Sensitivity and specificity of a procedure for early human screening of novel smoking cessation medications

Addiction. 2013 Nov;108(11):1962-8. doi: 10.1111/add.12273. Epub 2013 Jul 12.

Abstract

Background and aim: It is important to find economical methods in early Phase 2 studies to screen drugs potentially useful to aid smoking cessation. A method has been developed that detects efficacy of varenicline and nicotine patch. This study aimed to evaluate whether the method would detect the efficacy of bupropion and identify correctly the lack of efficacy of modafinil.

Design: Using a within-subject double cross-over design, smokers attempted to quit during each treatment, with bupropion (150 mg b.i.d.), modafinil [100 mg twice daily (b.i.d.)] or placebo (double-blind, counterbalanced order). In each of three medication periods, all smoked with no drug on week 1 (baseline or washout), began dose run-up on week 2, and tried to quit every day during week 3.

Setting: A university research center in the United States.

Participants: Forty-five adult smokers high in quit interest.

Measurements: Abstinence was verified daily each quit week by self-report of no smoking over the prior 24 hours and carbon monoxide (CO) < 5 parts per million.

Findings: Compared with placebo, bupropion did (F(1,44) = 6.98, P = 0.01), but modafinil did not (F(1,44) = 0.29, P = 0.60), increase the number of abstinent days. Also, bupropion (versus placebo) significantly increased the number of those able to maintain continuous abstinence on all 5 days throughout the quit week (11 versus four), Z = 2.11, P < 0.05, while modafinil did not (six).

Conclusions: Assessing days abstinent during 1 week of use of medication versus placebo in a cross-over design could be a useful early Phase 2 study design for discriminating between medications useful versus not useful in aiding smoking cessation.

Keywords: Bupropion; medication development; modafinil; pharmacotherapy; sensitivity; smoking cessation; specificity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Benzhydryl Compounds / therapeutic use*
  • Bupropion / therapeutic use*
  • Carbon Monoxide / analysis
  • Cross-Over Studies
  • Dopamine Uptake Inhibitors / therapeutic use*
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Mass Screening / methods
  • Middle Aged
  • Modafinil
  • Self Report
  • Sensitivity and Specificity
  • Smoking / drug therapy*
  • Smoking Cessation / methods*
  • Time Factors
  • Treatment Outcome
  • United States
  • Wakefulness-Promoting Agents / therapeutic use*
  • Young Adult

Substances

  • Benzhydryl Compounds
  • Dopamine Uptake Inhibitors
  • Wakefulness-Promoting Agents
  • Bupropion
  • Carbon Monoxide
  • Modafinil