Clinical Study Comparing 7 ENDS Products and 1 Combustible Cigarette Using 2 Delivery Methods.

• ClinicalTrials.gov Identifier: NCT03700112
• Recruitment Status: Completed
• First Posted: October 9, 2018
• Last Update Posted: June 14, 2021
• Sponsor: Juul Labs, Inc.
• Information provided by (Responsible Party): Juul Labs, Inc.

Study Description

Brief Summary:

A Randomized Study Comparing Nicotine Pharmacokinetics of Seven Electronic Cigarette Products and One Traditional Cigarette Across Two Delivery (10 puff and ad- libitum) Conditions, in Healthy Adult Smokers

Condition or disease	Intervention/treatment	Phase
Nicotine Dependence; Nicotine Dependence, Cigarettes; Tobacco Use; Tobacco Smoking	Other: JUUL Virginia Tobacco flavored 5.0% ENDS; Other: PMI iQOS Heat sticks; Other: Reynolds VUSE Solo ENDS - Original; Other: Imperial MyBlu ENDS - Original; Other: Altria MarkTen ENDS - Bold Classic; Other: MLV PHIX ENDS - Original Tobacco; Other: NJOY Daily EXTRA ENDS - Rich Tobacco; Other: Altria Marlboro combustible cigarette - Red	Not Applicable

Detailed Description:

E- cigarettes may be an acceptable alternative to traditional cigarette smoking. By utilizing vaporization rather than combustion, the generation and inhalation of HPHCs, smoke, and carbon monoxide (CO) may be reduced or avoided. This study will provide an understanding of the in vitro levels of nicotine obtained with use of the company's ENDS products compared to competitor products marketed in the United States of America (USA), and to a popular brand of combustible cigarette smoked in the USA.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 25 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: An Open Label, Randomized Crossover Study Comparing Nicotine Pharmacokinetics of Seven Electronic Cigarette Products and One Traditional Cigarette Across Two Delivery (10 Puff and Ad-libitum) Conditions, in Healthy Adult Smokers.
• Actual Study Start Date: December 4, 2018
• Actual Primary Completion Date: February 24, 2019
• Actual Study Completion Date: April 9, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: JUUL Virginia Tobacco flavored 5.0% ENDS; Administration of JUUL Virginia Tobacco flavored 5.0% ENDS product consumed using 10 puffs delivery method Administration of JUUL Virginia Tobacco flavored 5.0% ENDS product consumed Ad-libitum delivery method	Other: JUUL Virginia Tobacco flavored 5.0% ENDS; Virginia Tobacco Flavored 5.0% ENDS product is administered using a controlled method and adlibitum
Experimental: PMI iQOS Heat sticks; Administration of PMI iQOS Heat sticks - Regular consumed using 10 puffs delivery method Administration of PMI iQOS Heat sticks - Regular consumed ad-libitum delivery method	Other: PMI iQOS Heat sticks; PMI IQOS Heat sticks is administered using a controlled method and ad-libitum
Experimental: Reynolds VUSE Solo ENDS - Original; Administration of Reynolds VUSE Solo ENDS - Original consumed using 10 puffs delivery method Administration of Reynolds VUSE Solo ENDS - Original consumed using ad-libitum delivery method	Other: Reynolds VUSE Solo ENDS - Original; Reynolds VUSE solo ENDS - Original is administered using a controlled method and ad-libitum
Experimental: Imperial MyBlu ENDS - Original; Administration of Imperial MyBlu ENDS - Original consumed using 10 puffs delivery method Administration of Imperial MyBlu ENDS - Original consumed using ad-libitum delivery method	Other: Imperial MyBlu ENDS - Original; Imperial MyBlu ENDS- original is administered using a controlled method and ad-libitum
Experimental: Altria MarkTen ENDS - Bold Classic; Administration of Altria MarkTen ENDS - Bold Classic consuming using 10 puffs delivery method Administration of Altria MarkTen ENDS - Bold Classic consuming using ad-libitum delivery method	Other: Altria MarkTen ENDS - Bold Classic; Altria MarkTen ENDS - Bold Classic is administered using a controlled method and ad-libitum
Experimental: MLV PHIX ENDS - Original Tobacco; Administration of MLV PHIX ENDS - Original Tobacco consumed using 10 puffs delivery method Administration of with MLV PHIX ENDS - Original Tobacco consumed using ad-libitum delivery method	Other: MLV PHIX ENDS - Original Tobacco; MLV PHIX ENDS - Original Tobacco is administered using a controlled method and ad-libitum
Experimental: NJOY Daily EXTRA ENDS - Rich Tobacco; Administration of NJOY Daily EXTRA ENDS - Rich Tobacco consumed using 10 puffs delivery method Administration of NJOY Daily EXTRA ENDS - Rich Tobacco consumed using delivery method and ad-libitum	Other: NJOY Daily EXTRA ENDS - Rich Tobacco; NJOY Daily EXTRA ENDS - Rich Tobacco is administered using a controlled method and ad-libitum
Experimental: Altria Marlboro combustible cigarette - Red; Administration of Altria Marlboro combustible cigarette - Red consumed using 10 puffs delivery method Administration of Altria Marlboro combustible cigarette - Red consumed using ad-libitum delivery method	Other: Altria Marlboro combustible cigarette - Red; Altria Marlboro combustible cigarette - Red is administered using a controlled method and ad-libitum

Outcome Measures

Primary Outcome Measures :

