United States Pre-Market Tobacco Application Pharmacokinetics

Nicotine Dependence Clinical Trial

— US-PMTA-PK  

Official title:

A Randomized, Open-Label, Cross-Over Study to Assess Nicotine Uptake and Subjective Measures With Use of JUUL 5% Electronic Nicotine Delivery Systems (ENDS) Compared to Usual Brand Combustible Cigarettes, a Comparator E-Cigarette, and Nicotine Gum in Healthy Adult Smokers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03719391
• Other study ID #: PROT-00009
• Status: Completed
• Phase: N/A
• Start date: October 19, 2018
• Est. completion date: November 28, 2018

Study information

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

Clinical Trial Summary

A Randomized, Open-Label, Cross-Over Study to Assess Nicotine Uptake and Subjective Measures with Use of JUUL 5% Electronic Nicotine Delivery Systems (ENDS) Compared to Usual Brand Combustible Cigarettes, a Comparator E-Cigarette, and Nicotine Gum in Healthy Adult Smokers

Description:

E-cigarettes may be an acceptable alternative to traditional cigarette smoking. In utilizing vaporization rather than combustion, the generation and inhaltion of smoke and carbon monoxide (CO) may be reduced or avoided. JUUL has developed several nicotine based liquid blends for use in e-cigarettes. This study will assess nicotine uptake during a 10-puff controlled and a 5-minute ad libitum use of four JUUL 5% electronic nicotine delivery systems (ENDS) relative to usual brand (UB) combustible cigarettes, a comparator electronic cigarette (e-cigarette), and nicotine gum.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 67
• Est. completion date: November 28, 2018
• Est. primary completion date: November 21, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 65 Years

Eligibility

Inclusion Criteria:

• Healthy, adult, male or female smoker, 21 to 65 years of age, inclusive

• Has been a smoker for at least 12 months prior to Screening. Brief periods of non-smoking (e.g., up to ~7 consecutive days due to illness, trying to quit, participation in a study where smoking was prohibited) during that time will be permitted at the discretion of the PI.

• Currently smokes an average of 10 or more king size or 100s manufactured combustible CPD, as reported at Screening.

• Has a positive urine cotinine (= 500 ng/mL) at Screening

• Has an exhaled CO > 12 ppm at Screening.

• Is willing to comply with the requirements of the study, including a willingness to use the study products during the study.

Exclusion Criteria:

• Has a history or presence of clinically significant gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, urologic, pulmonary, immunologic, psychiatric, or cardiovascular disease, or any other condition that, in the opinion of the PI, would jeopardize the safety of the subject or impact the validity of the study results.

• Has a clinically significant abnormal finding on the physical examination, medical history, vital signs, ECG, or clinical laboratory results, in the opinion of the PI.

• Has a positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) at Screening.

• Has had an acute illness (e.g., upper respiratory infection, viral infection) requiring treatment within 14 days prior to Check-in.

• Has a fever (> 100.5°F) at Screening or Check-in.

• Has a body mass index (BMI) > 40.0 kg/m2 or < 18.0 kg/m2 at Screening.

• Has a history of drug or alcohol abuse within 24 months of Check-in, as determined by the PI.

• Has diabetes mellitus, asthma, or chronic obstructive pulmonary disease.

• Has a systolic blood pressure < 90 mmHg or > 150 mmHg, diastolic blood pressure < 40 mmHg or > 95 mmHg, or heart rate < 40 bpm or > 99 bpm at Screening.

• Has experienced an allergic reaction following previous e-cigarette use or with exposure to any primary components of the e-liquids (benzoic acid, propylene glycol and glycerol).

• Has an estimated creatinine clearance < 80 mL/minute (using the Cockcroft-Gault equation) at Screening.

• Has a positive urine screen for alcohol or drugs of abuse at Screening or Check-in.

• Has used medications known to interact with cytochrome P450 (CYP) 2A6 (including, but not limited to, amiodarone, amlodipine, amobarbital, buprenorphine, clofibrate, clotrimazole, desipramine, disulfiram, entacapone, fenofibrate, isoniazid, ketoconazole, letrozole, methimazole, methoxsalen, metyrapone, miconazole, modafinil, orphenadrine, pentobarbital, phenobarbital, pilocarpine, primidone, propoxyphene, quinidine, rifampicin, rifampin, secobarbital, selegiline, sulconazole, tioconazole, tranylcypromine) within 14 days or 5 half-lives of the drug, whichever is longer, prior to Check-in.

• Has used nicotine-containing products other than manufactured cigarettes (e.g., ENDS, roll-your-own cigarettes, bidis, snuff, nicotine inhaler, pipe, cigar, chewing tobacco, nicotine patch, nicotine spray, nicotine lozenge, or nicotine gum) within 14 days prior to Check-in.

• Has a prior history of JUUL product use prior to Screening

• Has used any prescription smoking cessation treatments, including, but not limited to, varenicline (Chantix®) or buproprion (Zyban®) within 3 months prior to Check-in.

• Is a self-reported puffer (i.e., adult smokers who draw smoke from the cigarette into the mouth and throat but do not inhale).

• Is planning to quit smoking during the study or postponing a quit attempt in order to participate in the study.

• Has donated plasma within 7 days prior to Check-in.

• Has donated blood or blood products (with the exception of plasma as noted above), had significant blood loss, or received whole blood or a blood product transfusion within 56 days prior to Check-in.

