A Study to Evaluate Changes in Smokers Using Oral Tobacco-derived Nicotine Products.

Study Overview
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Brief Summary
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The purpose of this study is to evaluate changes in exposure to selected harmful and potentially harmful constituents (HPHC) by measuring biomarkers in adult smokers who partially or completely switch from smoking cigarettes to oral tobacco-derived nicotine (OTDN) products compared to those who continue exclusive smoking cigarettes or stop using all tobacco products.

Detailed Description
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This is an open label, randomized, 6 parallel-group clinical study evaluating changes in exposure to selected HPHCs, subjective effects, and product use behavior in adult smokers relative to continued smoking who are randomly assigned to continue smoking, partially or completely switch to oral tobacco-derived nicotine products, or stop using any tobacco products for 7 days.

Official Title
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A Randomized, Controlled, Study to Evaluate Changes in Exposure to Harmful and Potentially Harmful Constituents in Adult Smokers Who Partially or Completely Switch to Oral Tobacco-derived Nicotine Products in a Clinical Setting.

Conditions
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Tobacco Use

Intervention / Treatment
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* Other: OTDN product 1
* Other: OTDN product 2
* Other: Tobacco Cessation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Voluntary consent to participate in this study documented on the signed informed consent form (ICF). Healthy adult males and females 21 to 65 years of age, inclusive, at Screening Smoking history of an average of at least 10 but no more than 30 factory manufactured combustible cigarettes daily for at least 1 year prior to Screening. Brief periods (i.e., up to 7 consecutive days) of non-smoking during the 3 months prior to Screening (e.g., due to illness or participation in a study where smoking was prohibited) will be permitted. Positive urine cotinine (≥ 500 ng/mL) at Screening. Willing to comply with the requirements of the study. Willing to use all test products after product trial at Check in. Willing and able to abstain from cigarettes from Day 1 through the End of the study. Exclusion Criteria: Use of any type of tobacco or nicotine containing products other than manufactured cigarettes (e.g., e vapor products, roll-your-own cigarettes, bidis, snuff, nicotine inhaler, pipe, cigar, chewing tobacco, nicotine patch, nicotine spray, nicotine lozenge, or nicotine gum) in the 7 days prior to Check in Self-reported puffers (i.e., adult smokers who draw smoke from the cigarette into the mouth and throat but do not inhale). Planning to quit smoking in the next 30 days (from Screening visit). History or presence of clinically significant gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, urologic, existing respiratory diseases, immunologic, psychiatric, lymphatic, or cardiovascular disease, or any other condition that, in the opinion of the Investigator, would jeopardize the safety of the subject or impact the validity of the study results. Clinically significant abnormal findings on the vital signs, physical examination, medical history, ECG, or clinical laboratory results, in the opinion of the Investigator.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: GROUP 1: Continue Smoking<br>Subjects will be asked to continue smoking their OB cigarettes ad libitum for 7 days. | |
| Experimental: GROUP 2: OTDN product 1<br>Subjects will reduce their normal daily cigarette consumption by at least 50% of their baseline CPD and use at least 3 product units per day for 7 days. | Other: OTDN product 1<br>* Oral tobacco-derived nicotine product<br>|
| Experimental: GROUP 3: OTDN product 2<br>Subjects will reduce their normal daily cigarette consumption by at least 50% of their baseline CPD and use at least 3 product units per day for 7 days. | Other: OTDN product 2<br>* Oral tobacco-derived nicotine product<br>|
| Experimental: GROUP 4: OTDN product 1<br>Subjects will completely switch to exclusive use of an oral tobacco-derived nicotine product, using at least 3 product units per day for 7 days. | Other: OTDN product 1<br>* Oral tobacco-derived nicotine product<br>|
| Experimental: GROUP 5: OTDN product 2<br>Subjects will completely switch to exclusive use of an oral tobacco-derived nicotine product, using at least 3 product units per day for 7 days. | Other: OTDN product 2<br>* Oral tobacco-derived nicotine product<br>|
| Experimental: GROUP 6: Tobacco Cessation<br>Subjects will completely stop all tobacco product usage for 7 days. | Other: Tobacco Cessation<br>* Tobacco Cessation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 24 hour total urinary NNAL (mg/24 hours) excreted on Day 7. | 24 hour total urinary NNAL | Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 24 hour urinary total total NNN, NE, 2-AN, 4-ABP, HEMA, CEMA, S-PMA, 3 HMPMA, 3-HPMA, 2-HPMA, AAMA, GAMA, 2-MHBMA, 2 OHFle, 2-Naphthol, 1 OHPhe, mutagenicity, and 1-OHP excreted on Day 5 and Day 7. | 24 hour urinary total total NNN, NE, 2-AN, 4-ABP, HEMA, CEMA, S-PMA, 3 HMPMA, 3-HPMA, 2-HPMA, AAMA, GAMA, 2-MHBMA, 2 OHFle, 2-Naphthol, 1 OHPhe, mutagenicity, and 1-OHP | Day 5 and 7 | 
| 24-hour urinary total NNAL excreted on Day 5. | 24-hour urinary total NNAL | Day 5 | 
| COHb on Day 5 and Day 7. | COHb | Day 5 and 7 | 
| Questionnaire of Smoking Urges-Brief | The QSU-Brief is a 10-item instrument (Cox et al., 2001) intended to capture urge to smoke. Participants respond to the 10 items using a 7-point Likert-type rating scale ranging from Strongly Disagree to Strongly Agree. Both a total score (reflecting urge to smoke) and two factor scores (Factor 1: Intention to smoke with smoking perceived as rewarding; Factor 2: anticipation of relief from negative affect with an urgent desire to smoke) will be calculated by averaging the items. | Day 1, 5 and 7 | 
| Modified Cigarette Evaluation Questionnaire | The modified cigarette evaluation questionnaire (mCEQ) is a 12-item instrument intended to capture the degree to which a person experiences the reinforcing effects of smoking from 1 (Not at All) to 7 (Extremely) (Cappelleri et al., 2007). Scores for the five mCEQ subscales range from 1 to 7, with higher scores reflecting greater smoking satisfaction, psychological reward, aversion, enjoyment of respiratory tract sensations, and craving reduction. | Day 1, 5 and 7 | 
| Use the Product Again Questionnaire | The Use this Product Again Questionnaire is a single-item bipolar visual analogue scale (VAS). Subjects are asked to respond to this item using a 100 mm VAS with three labeled points: Definitely Would Not, Don't Care and Definitely Would. | Day 7 | 
| Product use behavior | The number of each product used per day (cigarettes and OTDN products) and the duration of each OTDN product used during each product use period will be listed and summarized by study product. | Day 1 to Day 7 |