A Bioequivalence Study of Two Nicotine Lozenges in Fasting Conditions in Healthy Smokers
Condition: Tobacco Use Disorder
MeSH terms: Tobacco Use Disorder
Intervention: Nicotine Prototype Mini lozenge; Nicorette Mini Lozenge
Intervention description: A single dose of a prototype nicotine 2mg lozenge will be placed in participants mouth, occasionally moving it side to side. Allowing it to slowly dissolve and try to minimize swallowing. Participants will be instructed not to chew lozenge. The lozenge should be completely dissolved.; A single dose of a 2 mg nicotine polacrilex mini lozenge (Nicorette Minis) will be placed in participants mouth, occasionally moving it side to side. Allowing it to slowly dissolve and try to minimize swallowing. Participants will be instructed not to chew lozenge. The lozenge should be completely dissolved.
Intervention MeSH terms: Nicotine
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 46.0
Sex: All
Minimum age: 19 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      This study will assess the bioequivalence of the test product (Nicotine Prototype Mini
      lozenge 2 milligrams [mg]) to a commercial reference product (nicotine polacrilex mini
      lozenge 2 mg) in healthy smokers under fasting conditions.
    

Eligibility criteria:

        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.