ORLANDO, FLA. – Varenicline, a first-of-its-kind selective nicotinic receptor partial agonist, has racked up unprecedented smoking-cessation success rates in a pair of phase II clinical trials, Cheryl A. Oncken, M.D., reported at the annual meeting of the American College of Cardiology.
Based on these extremely encouraging albeit short-term results, multiple yearlong phase III trials are underway using varenicline at 1.0 mg twice daily, a Pfizer spokesman told this newspaper.
The two phase II placebo-controlled studies totaled 1,253 smokers. In one 6-week study, 48% of participants assigned to 1.0 mg of varenicline twice daily quit smoking for a 28-day period as determined by review of daily smoking diaries, compared with 37% on 1.0 mg/day of the drug, 33% on 150 mg of bupropion twice daily, 29% on 0.3 mg/day of varenicline, and 17% on placebo, said Dr. Oncken of the University of Connecticut, Farmington.
In the other study, which lasted 12 weeks, 51% of patients on 1.0 mg of varenicline twice daily abstained from smoking during weeks 9–12 as confirmed by carbon monoxide testing. This was also the case for 45% of those randomized to 0.5 mg of the drug twice daily and for 12% of the placebo group. The adjusted odds ratios for abstinence were 6.1 and 7.8 for 0.5 and 1.0 mg of varenicline twice daily, respectively, compared with placebo.
The most common varenicline-related side effect was transient mild to moderate nausea. Tolerability compared favorably with placebo in both studies. It also compared favorably with bupropion–a drug with a Food and Drug Administration indication for smoking cessation–in the one comparative trial where it was used, with discontinuation due to adverse events occurring in 11% of patients in the high-dose varenicline group and 16% of those on bupropion. No varenicline-related safety issues arose during monitoring of laboratory tests and ECGs.
Nicotine dependence in smokers is mediated via the neuronal α4 β2 nicotinic receptor. Varenicline is believed to act by blocking nicotine binding to the receptor during smoking, thereby interfering with smoking's extremely potent reinforcement and reward effects. Moreover, partial activation of the α4 β2 receptor by varenicline during abstinence has been hypothesized to relieve nicotine craving and withdrawal symptoms, Dr. Oncken explained.
Her studies were sponsored by Pfizer Global Research and Development.