A Bioequivalence Study of Two Nicotine Lozenges in Fasting Conditions in Healthy Smokers

This study will be a single center, randomized, open label, single dose, two-way crossover in
healthy smokers that smoke their first cigarette more than 30 minutes of waking. This study
will consist of following Visits: Visit 1 (Screening), Visit 2 (Study Period 1), followed by
a Washout period and Visit 3 (Study Period 2). Each participant will be treated with a single
dose of the two study treatments (test and reference) in a randomized sequence. Participants
will be confined in the study facility for approximately 60 hours during each study session
(for 36 hours pre-dosing and for 24 hours post dosing) during which pharmacokinetic (PK)
blood samples will be obtained. Participants are to abstain from smoking during the
confinement periods and be subject to random measurements of expired carbon monoxide (CO) to
confirm abstinence. The CO levels must be ≤10 parts per million (ppm) throughout the study
session. There will be at least 5-day and not more than 7-day clinical furlough period
between treatment periods. For each treatment period, the clinical confinement period with
restriction of smoking is at least 36 hours prior to dosing.

Inclusion Criteria:

- Evidence of a personally signed and dated informed consent document indicating that
the participant has been informed of all pertinent aspects of the study before any
assessment is performed.

- Participants who are willing and able to comply with scheduled visits, treatment plan,
laboratory tests, and other study procedures.

- Healthy participants which is defined as in general good physical health, as judged by
the investigator and no clinically relevant abnormalities identified by a detailed
medical history, full physical examination, including blood pressure, respiratory
rate, oral body temperature and pulse rate measurement, 12-lead ECG or clinical
laboratory tests.

- Body Mass Index (BMI) of 19 to 27 Kilogram per meter square (kg/m2), inclusive; and a
total body weight >50 kg (110 pounds [lbs]).

- Female participants of childbearing potential and at risk for pregnancy must agree to
use a highly effective method of contraception throughout the study and for at least 5
days after the last dose of assigned treatment. Female participants who are not of
childbearing potential must meet at least one of the following criteria: a) Achieved
postmenopausal status, defined as follows: cessation of regular menses for at least 12
consecutive months with no alternative pathological or physiological cause; and have a
serum follicle-stimulating hormone (FSH) level confirming the post-menopausal state.
b) Have undergone a documented hysterectomy and/or bilateral oophorectomy.

- Participant admits to having smoked commercially available cigarettes daily for the
preceding 12 months and to routinely smoking his or her first cigarette more than 30
minutes upon awakening. Brief periods of non-smoking (e.g. due to illness, trying to
quit, participation in a study where smoking was prohibited) during that time will be
permitted at the discretion of the PI (Principal Investigator).

Exclusion Criteria:

- Participants who are investigational site staff members directly involved in the
conduct of the study and their family members, site staff members otherwise supervised
by the investigator, or Participants who are GSK employees directly involved in the
conduct of the study.

- Participation in other studies involving investigational drug(s) within 30 days prior
to first dose and during study participation.

- Acute or chronic medical or psychiatric condition or laboratory abnormality that may
increase the risk associated with study participation or investigational product
administration or may interfere with the interpretation of study results and, in the
judgment of the investigator, would make the Participant inappropriate for entry into
this study.

- Pregnant female Participants.

- Breastfeeding female Participants.

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

- Unwilling or unable to comply with the Lifestyle guidelines described in this
protocol.

- Participant has used any nicotine replacement therapy within 21 days prior to the
first study session.

- Participant has used chewing tobacco, tobacco products or electronic cigarettes other
than cigarettes within 21 days of Visit 1.

- Use of prescription or non-prescription drugs and dietary supplements within two weeks
or 5 half-lives, whichever is longer, prior to the first dose of investigational
product until the end of the study. Allowed treatments are: Systemic contraceptives
and hormone replacement therapy, as long as female Participant is on stable treatment
for at least 3 months and continues treatment throughout the study. Evidence or
history of clinically significant laboratory abnormality, hematological, renal,
endocrine, pulmonary, cardiovascular, hepatic, psychiatric, neurologic, or allergic
disease within the last 5 years that may increase the risk associated with study
participation.

