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

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

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.

Study Overview

• Status: Completed
• Conditions: Tobacco Use
• Intervention / Treatment: Other: e-Vapor Product A; Other: e-Vapor Product B; Other: e-Vapor Product C; Other: e-Vapor Product D

Detailed 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 (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.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • High Point, North Carolina, United States, 27265
      • High Point Clinical Trials Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Subject candidates must satisfy the following criteria before being enrolled in the study:

  1. provide voluntary consent to participate, as documented by the signed institutional review board (IRB)-approved informed consent form (ICF) for the study;
  2. be between the ages of 21 and 65 years, inclusive, at the time of screening (Visit 1);
  3. be positive for tobacco use by urine cotinine measurement (≥ 500 ng/mL) at Visit 1 (screening);
  4. 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;
  5. 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;
  6. 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;

  7. 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);
  8. 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;
  9. not plan to quit e-vapor use in the next 30 days;
  10. be willing to use all assigned EVPs during the study; and
  11. 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.

  1. 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);
  2. have current evidence or any history of congestive heart failure;
  3. have clinically significant abnormal findings on physical examination, vital signs, ECG, clinical laboratory results, or medical history, in the opinion of the investigator;
  4. 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;
  5. have estimated creatinine clearance (by Cockcroft-Gault equation) <80 mL/minute;
  6. have liver enzymes (aspartate aminotransferase and alanine aminotransferase) ≥1.5 times the upper limit of normal at Visit 1 (screening);
  7. have an acute illness (e.g., upper respiratory infection or viral infection) requiring treatment within 2 weeks before check-in at Visit 2;
  8. have fever (>100.5°F) at Visit 1 (screening) or at check-in for Visit 2;
  9. have body mass index (BMI) greater than 40.0 kg/m2 or less than 18.0 kg/m2 at Visit 1 (screening);
  10. have positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) at Visit 1 (screening);
  11. 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;
  12. have diabetes mellitus that is not controlled by diet/exercise alone, in the opinion of the investigator;
  13. have used prescription antidiabetic medication or insulin therapy within 12 months of Visit 1 (screening) and Visit 2;
  14. have used medication for depression or asthma within 12 months of Visit 1 (screening) and Visit 2;
  15. have a history of drug or alcohol abuse within 12 months of Visit 1 (screening) and Visit 2;
  16. have had allergic or other known adverse reactions to menthol, propylene glycol, or glycerol;
  17. if female, be pregnant, nursing, or planning to become pregnant during the study;
  18. 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;
  19. 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;
  20. 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;
  21. be a current employee or personnel involved with the study at the site; or
  22. have participated in two or more ALCS studies within the past 12-month period before Visit 1 (screening) and check in at Visit 2.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ABDC; Subjects administered 2 menthol and and 2 non-menthol test e-vapor products: Product A (XL25F) on Day 1, Product B (XL40CB) on Day 2, Product D (XL40MB) on Day 3 and Product C (XL35WM) on Day 4	Other: e-Vapor Product A; e-Vapor product XL25F; Other Names: MarkTen® XL Fusion [2.5% nicotine by weight {NBW}] formerly marketed by NuMark LLC; Other: e-Vapor Product B; e-Vapor product XL40CB; Other Names: MarkTen® XL Bold Classic [4.0% NBW] formerly marketed by NuMark LLC; Other: e-Vapor Product C; e-Vapor product XL35WM; Other Names: MarkTen® XL Winter Mint [3.5% NBW] formerly marketed by NuMark LLC; Other: e-Vapor Product D; e-Vapor product XL40MB; Other Names: MarkTen® XL Bold Menthol [4.0% NBW] formerly marketed by NuMark LLC
Experimental: BCAD; Subjects administered 2 menthol and and 2 non-menthol test e-vapor products: Product B (XL40CB) on Day 1, Product C (XL35WM) on Day 2, Product A (XL25F) on Day 3 and Product D (XL40MB) on Day 4	Other: e-Vapor Product A; e-Vapor product XL25F; Other Names: MarkTen® XL Fusion [2.5% nicotine by weight {NBW}] formerly marketed by NuMark LLC; Other: e-Vapor Product B; e-Vapor product XL40CB; Other Names: MarkTen® XL Bold Classic [4.0% NBW] formerly marketed by NuMark LLC; Other: e-Vapor Product C; e-Vapor product XL35WM; Other Names: MarkTen® XL Winter Mint [3.5% NBW] formerly marketed by NuMark LLC; Other: e-Vapor Product D; e-Vapor product XL40MB; Other Names: MarkTen® XL Bold Menthol [4.0% NBW] formerly marketed by NuMark LLC
