Nicorette

The oral tobacco product chosen was Camel snus (Winterchill and Robust, 2.5 and 2.6 mg nicotine/pouch, respectively, distributed by Reynolds American Inc). These snus products were chosen because of the higher levels of unprotonated nicotine in them compared to other US manufactured snus products and prior research showing that suppression of smoking is greater with oral non-combusted products with higher nicotine levels.17 (link) Participants who experienced adverse effects from these doses were provided Frost or Mellow (1.5 and 1.3 mg nicotine/pouch, respectively). A Swedish snus product with even higher levels of nicotine may have been preferable to compare with the Swedish experience. However, our prior preference study showed that no smoker chose the Swedish snus (General Snus).17 (link) nicotine gum (4 mg Nicorette distributed by GlaxoSmithKline) was chosen as the medicinal nicotine product, and participants who experienced adverse effects were down-titrated to 2 mg nicotine gum.

The three prototype 4-mg nicotine lozenges (prototypes I, II, and III), which differ in their dissolution properties and nicotine-release profiles, were supplied by the New Product Development Department – Wellness and Oral HealthCare, GlaxoSmithKline Asia Private Limited, Gurgaon, India, and were manufactured by Kemwell Biopharm Private, Bangalore, India. An internationally marketed 4-mg nicotine lozenge (Nicorette^®, GlaxoSmithKline Consumer Healthcare, Warren, NJ, USA) was used as the reference product for PK analysis.
At each study session, subjects received one of the four study treatments according to a computerized randomization schedule generated by the Biostatistics Department at GlaxoSmithKline Consumer Healthcare; in total, 24 treatment sequences were used. Nicotine lozenges were administered as a single 4-mg dose, and subjects were instructed not to swallow or chew the lozenge; time to complete dissolution of the dose was recorded by investigators.