Study to Evaluate Constituents in Exhaled Breath and Room Air From Use of E-vapor Products and Conventional Cigarettes

• ClinicalTrials.gov Identifier: NCT03605641
• Recruitment Status: Completed
• First Posted: July 30, 2018
• Last Update Posted: June 14, 2021
• Sponsor: Juul Labs, Inc.
• Collaborator: Inflamax Research Incorporated
• Information provided by (Responsible Party): Juul Labs, Inc.

Study Description

Brief Summary:

An open-label, single center, three-arm observational study to examine emissions from e-cigarettes versus conventional cigarettes under three environmental settings of typical residential, office and hospitality facilities.

Condition or disease	Intervention/treatment	Phase
Second Hand Tobacco Smoke	Other: JUUL; Other: VUSE Solo; Other: Conventional Cigarette	Not Applicable

Detailed Description:

Specific constituents will be measured in exhaled breath samples (EBS) from adult e-vapor product users and smokers when they are using e-vapor products or smoking conventional cigarettes. These constituents and particle counts (PC), will be measured in the room air samples (RAS) collected in the environmental exposure chamber (EEC) where adult e-cigarette users and smokers are using electronic cigarettes or smoking conventional cigarettes.

All subjects will undergo a Screening Visit to assess if they meet study eligibility criteria. If all eligibility criteria are met and the subject signs informed consent, the subject will be assigned to one of three groups: Group I (JUUL), Group II (VUSE Solo), or Group III (Conventional Cigarettes).

All three Groups will be sequentially observed in environmental settings 1 (residential), 2 (office), and 3 (hospitality). The observation period allocated for each environmental setting will be 2-days and 2-overnights for Groups I and II, and 1-day and 1-overnight for Group III. Each observation period will be referred to as a "Clinic Visit".

Subjects will move on to subsequent Environment Settings (Clinic Visits 2 or 3) after completion of the previous Clinic Visit (1 or 2).

Subjects must return to the clinic for Clinic Visit 1 within 60 days of the Screening Visit. Clinic Visit 2 must occur 7 ± 2 days after the Clinic Visit 1, and Clinic Visit 3 must occur 7 ± 2 days after Clinic Visit 2.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 43 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: An Open-Label, Single-Center Clinical Trial to Evaluate Selected Constituents in the Exhaled Breath and Room Air From the Use of E-vapor Products and Conventional Cigarettes Studied Under Residential, Office and Hospitality Environmental Conditions
• Actual Study Start Date: September 17, 2018
• Actual Primary Completion Date: December 2, 2018
• Actual Study Completion Date: December 2, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: JUUL electronic cigarette; JUUL electronic cigarette. Virginia Tobacco 5% tobacco-derived nicotine.	Other: JUUL; JUUL Virginia Tobacco
Active Comparator: VUSE Solo electronic cigarette; Reynolds American International VUSE Solo electronic cigarette. Original flavor 4.8% tobacco-derived nicotine.	Other: VUSE Solo; VUSE SOLO Original
Active Comparator: Conventional cigarette; Canadian purchased, store bought (not hand-rolled) conventional full-flavored cigarettes of subjects' preference.	Other: Conventional Cigarette; Subject preferred conventional cigarette

Outcome Measures

Primary Outcome Measures :