Experimental: CDBA; Subjects administered 2 menthol and and 2 non-menthol test e-vapor products: Product C (XL35WM) on Day 1 Product D (XL40MB) on Day 2, Product B (XL40CB) on Day 3 and Product A (XL25F) on Day 4	Other: e-Vapor Product A; e-Vapor product XL25F; Other Names: MarkTen® XL Fusion [2.5% nicotine by weight {NBW}] formerly marketed by NuMark LLC; Other: e-Vapor Product B; e-Vapor product XL40CB; Other Names: MarkTen® XL Bold Classic [4.0% NBW] formerly marketed by NuMark LLC; Other: e-Vapor Product C; e-Vapor product XL35WM; Other Names: MarkTen® XL Winter Mint [3.5% NBW] formerly marketed by NuMark LLC; Other: e-Vapor Product D; e-Vapor product XL40MB; Other Names: MarkTen® XL Bold Menthol [4.0% NBW] formerly marketed by NuMark LLC
Experimental: DACB; Subjects administered 2 menthol and and 2 non-menthol test e-vapor products: Product D (XL40MB) on Day 1, Product A (XL25F) on Day 2, Product C (XL35WM) on Day 3 and Product B (XL40CB) on Day 4	Other: e-Vapor Product A; e-Vapor product XL25F; Other Names: MarkTen® XL Fusion [2.5% nicotine by weight {NBW}] formerly marketed by NuMark LLC; Other: e-Vapor Product B; e-Vapor product XL40CB; Other Names: MarkTen® XL Bold Classic [4.0% NBW] formerly marketed by NuMark LLC; Other: e-Vapor Product C; e-Vapor product XL35WM; Other Names: MarkTen® XL Winter Mint [3.5% NBW] formerly marketed by NuMark LLC; Other: e-Vapor Product D; e-Vapor product XL40MB; Other Names: MarkTen® XL Bold Menthol [4.0% NBW] formerly marketed by NuMark LLC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nicotine Residue Summary Statistics by Test-Product Group	Table summarizes the amount of analyte present in exhaled breath after test product use. Analyte was collected over an approximately 10-min collection period in the exhaled breath product use session on day the subject was assigned the indicated test product according to the randomization scheme. In the exhaled breath test product use session, one exhaled breath sample was collected using an empty cartridge and inactive battery [sham condition] followed by an exhaled breath sample using the test product. Each exhaled breath sample was collected separately into the same type of trapping container (capturing the specific analyte). Each sample consisted of all the exhaled breath occurring during 10 puffs, each with 5 second puff duration (+/- 1 sec), over ~5 min (one puff approximately every 30 secs) collected in the respective sample collection containers. Sham-corrected analyte amounts were computed by subtracting corresponding sham response values from test product response values.	Data collected over an approximately 10-minute timeframe (2 consecutive exhaled breath samples of 5-minute durations each) on the day the subject was assigned to use the test product (Day 1 or Day 2 or Day 3 or Day 4 according to the randomization scheme)
Sham Nicotine Residue Summary Statistics by Test-Product Group	Table summarizes the amount of analyte present in exhaled breath after sham. The analyte was collected over an approximately 10-min collection period in the exhaled breath product use session on the day the subject was assigned the indicated test product according to the randomization scheme. In the exhaled breath test product use session, one exhaled breath sample was collected using an empty cartridge and inactive battery [sham condition] followed by an exhaled breath sample using the test product. Each exhaled breath sample was collected separately into the same type of trapping container (capturing the specific analyte). Each sample consisted of all the exhaled breath occurring during 10 puffs, each with 5 second puff duration (+/- 1 sec), over ~5 min (one puff approximately every 30 sec) collected in the respective sample collection containers. Sham-corrected analyte amounts were computed by subtracting corresponding sham response values from test product response values.	Data collected over an approximately 10-minute timeframe (2 consecutive exhaled breath samples of 5-minute durations each) on the day the subject was assigned to use the test product (Day 1 or Day 2 or Day 3 or Day 4 according to the randomization scheme)
Total Sham-Corrected Nicotine Summary Statistics by Test Product Group	Table presents difference in total analyte amount in exhaled breath samples between sham (inactive battery & empty cartridge) and controlled test product use. Analyte was collected over an approximately 10-min collection period in the exhaled breath product use session on day the subject was assigned the indicated test product. In the exhaled breath test product use session, 1 exhaled breath sample was collected using an empty cartridge & inactive battery [sham condition] followed by an exhaled breath sample using the test product. Each exhaled breath sample was collected separately into the same type of trapping container. Each sample consisted of all the exhaled breath occurring during 10 puffs, each with 5 second puff duration (+/- 1 sec), over ~5 min (one puff approximately every 30 secs) collected in the respective sample collection containers. Sham-corrected analyte amounts were computed by subtracting corresponding sham response values from test product response values.	Data collected over an approximately 10-minute timeframe (2 consecutive exhaled breath samples of 5-minute durations each) on the day the subject was assigned to use the test product (Day 1 or Day 2 or Day 3 or Day 4 according to the randomization scheme)
