Oral Mucosal Effects In Adult Smokers Associated With Two Nicotine Lozenge Formulations

To assess the oral mucosal health associated with 3 weeks of use of test product, Nicotine
Bitartrate 4 mg mint lozenge, relative to a reference product, Nicorette® [Nicotine
Polacrilex] 4 mg mint lozenge, in healthy adult smokers motivated to quit smoking.

To evaluate the safety and tolerability of Nicotine Bitartrate 4 mg mint lozenge and
Nicorette® [Nicotine Polacrilex] 4 mg mint lozenge in this subject population.

Inclusion Criteria:

Potential subjects who meet the following criteria at Screening may be included in the
study.

1. Sex and Age: Males and females aged at least 18 years and older.

2. Informed of the nature of the study and have agreed to and are able to read, review,
and sign the informed consent document prior to commencing any study specific
procedures. The informed consent document will be written in English, therefore the
volunteer must have the ability to read and communicate in English.

3. Must have smoked at least 10 cigarettes per day for the previous 12 months prior to
screening.

4. Must smoke first cigarette within 30 minutes of waking up.

5. Must be motivated to quit smoking upon enrollment into the study.

6. Contraception: Females of childbearing potential who have been, in the opinion of the
Investigator, practicing a reliable method of contraception for at least two months
prior to study participation and must agree to remain on an acceptable method of
contraception while participating in the study period using the study medication.
Acceptable methods of contraception are hormonal birth control, intrauterine device,
double barrier methods, vasectomized partner or abstinence.

7. Females of childbearing potential will be required to undergo a serum (Screening) and
urine (Day 0) pregnancy test (must be negative).

8. Females of non-childbearing potential must be surgically sterile for at least three
months prior to Screening or post-menopausal for at least two years.

9. General health: All study participants must have good general health and no
impairment that would impede or affect ability to participate in the study as deemed
acceptable by the Investigator.

10. Compliance: All study participants must understand and be willing to comply with all
study procedures and restrictions.

11. Consent: All study participants must demonstrate willingness to participate as
evidenced by voluntary written informed consent and must have received a signed and
dated copy of the informed consent form.

Exclusion Criteria:

1. Females who have a positive pregnancy test, are pregnant, breastfeeding, or intend to
become pregnant during the course of the study.

2. Nicotine use:

1. Is unable/unwilling to stop using forms of tobacco (e.g., traditional
cigarettes, chewing tobacco, nicotine gels, cigars, snuff tobacco, nicotine
patch and electronic cigarettes) for the duration of the study.

2. Is unable/unwilling to stop using other nicotine replacement therapy products
throughout the duration of the study.

3. Disease: Has a medical history, which in the opinion of the investigator, would
jeopardize the safety of the subject or impact the validity of the study results,
e.g., known history of heart disease, recent myocardial infarction or cerebrovascular
accident (i.e., within 12 weeks prior to enrollment), unstable angina, severe cardiac
arrhythmia, diabetes or peptic ulcer.

4. Demonstrates a reactive screen for Hepatitis B surface antigens, hepatitis C
antibody, or HIV antibody.

5. Oral condition:

1. Has history of oral surgery (including extractions) within four weeks of
screening, operative dental work within seven days of screening, or a presence
of any clinically significant oral pathology (as determined by an oral health
professional - dentist or dental hygienist) including lesions, sores or
inflammation of the mouth which would interfere with study assessments or
confound the results.

2. Has fixed retainers, orthodontic appliances, or either maxillary and/or
mandibular dentures or other appliances which may interfere with the placement
of the product.

3. Has current or recurrent disease that could affect the site of application, the
action, absorption of the study treatment, or clinical assessment.

4. Has severe gingivitis, periodontitis or rampant caries (extensive dental decay,
i.e., big/deep cavities, in many teeth), as diagnosed by an oral health
professional- dentist or dental hygienist.

5. Has the presence of oral or peri-oral ulceration including herpetic lesions at
screening (subjects with these lesions may be re-examined at a subsequent
appointment and may be able to be admitted at a later date if the ulceration or
herpetic lesion heals) or Study Visit Day 0.

6. Has elective dentistry scheduled during the study duration.

6. Allergy/Intolerance:

1. Has a known or suspected intolerance or hypersensitivity to the study materials
(or closely-related compounds) or any of their stated ingredients.

2. Has a known genetic deficiency with an inability to metabolize aspartame or
phenylalanine or has been diagnosed with phenylketonuria.

7. Clinical Study Participation:

1. Participation in another clinical study or receipt of an investigational drug
within 30 days of the screening visit at the start of the study.

2. Previous participation in this study.

8. Substance abuse:

1. Current or recent (within two years of screening) history of drug or alcohol
abuse, misuse, physical or psychological dependence.

2. Demonstrates a positive alcohol breath test.

3. Demonstrates a positive urine drug screen without disclosure of corresponding
prescribed concomitant medication(s) at Screening and Study Visit Day 0.

9. Urine glucose:

a) Positive glucose urine screen.

10. Personnel:

1. Is an employee of the Sponsor or the study site.

2. Is a member of the same household as another subject in this trial.

11. Use of all over the counter (OTC) and prescription (Rx) lozenges after starting the
study (Day 0 and onward).