Effects of Varenicline in Adult Smokers: A Multinational, 24-Week, Randomized, Double-Blind, Placebo-Controlled Study

• Published in: Clinical therapeutics Vol. 33; no. 4; pp. 465 - 477
• Main Authors: Bolliger, Chris T., MD, PhD, Issa, Jaqueline S., MD, PhD, Posadas-Valay, Rodolfo, MD, Safwat, Tarek, MD, FCCP, Abreu, Paula, DR.PH, Correia, Eurico A., MD, MSc, Park, Peter W., PhD, Chopra, Pravin, MD
• Format: Journal Article
• Language: English
• Published: Bridgewater, NJ EM Inc USA 01-04-2011; Elsevier; Elsevier Limited
• Subjects: Adolescent; Adult; Africa; Aged; Benzazepines - adverse effects; Benzazepines - therapeutic use; Biological and medical sciences; Clinical trials; continuous abstinence rate; Double-Blind Method; Drug therapy; Female; Follow-Up Studies; Humans; Internal Medicine; Latin America; Male; Medical Education; Medical sciences; Middle Aged; Middle East; Nicotine; Nicotinic Agonists - adverse effects; Nicotinic Agonists - therapeutic use; Pharmacology. Drug treatments; Quinoxalines - adverse effects; Quinoxalines - therapeutic use; randomized trial; Smoking - epidemiology; Smoking cessation; Smoking Cessation - methods; Smoking Prevention; Studies; Tobacco, tobacco smoking; Toxicology; Varenicline; Young Adult; Middle East; Africa; Latin America; varenicline; continuous abstinence rate; smoking cessation; randomized trial; Human; Partial agonist; Continuous; Varenicline; Tobacco smoking; Contraception; Abstinence; Cholinergic receptor; Randomization; Smoker; Placebo; Double blind study; Adult; Clinical trial; Nicotinic receptor
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/j.clinthera.2011.04.013

Abstract Background Prevalence rates of smoking are rising in developing countries. Previous trials evaluating the efficacy and tolerability of the smoking-cessation medication varenicline have used largely participants of Caucasian origin. Objective This study was conducted to evaluate the efficacy and tolerability of varenicline in populations of participants from Latin America, Africa, and the Middle East to investigate potential differences in the therapeutic response to varenicline. Methods This multinational, randomized, double-blind, placebo-controlled trial was conducted at 42 centers in 11 countries (Latin America: Brazil, Colombia, Costa Rica, Mexico, and Venezuela; Africa: Egypt and South Africa; Middle East: Jordan, Lebanon, Saudi Arabia, and the United Arab Emirates). Participants were male and female smokers aged 18 to 75 years who were motivated to stop smoking; smoked ≥10 cigarettes/d, with no cumulative period of abstinence >3 months in the previous year; and who had no serious or unstable disease within the previous 6 months. Subjects were randomized in a 2:1 ratio to receive varenicline 1 mg or placebo, BID for 12 weeks, with a 12-week nontreatment follow-up. Brief smoking-cessation counseling was provided. The main outcome measures were carbon monoxide–confirmed continuous abstinence rate (CAR) at weeks 9 to 12 and weeks 9 to 24. Adverse events (AEs) were recorded for tolerability assessment. Results Overall, 588 subjects (varenicline, 390; placebo, 198) were randomized and treated. The mean (SD) ages of subjects in the varenicline and placebo groups were 43.1 (10.8) and 43.9 (10.8) years, respectively; 57.7% and 65.7% were male; and the mean (SD) weights were 75.0 (16.0) and 76.7 (16.3) kg (range, 40.0–130.0 and 45.6–126.0 kg). CAR at weeks 9 to 12 was significantly higher with varenicline than with placebo (53.59% vs 18.69%; odds ratio [OR] = 5.76; 95% CI, 3.74–8.88; P < 0.0001), and this rate was maintained during weeks 9 to 24 (39.74% vs 13.13%; OR = 4.78; 95% CI, 2.97–7.68; P < 0.0001). Nausea, headache, and insomnia were the most commonly reported AEs with varenicline and were reported numerically more frequently in the varenicline group compared with the placebo group. Serious AEs (SAEs) were reported in 2.8% of varenicline recipients compared with 1.0% in the placebo group, with 6 subjects reporting psychiatric SAEs compared with none in the placebo group. Conclusion Based on these data, varenicline was apparently efficacious and generally well tolerated as a smoking-cessation aid in smokers from selected sites in Latin America, Africa, and the Middle East. ClinicalTrials.gov identifier: NCT00594204.