Glycerin Residue Summary Statistics by Test-Product Group	Table summarizes the amount of analyte present in exhaled breath after test product use. Analyte was collected over an approximately 10-min collection period in the exhaled breath product use session on day the subject was assigned the indicated test product according to the randomization scheme. In the exhaled breath test product use session, one exhaled breath sample was collected using an empty cartridge and inactive battery [sham condition] followed by an exhaled breath sample using the test product. Each exhaled breath sample was collected separately into the same type of trapping container (capturing the specific analyte). Each sample consisted of all the exhaled breath occurring during 10 puffs, each with 5 second puff duration (+/- 1 sec), over ~5 min (one puff approximately every 30 secs) collected in the respective sample collection containers. Sham-corrected analyte amounts were computed by subtracting corresponding sham response values from test product response values.	Data collected over an approximately 10-minute timeframe (2 consecutive exhaled breath samples of 5-minute durations each) on the day the subject was assigned to use the test product (Day 1 or Day 2 or Day 3 or Day 4 according to the randomization scheme)
Sham Glycerin Residue Summary Statistics by Test-Product Group	Table summarizes the amount of analyte present in exhaled breath after sham. The analyte was collected over an approximately 10-min collection period in the exhaled breath product use session on the day the subject was assigned the indicated test product according to the randomization scheme. In the exhaled breath test product use session, one exhaled breath sample was collected using an empty cartridge and inactive battery [sham condition] followed by an exhaled breath sample using the test product. Each exhaled breath sample was collected separately into the same type of trapping container (capturing the specific analyte). Each sample consisted of all the exhaled breath occurring during 10 puffs, each with 5 second puff duration (+/- 1 sec), over ~5 min (one puff approximately every 30 sec) collected in the respective sample collection containers. Sham-corrected analyte amounts were computed by subtracting corresponding sham response values from test product response values.	Data collected over an approximately 10-minute timeframe (2 consecutive exhaled breath samples of 5-minute durations each) on the day the subject was assigned to use the test product (Day 1 or Day 2 or Day 3 or Day 4 according to the randomization scheme)
Total Sham-Corrected Glycerin Summary Statistics by Test Product Group	Table presents difference in total analyte amount in exhaled breath samples between sham (inactive battery & empty cartridge) and controlled test product use. Analyte was collected over an approximately 10-min collection period in the exhaled breath product use session on day the subject was assigned the indicated test product. In the exhaled breath test product use session, 1 exhaled breath sample was collected using an empty cartridge & inactive battery [sham condition] followed by an exhaled breath sample using the test product. Each exhaled breath sample was collected separately into the same type of trapping container. Each sample consisted of all the exhaled breath occurring during 10 puffs, each with 5 second puff duration (+/- 1 sec), over ~5 min (one puff approximately every 30 secs) collected in the respective sample collection containers. Sham-corrected analyte amounts were computed by subtracting corresponding sham response values from test product response values.	Data collected over an approximately 10-minute timeframe (2 consecutive exhaled breath samples of 5-minute durations each) on the day the subject was assigned to use the test product (Day 1 or Day 2 or Day 3 or Day 4 according to the randomization scheme)
Menthol Residue Summary Statistics by Test-Product Group	Table summarizes the amount of analyte present in exhaled breath after test product use. Analyte was collected over an approximately 10-min collection period in the exhaled breath product use session on day the subject was assigned the indicated test product according to the randomization scheme. In the exhaled breath test product use session, one exhaled breath sample was collected using an empty cartridge and inactive battery [sham condition] followed by an exhaled breath sample using the test product. Each exhaled breath sample was collected separately into the same type of trapping container (capturing the specific analyte). Each sample consisted of all the exhaled breath occurring during 10 puffs, each with 5 second puff duration (+/- 1 sec), over ~5 min (one puff approximately every 30 secs) collected in the respective sample collection containers. Sham-corrected analyte amounts were computed by subtracting corresponding sham response values from test product response values.	Data collected over an approximately 10-minute timeframe (2 consecutive exhaled breath samples of 5-minute durations each) on the day the subject was assigned to use the test product (Day 1 or Day 2 or Day 3 or Day 4 according to the randomization scheme)