1. Exhaled Breath Sample (EBS) - Nicotine [ Time Frame: Clinic Visit (JUUL/VUSE: 2 days and 2 overnights; conventional cigarette: 1 day and 1 overnight) ]
   Absolute change from baseline in nicotine levels in the EBS of subjects who use JUUL, VUSE Solo, or conventional cigarettes.
2. Exhaled Breath Sample (EBS) - Propylene glycol [ Time Frame: Clinic Visit (JUUL/VUSE: 2 days and 2 overnights; conventional cigarette: 1 day and 1 overnight) ]
   Absolute change from baseline in propylene glycol levels in the EBS of subjects who use JUUL, VUSE Solo, or conventional cigarettes.
3. Exhaled Breath Sample (EBS) - Vegetable Glycerin [ Time Frame: Clinic Visit (JUUL/VUSE: 2 days and 2 overnights; conventional cigarette: 1 day and 1 overnight) ]
   Absolute change from baseline in vegetable glycerin levels in the EBS of subjects who use JUUL, VUSE Solo, or conventional cigarettes.
4. Exhaled Breath Sample (EBS) - Carbonyls [ Time Frame: Clinic Visit (JUUL/VUSE: 2 days and 2 overnights; conventional cigarette: 1 day and 1 overnight) ]
   Absolute change from baseline in carbonyl levels in the EBS of subjects who use JUUL, VUSE Solo, or conventional cigarettes. Carbonyl compounds include: formaldehyde, acetaldehyde, and acrolein.
5. Room Air Sample (RAS) - Nicotine [ Time Frame: Clinic Visit (JUUL/VUSE: 2 days and 2 overnights; conventional cigarette: 1 day and 1 overnight) ]
   Absolute change from baseline in nicotine levels in the room air when subjects use JUUL or VUSE Solo over 4-hour prescribed conditions and JUUL, VUSE Solo, or conventional cigarettes over 4-hour ad libitum conditions.
6. Room Air Sample (RAS) - Propylene glycol [ Time Frame: Clinic Visit (JUUL/VUSE: 2 days and 2 overnights; conventional cigarette: 1 day and 1 overnight) ]
   Absolute change from baseline in propylene glycol levels in the room air when subjects use JUUL or VUSE Solo over 4-hour prescribed conditions and JUUL, VUSE Solo, or conventional cigarettes over 4-hour ad libitum conditions.
7. Room Air Sample (RAS) - Vegetable Glycerin [ Time Frame: Clinic Visit (JUUL/VUSE: 2 days and 2 overnights; conventional cigarette: 1 day and 1 overnight) ]
   Absolute change from baseline in vegetable glycerin levels in the room air when subjects use JUUL or VUSE Solo over 4-hour prescribed conditions and JUUL, VUSE Solo, or conventional cigarettes over 4-hour ad libitum conditions.
8. Room Air Sample (RAS) - Carbonyls [ Time Frame: Clinic Visit (JUUL/VUSE: 2 days and 2 overnights; conventional cigarette: 1 day and 1 overnight) ]
   Absolute change from baseline in carbonyl levels in the room air when subjects use JUUL or VUSE Solo over 4-hour prescribed conditions and JUUL, VUSE Solo, or conventional cigarettes over 4-hour ad libitum conditions. Carbonyl compounds include: formaldehyde, crotonaldehyde, o-tolualdehyde, acetaldehyde, butyraldehyde (butanal), m&p-tolualdehyde, acetone, benzaldehyde, propionaldehyde, isovaleraldehyde, hexanaldehyde (aka hexaldehyde), valeraldehyde, 2, 5-dimethylbenzaldehyde, methyl ethyl ketone (MEK), acrolein.
9. Room Air Sample (RAS) - Volatile organic compounds [ Time Frame: Clinic Visit (JUUL/VUSE: 2 days and 2 overnights; conventional cigarette: 1 day and 1 overnight) ]
   Absolute change from baseline in volatile organic compound levels in the room air when subjects use JUUL or VUSE Solo over 4-hour prescribed conditions and JUUL, VUSE Solo, or conventional cigarettes over 4-hour ad libitum conditions. Volatile organic compounds include: 1,3-butadiene, Benzene, isoprene, toluene, furan, ethylene oxide, vinyl chloride, propylene oxide, nitromethane, 2-nitropropane, vinyl acetate, ethylbenzene
10. Room Air Samples (RAS) - Metals [ Time Frame: Clinic Visit (JUUL/VUSE: 2 days and 2 overnights; conventional cigarette: 1 day and 1 overnight) ]
    Absolute change from baseline in metal levels in the room air when subjects use JUUL or VUSE Solo over 4-hour prescribed conditions and JUUL, VUSE Solo, or conventional cigarettes over 4-hour ad libitum conditions. Metals include: arsenic, cadmium, chromium, nickel.
11. Room Air Samples (RAS) - PM2.5 Particles [ Time Frame: Clinic Visit (JUUL/VUSE: 2 days and 2 overnights; conventional cigarette: 1 day and 1 overnight) ]
    Absolute change from baseline levels of PM2.5 particles in room air when subjects use JUUL or VUSE Solo over 4-hour prescribed conditions and JUUL, VUSE Solo, or conventional cigarettes over 4-hour ad libitum conditions.
12. Room Air Samples (RAS) - PM10 Particles [ Time Frame: Clinic Visit (JUUL/VUSE: 2 days and 2 overnights; conventional cigarette: 1 day and 1 overnight) ]
    Absolute change from baseline levels of PM10 particles in room air when subjects use JUUL or VUSE Solo over 4-hour prescribed conditions and JUUL, VUSE Solo, or conventional cigarettes over 4-hour ad libitum conditions.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

Subjects must satisfy the following criteria before being enrolled into the study. Subjects must:

1. Be informed of the nature of the study and agree to and are able to read, review, and sign the informed consent document (in English) prior to the first study procedure. The Investigator must be satisfied that the volunteer has the ability to read and communicate in English in order to participate in the study.
2. Subjects screened as a part of an IRB-approved General Screening Protocol at the CRO site may be included in this study without additional Screening procedures provided all the required Screening procedures have been performed within 60 days prior to Clinic Visit 1.
3. Be a healthy male or female volunteer aged 21 - 65 years at the time of Screening Visit.
4. Have a positive urine cotinine result at Screening (Screening Visit) of >200 ng/ml.
5. Be judged by the Investigator to be in good general health as documented by the medical history, physical examination (including but may not be limited to an evaluation of the cardiovascular, gastrointestinal, respiratory and central nervous systems), vital sign assessments, 12-lead electrocardiogram (ECG), clinical laboratory assessments, and by general observations. Any abnormalities or deviations outside the normal ranges for any clinical testing (laboratory tests, ECG, vital signs) can be repeated at the discretion of the Investigator and judged to be not clinically significant for study participation.
6. Agree to abide by the study restrictions and return for the required assessments.
7. Have a self-reported daily conventional cigarette consumption rate of a minimum of 10 cigarettes per day for a minimum of 3 months prior to Screening Visit.

