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

Study Overview
=================
Brief Summary
-----------------
To study the oral mucosal effects in adult smokers associated with the use of two Nicotine Lozenge formulations.

Detailed Description
-----------------
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.

Official Title
-----------------
Randomized, Parallel-Group, Assessor Blind Study To Evaluate Oral Mucosal Effects In Healthy Adult Smokers Associated With 3 Week Use Of Nicotine Bi-tartrate 4mg Mint Lozenges Relative To The Use Of Nicotine Polacrilex 4mg Mint Lozenges

Conditions
-----------------
Safety Issues

Intervention / Treatment
-----------------
* Drug: Nicotine Bitartrate Lozenge 4mg
* Drug: Nicotine Polacrilex 4Mg Lozenge


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Potential subjects who meet the following criteria at Screening may be included in the study. Sex and Age: Males and females aged at least 18 years and older. 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. Must have smoked at least 10 cigarettes per day for the previous 12 months prior to screening. Must smoke first cigarette within 30 minutes of waking up. Must be motivated to quit smoking upon enrollment into the study. 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. Females of childbearing potential will be required to undergo a serum (Screening) and urine (Day 0) pregnancy test (must be negative). 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. 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. Compliance: All study participants must understand and be willing to comply with all study procedures and restrictions. 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: Females who have a positive pregnancy test, are pregnant, breastfeeding, or intend to become pregnant during the course of the study. Nicotine use: 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. Is unable/unwilling to stop using other nicotine replacement therapy products throughout the duration of the study. 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. Demonstrates a reactive screen for Hepatitis B surface antigens, hepatitis C antibody, or HIV antibody. Oral condition: 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. Has fixed retainers, orthodontic appliances, or either maxillary and/or mandibular dentures or other appliances which may interfere with the placement of the product. Has current or recurrent disease that could affect the site of application, the action, absorption of the study treatment, or clinical assessment. 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. 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. Has elective dentistry scheduled during the study duration. Allergy/Intolerance: Has a known or suspected intolerance or hypersensitivity to the study materials (or closely-related compounds) or any of their stated ingredients. Has a known genetic deficiency with an inability to metabolize aspartame or phenylalanine or has been diagnosed with phenylketonuria. Clinical Study Participation: Participation in another clinical study or receipt of an investigational drug within 30 days of the screening visit at the start of the study. Previous participation in this study. Substance abuse: Current or recent (within two years of screening) history of drug or alcohol abuse, misuse, physical or psychological dependence. Demonstrates a positive alcohol breath test. Demonstrates a positive urine drug screen without disclosure of corresponding prescribed concomitant medication(s) at Screening and Study Visit Day 0. Urine glucose: a) Positive glucose urine screen. Personnel: Is an employee of the Sponsor or the study site. Is a member of the same household as another subject in this trial. Use of all over the counter (OTC) and prescription (Rx) lozenges after starting the study (Day 0 and onward).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nicotine Bitartrate 4mg Lozenge<br>Nicotine Bitartrate Lozenge 4mg. Take 1 lozenge every 1-2 hours, as needed for 21 days | Drug: Nicotine Bitartrate Lozenge 4mg<br>* Test Product<br>* Other names: Test Product;|