• Has participated in a previous clinical study for an investigational drug, device, biologic, or tobacco product within 30 days prior to Check-in.

• Is or has a first-degree relative (i.e., parent, sibling, child) who is a current employee of the study site.

• Is or has a first-degree relative (i.e., parent, sibling, child) who is a current employee, shareholder, or is member of the board of directors of JUUL Labs Inc.

• Has previously been diagnosed with any form of cancer, except for basal cell or squamous epithelial carcinomas of the skin that have been resected at least 1 year prior to Screening.

Related Conditions & MeSH terms

• Nicotine Dependence
• Nicotine Dependence, Cigarettes
• Tobacco Smoking
• Tobacco Use
• Tobacco Use Disorder

Intervention

Other:
• Virginia Tobacco flavored JUUL 5% ENDS
Treatment with Virginia Tobacco flavored JUUL 5% ENDS (10 puffs).
• Cool Mint flavored JUUL 5% ENDS
Treatment with Cool Mint flavored JUUL 5% ENDS (10 puffs).
• Mango flavored JUUL 5% ENDS
Treatment with Mango flavored JUUL 5% ENDS (10 puffs).
• Creme Brulee flavored JUUL 5% ENDS
Treatment with Creme Brulee flavored JUUL 5% ENDS (10 puffs).
• VUSE Solo e-cigarette
Treatment with VUSE Solo Original with 4.8% nicotine e-cigarette (10 puffs).
• Nicorette White Ice Mint 4mg nicotine polacrilex gum
Treatment with Nicorette White Ice Mint 4mg Nicotine polacrilex gum (30 minutes Chew and Park method)
• Usual Brand combustible cigarette
Treatment with usual brand cigarette (10 puffs).

Locations

Country	Name	City	State
United States	Vince & Associates Clinical Research	Overland Park	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Juul Labs, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (7)

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. — View Citation

Fagerström K. Determinants of tobacco use and renaming the FTND to the Fagerstrom Test for Cigarette Dependence. Nicotine Tob Res. 2012 Jan;14(1):75-8. doi: 10.1093/ntr/ntr137. Epub 2011 Oct 24. — View Citation

Hatsukami DK, Zhang Y, O'Connor RJ, Severson HH. Subjective responses to oral tobacco products: scale validation. Nicotine Tob Res. 2013 Jul;15(7):1259-64. doi: 10.1093/ntr/nts265. Epub 2012 Dec 13. — 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_ 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To assess nicotine uptake during a 10-puff controlled use of four JUUL 5% electronic nicotine delivery systems (ENDS) relative to usual brand (UB) combustible cigarettes, a comparator electronic cigarette (e-cigarette), and nicotine gum.	Nicotine PK parameters will be calculated from the individual plasma concentrations per details provided in the SAP. Baseline adjustments to the (non-adjusted) PK endpoints will also be presented.	7 days
Secondary	To assess exhaled carbon monoxide [CO] following controlled use of four JUUL 5% ENDS relative to UB combustible cigarettes, a comparator e-cigarette, and nicotine gum	Exhaled CO levels will be measured using a Bedfont Micro+ Smokerlyzer or similar device and levels at Screening and after product use will be assessed.	7 Days
Secondary	To assess measures of subjective effects with controlled use of four JUUL 5% ENDS relative to UB combustible cigarettes, a comparator e-cigarette, and nicotine gum 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.	7 Days
Secondary	To assess blood pressure following controlled use of four JUUL 5% ENDS relative to UB combustible cigarettes, a comparator e-cigarette, and nicotine gum.		7 Days
Secondary	To assess heart rate following controlled use of four JUUL 5% ENDS relative to UB combustible cigarettes, a comparator e-cigarette, and nicotine gum.		7 Days
Secondary	To assess the safety and tolerability of short-term use of four JUUL 5% ENDS.	Number of participants with Adverse Events associated with use of JUUL 5% Device will be described by individual listings and frequency tables.	7 Days
Secondary	To characterize product use of four JUUL 5% ENDS during controlled use sessions.	All product use data will be summarized using descriptive statistics. The difference in weight pre- and post- product use of each JUUL product and comparator e-cigarettes will be summarized.	7 Days
Secondary	To assess measures of subjective effects with controlled use of four JUUL 5% ENDS relative to UB combustible cigarettes, a comparator e-cigarette, and nicotine gum using Intent to Use Again Questionnaire.	The Intent to Use Again questionnaire will be assessed using a 100 mm bipolar VAS	7 Days
Secondary	To assess measures of subjective effects with controlled use of four JUUL 5% ENDS relative to UB combustible cigarettes, a comparator e-cigarette, and nicotine gum using Nicotine Withdrawal Questionnaire.	The nicotine withdrawal will be assessed using a 100mm visual analog scale (VAS)	7 Days
Secondary	To assess measures of subjective effects with controlled use of four JUUL 5% ENDS relative to UB combustible cigarettes, a comparator e-cigarette, and nicotine gum using Product Direct Effect Questionnaire.	Product direct effect will be assessed using a 100 mm VAS	7 Days
Secondary	To assess measures of subjective effects with controlled use of four JUUL 5% ENDS relative to UB combustible cigarettes, a comparator e-cigarette, and nicotine gum using Product Liking Questionnaire.	Product liking will be assessed using a 100 mm VAS	7 Days