Sham Menthol Residue Summary Statistics by Test-Product Group	Table summarizes the amount of analyte present in exhaled breath after sham. The analyte was collected over an approximately 10-min collection period in the exhaled breath product use session on the day the subject was assigned the indicated test product according to the randomization scheme. In the exhaled breath test product use session, one exhaled breath sample was collected using an empty cartridge and inactive battery [sham condition] followed by an exhaled breath sample using the test product. Each exhaled breath sample was collected separately into the same type of trapping container (capturing the specific analyte). Each sample consisted of all the exhaled breath occurring during 10 puffs, each with 5 second puff duration (+/- 1 sec), over ~5 min (one puff approximately every 30 sec) collected in the respective sample collection containers. Sham-corrected analyte amounts were computed by subtracting corresponding sham response values from test product response values.	Data collected over an approximately 10-minute timeframe (2 consecutive exhaled breath samples of 5-minute durations each) on the day the subject was assigned to use the test product (Day 1 or Day 2 or Day 3 or Day 4 according to the randomization scheme)
Total Sham-Corrected Menthol Summary Statistics by Test Product Group	Table presents difference in total analyte amount in exhaled breath samples between sham (inactive battery & empty cartridge) and controlled test product use. Analyte was collected over an approximately 10-min collection period in the exhaled breath product use session on day the subject was assigned the indicated test product. In the exhaled breath test product use session, 1 exhaled breath sample was collected using an empty cartridge & inactive battery [sham condition] followed by an exhaled breath sample using the test product. Each exhaled breath sample was collected separately into the same type of trapping container. Each sample consisted of all the exhaled breath occurring during 10 puffs, each with 5 second puff duration (+/- 1 sec), over ~5 min (one puff approximately every 30 secs) collected in the respective sample collection containers. Sham-corrected analyte amounts were computed by subtracting corresponding sham response values from test product response values.	Data collected over an approximately 10-minute timeframe (2 consecutive exhaled breath samples of 5-minute durations each) on the day the subject was assigned to use the test product (Day 1 or Day 2 or Day 3 or Day 4 according to the randomization scheme)
Propylene Glycol Residue Summary Statistics by Test-Product Group	Table summarizes the amount of analyte present in exhaled breath after test product use. Analyte was collected over an approximately 10-min collection period in the exhaled breath product use session on day the subject was assigned the indicated test product according to the randomization scheme. In the exhaled breath test product use session, one exhaled breath sample was collected using an empty cartridge and inactive battery [sham condition] followed by an exhaled breath sample using the test product. Each exhaled breath sample was collected separately into the same type of trapping container (capturing the specific analyte). Each sample consisted of all the exhaled breath occurring during 10 puffs, each with 5 second puff duration (+/- 1 sec), over ~5 min (one puff approximately every 30 secs) collected in the respective sample collection containers. Sham-corrected analyte amounts were computed by subtracting corresponding sham response values from test product response values.	Data collected over an approximately 10-minute timeframe (2 consecutive exhaled breath samples of 5-minute durations each) on the day the subject was assigned to use the test product (Day 1 or Day 2 or Day 3 or Day 4 according to the randomization scheme)
Sham Propylene Glycol Residue Summary Statistics by Test-Product Group	Table summarizes the amount of analyte present in exhaled breath after sham. The analyte was collected over an approximately 10-min collection period in the exhaled breath product use session on the day the subject was assigned the indicated test product according to the randomization scheme. In the exhaled breath test product use session, one exhaled breath sample was collected using an empty cartridge and inactive battery [sham condition] followed by an exhaled breath sample using the test product. Each exhaled breath sample was collected separately into the same type of trapping container (capturing the specific analyte). Each sample consisted of all the exhaled breath occurring during 10 puffs, each with 5 second puff duration (+/- 1 sec), over ~5 min (one puff approximately every 30 sec) collected in the respective sample collection containers. Sham-corrected analyte amounts were computed by subtracting corresponding sham response values from test product response values.	Data collected over an approximately 10-minute timeframe (2 consecutive exhaled breath samples of 5-minute durations each) on the day the subject was assigned to use the test product (Day 1 or Day 2 or Day 3 or Day 4 according to the randomization scheme)
