The efficacy and safety of varenicline for smoking cessation using a flexible dosing strategy in adult smokers: a randomized controlled trial

ABSTRACT

Objective: To determine whether self-regulated flexible dosing with varenicline tartrate is safe and effective for smoking cessation.

Research design and methods: 320 healthy, motivated-to-quit smokers (≥10 cigarettes/day) aged 18–65 years, entered a multicenter, randomized, double-blind, placebo-controlled study – conducted between December 26, 2001 and June 24, 2003 – with a 12-week treatment phase and 40-week, double-blind, non-treatment follow-up. Treatment consisted of varenicline or placebo in fixed doses (Week 1: titrated from 0.5 to 1.0 mg/day) followed by a self-regulated flexible schedule (Weeks 2–12: 0.5–2.0 mg/day).

Main outcome measures: Primary outcomes included carbon monoxide-confirmed continuous abstinence rate (CAR) from smoking for Weeks 4 through 7, 9 through 12, and 9 through 52. Secondary outcomes included CAR from Weeks 9 through 24, 7-day point prevalence of abstinence, safety assessments, and measures of craving, withdrawal, and smoking reward.

Results: Superior CARs were observed in varenicline-treated (n = 157) versus placebo participants (n = 155) for Weeks 4 through 7 (38.2 vs. 11.6%), 9 through 12 (40.1 vs. 11.6%), 9 through 24 (28.0 vs. 9.0%), and 9 through 52 (22.3 vs. 7.7%) (all p < 0.001). Seven-day point prevalence was higher in varenicline-treated than placebo participants at Weeks 12 (46.5 vs. 14.2%; p < 0.001), 24 (32.5 vs. 13.5%; p < 0.001), and 52 (28.0 vs. 13.5%; p = 0.001). Overall, medication compliance was high, although varenicline-treated, but not placebo, participants tended to taper down their dosage over time. Total treatment-emergent AEs were 77.1% (varenicline: 121/157) and 65.8% (placebo: 102/155). Few AEs led to treatment discontinuation (varenicline: 11/157, 7.0% and placebo: 7/155, 4.5%). Participants were primarily healthy Caucasians, so more research is necessary to determine how applicable these findings are to other populations.

Conclusions: A self-regulated, flexible dosing regimen of varenicline is well tolerated, with superior effectiveness versus placebo for smoking cessation.

Trial registration: ClinicalTrials.gov identifier: NCT00150228.

Key words: :

• Drug therapy
• Partial agonist
• Smoking cessation
• Varenicline

Acknowledgments

Declaration of interest: This study was funded by Pfizer, Inc. KEW, KRR, and CBB are employees of Pfizer and have stock or stock options in Pfizer. RN has received consulting fees from Pfizer, GlaxoSmithKline, Sanofi-Aventis, Merck, Constella, and LLC. DEJ has received consulting fees from Nabi Biopharmaceutical and receives research support from Pfizer, Nabi Biopharmaceutical, and Sanofi-Aventis. FTL serves on speakers’ bureaus for Pfizer and Merck and is a consultant on an advisory panel with Pfizer. JTH received grant support from Pfizer. JEP received grant support from Merck, DepoMed, Pfizer, Novartis, Takeda, Sanofi-Aventis, Symbollon, TAP, and GlaxoSmithKline. Editorial support was provided by Ray Beck, Jr, PhD of Envision Pharma and was funded by Pfizer, Inc. The ClinicalTrials.gov registration number is NCT00150228.