Clinical trial NCT03719391: United States Pre-Market Tobacco Application Pharmacokinetics
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Nicotine Dependence
Nicotine Dependence, Cigarettes
Tobacco Use
Tobacco Smoking
Keywords: Electronic Nicotine Delivery System
Combustible Cigarettes
Nicotine
Lead sponsor: Juul Labs, Inc.
Sponsor class: INDUSTRY
First posted: 2018-10-25
Enrollment: 67
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Randomized, Open-Label, Cross-Over
Primary purpose: OTHER

Brief 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

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: 7 days
Secondary outcomes:
measure: 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
timeFrame: 7 Days
measure: 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)"
timeFrame: 7 Days
measure: To assess blood pressure following controlled use of four JUUL 5% ENDS relative to UB combustible cigarettes, a comparator e-cigarette, and nicotine gum.
timeFrame: 7 Days
measure: To assess heart rate following controlled use of four JUUL 5% ENDS relative to UB combustible cigarettes, a comparator e-cigarette, and nicotine gum.
timeFrame: 7 Days
measure: To assess the safety and tolerability of short-term use of four JUUL 5% ENDS.
timeFrame: 7 Days
measure: To characterize product use of four JUUL 5% ENDS during controlled use sessions.
timeFrame: 7 Days
measure: 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.
timeFrame: 7 Days
measure: 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.
timeFrame: 7 Days
measure: 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.
timeFrame: 7 Days
measure: 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.
timeFrame: 7 Days
Other outcomes:
Locations:
city: Overland Park
country: United States
facility: Vince & Associates Clinical Research
state: Kansas
Study officials:
References:
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