A Bioequivalence Study Between Two Nicotine Replacement Therapies in Adult Healthy Smokers Motivated to Quit.
A Bioequivalence Study Between Two Nicotine Replacement Therapies in Adult Healthy Smokers Motivated to Quit.
This is a research study to verify the same effectiveness and safety profile for the test
 product, Nicorette Strongmint lozenge, as for an already approved product, NiQuitin® Minimint
 lozenge (reference product), in a standardized mode. This verification is done in a so-called
 bioequivalence study, which means that the same amount of the same active substance
 (nicotine), in the same dosage form, for the same route of administration, and meeting the
 same or comparable standards is performed.

 During the study visits, blood samples will be drawn to measure the level of the substance in
 the blood to verify that the two products are comparable. Tolerability of the treatments will
 be evaluated based on reported and observed adverse events.
This is a single-dose, two-period crossover, randomized, fasting, open-label, bioequivalence
 study.

 244 male and female volunteers with a smoking history of minimum 3 months and aged between 18
 and 45 years, inclusive, and motivated to quit will be included. The treatment administration
 order will be randomized with an equal number of subjects in each treatment sequence.

 Single doses of 4 mg Nicorette Strongmint Lozenge (i.e. test product) and 4 mg NiQuitin®
 Minimint Lozenge (i.e. reference product) will be administered in a standardized mode, on two
 separate treatment visits. A washout period of minimum 48 hours will separate the treatment
 administrations.

 An abstinence period of 12 hours including an overnight stay at the clinic is required at
 both treatment occasions.

 Blood for pharmacokinetic analyses will be drawn pre-dose (i.e. within 5 minutes before drug
 administration) and at 10, 15, 20, 30, 40, 50, and 60 minutes, as well as 1.25, 1.5, 2, 3, 4,
 6, 8, 10, and 12 hours after start of drug administration. Thus, 17 samples will be collected
 per treatment visit.

 Subjects will be monitored to capture any adverse events that may occur.
Inclusion Criteria:

 1. Male and/or female subjects 18 to 45 years of age, inclusive, and being verified
 "Healthy". ("Healthy" is defined as absence of any diseases or abnormalities on the
 basis of physical examination, standard clinical laboratory and instrumental
 examinations performed at the screening visit).

 2. Smoking at least 10 tobacco cigarettes daily for at least three months preceding
 inclusion and presence of motivation to quit smoking.

 3. Subjects with a Body Mass Index (BMI) between 18.5 to 30 kg/m2, inclusive, and a body
 weight >50 kg.

 4. Females of childbearing potential must have a negative urine pregnancy test at the
 screening visit.

 5. Male or non-pregnant, non-lactating female agree to the contraceptive requirements
 (including male's and female partner's use of a highly effective methods of birth
 control for at least 3 months before the study, during the study and for 30 days after
 the last dose of study drug) as outlined in Section 10.7

 6. Has a personally signed and dated informed consent document before participating in
 any study-specific procedures, indicating that the subject has been informed of all
 pertinent aspects of the study; and

 7. Is able to comprehend the requirements of the study (based upon clinical site
 personnel's assessment), and is willing and able to comply with scheduled
 visits,treatment plan, laboratory tests, and other study procedures specified in the
 protocol.

 Exclusion Criteria:

 1. Deviations from normal ranges as a result of standard clinical laboratory and
 instrumental examinations including ECG, performed at the screening visit.

 2. Use of vitamins, herbal supplements and medicinal plants (e.g. garlic) within 7 days
 before the first dose of study medication. Use of products containing St. John's wort
 [Hypericum perforatum] 30 days prior to the study start.

 3. Intake of medications having a significant impact on hemodynamics, hepatic function
 etc. (e.g. [but not limited to] barbiturates, omeprazole cimetidine).

 4. Subjects who will not abstain from using nicotine-containing products (besides
 treatments specified in this protocol) and smoking from 12 hours before planned
 treatment intake and throughout each visit.

 5. Is hypersensitive, intolerant, or experienced an allergic reaction to the active
 ingredient(s) or excipients of drug products that will be used in the study or has
 severe allergy (e.g. anaphylaxis, angioedema) in the past.

 6. Females with a positive pregnancy test and/or are breast-feeding.

 7. Females, currently using hormonal contraceptives, (including use less than 2 weeks
 prior to enrollment)

 8. Males with a pregnant spouse or partner or males who are not willing to prevent
 conception in a spouse or partner.

 9. Has a positive test for human immunodeficiency virus (HIV) 1 and 2 antibodies,
 hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (anti-HCV) or syphilis
 (RW).

 10. Has a positive test for psychoactive and narcotic substances, psychoactive drugs at
 screening and/or at any admission to the clinical center or has drugs abuse in the
 past.

 11. Consumes alcohol regularly in excess of the following: >10 units per week (1 unit of
 alcohol is equivalent to ½ liter of beer, 200 ml wine or 50 ml of vodka) or presence
 of information on alcoholism in medical history. The subject must also abstain from
 alcohol consumption within 48 hours prior to the screening visit and have a negative
 respiratory alcohol test at the screening visit and/or at any admission clinical
 center (breathalyzer).

 12. Use of xanthine products within 48 hours prior to the first dose of the
 investigational product.

 13. Ingestion of food or beverages containing grapefruit, Chinese grapefruit (pomelo) or
 Seville oranges (including marmalade) within 10 days prior to the first dose of the
 investigational product and inability to stop these products taking during the study.

 14. Abuse of caffeine products exceeding 500mg caffeine daily (5 cups of coffee) and the
 ability to abstain from caffeine products at least 48 hours before the first dose of
 investigational product intake and prior to prior to collection of the last blood
 sample in each period of the study.

 15. Renal or hepatic impairment.

 16. Has a history of gastrointestinal surgery other than appendectomy, ulcers or any other
 lesions in the mouth.

 17. Erosive and ulcerative lesions of oral mucosa, xerostomia, including a history of
 these diseases, jaw trauma and surgery.

 18. Heart rate < 60 or > 80 per minute at rest, or systolic blood pressure <100 or >130 mm
 Hg, or diastolic blood pressure < 70 or > 90 mm Hg.

 19. Acute infections within 4 weeks prior to the study.

 20. Treatment with an investigational drug within 3 months preceding the first dose of
 study treatment.

 21. Donation of ≥450mL blood or plasma, or loss of ≥500mL of blood 3 months prior to the
 first of investigational product intake.

 22. Preplanned surgery or procedures during the study period, if this may interfere with
 the conduct of the study.

 23. Inability to give written informed consent or comply with the protocol requirements.

 24. Probability to refuse to comply with the protocol requirements, instructions and
 restrictions; for example, unwillingness to cooperate, inability to return to the
 clinical center for follow-up visits and the probability of incomplete participation
 in the clinical trial.

 25. Participation in clinical trials less than 3 months prior to the study.

 26. Relationship to persons involved directly with the conduct of the study (i.e.,
 principal investigator; sub investigators; study coordinators; other study personnel;
 employees or contractors of the Sponsor or Johnson & Johnson subsidiaries; and the
 families of each).