- History of regular alcohol consumption exceeding 14 drinks/week (1 drink = 5 ounces
(150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor)
within 6 months of Screening.

- A positive urine drug screen for THC, amphetamine, cocaine,
3,4-methylenedioxy-N-methylamphetamine (MDMA)/ecstasy, methamphetamine, or opiates;
and urine alcohol testing during screening or baseline testing.

- Participant is unwilling to abstain from tobacco or nicotine-containing product use
during each study session (from start of baseline to the completion of the last PK
blood sampling). CO measurement immediately prior to randomization (first treatment
session) and dosing (second treatment session) should be ≤ 10 parts per million (ppm)
for the Participant to be dosed.

- Participant ingests more than 5 cups of coffee or tea a day (or equivalent xanthine
consumption using other products).

- Treatment with an investigational drug within 30 days (or as determined by the local
requirement) or 5 half-lives preceding the first dose of investigational product
(whichever is longer).

- A medical history that, in the opinion of the investigator, might jeopardize the
safety of the Participant, e.g., recent myocardial infarction or cerebrovascular
accident (i.e., within 12 weeks prior to the first study session), severe cardiac
arrhythmia, history of seizures, orthostatic hypotension, cardiovascular disease,
stroke, or TIA.

- A medical history, which, in the opinion of the investigator, might impact the
validity of the study results, may require treatment, or make the Participant unlikely
to finish the study.

- Oral surgery within 4 weeks of dosing, dental work or extractions within 2 weeks of
dosing, or presence of any clinically significant (as determined by the principal
investigator or designee) oral pathology including lesions, sores or inflammation.

- Diagnosis of long QT syndrome or QTc > 460 msec for males and > 470 msec for females
at screening.

- Any surgical or medical condition which may significantly alter the absorption,
distribution, metabolism or excretion of any drug substance including, but not limited
to, any of the following: i)Presence of active oesophagitis, oral or pharyngeal
ulceration, inflammation, gastritis, gastric ulcer or peptic ulcer or other diseases;
ii) Presence of gum disease, xerostomia, dentures or any dental work that could affect
the conduct of the study as determined by the investigator or designee; iii) Renal
disease or impaired renal function at screening as indicated by abnormal levels of
serum creatinine or urea or the presence of clinically significant abnormal urinary
constituents (e.g. albuminuria). Minor deviations of laboratory values from the normal
range are permitted, if judged by the investigator to have no clinical relevance; iv)
Ongoing hepatic disease or impaired hepatic function at screening. A candidate will be
excluded if more than one of the following lab value deviations are found and are
clinical ly relevant: aspartate aminotransferase/serum glutamic-oxaloacetic
transaminase (AST/SGOT), Alanine Aminotransferase/ serum glutamic-pyruvic transaminase
(ALT/SGPT), γ-glutamyl transpeptidase (γGGT), alkaline phosphatase, bilirubin or CK.
Minor deviations of laboratory values from the normal range are permitted, if judged
by the investigator to have no clinical relevance; v) History or clinical evidence at
screening of pancreatic injury or pancreatitis; vi) Evidence of urinary obstruction or
difficulty in voiding at screening; vii) History of malignancy or neoplastic disease
of any organ system (except for localized basal cell skin carcinoma), treated or
untreated, within the past 5 years prior to screening, regardless of whether there is
evidence of local recurrence or metastases. viii) Clinically relevant chronic or acute
infectious illnesses or febrile infections within 2 weeks prior to start of the study
(enrollment). ix) Other clinically significant laboratory findings in the opinion of
the Investigator at screening.

- A positive serum Hepatitis B surface antigen, Hepatitis C antibodies, or human
immunodeficiency virus (HIV) test result.

- Blood: a) Has donated or experienced significant blood loss (470 mL) within 56 days of
Visit b) Hemoglobin value < 12.0 grams per deciliter (g/dL).

- Participants who have previously been enrolled in this study.