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

Arch Intern Med. 2006 Aug 14-28;166(15):1561-8. doi: 10.1001/archinte.166.15.1561.

Abstract

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Benzazepines / adverse effects
  • Benzazepines / therapeutic use*
  • Bupropion / therapeutic use
  • Dopamine Uptake Inhibitors / therapeutic use
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Health Status
  • Humans
  • Male
  • Middle Aged
  • Nicotinic Agonists / adverse effects
  • Nicotinic Agonists / therapeutic use*
  • Nicotinic Antagonists / adverse effects
  • Nicotinic Antagonists / therapeutic use*
  • Quinoxalines / adverse effects
  • Quinoxalines / therapeutic use*
  • Smoking Cessation / methods*
  • Tobacco Use Disorder / drug therapy*
  • Treatment Outcome
  • Varenicline

Substances

  • Benzazepines
  • Dopamine Uptake Inhibitors
  • Nicotinic Agonists
  • Nicotinic Antagonists
  • Quinoxalines
  • Bupropion
  • Varenicline