A randomized, controlled trial to assess the efficacy and safety of a transdermal delivery system of nicotine/mecamylamine in cigarette smokers

Aims To determine the efficacy and safety of nicotine transdermal therapy co-administered with the nicotine antagonist, mecamylamine, compared to a nicotine transdermal patch alone (21 mg nicotine + 6 mg mecamylamine, 21 mg nicotine + 3 mg mecamylamine, and 21 mg nicotine + 0 mg mecamylamine). Design Multi-center (n = 4), double-blind, randomized, parallel group, repeat-dose study. Setting Clinical laboratory. Participants A total of 540 subjects were enrolled into the study-135 from each of four sites; 180 patients in each of three treatment arms. Intervention Treatment was administered for the first 6 weeks of the 8-week study. Patients were instructed to continue smoking for the first 2 weeks of treatment. Measurements The primary efficacy parameter was 4-week continuous abstinence after the quit date, confirmed with an expired carbon monoxide of < 10 parts per million. Findings Analysis of the 4-week continuous abstinence for the intent-to-treat population showed overall rates of 29% (nicotine + 6 mg mecamylamine), 29% (nicotine + 3 mg mecamylamine) and 23% (nicotine only) using the slip definition which allows smoking in the first 2 weeks after the quit date. Statistical analyses revealed no significant treatment differences. Analyses using the strict definition (no smoking after the quit date) yielded similar non-significant group differences (29%, 27%, 26%). Conclusion If adding mecamylamine to nicotine replacement therapy (NRT) improves the chances of success at stopping smoking, the results of this study suggest that the effect is very small.