A randomized placebo-controlled trial of varenicline for smoking cessation allowing flexible quit dates

Stephen Rennard, John Hughes, Paul M Cinciripini, Eva Kralikova, Tobias Raupach, Carmen Arteaga, Lisa B St Aubin, Cristina Russ, Flexible Quit Date Study Group, Marta Angueira, Elie Fiss, Claude Gagne, Douglas S Helmersen, Ping Chen, Rong Chang Chen, Chen Wang, Ondrej Sochor, Beatrice Le Maitre, Isabelle Schenkenberger, Iren Herjavecz, Maria Szilasi, Laura Carrozzi, Rodolfo Posadas, Jose E Gonzalez, Ho Joong Kim, Young Whan Kim, Huey-Shinn Cheng, Chang Gung Memorial Hospital-Linkou, Kuang-Chieh Hsueh, Alex Bobak, Corey G Anderson, James L Borders, Victor Alan Elinoff, Gary E Johnson, Nabil Charle Morcos, Anthony D Puopolo, Jon Andrew Shapiro, Stephan C Sharp, Mark Edward Shirley, Donald P Tashkin, Bradley D Vince, Stephen Rennard, John Hughes, Paul M Cinciripini, Eva Kralikova, Tobias Raupach, Carmen Arteaga, Lisa B St Aubin, Cristina Russ, Flexible Quit Date Study Group, Marta Angueira, Elie Fiss, Claude Gagne, Douglas S Helmersen, Ping Chen, Rong Chang Chen, Chen Wang, Ondrej Sochor, Beatrice Le Maitre, Isabelle Schenkenberger, Iren Herjavecz, Maria Szilasi, Laura Carrozzi, Rodolfo Posadas, Jose E Gonzalez, Ho Joong Kim, Young Whan Kim, Huey-Shinn Cheng, Chang Gung Memorial Hospital-Linkou, Kuang-Chieh Hsueh, Alex Bobak, Corey G Anderson, James L Borders, Victor Alan Elinoff, Gary E Johnson, Nabil Charle Morcos, Anthony D Puopolo, Jon Andrew Shapiro, Stephan C Sharp, Mark Edward Shirley, Donald P Tashkin, Bradley D Vince

Abstract

Introduction: Current smoking cessation guidelines recommend setting a quit date prior to starting pharmacotherapy. However, providing flexibility in the date of quitting may be more acceptable to some smokers. The objective of this study was to compare varenicline 1 mg twice daily (b.i.d.) with placebo in subjects using a flexible quit date paradigm after starting medication.

Methods: In this double-blind, randomized, placebo-controlled international study, smokers of ≥10 cigarettes/day, aged 18-75 years, and who were motivated to quit were randomized (3:1) to receive varenicline 1 mg b.i.d. or placebo for 12 weeks. Subjects were followed up through Week 24. Subjects were instructed to quit between Days 8 and 35 after starting medication. The primary endpoint was carbon monoxide-confirmed continuous abstinence during Weeks 9-12, and a key secondary endpoint was continuous abstinence during Weeks 9-24.

Results: Overall, 493 subjects were randomized to varenicline and 166 to placebo. Continuous abstinence was higher for varenicline than for placebo subjects at the end of treatment (Weeks 9-12: 53.1% vs. 19.3%; odds ratio [OR] 5.9; 95% CI, 3.7-9.4; p < .0001) and through 24 weeks follow-up (Weeks 9-24: 34.7% vs. 12.7%; OR 4.4; 95% CI, 2.6-7.5; p < .0001). Serious adverse events occurred in 1.2% varenicline (none were psychiatric) and 0.6% placebo subjects. Fewer varenicline than placebo subjects reported depression-related adverse events (2.3% vs. 6.7%, respectively).

Conclusions: Varenicline 1 mg b.i.d. using a flexible quit date paradigm had similar efficacy and safety compared with previous fixed quit date studies.

Trial registration: ClinicalTrials.gov NCT00691483.

Figures

Figure 1.
Figure 1.
Continuous abstinence at Weeks 9–12 and 9–24. OR = odds ratio (shown with 95% CI).
Figure 2.
Figure 2.
Time to first quit attempt (Kaplan–Meier).

