Abstract 3981: Efficacy and Safety of Varenicline, an α4β2 Acetylcholine Nicotinic Receptor Partial Agonist, for Smoking Cessation in Japanese Smokers
Background: Smoking is the leading preventable cause of illness and premature death by increasing the risk of acute MI, sudden death and cerebrovascular disease. Varenicline, an α4β2 nicotinic acetylcholine receptor (nAChR) partial agonist, was developed specifically for smoking cessation with the potential to relieve nicotine craving and withdrawal symptoms while reducing the reinforcing effects of nicotine. Superior efficacy of varenicline 1 mg BID compared with bupropion 150 mg BID and placebo in achieving smoking cessation at the end of the 12-week treatment and one year was demonstrated in two identically designed, randomized, double-blind, 52-week studies conducted in the United States. The objective of this study was to evaluate the effect of varenicline in conjunction with smoking cessation counseling in Japanese smokers.
Methods and Results: In a randomized, double-blind placebo-controlled study in Japanese smokers, treatment with three doses of varenicline (0.25 mg BID, 0.5 mg BID, 1 mg BID) for 12 weeks was followed by a 40-week non-drug treatment period. All subjects were given brief counseling at each study visit. A total of 618 smokers from 19 centers in Japan were treated; 515 smokers were diagnosed as nicotine dependent, scoring 5 or greater on the Tobacco Dependence Screener (TDS). The 4-week continuous quit rate (CQR) during weeks 9–12, the primary endpoint, was significantly higher for all doses of varenicline than for placebo (39.5%), and the highest quit rate was achieved in the 1 mg BID group (65.4%, p<0.0001). The continuous abstinence (CA) rate during weeks 9–52 in the 1 mg BID group (34.6%) was also significantly higher than placebo (23.3%, p=0.0355). All doses of varenicline were safe and well-tolerated, with overall discontinuation rates similar to placebo. Nausea occurred more frequently with varenicline and was mild to moderate in intensity.
Conclusions: This was the first randomized, double-blind, placebo-controlled study that evaluated the effect of varenicline in conjunction with smoking cessation counseling using the 4-week CQR and CA rate in Japan. Results demonstrate that varenicline, the first in a new class of compounds developed for smoking cessation, is efficacious and well tolerated in the Japanese population.