Identify Biomarkers of Tobacco Exposure and Nicotine Uptake From JUUL 5% in Adult Smokers (Diamond)

A Randomized, Open-Label, Parallel-Group Study to Characterize Biomarkers of Tobacco Exposure and Nicotine Uptake From JUUL 5% Electronic Nicotine Delivery Systems (ENDS) in Adult Smokers

The JUUL 5% Electronic Nicotine Delivery System (ENDS) is being studied as an alternative to combustible cigarette use. This study aims to find out how much nicotine is in the blood and urine of healthy adult subjects after using three JUUL 5% ENDS compared to smoking usual brands of combustible cigarettes and stopping smoking.

Study Overview

• Status: Completed
• Conditions: Tobacco Use; Smoking, Tobacco; Nicotine Dependence, Other Tobacco Product
• Intervention / Treatment: Other: Treatment with JUUL 5%, Virginia Tobacco; Other: Treatment with JUUL 5%, Cool Mint, ENDS; Other: Treatment with JUUL 5%, Mango, ENDS; Other: JUUL 5%, Creme Bruele, ENDS; Other: Combustible cigarette; Other: Smoking Cessation

Detailed Description

This study will serve as a clinical evaluation of the exclusive use of selected JUUL ENDS, with the purpose of gaining an understanding of toxicant exposure.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Lincoln, Nebraska, United States, 68516
      • Celerion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

1. Healthy, adult, male or female smoker, 21 to 65 years of age.
2. Has been a smoker for at least 12 months prior to Screening.
3. Currently smokes an average of 10 cigarettes each day.
4. Has a positive urine cotinine (≥ 500 ng/mL).
5. Has an exhaled carbon monoxide (CO) > 12 ppm.
6. A female subject of childbearing potential must have been using contraception and agree to continue using it through completion of the study:
7. Provides voluntary consent to participate in this study documented on the signed informed consent form (ICF).

Key Exclusion Criteria

1. Has a history or presence of clinically significant conditions.
2. Has a body mass index (BMI) > 40 kg/m2 or < 18 kg/m2 at Screen
3. Has a history of drug or alcohol abuse
4. Has an estimated creatinine clearance < 80 mL/minute
5. If female, the subject is pregnant, lactating, or intends to become pregnant during the time period from Screening through the end of study.
6. Has used nicotine-containing products other than manufactured cigarettes within 14days of screening.
7. Is planning to quit smoking during the study, planning to quit within 3 months following Day 1

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment with JUUL 5%, Virginia Tobacco; JUUL 5%,Virginia Tobacco [5 days] in confinement.	Other: Treatment with JUUL 5%, Virginia Tobacco; JUUL 5%, ENDS for 5-days in confinement; Other Names: JUUL
Experimental: Treatment with JUUL 5%, Cool Mint, ENDS; JUUL 5%, Cool Mint [5 days] in confinement.	Other: Treatment with JUUL 5%, Cool Mint, ENDS; JUUL 5%, ENDS for 5-days in confinement; Other Names: JUUL
Experimental: Treatment with JUUL 5%, Mango, ENDS; JUUL 5%, Mango [5 days] in confinement.	Other: Treatment with JUUL 5%, Mango, ENDS; JUUL 5%, ENDS for 5-days in confinement; Other Names: JUUL
Experimental: JUUL 5%, Creme Bruele, ENDS; JUUL 5%, Creme Bruele [5 days] in confinement.	Other: JUUL 5%, Creme Bruele, ENDS; JUUL 5%, ENDS for 5-days in confinement; Other Names: JUUL
Active Comparator: Combustible cigarette; Exclusive use of combustible cigarette [5 days] in confinement.	Other: Combustible cigarette; Exclusive use of combustible cigarette for 5 days in confinement.
Sham Comparator: Smoking cessation (no smoking); Smoking cessation (no smoking).	Other: Smoking Cessation; No smoking for 5-days in confinement.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in primary biomarkers day 5 values for each JUUL 5% product will be compared to baseline:	Change in ; Urine N nitrosonornicotine (NNN), 4 (methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), 3 hydroxypropylmercapturic acid (3-HPMA), monohydroxybutenylmercapturic acid (MHBMA), and S-phenyl mercapturic acid (S-PMA) "Blood carboxyhemoglobin (COHb)	[Time Frame: 5 days]

