Single-dose Pharmacokinetics of Oral Nicotine Replacement Products

• Maximum Concentration [ Time Frame: Baseline to 10 hours post-dose ] [ Designated as safety issue: No ]
  The maximum observed nicotine concentration in plasma (Cmax)
• Area under the Curve [ Time Frame: 10 hours post-dose ] [ Designated as safety issue: No ]
  The area under the plasma concentration-vs.-time curve until the last measurable concentration (AUCt)and the area under the plasma concentration-vs.-time curve until infinity (AUC∞)

• Time to Maximum Concentration [ Time Frame: 10 hours post-dose ] [ Designated as safety issue: No ]
  Time to Maximum Concentration (Tmax)
• Residual Nicotine [ Time Frame: 30 minutes ] [ Designated as safety issue: No ]
  The amount of residual nicotine in the product after being chewed.
• Dissolution Time [ Time Frame: 10 hours post-dose ] [ Designated as safety issue: No ]
  Actual time required for oral dissolution of new NRT products following product administration

This is an explorative study comparing new prototypes of Nicotine Replacement Products with Nicorette® gum.

This study included 40 subjects who were randomly assigned to one of eight treatment sequences. In four of the sequences, the three prototypes with the shorter dissolution time and the reference were used; in the remaining four sequences, the three prototypes with the longer dissolution time and the reference were used. Hence, half of the subjects received the Short prototypes and half received the Long prototypes. Subjects in both treatment groups (short and long) attended four treatment visits, each of 11 hours' duration, and periods of at least 36 hours' duration between treatment visits.

• Drug: Nicotine
  Following a 12-hour nicotine abstinence period, subjects receive a single 2 mg dose of their assigned nicotine replacement therapy in the morning of the treatment visit day
  Other Name: Not yet marketed
• Drug: Nicotine Gum
  Following a 12-hour nicotine abstinence period, subjects will be instructed to chew the gum once every 2 seconds, for 30 minutes.
  Other Name: Nicorette®

• Experimental: A1 Short, no buffer
  Nicotine / not yet marketed
  Intervention: Drug: Nicotine
• Experimental: A2 Short, low buffer
  Nicotine / not yet marketed
  Intervention: Drug: Nicotine
• Experimental: A3 Short, high buffer
  Nicotine / not yet marketed
  Intervention: Drug: Nicotine
• Experimental: B1 Long, no buffer
  Nicotine / not yet marketed
  Intervention: Drug: Nicotine
• Experimental: B2 Long, low buffer
  Nicotine / not yet marketed
  Intervention: Drug: Nicotine
• Experimental: B3 Long, high buffer
  Nicotine / not yet marketed
  Intervention: Drug: Nicotine
• Active Comparator: R = Nicotine Gum
  Nicorette® Gum
  Intervention: Drug: Nicotine Gum

Inclusion Criteria:

• Healthy smokers, smoking at least 10 cigarettes daily during at least one year preceding inclusion and BMI between 17.5 and 30.0 kg/m2.
• Female participants of child-bearing potential are required to use a medically acceptable means of birth control.
• A personally signed and dated informed consent document, indicating that the subject has been informed of all pertinent aspects of the study.

Exclusion Criteria:

• Pregnancy, lactation or intended pregnancy.
• Treatment with an investigational product or donation or loss of blood within 3 month preceding the first dose of study medication.