Characterization of Selected Aerosol Constituents Levels in the Exhaled Breath of Adult e-Vapor Users

Study Overview
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Brief Summary
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This is an open-label, 4-way crossover study designed to estimate the nicotine, glycerin, propylene glycol, menthol, formaldehyde, acetaldehyde, and acrolein levels in exhaled breath samples during use of four MarkTen® XL e-vapor products. The study will enroll approximately 32 adult e-vapor-using subjects at one site in the United States in High Point, NC.

Detailed Description
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This is an open-label, 4-way crossover study designed to estimate the nicotine, glycerin, propylene glycol, menthol, formaldehyde, acetaldehyde, and acrolein levels in exhaled breath samples during use of four MarkTen® XL e-vapor products (which are no longer manufactured or sold commercially). The study will enroll approximately 32 adult e-vapor-using (with no more that 60% of either sex). Each of the 32 subjects will provide two exhaled breath samples (10 puffs for each sample) for all four test products. Subjects will make two visits to the site, one screening visit and one 4 day in-clinic visit to provide exhalation samples for four test products (one each day for 4 days). Subjects will also use their assigned test product ad libitum for 12 hours each day after the collection of exhaled breath samples. Subjects will be randomly assigned to a test product-use schedule at Visit 2, with one test product used per day. The anticipated study duration for each subject from screening through completion of all study participation will be approximately 34 days.

Official Title
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Characterization of Selected Aerosol Constituents Levels in the Exhaled Breath of Adult e-Vapor Users During Use of Four e-Vapor Products

Conditions
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Tobacco Use

Intervention / Treatment
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* Other: e-Vapor Product A
* Other: e-Vapor Product B
* Other: e-Vapor Product C
* Other: e-Vapor Product D


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject candidates must satisfy the following criteria before being enrolled in the study: provide voluntary consent to participate, as documented by the signed institutional review board (IRB)-approved informed consent form (ICF) for the study; be between the ages of 21 and 65 years, inclusive, at the time of screening (Visit 1); be positive for tobacco use by urine cotinine measurement (≥ 500 ng/mL) at Visit 1 (screening); have used nicotine-containing EVPs for the 3 months before Visit 1 (screening) and use of nicotine-containing EVPs (some days or every day) for the past 30 days and at least 4 out of the past 7 days before Visit 1 (screening) and at check-in for Visit 2; have negative alcohol, amphetamines, opiates, cannabinoids, phencyclidine, and cocaine urine drug screening results (exhaled breath test for alcohol is also acceptable) at Visit 1 (screening) and at check-in for Visit 2; if female (all females), have a negative serum pregnancy test at Visit 1 (screening) and have a negative urine pregnancy test at check-in for Visit 2; if female and heterosexually active and of childbearing potential (e.g., not surgically sterile [i.e., bilateral tubal ligation, hysterectomy, or bilateral oophorectomy] at least 6 months before Visit 1 [screening] or at least 2 years naturally postmenopausal [follicle-stimulating hormone ≥40 IU/L at Visit 1 (screening)]), must be using one of the following forms of contraception and agree to continue using it through at least 30 days after the last study product use (if early terminated) or completion of the study: hormonal (e.g., oral, transdermal patch, implant, or injection) consistently for at least 3 months before Visit 1 (screening); double barrier (i.e., condom with spermicide or diaphragm with spermicide) consistently for at least 30 days before Visit 1 (screening); intrauterine device for at least 3 months before Visit 1 (screening); Essure® or similar nonsurgical sterilization procedure at least 3 months before Visit 1 (screening); or partner who has been vasectomized for at least 6 months (inclusive) before Visit 1 (screening); if male and heterosexually active and capable of fathering a child (e.g., not vasectomized at least 6 months before Visit 1 [screening]), must be using a double barrier (i.e., condom with spermicide or diaphragm with spermicide) method of contraception from check-in at Visit 2 until at least 90 days after the last study product use (if early terminated) or completion of the study; not plan to quit e-vapor use in the next 30 days; be willing to use all assigned EVPs during the study; and be willing and able to comply with the requirements of the study. Exclusion Criteria: Subjects may be excluded from the study if the subject meets any of the criteria listed below at Visit 1 (screening) and Visit 2 or at any time during the study as appropriate. Exceptions may be permitted at the discretion of the investigator in consultation with the Sponsor, providing there would be no additional risk involved for the subject. Any exceptions will be documented. have a history or presence of clinically significant gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, urologic, diabetes, existing respiratory diseases (especially bronchospastic diseases and asthma), immunologic, psychiatric, cardiovascular disease, or any other condition(s) that, in the opinion of the investigator, would jeopardize the safety of the subject or impact the validity of the study results (Note: Chronic medical conditions controlled and on stable medications [over the past 3 months] may not be exclusionary per investigator discretion); have current evidence or any history of congestive heart failure; have clinically significant abnormal findings on physical examination, vital signs, ECG, clinical laboratory results, or medical history, in the opinion of the investigator; have systolic blood pressure >140 mm Hg or diastolic blood pressure >90 mm Hg at Visit 1 (screening) or at check-in for Visit 2; have estimated creatinine clearance (by Cockcroft-Gault equation) <80 mL/minute; have liver enzymes (aspartate aminotransferase and alanine aminotransferase) ≥1.5 times the upper limit of normal at Visit 1 (screening); have an acute illness (e.g., upper respiratory infection or viral infection) requiring treatment within 2 weeks before check-in at Visit 2; have fever (>100.5°F) at Visit 1 (screening) or at check-in for Visit 2; have body mass index (BMI) greater than 40.0 kg/m2 or less than 18.0 kg/m2 at Visit 1 (screening); have positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) at Visit 1 (screening); have used prescription or over-the-counter bronchodilator medication (e.g., inhaled or oral β-agonists) within 12 months of Visit 1 (screening) and Visit 2; have diabetes mellitus that is not controlled by diet/exercise alone, in the opinion of the investigator; have used prescription antidiabetic medication or insulin therapy within 12 months of Visit 1 (screening) and Visit 2; have used medication for depression or asthma within 12 months of Visit 1 (screening) and Visit 2; have a history of drug or alcohol abuse within 12 months of Visit 1 (screening) and Visit 2; have had allergic or other known adverse reactions to menthol, propylene glycol, or glycerol; if female, be pregnant, nursing, or planning to become pregnant during the study; have participated in a clinical study for an investigational drug, medical device, biologic, or for a tobacco product within 30 days before Visit 1 (screening) and Visit 2; be a current or former employee of the tobacco industry or a first-degree relative (e.g., parent, spouse, sibling, child) of a current or former employee of the tobacco industry or a named party or class representative in litigation with any tobacco company; have been involved in the development of the study design/conduct or be a first-degree relative (e.g., parent, spouse, sibling, child) of someone involved in the development of the study design/conduct; be a current employee or personnel involved with the study at the site; or have participated in two or more ALCS studies within the past 12-month period before Visit 1 (screening) and check in at Visit 2.

