Elsevier

Clinical Therapeutics

Volume 33, Issue 4, April 2011, Pages 465-477
Clinical Therapeutics

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

https://doi.org/10.1016/j.clinthera.2011.04.013Get rights and content

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.

Introduction

Smoking remains an important preventable cause of disease, and the estimated disease burden attributable to smoking is >6 million premature deaths each year worldwide.1 If current trends continue, the estimated deaths from tobacco during the 21st century will be 1 billion.2 Smokers trying to quit frequently fail due to the addictive effect of nicotine. Pharmaceutical aids have been used successfully to help smokers quit; for example, nicotine-replacement therapy (NRT) has been found to increase the rate of abstinence by 50% to 70% compared with placebo.3 Currently, 3 compounds are considered first-line therapies: NRT in various formulations; the antidepressant bupropion; and, more recently, varenicline, an α4β2 nicotinic acetylcholine receptor partial antagonist.4 Based on data from various published reports in the 2008 US Clinical Practice Guideline,4 varenicline seems to be associated with higher abstinence rates than NRT5 or bupropion.6 However, these reports came from studies mainly conducted in the United States, Europe, and Asia.

Based on a MEDLINE search of studies published through 2008, no clinical trials of varenicline had been conducted in Latin America, Africa, or the Middle East. Nicotine use varies within these regions (Table I),7, 8, 9, 10 and while smoking rates are declining in the developed world, they are still rising in developing countries.2

Varenicline may have benefits in smokers in these countries with often-limited access to smoking-cessation interventions. While results from pivotal Phase III clinical trials are sufficient for many national health agencies to render a decision on the approval of a medication, clinical data from local patients are useful for assisting physicians in making individual treatment decisions. It is therefore important to determine the efficacy and tolerability of varenicline in smokers in unstudied populations. The aim of the present study was to evaluate the efficacy and tolerability of varenicline as an aid for smoking cessation in populations of cigarette smokers in Latin America, Africa, and the Middle East.

Section snippets

Study Design

This multinational, 24-week, randomized, double-blind, placebo-controlled efficacy and tolerability trial of varenicline was conducted from April 10, 2008, to August 17, 2009, at sites in Latin America (Brazil [7 sites], Venezuela [4], Mexico [3], Colombia [2], and Costa Rica [1]); Africa (South Africa [13] and Egypt [1]); and the Middle East (United Arab Emirates [6], Lebanon [2], Saudi Arabia [2], and Jordan [1]) (Table II). The investigative sites were smoking cessation clinics, medical

Participant Disposition

Of the 689 individuals who were screened, 593 (86.1%) were randomized (Figure 1). Overall, 588 participants received at least 1 dose of study treatment (varenicline, 390; placebo, 198) and were included in the full-analysis population. Of the 5 participants who were randomized but did not receive study treatment, 3 were no longer willing to participate (all in the varenicline group) and 2 were lost to follow-up (varenicline, 1; placebo, 1). A total of 336 of 394 (85.3%) participants assigned to

Discussion

In this randomized, placebo-controlled study in smokers from Latin America, Africa, and the Middle East, varenicline was apparently efficacious in achieving smoking cessation, and was considered generally well tolerated. In this study, varenicline was associated with a significantly higher CAR for the last 4 weeks of treatment (CAR weeks 9–12; 53.59% vs 18.69%; OR = 5.76; 95% CI, 3.74–8.88; P < 0.0001) compared with placebo. Importantly, varenicline also was associated with a significantly

Conclusion

Varenicline was efficacious as an aid for smoking cessation but was associated with a numerically larger number of AEs compared with placebo in these adult smokers from 11 countries in Latin America, Africa, and the Middle East.

Acknowledgments

This work was supported by Pfizer Inc, which was the sponsor and funding source for the clinical trial reported here.

All of the authors completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare that: (1) the institutions of Drs. Bolliger, Issa, Posadas-Valay, and Safwat received financial support from Pfizer for the clinical trial; (2) Drs. Bolliger, Issa, Posadas-Valay, and Safwat received no financial

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