References

    1. Cahill K, Stead LF, Lancaster T. Nicotine receptor partial agonists for smoking cessation. Cochrane Database of Systemic Reviews. 2008;(3) CD006103. doi:10.1002/14651858.CD006103.pub3.
    1. Chambers M. NHS stop smoking services: Service and monitoring guidance 2010/11. 2009. Retrieved. from .
    1. Coe JW, Brooks PR, Vetelino MG, Wirtz MC, Arnold EP, Huang J, et al. Varenicline: An α4β2 nicotinic receptor partial agonist for smoking cessation. Journal of Medicinal Chemistry. 2005;48:3474–3477. doi:10.1021/jm050069n.
    1. Fiore MC, Jaén CR, Baker TB, Bailey WC, Benowitz NL, Curry SJ, et al. Treating tobacco use and dependence: 2008 update. Clinical practice guideline. 2008. Retrieved from .
    1. Gonzales D, Rennard SI, Nides M, Oncken C, Azoulay S, Billing CB, et al. Varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: A randomized controlled trial. Journal of the American Medical Association. 2006;296:47–55. doi:10.1001/jama.296.1.47.
    1. Hughes JR, Keely J, Naud S. Shape of the relapse curve and long-term abstinence among untreated smokers. Addiction. 2004;99:29–38. doi:10.1111/j.1360-0443.2004.00540.x.
    1. Hughes JR, Solomon LJ, Livingston AE, Callas PW, Peters EN. A randomized, controlled trial of NRT-aided gradual vs. abrupt cessation in smokers actively trying to quit. Drug and Alcohol Dependence. 2010;111:105–113. doi:10.1016/j.drugalcdep.2010.04.007.
    1. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. ICH harmonised tripartite guideline: Guideline for good clinical practice E6(R1) 1996. Retrieved from .
    1. Jorenby DE, Hays JT, Rigotti NA, Azoulay S, Watsky EJ, Williams KE, et al. Efficacy of varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: A randomized controlled trial. Journal of the American Medical Association. 2006;296:56–63. doi:10.1001/jama.296.1.56.
    1. Kroenke K, Spitzer RL, Williams JB. The PHQ-9: Validity of a brief depression severity measure. Journal of General Internal Medicine. 2001;16:606–613. doi:10.1046/j.1525-1497.2001.016009606.x.
    1. Molyneux A, Lewis S, Leivers U, Anderton A, Antoniak M, Brackenridge A, et al. Clinical trial comparing nicotine replacement therapy (NRT) plus brief counselling, brief counselling alone, and minimal intervention on smoking cessation in hospital inpatients. Thorax. 2003;58:484–488. doi:10.1136/thorax.58.6.484.
    1. Nakamura M, Oshima A, Fujimoto Y, Maruyama N, Ishibashi T, Reeves KR. Efficacy and tolerability of varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, in a 12-week, randomized, placebo-controlled, dose-response study with 40-week follow-up for smoking cessation in Japanese smokers. Clinical Therapeutics. 2007;29:1040–1056. doi:10.1016/j.clinthera.2007.06.012.
    1. National Cancer Institute (U.S.) Clearing the air: Quit smoking today. 2003. NIH publication 03-1647. Retrieved from .
    1. Oncken C, Gonzales D, Nides M, Rennard S, Watsky E, Billing CB, et al. Efficacy and safety of the novel selective nicotinic acetylcholine receptor partial agonist, varenicline, for smoking cessation. Archives of Internal Medicine. 2006;166:1571–1577. doi:10.1001/archinte.166.15.1571.
    1. Posner K, Oquendo MA, Gould M, Stanley B, Davies M. Columbia Classification Algorithm of Suicide Assessment (C-CASA): Classification of suicidal events in the FDA's pediatric suicidal risk analysis of antidepressants. American Journal of Psychiatry. 2007;164:1035–1043. doi:10.1176/appi.ajp.164.7.1035.
    1. Rigotti NA, Pipe AL, Benowitz NL, Arteaga C, Garza D, Tonstad S. Efficacy and safety of varenicline for smoking cessation in patients with cardiovascular disease: A randomized trial. Circulation. 2010;121:221–229. doi:10.1161/CIRCULATIONAHA.109.869008.
    1. Rose JE, Herskovic JE, Behm FM, Westman EC. Precessation treatment with nicotine patch significantly increases abstinence rates relative to conventional treatment. Nicotine & Tobacco Research. 2009;11:1067–1075. doi:10.1093/ntr/ntp103.
    1. Shiffman S, Brockwell SE, Pillitteri JL, Gitchell JG. Use of smoking-cessation treatments in the United States. American Journal of Preventive Medicine. 2008;34:102–111. doi:10.1016/j.amepre.2007.09.033.
    1. Shiffman S, Ferguson SG, Strahs KR. Quitting by gradual smoking reduction using nicotine gum: A randomized controlled trial. American Journal of Preventive Medicine. 2009;36:96–104. doi:10.1016/j.amepre.2008.09.039.
    1. Tashkin DP, Rennard S, Hays JT, Ma W, Lawrence D, Lee TC. Effects of varenicline on smoking cessation in mild-to-moderate COPD: A randomized controlled trial. Chest. 2010;139:591–599. doi:10.1378/chest.10-0865.
    1. Tsai ST, Cho HJ, Cheng HS, Kim CH, Hsueh KC, Billing CB, Jr., et al. A randomized, placebo-controlled trial of varenicline, a selective α4β2 nicotinic acetylcholine receptor partial agonist, as a new therapy for smoking cessation in Asian smokers. Clinical Therapeutics. 2007;29:1027–1039. doi:10.1016/j.clinthera.2007.06.011.
    1. Wang C, Xiao D, Chan KP, Pothirat C, Garza D, Davies S. Varenicline for smoking cessation: A placebo-controlled, randomized study. Respirology. 2009;14:384–392. doi:10.1111/j.1440-1843.2008.01476.x.
    1. West R, Baker CL, Cappelleri JC, Bushmakin AG. Effect of varenicline and bupropion SR on craving, nicotine withdrawal symptoms, and rewarding effects of smoking during a quit attempt. Psychopharmacology. 2008;197:371–377. doi:10.1007/s00213-007-1041-3.
    1. World Health Organization. WHO report on the global tobacco epidemic, 2008. The MPower package. 2008. Retrieved from .
    1. World Medical Association. World Medical Association Declaration of Helsinki—ethical principles for medical research involving human subjects. 2008. Retrieved from .

Source: PubMed

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