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: Crossover Assignment
Interventional Model Description: This is an open-label, 4-way crossover study designed to estimate the nicotine, glycerin, propylene glycol, menthol, formaldehyde, acetaldehyde, and acrolein levels in exhaled breath samples during use of four MarkTen® XL e-vapor products.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: e-Vapor Product A<br>Product XL25F = Test e-vapor product (EVP) (formerly marketed by Nu Mark LLC as MarkTen® XL Fusion [2.5% nicotine by weight {NBW}]) | Other: e-Vapor Product A<br>* e-Vapor product<br>* Other names: MarkTen® XL Fusion [2.5% nicotine by weight {NBW}] formerly marketed by NuMark LLC;|
| Experimental: e-Vapor Product B<br>Product XL40CB = Test EVP (formerly marketed by Nu Mark LLC as MarkTen® XL Bold Classic [4.0% NBW]) | Other: e-Vapor Product B<br>* e-Vapor product<br>* Other names: MarkTen® XL Bold Classic [4.0% NBW] formerly marketed by NuMark LLC;|
| Experimental: e-Vapor Product C<br>Product XL35WM = Test EVP (formerly marketed by Nu Mark LLC as MarkTen® XL Winter Mint [3.5% NBW]) | Other: e-Vapor Product C<br>* e-Vapor product<br>* Other names: MarkTen® XL Winter Mint [3.5% NBW] formerly marketed by NuMark LLC;|
| Experimental: e-Vapor Product D<br>Product XL40MB = Test EVP (formerly marketed by Nu Mark LLC as MarkTen® XL Bold Menthol [4.0% NBW]) | Other: e-Vapor Product D<br>* e-Vapor product<br>* Other names: MarkTen® XL Bold Menthol [4.0% NBW] formerly marketed by NuMark LLC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nicotine | ug (micrograms) in exhaled breath samples collected during each product use session | 4 Days (Day 1 through Day 4) | 
| Glycerin | ug (micrograms) in exhaled breath samples collected during each product use session | 4 Days (Day 1 through Day 4) | 
| Propylene Glycol | ug (micrograms) in exhaled breath samples collected during each product use session | 4 Days (Day 1 through Day 4) | 
| Menthol | ug (micrograms) in exhaled breath samples collected during each product use session | 4 Days (Day 1 through Day 4) | 
| Formaldehyde | ug (micrograms) in exhaled breath samples collected during each product use session | 4 Days (Day 1 through Day 4) | 
| Acetaldehyde | ug (micrograms) in exhaled breath samples collected during each product use session | 4 Days (Day 1 through Day 4) | 
| Acrolein | ug (micrograms) in exhaled breath samples collected during each product use session | 4 Days (Day 1 through Day 4) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cartridge Weight | mg (milligrams) collected before and after each product use | 4 Days (Day 1 through Day 4) | 
| Puff count | Number of puffs taken during 12-hour ad libitum product use session | 4 Days (Day 1 through Day 4) | 
| Puff Duration | Seconds per puff taken during 12-hour ad libitum product use session | 4 Days (Day 1 through Day 4) | 
| Use Product Again Questionnaire | Visual Analog Scale (VAS) measuring self-reported response to willingness to use study product again questionnaire collected after each product use session. Questionnaire consists of a single question (If given the opportunity, I would want to use this product again) with VAS response range from Definitely Would Not to Don't Care to Definitely Would | 4 Days (Day 1 through Day 4) |