Total Sham-Corrected Propylene Glycol Summary Statistics by Test Product Group	Table presents difference in total analyte amount in exhaled breath samples between sham (inactive battery & empty cartridge) and controlled test product use. Analyte was collected over an approximately 10-min collection period in the exhaled breath product use session on day the subject was assigned the indicated test product. In the exhaled breath test product use session, 1 exhaled breath sample was collected using an empty cartridge & inactive battery [sham condition] followed by an exhaled breath sample using the test product. Each exhaled breath sample was collected separately into the same type of trapping container. Each sample consisted of all the exhaled breath occurring during 10 puffs, each with 5 second puff duration (+/- 1 sec), over ~5 min (one puff approximately every 30 secs) collected in the respective sample collection containers. Sham-corrected analyte amounts were computed by subtracting corresponding sham response values from test product response values.	Data collected over an approximately 10-minute timeframe (2 consecutive exhaled breath samples of 5-minute durations each) on the day the subject was assigned to use the test product (Day 1 or Day 2 or Day 3 or Day 4 according to the randomization scheme)
Formaldehyde Residue Summary Statistics by Test-Product Group	Table summarizes the amount of analyte present in exhaled breath after test product use. Analyte was collected over an approximately 10-min collection period in the exhaled breath product use session on day the subject was assigned the indicated test product according to the randomization scheme. In the exhaled breath test product use session, one exhaled breath sample was collected using an empty cartridge and inactive battery [sham condition] followed by an exhaled breath sample using the test product. Each exhaled breath sample was collected separately into the same type of trapping container (capturing the specific analyte). Each sample consisted of all the exhaled breath occurring during 10 puffs, each with 5 second puff duration (+/- 1 sec), over ~5 min (one puff approximately every 30 secs) collected in the respective sample collection containers. Sham-corrected analyte amounts were computed by subtracting corresponding sham response values from test product response values.	Data collected over an approximately 10-minute timeframe (2 consecutive exhaled breath samples of 5-minute durations each) on the day the subject was assigned to use the test product (Day 1 or Day 2 or Day 3 or Day 4 according to the randomization scheme)
Sham Formaldehyde Residue Summary Statistics by Test-Product Group	Table summarizes the amount of analyte present in exhaled breath after sham. The analyte was collected over an approximately 10-min collection period in the exhaled breath product use session on the day the subject was assigned the indicated test product according to the randomization scheme. In the exhaled breath test product use session, one exhaled breath sample was collected using an empty cartridge and inactive battery [sham condition] followed by an exhaled breath sample using the test product. Each exhaled breath sample was collected separately into the same type of trapping container (capturing the specific analyte). Each sample consisted of all the exhaled breath occurring during 10 puffs, each with 5 second puff duration (+/- 1 sec), over ~5 min (one puff approximately every 30 sec) collected in the respective sample collection containers. Sham-corrected analyte amounts were computed by subtracting corresponding sham response values from test product response values.	Data collected over an approximately 10-minute timeframe (2 consecutive exhaled breath samples of 5-minute durations each) on the day the subject was assigned to use the test product (Day 1 or Day 2 or Day 3 or Day 4 according to the randomization scheme)
Total Sham-Corrected Formaldehyde Summary Statistics by Test Product Group	Table presents difference in total analyte amount in exhaled breath samples between sham (inactive battery & empty cartridge) and controlled test product use. Analyte was collected over an approximately 10-min collection period in the exhaled breath product use session on day the subject was assigned the indicated test product. In the exhaled breath test product use session, 1 exhaled breath sample was collected using an empty cartridge & inactive battery [sham condition] followed by an exhaled breath sample using the test product. Each exhaled breath sample was collected separately into the same type of trapping container. Each sample consisted of all the exhaled breath occurring during 10 puffs, each with 5 second puff duration (+/- 1 sec), over ~5 min (one puff approximately every 30 secs) collected in the respective sample collection containers. Sham-corrected analyte amounts were computed by subtracting corresponding sham response values from test product response values.	Data collected over an approximately 10-minute timeframe (2 consecutive exhaled breath samples of 5-minute durations each) on the day the subject was assigned to use the test product (Day 1 or Day 2 or Day 3 or Day 4 according to the randomization scheme)
