A pilot study of the tolerability and effect on smoking urges of flavoured and unflavoured nicotine inhalers that contain either pure nicotine or a nicotine salt, compared to placebo.

All subjects will inhale one puff from a series of placebo and nicotine formulations during one visit to the clinic, which will last approximately 1 to 3 hours. Initially subjects will take just one puff of each formulation and rate its effects. They will wait until they feel another urge to smoke before they try one puff of the next formulation. All subjects will begin with the lowest dose of the placebo formulations (0.5% menthol), have one puff, then progress to the 0.75% menthol dose (when they feel an urge to smoke), then they will go on to take one puff of the 1% dose (when they feel an urge to smoke). When subjects once again feel an urge to smoke, they will take up to ten puffs of the highest dose of the placebo formulation that they found tolerable and effective, and rate its effects. Then subjects will be randomised to take one puff of a range of 50mcg nicotine doses in random cross-over order. All these puffs will be taken on the same day, subjects will be asked to delay taking a puff of the next formulation until they once again feel an urge to smoke. The formulations that subjects will take in random order are: nicotine base, nicotine base plus menthol, nicotine base plus vanillin, nicotine lactate, nicotine lactate plus menthol, nicotine lactate plus vanillin. Subjects may then choose whether or not to take one puff of the 100mcg per puff dose of one or more of the formulations of which they sampled the 50mcg dose version (presented in the same random order as the 50mcg doses were). Subjects will only take a puff of the 100mcg dose of those formulations which they thought the 50mcg dose was tolerable. Subjects will take one puff of each of the 100mcg dose formulations, and after taking a puff of one formulation, they will wait until they feel an urge to smoke before they take a puff of the next formulation. Subjects can then choose to inhale one or more of the 200mcg doses of those formulations which they thought were tolerable at the lower doses. Just as they did with the lower dose formulations, before they take one puff of each of the 200mcg formulations, they will wait until they feel an urge to smoke before they take a puff of the next formulation, and they will only inhaler the higher dose of those formulations for which they felt the lower dose was tolerable. Subjects may then sample up to ten puffs of one or more of the formulations, which they thought was the most tolerable and efficacious. Subjects will be encouraged to choose the highest dose of the formulations that they thought were tolerable and efficacious (in terms of reducing the urge to smoke). The time over which subjects inhale the ten puffs will be limited to a maximum of ten minutes, and subjects can have a shorter duration if they wish. Subjects will wait until they feel an urge to smoke before they try the next formulation.