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

Tobacco Use Clinical Trial

— Diamond  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03463837
• Other study ID #: 755-00041
• Status: Completed
• Phase: N/A
• Start date: March 4, 2018
• Est. completion date: August 13, 2018

Study information

• Verified date: January 2019
• Source: Juul Labs, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: August 13, 2018
• Est. primary completion date: July 27, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Nicotine Dependence, Other Tobacco Product
• Smoking, Tobacco
• Tobacco Use
• Tobacco Use Disorder

Intervention

Other:
• Treatment with JUUL 5%, Virginia Tobacco
JUUL 5%, ENDS for 5-days in confinement
• Treatment with JUUL 5%, Cool Mint, ENDS
JUUL 5%, ENDS for 5-days in confinement
• Treatment with JUUL 5%, Mango, ENDS
JUUL 5%, ENDS for 5-days in confinement
• JUUL 5%, Creme Bruele, ENDS
JUUL 5%, ENDS for 5-days in confinement
• Combustible cigarette
Exclusive use of combustible cigarette for 5 days in confinement.
• Smoking Cessation
No smoking for 5-days in confinement.

Locations

Country	Name	City	State
United States	Celerion	Lincoln	Nebraska

Sponsors (2)

Lead Sponsor	Collaborator
Juul Labs, Inc.	Celerion

Country where clinical trial is conducted

United States, 

References & Publications (5)

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 — View Citation

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.

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. — View Citation

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_ Pub

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) — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change in concentration of 3-hydroxy-1-methylpropylmercapturic acid (HMPMA) in urine	Change in Biomarker	[Time Frame: 5 days]
Secondary	Change in concentration of 2-cyanoethyl-mercapturic acid (CEMA) in urine	Change in Biomarker	[Time Frame: 5 days]
Secondary	Change in concentration of 1-hydroxypyrene (1-OHP) in urine	Change in Biomarker	[Time Frame: 5 days]
Secondary	Change in concentration of Nicotine in urine	Change in Biomarker	[Time Frame: 5 days]
Secondary	Change in concentration of Cotinine in urine	Change in Biomarker	[Time Frame: 5 days]
Secondary	Change in concentration of trans-3'-hydroxycotinine in urine	Change in Biomarker	[Time Frame: 5 days]
Secondary	Change in concentration of Glucuronides in urine	Change in Biomarker	[Time Frame: 5 days]
Secondary	Change in concentration of Nicotine in blood	Change in Biomarker	[Time Frame: 5 days]
Secondary	Change in concentration of Cotinine in blood	Change in Biomarker	[Time Frame: 5 days]
Secondary	Change in concentration of trans-3'-hydroxycotinine in blood	Change in Biomarker	[Time Frame: 5 days
Secondary	Change in maximum concentration (Cmax) Plasma pharmacokinetic (PK) of Nicotine	Nicotine absorption	[Time Frame: Day 7,
Secondary	Change in time to maximum concentration (Tmax) Plasma PK of Nicotine	Nicotine absorption	[Time Frame: Day 7,
Secondary	Change of area under the curve (AUC) Plasma PK of Nicotine	Nicotine absorption	[Time Frame: Day 7,
Secondary	Product use over 5-day period and during 5-minute fixed and ad libitum use episodes	Change in product use	[Time Frame: 7 days]
Secondary	Measure of subjective Smoking Urge Assessment	Change in Assessment	[Time Frame: 6-7 days, intervention dependent]
Secondary	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]
Secondary	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]
Secondary	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]
Secondary	Incidence of JUUL 5% Device, including malfunction and/or misuse	Device performance	[Time Frame: 7 days]