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in concentration of 3-hydroxy-1-methylpropylmercapturic acid (HMPMA) in urine	Change in Biomarker	[Time Frame: 5 days]
Change in concentration of 2-cyanoethyl-mercapturic acid (CEMA) in urine	Change in Biomarker	[Time Frame: 5 days]
Change in concentration of 1-hydroxypyrene (1-OHP) in urine	Change in Biomarker	[Time Frame: 5 days]
Change in concentration of Nicotine in urine	Change in Biomarker	[Time Frame: 5 days]
Change in concentration of Cotinine in urine	Change in Biomarker	[Time Frame: 5 days]
Change in concentration of trans-3'-hydroxycotinine in urine	Change in Biomarker	[Time Frame: 5 days]
Change in concentration of Glucuronides in urine	Change in Biomarker	[Time Frame: 5 days]
Change in concentration of Nicotine in blood	Change in Biomarker	[Time Frame: 5 days]
Change in concentration of Cotinine in blood	Change in Biomarker	[Time Frame: 5 days]
Change in concentration of trans-3'-hydroxycotinine in blood	Change in Biomarker	[Time Frame: 5 days
Change in maximum concentration (Cmax) Plasma pharmacokinetic (PK) of Nicotine	Nicotine absorption	[Time Frame: Day 7,
Change in time to maximum concentration (Tmax) Plasma PK of Nicotine	Nicotine absorption	[Time Frame: Day 7,
Change of area under the curve (AUC) Plasma PK of Nicotine	Nicotine absorption	[Time Frame: Day 7,
Product use over 5-day period and during 5-minute fixed and ad libitum use episodes	Change in product use	[Time Frame: 7 days]
Measure of subjective Smoking Urge Assessment	Change in Assessment	[Time Frame: 6-7 days, intervention dependent]
Measure of subjective product evaluation using the "modified Product Evaluation Scale (mPES)"	Change in Evaluation; Scale: 1 = not at all, 2 = very little, 3 = a little, 4 = moderately, 5 = a lot, 6 = quite a lot, 7 = extremely Four multi-item subscales will be derived from "Satisfaction" (items 1, 2, 3, and 12); "Psychological Reward" (items 4 through 8); "Aversion" (items 9, 10, 16, and 18); and "Relief" (item 11, 13, 14, 15, and reversed for item 19) and single items 17 and 20 will be summarized.	[Time Frame: 6-7 days, intervention dependent]
Measure of future intent to use JUUL 5% Device device relative to usual combustible cigarette and smoking cessation.	Change in Intent	[Time Frame: 6-7 days, intervention dependent]
Number of participants with Adverse Events associated with use of JUUL 5% Device to combustible cigarette and smoking cessation	Safety	[Time Frame: 13-14 days, intervention dependent]
Incidence of JUUL 5% Device, including malfunction and/or misuse	Device performance	[Time Frame: 7 days]

Collaborators and Investigators

• Sponsor: Juul Labs, Inc.
• Collaborators: Celerion
• Investigators: Principal Investigator: Philip Mathew, M.D., Celerion

Publications and helpful links

General Publications

• HIPAA Privacy Rule. Information for Researchers. De-identifying Protected Health Information Under the Privacy Rule. U.S. Department of Health and Human Services. NIH (Feb 2007). Available at: http://privacyruleandresearch.nih.gov/pr_08.asp#8a. Last accessed 31-Jul-2017.
• D'Ruiz CD, Graff DW, Robinson E. Reductions in biomarkers of exposure, impacts on smoking urge and assessment of product use and tolerability in adult smokers following partial or complete substitution of cigarettes with electronic cigarettes. BMC Public Health. 2016 Jul 11;16:543. doi: 10.1186/s12889-016-3236-1.
• Jensen RP, Luo W, Pankow JF, Strongin RM, Peyton DH. Hidden formaldehyde in e-cigarette aerosols. N Engl J Med. 2015 Jan 22;372(4):392-4. doi: 10.1056/NEJMc1413069. No abstract available.
• McNeill A et al. E-cigarettes: An Evidence Update. A report commissioned by Public Health England. Available at: https://www.gov.uk/government/uploads/system/uploads/ attachment_data/file/457102/Ecigarettes_an_evidence_update_A_report_commissioned_by_ Public_Health_England_FINAL.pdf (Aug 2015).
• Polosa R, Morjaria J, Caponnetto P, Caruso M, Strano S, Battaglia E, Russo C. Effect of smoking abstinence and reduction in asthmatic smokers switching to electronic cigarettes: evidence for harm reversal. Int J Environ Res Public Health. 2014 May 8;11(5):4965-77. doi: 10.3390/ijerph110504965.

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2018
• Primary Completion (Actual): July 27, 2018
• Study Completion (Actual): August 13, 2018

Study Registration Dates

• First Submitted: March 7, 2018
• First Submitted That Met QC Criteria: March 7, 2018
• First Posted (Actual): March 13, 2018

Study Record Updates

• Last Update Posted (Actual): June 21, 2021
• Last Update Submitted That Met QC Criteria: June 15, 2021
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Tobacco Use Disorder
• Other Study ID Numbers: 755-00041

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
• product manufactured in and exported from the U.S.: No