Acetaldehyde Residue Summary Statistics by Test-Product Group	Table summarizes the amount of analyte present in exhaled breath after test product use. Analyte was collected over an approximately 10-min collection period in the exhaled breath product use session on day the subject was assigned the indicated test product according to the randomization scheme. In the exhaled breath test product use session, one exhaled breath sample was collected using an empty cartridge and inactive battery [sham condition] followed by an exhaled breath sample using the test product. Each exhaled breath sample was collected separately into the same type of trapping container (capturing the specific analyte). Each sample consisted of all the exhaled breath occurring during 10 puffs, each with 5 second puff duration (+/- 1 sec), over ~5 min (one puff approximately every 30 secs) collected in the respective sample collection containers. Sham-corrected analyte amounts were computed by subtracting corresponding sham response values from test product response values.	Data collected over an approximately 10-minute timeframe (2 consecutive exhaled breath samples of 5-minute durations each) on the day the subject was assigned to use the test product (Day 1 or Day 2 or Day 3 or Day 4 according to the randomization scheme)
Sham Acetaldehyde Residue Summary Statistics by Test-Product Group	Table summarizes the amount of analyte present in exhaled breath after sham. The analyte was collected over an approximately 10-min collection period in the exhaled breath product use session on the day the subject was assigned the indicated test product according to the randomization scheme. In the exhaled breath test product use session, one exhaled breath sample was collected using an empty cartridge and inactive battery [sham condition] followed by an exhaled breath sample using the test product. Each exhaled breath sample was collected separately into the same type of trapping container (capturing the specific analyte). Each sample consisted of all the exhaled breath occurring during 10 puffs, each with 5 second puff duration (+/- 1 sec), over ~5 min (one puff approximately every 30 sec) collected in the respective sample collection containers. Sham-corrected analyte amounts were computed by subtracting corresponding sham response values from test product response values.	Data collected over an approximately 10-minute timeframe (2 consecutive exhaled breath samples of 5-minute durations each) on the day the subject was assigned to use the test product (Day 1 or Day 2 or Day 3 or Day 4 according to the randomization scheme)
Total Sham-Corrected Acetaldehyde Summary Statistics by Test Product Group	Table presents difference in total analyte amount in exhaled breath samples between sham (inactive battery & empty cartridge) and controlled test product use. Analyte was collected over an approximately 10-min collection period in the exhaled breath product use session on day the subject was assigned the indicated test product. In the exhaled breath test product use session, 1 exhaled breath sample was collected using an empty cartridge & inactive battery [sham condition] followed by an exhaled breath sample using the test product. Each exhaled breath sample was collected separately into the same type of trapping container. Each sample consisted of all the exhaled breath occurring during 10 puffs, each with 5 second puff duration (+/- 1 sec), over ~5 min (one puff approximately every 30 secs) collected in the respective sample collection containers. Sham-corrected analyte amounts were computed by subtracting corresponding sham response values from test product response values.	Data collected over an approximately 10-minute timeframe (2 consecutive exhaled breath samples of 5-minute durations each) on the day the subject was assigned to use the test product (Day 1 or Day 2 or Day 3 or Day 4 according to the randomization scheme)
Acrolein Residue Summary Statistics by Test-Product Group	Table summarizes the amount of analyte present in exhaled breath after test product use. Analyte was collected over an approximately 10-min collection period in the exhaled breath product use session on day the subject was assigned the indicated test product according to the randomization scheme. In the exhaled breath test product use session, one exhaled breath sample was collected using an empty cartridge and inactive battery [sham condition] followed by an exhaled breath sample using the test product. Each exhaled breath sample was collected separately into the same type of trapping container (capturing the specific analyte). Each sample consisted of all the exhaled breath occurring during 10 puffs, each with 5 second puff duration (+/- 1 sec), over ~5 min (one puff approximately every 30 secs) collected in the respective sample collection containers. Sham-corrected analyte amounts were computed by subtracting corresponding sham response values from test product response values.	Data collected over an approximately 10-minute timeframe (2 consecutive exhaled breath samples of 5-minute durations each) on the day the subject was assigned to use the test product (Day 1 or Day 2 or Day 3 or Day 4 according to the randomization scheme)
Sham Acrolein Residue Summary Statistics by Test-Product Group	Table summarizes the amount of analyte present in exhaled breath after sham. The analyte was collected over an approximately 10-min collection period in the exhaled breath product use session on the day the subject was assigned the indicated test product according to the randomization scheme. In the exhaled breath test product use session, one exhaled breath sample was collected using an empty cartridge and inactive battery [sham condition] followed by an exhaled breath sample using the test product. Each exhaled breath sample was collected separately into the same type of trapping container (capturing the specific analyte). Each sample consisted of all the exhaled breath occurring during 10 puffs, each with 5 second puff duration (+/- 1 sec), over ~5 min (one puff approximately every 30 sec) collected in the respective sample collection containers. Sham-corrected analyte amounts were computed by subtracting corresponding sham response values from test product response values.	Data collected over an approximately 10-minute timeframe (2 consecutive exhaled breath samples of 5-minute durations each) on the day the subject was assigned to use the test product (Day 1 or Day 2 or Day 3 or Day 4 according to the randomization scheme)
