Smoking cessation with varenicline, a selective alpha4beta2 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, double-blind, 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 mg once 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, 1.0 mg twice 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. No dose-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.
Nides
Mitchell
M
Los Angeles Clinical Trials, 2990 S. Sepulveda Boulevard, Los Angeles, CA 90064, USA. mnides@laclinicaltrials.com
Oncken
Cheryl
C
Gonzales
David
D
Rennard
Stephen
S
Watsky
Eric J
EJ
Anziano
Rich
R
Reeves
Karen R
KR
D000293:Adolescent; D000328:Adult; D000368:Aged; D001552:Benzazepines / Q000009:adverse effects / Q000627:therapeutic use*; D016642:Bupropion / Q000627:therapeutic use; D018765:Dopamine Uptake Inhibitors / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006304:Health Status; D006801:Humans; D008297:Male; D008875:Middle Aged; D018722:Nicotinic Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D018733:Nicotinic Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D011810:Quinoxalines / Q000009:adverse effects / Q000627:therapeutic use*; D016540:Smoking Cessation / Q000379:methods*; D014029:Tobacco Use Disorder / Q000188:drug therapy*; D016896:Treatment Outcome; D000068580:Varenicline
D001552:Benzazepines; D018765:Dopamine Uptake Inhibitors; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011810:Quinoxalines; D016642:Bupropion; D000068580:Varenicline