Oncken C, Azoulay S, Billing CB, Watsky EJ, Gong J, Williams KE, Reeves KR; Varenicline Phase 3 Study Group. Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial. JAMA. 2006 Jul 5;296(1):47-55. doi: 10.1001/jama.296.1.47.

  PMID: 16820546 BACKGROUND

• Jorenby DE, Hays JT, Rigotti NA, Azoulay S, Watsky EJ, Williams KE, Billing CB, Gong J, Reeves KR; Varenicline Phase 3 Study Group. Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial. JAMA. 2006 Jul 5;296(1):56-63. doi: 10.1001/jama.296.1.56.

  PMID: 16820547 BACKGROUND

• Tonstad S, Tonnesen P, Hajek P, Williams KE, Billing CB, Reeves KR; Varenicline Phase 3 Study Group. Effect of maintenance therapy with varenicline on smoking cessation: a randomized controlled trial. JAMA. 2006 Jul 5;296(1):64-71. doi: 10.1001/jama.296.1.64.

  PMID: 16820548 BACKGROUND

• Tonnesen P, Paoletti P, Gustavsson G, Russell MA, Saracci R, Gulsvik A, Rijcken B, Sawe U. Higher dosage nicotine patches increase one-year smoking cessation rates: results from the European CEASE trial. Collaborative European Anti-Smoking Evaluation. European Respiratory Society. Eur Respir J. 1999 Feb;13(2):238-46. doi: 10.1034/j.1399-3003.1999.13b04.x.

  PMID: 10065662 BACKGROUND

• Schuurmans MM, Diacon AH, van Biljon X, Bolliger CT. Effect of pre-treatment with nicotine patch on withdrawal symptoms and abstinence rates in smokers subsequently quitting with the nicotine patch: a randomized controlled trial. Addiction. 2004 May;99(5):634-40. doi: 10.1111/j.1360-0443.2004.00711.x.

  PMID: 15078238 BACKGROUND

• Shiffman S, Ferguson SG. Nicotine patch therapy prior to quitting smoking: a meta-analysis. Addiction. 2008 Apr;103(4):557-63. doi: 10.1111/j.1360-0443.2008.02138.x.

  PMID: 18339101 BACKGROUND

• Bolliger CT, Zellweger JP, Danielsson T, van Biljon X, Robidou A, Westin A, Perruchoud AP, Sawe U. Smoking reduction with oral nicotine inhalers: double blind, randomised clinical trial of efficacy and safety. BMJ. 2000 Aug 5;321(7257):329-33. doi: 10.1136/bmj.321.7257.329.

  PMID: 10926587 BACKGROUND

• Ebbert JO, Burke MV, Hays JT, Hurt RD. Combination treatment with varenicline and nicotine replacement therapy. Nicotine Tob Res. 2009 May;11(5):572-6. doi: 10.1093/ntr/ntp042. Epub 2009 Apr 7.

  PMID: 19351781 BACKGROUND

• Bolliger CT, van Biljon X, Axelsson A. A nicotine mouth spray for smoking cessation: a pilot study of preference, safety and efficacy. Respiration. 2007;74(2):196-201. doi: 10.1159/000097136. Epub 2006 Nov 14.

  PMID: 17108670 BACKGROUND

• Livingstone-Banks J, Fanshawe TR, Thomas KH, Theodoulou A, Hajizadeh A, Hartman L, Lindson N. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev. 2023 May 5;5(5):CD006103. doi: 10.1002/14651858.CD006103.pub8.

  PMID: 37142273 DERIVED

• Koegelenberg CF, Noor F, Bateman ED, van Zyl-Smit RN, Bruning A, O'Brien JA, Smith C, Abdool-Gaffar MS, Emanuel S, Esterhuizen TM, Irusen EM. Efficacy of varenicline combined with nicotine replacement therapy vs varenicline alone for smoking cessation: a randomized clinical trial. JAMA. 2014 Jul;312(2):155-61. doi: 10.1001/jama.2014.7195.

  PMID: 25005652 DERIVED

MeSH Terms

Conditions

Tobacco Use Disorder; Smoking; Smoking Cessation

Interventions

Varenicline; Tobacco Use Cessation Devices; Nicotine Chewing Gum

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quinoxalines; Therapeutics; Chewing Gum; Plant Gums; Biopolymers; Polymers; Macromolecular Substances; Polysaccharides; Carbohydrates; Candy; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Elvis M Irusen, MBChB, FCP, PhD

  University of Stellenbosch

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: September 27, 2011
• First Posted: September 30, 2011
• Study Start: April 1, 2011
• Primary Completion: April 1, 2013
• Study Completion: June 1, 2013
• Last Updated: March 26, 2014

Record last verified: 2014-03

Locations

ZA (7)