Smoking cessation with varenicline, a selective α4β2 nicotinic receptor partial agonist -: Results from a 7-week, randomized, placebo- and bupropion-controlled trial with 1-year follow-up

Background: Currently available smoking cessation therapies have limited success rates. Varenicline tartrate is a novel, selective nicotinic receptor partial agonist developed specifically for smoking cessation. This study evaluated the efficacy, tolerability, and safety of 3 varenicline doses for smoking cessation. Bupropion hydrochloride was included as an active control. Methods: A phase 2, multicenter, randomized, doubleblind, placebo-controlled study of healthy smokers (18-65 years old). Subjects were randomized to varenicline tartrate, 0.3 mg once daily (n=128), 1.0 mg once daily (n=128), or 1.0 mg twice daily (n=127), for 6 weeks plus placebo for 1 week; to 150-mg sustained-release bupropion hydrochloride twice daily (n=128) for 7 weeks; or to placebo (n=127) for 7 weeks. Results: During the treatment phase, the continuous quit rates for any 4 weeks were significantly higher for varenicline tartrate, 1.0 mg twice daily (48.0%; P <. 001) and 1.0 mgonce daily (37.3%; P < . 001), than for placebo ( 17.1%). The bupropion rate was 33.3%( P = .002 vs placebo). The carbon monoxide - confirmed continuous quit rates from week 4 to week 52 were significantly higher in the varenicline tartrate, 1.0mgtwice daily, group compared with the placebo group( 14.4% vs 4.9%; P =. 002). The bupropion rate was 6.3% ( P =. 60 vs placebo). Discontinuation owing to treatment-emergent adverse events was 15.9% for bupropion, 11.2% to 14.3% for varenicline, and 9.8% for placebo. Nodose-related increases occurred in adverse events for varenicline. Conclusions: Varenicline tartrate demonstrated both short-term ( 1 mg twice daily and 1 mg once daily) and long-term efficacy ( 1 mg twice daily) vs placebo. Varenicline was well tolerated and may provide a novel therapy to aid smoking cessation.