Efficacy of modified doses of varenicline on quitting smoking attempts in Townsville, Australia

Varenicline remains the most effective pharmacological agent in supporting smokers to quit, though its effectiveness in promoting long term abstinence is inhibited by a number of issues 1. A recent meta-analysis reported that varenicline caused an increase in discontinuation compared to placebo as a result of adverse events, negatively impacting medication adherence and the likelihood of a quit attempt being successful 2. As adherence to varenicline is a major predictor of success during a quit attempt, ensuring completion of the prescribed regimen is needed to optimise the likelihood of a successful quit attempt 3. An additional issue during varenicline treatment is the resurgence of cravings and withdrawal symptoms at the end of the prescribed treatment period. Experiencing these symptoms increase the likelihood of lapse and relapse after achieving initial abstinence 4. The primary objective of this clinical study is to compare differences in safety and efficacy outcomes of three different varenicline regimens for smoking cessation over a treatment period of 16 weeks, followed by 12 weeks of follow-up. The regimens are designed to reduce the frequency and severity of adverse effects, cravings and withdrawal symptoms. The secondary objectives are a comparison of carbon monoxide (CO) confirmed continuous abstinence rates (CAR), 7-day point prevalence abstinence rates, and adherence to the study medication throughout treatment. The primary endpoints are the frequency, severity and duration of adverse events, cravings and withdrawal symptoms. The secondary endpoints are 7 day point prevalence and CO confirmed continuous abstinence rates from weeks 12-16, and weeks 16-28, and medication adherence. This study is a phase 4, randomized, double-blinded, placebo-controlled single-center study designed to evaluate the safety and efficacy of varenicline in motivated, smoking subjects allocated to a control group, step-up intervention group, or step-down intervention group. A total of up to 201 participants will be enrolled in to this study at a single site, with 67 participants randomly allocated in a 1:1:1 ratio to one of the three treatment groups. This will provide at least 80% power to detect a moderate effect in the primary endpoints. Participants meeting eligibility criteria will enter the 16-week double-blind treatment phase, followed by a 12-week follow-up phase, with the study completing at week 28. Follow-up will continue for participants who cease treatment early. Participant enrollment will run from December 2016 to December 2017, with data analysis occurring during and after this period.