Total Sham-Corrected Acrolein Summary Statistics by Test Product Group	Table presents difference in total analyte amount in exhaled breath samples between sham (inactive battery & empty cartridge) and controlled test product use. Analyte was collected over an approximately 10-min collection period in the exhaled breath product use session on day the subject was assigned the indicated test product. In the exhaled breath test product use session, 1 exhaled breath sample was collected using an empty cartridge & inactive battery [sham condition] followed by an exhaled breath sample using the test product. Each exhaled breath sample was collected separately into the same type of trapping container. Each sample consisted of all the exhaled breath occurring during 10 puffs, each with 5 second puff duration (+/- 1 sec), over ~5 min (one puff approximately every 30 secs) collected in the respective sample collection containers. Sham-corrected analyte amounts were computed by subtracting corresponding sham response values from test product response values.	Data collected over an approximately 10-minute timeframe (2 consecutive exhaled breath samples of 5-minute durations each) on the day the subject was assigned to use the test product (Day 1 or Day 2 or Day 3 or Day 4 according to the randomization scheme)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cartridge Weight (g) Change Summary Statistics for Sample 1 (Propylene Glycol, Glycerin, Nicotine, Menthol) by Test Product in the Exhaled-Breath Sessions	Difference in recorded weight of Sample 1, measured in grams, collected before and after product use in Exhaled Breath Sessions. Sample 1 was used to collect propylene glycol, glycerin, nicotine and menthol, and was collected approximately 1 hour before Sample 2.	Samples collected during the approximately 1 hour controlled exhaled breath product use session on the day the subject was assigned to use the test product (Day 1 or Day 2 or Day 3 or Day 4 according to the randomization scheme)
Cartridge Weight (g) Change Summary Statistics for Sample 2 (Formaldehyde, Acetaldehyde, Acrolein) by Test Product in the Exhaled-Breath Sessions	Difference in recorded weight of Sample 2, measured in grams, collected before and after product use in Exhaled Breath Sessions, Sample 2 was used to collect formaldehyde, acetaldehyde and acrolein, and was collected approximately 1 hour after Sample 1.	Samples collected during the approximately 1 hour controlled exhaled breath product use session on the day the subject was assigned to use the test product (Day 1 or Day 2 or Day 3 or Day 4 according to the randomization scheme)
Summary Statistics of Total Cartridge Weight Change by Test Product, Per Subject, During the Ad Libitum-Use Sessions	Difference in recorded weight (measured in grams) by test product, per subject, collected before and after product use in ad libitum sessions	Samples were collected over the 12-hour ad libitum product use session on the day the subject was assigned the test product (according to the randomization scheme)
Total Weight Change by Test Product and Individual Cartridge During the Ad-Libitum-Use Sessions	Change in cartridge weight (measured in grams) as measured before and after a 12-hour ad-libitum use session of the product.	Samples were collected over the 12-hour ad libitum product use session on the day the subject was assigned the test product (according to the randomization scheme)
Summary Statistics of Puff Count by Test Product During the Ad Libitum-Use Sessions	Number of puffs, by test product, per subject, taken during 12-hour ad libitum product use session	Data was collected over the 12-hour ad libitum product use session on the day the subject was assigned the test product (according to the randomization scheme)
Average Puff Duration by Test Product During the Ad Libitum-Use Sessions	Seconds per puff taken, by test product, per subject, during 12-hour ad libitum product use session	Data was collected over the 12-hour ad libitum product use session on the day the subject was assigned the test product (according to the randomization scheme)
Total Puff Duration by Test Product During the Ad Libitum-Use Sessions	Total seconds puffing by test product, per subject, taken during 12-hour ad libitum product use session	Data was collected over the 12-hour ad libitum product use session on the day the subject was assigned the test product (according to the randomization scheme)
Total Cartridges Used by Test Product During the Ad Libitum-Use Sessions	Total cartridges used by test product, per subject, taken during 12-hour ad libitum product use session	Data was collected over the 12-hour ad libitum product use session on the day the subject was assigned the test product (according to the randomization scheme)
