PURPOSE: Varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, has demonstrated significant efficacy for smoking cessation versus placebo and bupropion SR. The objective of this analysis was to evaluate continuous abstinence from smoking and the incidence of adverse events (AEs) over time using pooled data from multiple trials of varenicline versus placebo.
METHODS: Data were pooled from 3 randomized, double-blind trials to examine the efficacy and safety of 12 weeks of varenicline 1.0 mg twice daily (BID) (n=945) versus placebo (n=805) with a 40-week non-treatment follow-up period. The primary endpoint was the carbon monoxide-confirmed (≤;10 ppm exhaled) continuous abstinence rate (CAR) for Weeks 9-12. Secondary endpoints included CAR for Weeks 9-52 and safety measures.
RESULTS: Demographic characteristics were similar between groups. The CAR for varenicline was significantly higher than for placebo at Weeks 9-12 (varenicline: 45.9% vs placebo: 16.9%; odds ratio [OR]=4.13; 95% confidence interval [CI]=3.29-5.18; P<0.0001). Similarly, the Week 9-52 CAR for varenicline was significantly greater than for placebo (varenicline: 22.6% vs placebo: 8.6%; OR=3.17; 95% CI=2.36-4.24; P<0.0001). The most frequent AEs observed in varenicline-treated participants were nausea (varenicline: 31.3%; placebo: 9.9%), insomnia (varenicline: 16.5%; placebo: 12.1%), headache (varenicline: 16.1%; placebo: 13.0%), and abnormal dreams (varenicline: 13.4%; placebo: 4.4%). Most varenicline-treated participants who had AEs experienced their onset in the first two weeks of treatment (nausea: 23.9%; insomnia: 11.0%; headache: 7.8%; abnormal dreams: 9.4%). Onset of new AEs after 3 to 4 weeks of treatment was infrequent. The overall prevalence of AEs decreased over the 12 weeks of treatment. Most AEs were mild or moderate in intensity and discontinuations of study treatment due to AEs were low.
CONCLUSION: Varenicline significantly increases continuous abstinence from smoking at the end of treatment through to Week 52 compared with placebo. Varenicline is well-tolerated and its safety profile is acceptable. The onset and presence of nausea, headache, insomnia, and abnormal dreams peaks in the first week of varenicline treatment and then reduces steadily thereafter.
CLINICAL IMPLICATIONS: Varenicline is safe and effective for smoking cessation.
DISCLOSURE: Barry Make, No Product/Research Disclosure Information; Grant monies (from industry related sources) Funding for all 3 pooled studies was provided by Pfizer, Inc. Barry Make has received grants for clinical research from GlaxoSmithKline, Boehringer Ingelheim, and Pfizer. Dr Nides has also received grant support from Pfizer, Nabi Biopharmaceuticals, and GlaxoSmithKline. Dr Reus has received grant support from Nabi Biopharmaceuticals.; Shareholder Mr Billing and Dr Williams own stock or hold stock options in Pfizer; Employee Mr Billing and Dr Williams are employees of Pfizer, Inc.; Consultant fee, speaker bureau, advisory committee, etc. Dr Make has served as an advisor to GlaxoSmithKline, Boehringer Ingelheim, Pfizer, Dey, AstraZeneca, Altana, and Schering and has given education talks on behalf of GlaxoSmithKline, Boehringer Ingelheim, Pfizer, and Schering. Dr Nides has received speaking fees and honoraria for advisory board meetings from Pfizer; Other Editorial support was provided by Ray Beck, Jr of Envision Pharma and funded by Pfizer, Inc.