Exclusion Criteria:

Subjects who meet any of the following exclusion criteria will not be enrolled in the study.

Subjects must not:

1. Report receiving any investigational product within 30 days prior to Screening (Screening Visit).
2. Report any presence or history of a clinically significant disorder involving the cardiovascular, respiratory, renal, urologic, gastrointestinal, hepatic, immunologic, hematologic, endocrine, oncologic or neurologic system(s) or psychiatric disease as determined by the Investigator.
3. Have any clinically significant results from laboratory tests, physical examinations, vital signs assessments, and electrocardiograms, as judged by the Investigator.
4. Report a clinically significant illness during the 30 days prior to enrollment, as determined by the Investigator.
5. Report a history of drug or alcohol addiction or abuse within the past 1 year.
6. Have positive screen for alcohol or drugs of abuse at Screening (Screening Visit) or check-in at Clinical Visit 1.
7. Have positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg), or hepatitis C virus (anti-HCV).
8. Have body mass index (BMI) greater than 40 kg/m2 or less than 18 kg/m2 at Screening (Screening Visit).
9. Have used prescription anti-diabetic medication and/or insulin therapy within 12 months of Screening (Screening Visit).
10. Have taken medication for depression or asthma within 6 months of Screening (Screening Visit).
11. Have used prescription or over-the-counter bronchodilator medication (eg, inhaled or oral β-agonists) within 6 months of Screening (Screening Visit).
12. Be breast-feeding or pregnant female subjects (confirmed by a positive pregnancy test). Female subjects, who are considered women of child bearing potential (WOCBP) and sexually active, must be willing and able to use an acceptable method of contraception from Screening (Screening Visit) through the end of the study.
13. Be allergic to propylene glycol or glycerin.
14. Be or have a first-degree relative (ie, parent, sibling or child) be a current employee of the Sponsor or Site.

Contacts and Locations

Locations

Canada, Ontario

Inflamax Research Limited

Mississauga, Ontario, Canada, L4W 1A4

Sponsors and Collaborators

Juul Labs, Inc.

Inflamax Research Incorporated

Investigators

• Principal Investigator: Peter Couroux, MD; Inflamax Research

More Information

Publications:

Bam TS, Bellew W, Berezhnova I, Jackson-Morris A, Jones A, Latif E, Molinari MA, Quan G, Singh RJ, Wisotzky M; Tobacco Control Department International Union Against Tuberculosis and Lung Disease. Position statement on electronic cigarettes or electronic nicotine delivery systems. Int J Tuberc Lung Dis. 2014 Jan;18(1):5-7. doi: 10.5588/ijtld.13.0815.

Schober W, Szendrei K, Matzen W, Osiander-Fuchs H, Heitmann D, Schettgen T, Jörres RA, Fromme H. Use of electronic cigarettes (e-cigarettes) impairs indoor air quality and increases FeNO levels of e-cigarette consumers. Int J Hyg Environ Health. 2014 Jul;217(6):628-37. doi: 10.1016/j.ijheh.2013.11.003. Epub 2013 Dec 6.

Schripp T, Markewitz D, Uhde E, Salthammer T. Does e-cigarette consumption cause passive vaping? Indoor Air. 2013 Feb;23(1):25-31. doi: 10.1111/j.1600-0668.2012.00792.x. Epub 2012 Jul 2.

Czogala J, Goniewicz ML, Fidelus B, Zielinska-Danch W, Travers MJ, Sobczak A. Secondhand exposure to vapors from electronic cigarettes. Nicotine Tob Res. 2014 Jun;16(6):655-62. doi: 10.1093/ntr/ntt203. Epub 2013 Dec 11.

Chang H. Research gaps related to the environmental impacts of electronic cigarettes. Tob Control. 2014 May;23 Suppl 2:ii54-8. doi: 10.1136/tobaccocontrol-2013-051480. Review.

Liu J, Liang Q, Oldham MJ, Rostami AA, Wagner KA, Gillman IG, Patel P, Savioz R, Sarkar M. Determination of Selected Chemical Levels in Room Air and on Surfaces after the Use of Cartridge- and Tank-Based E-Vapor Products or Conventional Cigarettes. Int J Environ Res Public Health. 2017 Aug 28;14(9). pii: E969. doi: 10.3390/ijerph14090969.

Hess IM, Lachireddy K, Capon A. A systematic review of the health risks from passive exposure to electronic cigarette vapour. Public Health Res Pract. 2016 Apr 15;26(2). pii: 2621617. doi: 10.17061/phrp2621617. Review.

ANSI/ASHRAE Standard 62.1-2016. Ventilation for Acceptable Indoor Air Quality. American Society of Heating, Refrigerating and Air-Conditioning Engineers, Inc.

• Responsible Party: Juul Labs, Inc.
• ClinicalTrials.gov Identifier: NCT03605641
• Other Study ID Numbers: 755-00045
• First Posted: July 30, 2018
• Last Update Posted: June 14, 2021
• Last Verified: December 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Juul Labs, Inc.:

E-Cigarettes; Conventional Cigarettes; JUUL; VUSE