Efficacy and safety of the novel selective nicotinic acetylcholine receptor partial agonist, varenicline, for smoking cessation.
BACKGROUND
The selective nicotinic acetylcholine receptor partial agonist, varenicline tartrate, represents a novel type of therapy for smoking cessation. This study evaluated the efficacy, safety, and tolerability of 4 varenicline dose regimens, 2 with progressive dosing over the first week (eg, titrated) and 2 with a fixed dosing schedule (eg, non-titrated), for promoting smoking cessation.


METHODS
This multicenter, double-blind, placebo-controlled study randomized healthy smokers (aged 18-65 years) to varenicline tartrate, 0.5 mg twice daily nontitrated (n = 129), 0.5 mg twice daily titrated (n = 130), 1.0 mg twice daily nontitrated (n = 129), 1.0 mg twice daily titrated (n = 130), or placebo (n = 129) for 12 weeks to aid in smoking cessation. A 40-week follow-up period assessed long-term efficacy. The primary efficacy measures were the carbon monoxide-confirmed 4-week continuous quit rates by pooled dosage group for weeks 4 through 7 and 9 through 12 and the continuous abstinence rates for weeks 9 through 52.


RESULTS
Weeks 9 through 12 continuous quit rates were greater in the 1.0-mg group (49.4%) and the 0.5-mg group (44.0%) vs placebo (11.6%; P<.001 vs both doses). Weeks 9 through 52 abstinence rates were greater in the 1.0-mg group (22.4%; P<.001) and the 0.5-mg group (18.5%; P<.001) vs placebo (3.9%). Varenicline was generally well tolerated, with nausea occurring in 16% to 42% of varenicline-treated subjects. Reports of nausea were lower for the titrated vs nontitrated dosing and infrequently led to medication discontinuation.


CONCLUSIONS
Varenicline tartrate, 0.5 mg and 1.0 mg twice daily, is efficacious for smoking cessation.
Oncken
Cheryl
C
University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA. oncken@nso2.uchc.edu
Gonzales
David
D
Nides
Mitchell
M
Rennard
Stephen
S
Watsky
Eric
E
Billing
Clare B
CB
Anziano
Richard
R
Reeves
Karen
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D001552:Benzazepines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018733:Nicotinic Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011810:Quinoxalines / Q000008:administration & dosage / 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; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011810:Quinoxalines; D000068580:Varenicline