Summary of Binary VAS-Derived Categorical "Use Product Again Questionnaire" Scores by Test Product	Visual Analog Scale (VAS) measuring self-reported response to "Use the product again" questionnaire was collected after each product use session. The questionnaire consists of a single question ("If given the opportunity, I would want to use this product again"). Participants indicated their willingness to use the product again by pointing to a line measuring 100mm, with scores measured from left to right and ranging between 0 to 100 mm. Scores closer to the right, and thus higher on the scale, indicated a greater willingness to utilize the product again. Raw scores were converted to a binary score as follows: VAS scores < 50 mm ≈ unwillingness to use the product again, and VAS scores ≥ 50 mm ≈ willingness to use product again.	Data was collected at the end of the 12-hour ad libitum product use session on the day the subject was assigned the test product (according to the randomization scheme)
Summary of Ordinal VAS-Derived Categorical "Use Product Again Questionnaire" Scores by Test Product	Visual Analog Scale (VAS) measuring self-reported response to willingness to use study product again. Questionnaire was 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". Participants indicated their willingness to use the product again by pointing to a line measuring 100mm, with scores measured from left to right and ranging between 0 to 100 mm. Scores closer to the right, and thus higher on the scale, indicated a greater willingness to utilize the product again. The raw scores were then converted to a binary, "unwilling" vs. "willing" to use response. Additionally, a 3-level ordinal response was computed using "unwilling" (VAS < 50 mm), "don't care" (VAS = 50 mm), and "willing" (VAS > 50 mm).	Data was collected at the end of the 12-hour ad libitum product use session on the day the subject was assigned the test product (according to the randomization scheme)
Puff Count by Test Product and Individual Cartridge During the Ad-Libitum-Use Sessions	Puff Count by Test Product (Pooled Over Cartridges) during 12-hour ad-libitum-use session of the product.	Over the 12-hour ad libitum product use session on the day the subject was assigned the test product (according to the randomization scheme)
Average Puff Duration by Test Product and Individual Cartridge During the Ad-Libitum-Use Sessions	Average puff duration (measured in seconds) by Test Product (Pooled Over Cartridges) during 12-hour ad-libitum-use session of the product.	Over the 12-hour ad libitum product use session on the day the subject was assigned the test product (according to the randomization scheme)
Total Puff Duration by Test Product and Individual Cartridge During the Ad-Libitum-Use Sessions	Total Puff Duration (measured in seconds) by Test Product (pooled over cartridges) during 12-hour ad-libitum-use session of the product.	Over the 12-hour ad libitum product use session on the day the subject was assigned the test product (according to the randomization scheme)
Total Weight Change by Test Product, Per Completed Cartridge, During the Ad-Libitum-Use Sessions	Change in cartridge weight (measured in grams) as measured before and after a 12-hour ad-libitum use session of the product.	Over the 12-hour ad libitum product use session on the day the subject was assigned the test product (according to the randomization scheme)
Average Puff Duration by Test Product, Per Completed Cartridge, During the Ad-Libitum-Use Sessions	Average puff duration (measured in seconds) by Test Product, per completed cartridge, during a 12-hour ad-libitum use session of the product.	Over the 12-hour ad libitum product use session on the day the subject was assigned the test product (according to the randomization scheme)
Puff Count by Test Product, Per Completed Cartridge, During the Ad-Libitum-Use Sessions	Puff count by Test Product, per completed cartridge, during a 12-hour ad-libitum use session of the product.	Over the 12-hour ad libitum product use session on the day the subject was assigned the test product (according to the randomization scheme)
Total Puff Duration by Test Product, Per Completed Cartridge, During the Ad-Libitum-Use Sessions	Total Puff Duration (measured in seconds) by Test Product, per completed cartridge, during a 12-hour ad-libitum use session of the product.	Over the 12-hour ad libitum product use session on the day the subject was assigned the test product (according to the randomization scheme)

Collaborators and Investigators

• Sponsor: Altria Client Services LLC
• Collaborators: Cato Research
• Investigators: Study Director: Jeffery S Edmiston, PhD, Altria Client Services

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2017
• Primary Completion (Actual): April 21, 2017
• Study Completion (Actual): January 26, 2018

Study Registration Dates

• First Submitted: April 26, 2021
• First Submitted That Met QC Criteria: May 7, 2021
• First Posted (Actual): May 11, 2021

Study Record Updates

• Last Update Posted (Actual): July 30, 2024
• Last Update Submitted That Met QC Criteria: February 13, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Dermatologic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Antipruritics; Nicotine; Menthol
• Other Study ID Numbers: ALCS-RA-17-06-EV

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No