1. Nicotine PK parameters will be calculated from the individual plasma concentrations per details provided in the SAP. [ Time Frame: 48 days ]
   To estimate nicotine pharmacokinetics (PK) profiles across 8 E-Cigarette/cigarette products within-each and between-all delivery conditions (10 puffs versus ad libitum puffs) using Area Under the nicotine concentration-time curve (AUC1hour) calculated using linear trapezoidal summation from time zero (defined as the start of product use) to 60 minutes.
2. Nicotine PK parameters will be calculated from the individual plasma concentrations per details provided in the SAP. [ Time Frame: 48 days ]
   Nicotine Pharmacokinetics (PK) profiles across 8 e-cigarettes/cigarette will be estimated using AUC1hour-baseline (baseline adjusted AUC1hour)
3. Nicotine PK parameters will be calculated from the individual plasma concentrations per details provided in the SAP. [ Time Frame: 48 days ]
   Nicotine Pharmacokinetics (PK) profiles across 8 e-cigarettes/cigarette will be estimated using Cmax (Maximum measured plasma concentration over the duration of the measurement interval.
4. Nicotine PK parameters will be calculated from the individual plasma concentrations per details provided in the SAP. [ Time Frame: 48 days ]
   Nicotine Pharmacokinetics (PK) profiles across 8 e-cigarettes/cigarette will be estimated using Cmax-baseline(Baseline adjusted Cmax)
5. Nicotine PK parameters will be calculated from the individual plasma concentrations per details provided in the SAP. [ Time Frame: 48 days ]
   Nicotine Pharmacokinetics (PK) profiles across 8 e-cigarettes/cigarette will be estimated using Tmax(Time of the maximum measured plasma concentration over the duration of the measurement interval. If the maximum value occurs at more than one time point within the time span specified, Tmax is defined as the first time point with this value

Secondary Outcome Measures :

1. Measure exhaled Carbon Monoxide change in all product administration periods [ Time Frame: 48 days ]
   To estimate change in exhaled carbon monoxide (CO) for 8 E-cigarettes/cigarettes Products, in all product administration periods under 2 different delivery (10 puff and ad-libitum) conditions. Exhaled CO will be measured 5-15 minutes prior to initiation of the first inhalation, and up to 15 minutes after the collection of the 30 minute PK sample
2. Characterize level of user Satisfaction for 8e-cigarette/cigarettes products using Modified Product Evaluation Scale [ Time Frame: 48 days ]

   To characterize measures of subjective effects with use of 8 E-cigarettes/cigarettes Products under 2 different delivery (10 puff and ad-libitum) conditions using a modified Product Evaluations Scale questionnaire using scale below after collection of the 30-minute PK sample and exhaled CO measurement.

   Change in Evaluation: 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" (questions 1, 2, 3, and 12); "Psychological Reward" (questions 4 through 8); "Aversion" (questions 9, 10, 16, and 18) and "Relief" (questions 11, 13, 14, 15, and reversed for question 19) and single questions 17 and 20 will be summarized.

3. Characterize consumption of 8 E-cigarettes/cigarettes products by collecting total number of puffs for each e-cigarette [ Time Frame: 48 days ]
   To characterize consumptions of 8 E-cigarettes/cigarettes products within-each and between-all delivery conditions (10 puffs versus ad-libitum puffs), by collecting total number of puffs.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. Male or female aged 18 to 60 years of age inclusive.
2. BMI between 18 to 35 kg / m2 inclusive.
3. Healthy based on medical history and screening assessments, in the opinion of the Investigator.
4. Current smoker of at least 8 cigarettes per day on average.
5. Has been smoking 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) are permitted at the discretion of the Investigator.
6. Able to participate, and willing to give written informed consent and comply with study restrictions.

Exclusion Criteria:

1. Clinically relevant medical or psychiatric disorder, in the opinion of the Investigator.
2. Clinically significant abnormality on screening ECG.
3. Sustained blood pressure recordings at screening of < 90 mmHg or > 150 mmHg for systolic blood pressure, or < 50 mmHg or > 90 mmHg for diastolic blood pressure.
4. Sustained resting heart rate of > 100 or < 40 beats per minute at screening.
5. Positive result for urine drugs of abuse test or alcohol breath test at screening. If a positive urine drug test is observed, and it is believed the positive urine test is due to prescription drugs, the PI should obtain documentation that a) confirms the subject's use of the prescribed medication, and b) the prescribed medication will cause a false positive drug test.
6. Clinically significant abnormality in laboratory test results at screening, in the opinion of the Investigator.
7. Exposure to an investigational drug in a clinical trial within 1 month prior toAssessment Day 1.
8. Blood or plasma donation of > 500 mL within 1 month prior to Assessment Day 1.
9. Positive urine pregnancy test at screening or Assessment Day 1 in female subject.
10. Any clinically significant concomitant disease or condition that could interfere with, or for which the treatment of might interfere with, the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study.

Contacts and Locations

Locations

New Zealand

Christchurch Clinical Studies Trust Ltd

Christchurch, New Zealand, 8011

Sponsors and Collaborators

Juul Labs, Inc.

Investigators

• Study Director: Concetta Carbonaro; JUUL

More Information

• Responsible Party: Juul Labs, Inc.
• ClinicalTrials.gov Identifier: NCT03700112
• Other Study ID Numbers: PROT-00013
• First Posted: October 9, 2018
• Last Update Posted: June 14, 2021
• Last Verified: January 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Juul Labs, Inc.:

Electronic Nicotine Delivery System; Combustible Cigarettes; Nicotine

Additional relevant MeSH terms:

Tobacco Use Disorder; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders