An Exploratory Study Comparing Two Nicotine Inhalers

Blood for pharmacokinetic analyses will be drawn prior to the first administration and immediately before administration at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11 hours. Thereafter samples will be drawn at 5, 10, 15, 20, 25, 30, 45, and 60 minutes after the 11-hour administration. Easiness of use will be rated using an 8-grade ordered category scale at 10 minutes after the start of administrations at 3, 6, and 9 hours. Overall liking will be rated using an 8-grade ordered category scale at 12 hours. Urges to smoke will be rated on a 4-grade ordered category scale immediately before and at 15 minutes after the first administration, and as well as before and 15 minutes after the start of administrations at 3, 6, and 9 hours, and at 12 hours. Used cartridges will be collected. Pooled samples per subject and treatment will be analyzed to determine the amount of remaining nicotine. Tolerability of the treatments will be evaluated in terms of reported and observed adverse events (AE).

Since the primary objective is to compare steady-state nicotine pharmacokinetics of N1/3-I5 with that of Nicotine Inhaler 10 mg, this study will have a multiple-dose setting. A crossover design has been chosen for this study in order to allow within-subject comparisons of treatments. Healthy habituated adults smoking at least 10 cigarettes daily for at least one year preceding inclusion will be included in the study, since they are expected to tolerate the doses of nicotine that will be administered.

Inclusion criteria

• Healthy (per protocol-specified parameters) male or female subjects between the ages of 19 and 50 years, inclusive.
• Smoking of at least 10 cigarettes daily during at least one year preceding inclusion.
• For females: Postmenopausal state or premenopausal/perimenopausal state with a protocol-specified effective means of contraception or declared absence of sexual contact with a male partner during the study.
• For males: No pregnant spouse or partner at screening and willingness to protect potential spouse or partner from becoming pregnant during the study.
• Body Mass Index (BMI) within protocol-specified parameters.
• A personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
• Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures specified in the protocol

Exclusion criteria

• Evidence or history of an acute or chronic medical or psychiatric condition or allergy or laboratory abnormality, or of use of drugs that, in the judgment of the investigator or an authorized study physician, may increase the risk associated with study participation or interfere with the interpretability of study results.
• Females: Pregnancy, breast-feeding, premenopausal, or perimenopausal, state with insufficient contraception as specified under Inclusion Criteria.
• Males: Pregnant spouse or partner or no willingness to prevent conception in a spouse or partner.
• History of regular alcohol consumption outside the protocol-specified allowances.
• Treatment with an investigational drug within 3 months preceding the first dose of study treatment.
• Known sensitivity to heparin or history of heparin-induced thrombocytopenia.
• Pathological oral status interfering with normal muscular, sensory, or absorptive function of the oral cavity. Piercing of tongue and lips is considered to impair oral function.
• Relationship to persons involved directly with the conduct of the study, or their families.