| Active Comparator: Nicotine Polacrilex 4mg Lozenge<br>Nicotine Polacrilex Lozenge 4mg. Take 1 lozenge every 1-2 hours, as needed for 21 days | Drug: Nicotine Polacrilex 4Mg Lozenge<br>* Active Comparator<br>* Other names: Nicorette Lozenge 4mg;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OMI-20 Total Score Change From Baseline to Day 3 | Scale Title: The 20 Item Oral Mucositis Index (OMI-20) The OMI-20 consists of nine items measuring erythema, nine measuring ulceration, one measuring atrophy, and one measuring edema; all are scored from 0 [none] to 3 [severe] and summed for a total possible score of 0-60. A higher score means a worse outcome. | Day 3 | 
| OMI-20 Total Score Change From Baseline to Day 7 | Scale Title: The 20 Item Oral Mucositis Index (OMI-20) The OMI-20 consists of nine items measuring erythema, nine measuring ulceration, one measuring atrophy, and one measuring edema; all are scored from 0 [none] to 3 [severe] and summed for a total possible score of 0-60. A higher score means a worse outcome. | Day 7 | 
| OMI-20 Total Score Change From Baseline to Day 14 | Scale Title: The 20 Item Oral Mucositis Index (OMI-20) The OMI-20 consists of nine items measuring erythema, nine measuring ulceration, one measuring atrophy, and one measuring edema; all are scored from 0 [none] to 3 [severe] and summed for a total possible score of 0-60. A higher score means a worse outcome. | Day 14 | 
| OMI-20 Total Score Change From Baseline to Day 21 | Scale Title: The 20 Item Oral Mucositis Index (OMI-20) The OMI-20 consists of nine items measuring erythema, nine measuring ulceration, one measuring atrophy, and one measuring edema; all are scored from 0 [none] to 3 [severe] and summed for a total possible score of 0-60. A higher score means a worse outcome. | Day 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OMI-20 Erythema Subscore Change From Baseline to Day 3 | Scale Title: The 20 Item Oral Mucositis Index (OMI-20) The OMI-20 contains a subset of nine items measuring erythema, all are scored from 0 [none] to 3 [severe], and summed for a total possible score of 0-27. A higher score means a worse outcome. | Day 3 | 
| OMI-20 Erythema Subscore Change From Baseline to Day 7 | Scale Title: The 20 Item Oral Mucositis Index (OMI-20) The OMI-20 contains a subset of nine items measuring erythema, all are scored from 0 [none] to 3 [severe], and summed for a total possible score of 0-27. A higher score means a worse outcome. | Day 7 | 
| OMI-20 Erythema Subscore Change From Baseline to Day 14 | Scale Title: The 20 Item Oral Mucositis Index (OMI-20) The OMI-20 contains a subset of nine items measuring erythema, all are scored from 0 [none] to 3 [severe], and summed for a total possible score of 0-27. A higher score means a worse outcome. | Day 14 | 
| OMI-20 Erythema Subscore Change From Baseline to Day 21 | Scale Title: The 20 Item Oral Mucositis Index (OMI-20) The OMI-20 contains a subset of nine items measuring erythema, all are scored from 0 [none] to 3 [severe], and summed for a total possible score of 0-27. A higher score means a worse outcome. | Day 21 | 
| OMI-20 Ulcer Subscore Change From Baseline to Day 3 | Scale Title: The 20 Item Oral Mucositis Index (OMI-20) The OMI-20 contains a subset of nine items measuring ulcers, all are scored from 0 [none] to 3 [severe], and summed for a total possible score of 0-27. A higher score means a worse outcome. | Day 3 | 
| OMI-20 Ulcer Subscore Change From Baseline to Day 7 | Scale Title: The 20 Item Oral Mucositis Index (OMI-20) The OMI-20 contains a subset of nine items measuring ulcers, all are scored from 0 [none] to 3 [severe], and summed for a total possible score of 0-27. A higher score means a worse outcome. | Day 7 | 
| OMI-20 Ulcer Subscore Change From Baseline to Day 14 | Scale Title: The 20 Item Oral Mucositis Index (OMI-20) The OMI-20 contains a subset of nine items measuring ulcers, all are scored from 0 [none] to 3 [severe], and summed for a total possible score of 0-27. A higher score means a worse outcome. | Day 14 | 
| OMI-20 Ulcer Subscore Change From Baseline to Day 21 | Scale Title: The 20 Item Oral Mucositis Index (OMI-20) The OMI-20 contains a subset of nine items measuring ulcers, all are scored from 0 [none] to 3 [severe], and summed for a total possible score of 0-27. A higher score means a worse outcome. | Day 21 | 
| Number of Participants With Adverse Events (AEs) | Count of the number of participants with Adverse Events. | Day 21 | 
| Number of Participants With Serious Adverse Events (SAEs) | Count of the number of participants with Serious Adverse Events | Day 21 | 
| Number of Participants Who Discontinued Due to Adverse Events (AEs) | Count of the number of participants who discontinued due to Adverse Events. | Day 21 |