Pfizer Inc. announced results published in The Lancet from the largest clinical trial of approved smoking cessation medicines, called EAGLES (Evaluating Adverse Events in a Global Smoking Cessation Study). This smoking cessation trial included 8,144 adult smokers and was designed to compare the neuropsychiatric safety of CHANTIX®/CHAMPIX® (varenicline) and bupropion with placebo and nicotine patch in adult smokers with and without a history of psychiatric disorders. The authors concluded that the trial did not show a significant increase in the incidence of the composite primary safety endpoint of serious neuropsychiatric adverse events with CHANTIX/CHAMPIX or bupropion compared to placebo and nicotine patch. Differences between incidence rates were considered significant if their associated 95% confidence intervals (CIs) were entirely above or below zero. Approximately half of the trial participants had a history of psychiatric disorders, either past and in remission or present and clinically stable. The psychiatric diagnoses included primarily depressive, bipolar, anxiety and psychotic disorders.
The EAGLES trial also included an efficacy objective to determine smoking abstinence rates in patients treated with CHANTIX/CHAMPIX or bupropion, relative to placebo, during the last four weeks of the 12-week treatment period. Continuous abstinence was also evaluated relative to the nicotine patch. In addition, longer-term abstinence through a 12-week non-treatment follow-up period (weeks 9-24) was evaluated for all treatments. The results showed that patients with and without a history of psychiatric disorders taking CHANTIX/CHAMPIX had significantly higher continuous abstinence rates than patients treated with bupropion or nicotine patch during both time periods. Patients treated with each of the medications had higher abstinence rates than those treated with placebo. This is the first placebo-controlled trial of this size to directly compare the efficacy of CHANTIX/CHAMPIX, bupropion and nicotine patch to help people quit smoking
The incidence of the primary safety endpoint in patients without a history of psychiatric disorders was 1.3% (CHANTIX/CHAMPIX), 2.2% (bupropion), 2.5% (nicotine patch) and 2.4% (placebo). The incidence rates in patients with a history of psychiatric disorders were 6.5% (CHANTIX/CHAMPIX), 6.7% (bupropion), 5.2% (nicotine patch) and 4.9% (placebo). In patients without a history of psychiatric disorders, the CHANTIX/CHAMPIX–placebo and bupropion–placebo risk differences (RDs) for the primary safety endpoint were −1.28 (95% CI −2.40 to −0.15) and −0.08 (−1.37 to 1.21), respectively. The RDs for CHANTIX/CHAMPIX-nicotine patch and bupropion-nicotine patch comparisons were −1.07 (−2.21 to 0.08) and 0.13 (−1.19 to 1.45), respectively. In patients with a history of psychiatric disorders, the CHANTIX/CHAMPIX–placebo and bupropion–placebo RDs were 1.59 (−0.42 to 3.59) and 1.78 (−0.24 to 3.81), respectively; the RDs for CHANTIX/CHAMPIX-nicotine patch and bupropion-nicotine patch comparisons were 1.22 (−0.81 to 3.25) and 1.42 (−0.63 to 3.46), respectively. Across both patient cohorts, 95% CIs associated with these RDs were lower than or included zero. There were more neuropsychiatric adverse events in the psychiatric cohort than the non-psychiatric cohort across all treatment arms including placebo.
