Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618000800224
Ethics application status
Approved
Date submitted
1/02/2018
Date registered
11/05/2018
Date last updated
11/05/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Assessment of JUUL 5% nicotine salt based Electronic Nicotine Delivery System (ENDS) products, when used by healthy adult smokers
Scientific title
A Six-sequence, Randomized Crossover Study Comparing Nicotine Pharmacokinetics of Traditional Cigarettes and JUUL 5% Nicotine Salt Based ENDS Products, in Healthy Adult Smokers
Secondary ID [1] 293940 0
CH-1702
Universal Trial Number (UTN)
Not obtained
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Smoking 306433 0
Condition category
Condition code
Mental Health 305518 305518 0 0
Addiction

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Subjects will receive a total of six “doses” of nicotine (1-3 mg), delivered in a randomized order. There will be a washout of at least 120 minutes between the first inhalation of each product. The use of the term “dose” in this protocol does not mean to imply that the products are intended as therapeutics or smoking cessation products - dose will be variable depending on inhalation techniques - hence concentration and puffs given for strength of ''dose''.. Treatments to be administered in the current study are:
A. Tobacco flavored JUUL 5% nicotine salt (1-3 mg) based ENDS product, consumed in 10 puffs.
B. Mint flavored JUUL 5% nicotine salt (1-3 mg) based ENDS product, consumed in 10 puffs.
C. Tobacco flavored traditional Pall Mall cigarette (1-3 mg) , consumed in 10 puffs.
D. Mint flavored traditional Newport 100s cigarette (1-3 mg) , consumed in 10 puffs.
For Treatments A - D, the subject will be asked to inhale 10 times, with 30 seconds between inhalations, using the assigned product. With each inhalation procedure, subjects will be instructed to breathe in gently (“puff”) for 3 seconds, remove the JUUL from their mouth, and then inhale prior to exhaling. Total time for administration will be 4.5 minutes.
E. Tobacco flavored JUUL 5% nicotine salt based ENDS product, consumed in ad libitum puffs for a period of 4.5 minutes.
F. Tobacco flavored traditional Pall Mall cigarette, consumed in ad libitum puffs (if the cigarette is completed in less than 4.5 minutes, another cigarette will be made available to be smoked until the end of the 4.5-minute period).
All treatments delivered once on the same day.

all product administration will occur under medical supervision, compliance is not expected to present a problem.
Intervention code [1] 300205 0
Lifestyle
Comparator / control treatment
Tobacco flavored traditional cigarette (Pall Mall)
Mint flavored traditional cigarette (Newport 100s)
Control group
Active

Outcomes
Primary outcome [1] 304648 0
To compare nicotine pharmacokinetics (PK), nicotine Cmax, Tmax, AUC1hour and Cmax-baseline, obtained with:
- Tobacco flavored traditional cigarette versus tobacco flavored JUUL 5% ENDS product;
-Mint flavored traditional cigarette versus mint flavored JUUL 5% ENDS product;
-Tobacco flavored JUUL 5% ENDS product versus mint flavored JUUL 5% ENDS product;
-Tobacco flavored traditional cigarette versus mint flavored traditional cigarette
-cigarette / e-cigarette consumption under different delivery conditions (10 puffs versus ad libitum puffs).
Timepoint [1] 304648 0
On Day of dosing - Specific sampling time points - PK samples will be collected 5 minutes prior to initiation of the first inhalation (-5 min) and 0.0, 1.5, 3.0, 5.0, 7, 10, 12, 15, 30 and 60 minutes after initiation of the first inhalation for each treatment.
Secondary outcome [1] 342659 0
To compare change in exhaled Carbon Monoxide (CO). by using a carbon monoxide breath monitor (breath CO monitor). The breath carbon monoxide level has been shown to have a close relationship with the level of CO in the blood. This allows for the level of CO in the blood to be indirectly measured through a breath sample
Timepoint [1] 342659 0
On day of dosing - specific time points - CO measurement will occur 5-10 minutes prior to and 15-20 minutes after initiation of each treatment period

Eligibility
Key inclusion criteria
1. Male or female aged 18 to 45 years of age inclusive.
2. Body Mass Index (BMI) between 18 to 32kg / m2 inclusive.
3. Healthy on the basis of medical history and screening assessments, in the opinion of the Investigator.
4. Current smoker of at least 7 cigarettes per week on average.
5. Able to participate, and willing to give written informed consent and to comply with the study restrictions.
Minimum age
18 Years
Maximum age
45 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.
6. Regular use of e-cigarettes only, with no regular use of cigarettes (dual cigarette / e-cigarette users are permitted).
7. Clinically significant abnormality in laboratory test results at screening, in the opinion of the Investigator.
8. Exposure to an investigational drug in a clinical trial within 1 month prior to Day 1.
9. Blood or plasma donation of > 500 mL within 1 month prior to Day 1.
10. Positive urine pregnancy test at screening or Day 1 in female subject.
11. 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.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 3 / Phase 4
Type of endpoint/s
Pharmacokinetics
Statistical methods / analysis
A sample size of 24 subjects is expected to be adequate for the investigation of the pharmacokinetic profiles of the JUUL 5% ENDS and the cigarette products and for the planned comparisons of interest.
Plasma concentrations and the computed plasma PK parameters will be listed for each treatment and subject.
Individual plasma concentrations will be plotted on both a linear and a semi-logarithmic scale. Mean values will also be presented graphically. The following pharmacokinetic parameters will be calculated:
-max = Time of maximum plasma concentration;
-max = Maximum plasma concentration;
-max-baseline = Cmax at Tmax minus period 1 pre-dose plasma concentration;
-UC1hour = Area under the plasma concentration-time curve from time zero to 1 hour

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
16/07/2017
Date of last participant enrolment
Anticipated
Actual
26/07/2017
Date of last data collection
Anticipated
Actual
26/07/2017
Sample size
Target
24
Accrual to date
Final
24
Recruitment outside Australia
Country [1] 9545 0
New Zealand
State/province [1] 9545 0
Christchurch

Funding & Sponsors
Funding source category [1] 298567 0
Commercial sector/Industry
Name [1] 298567 0
JUUL Labs
Country [1] 298567 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
JUUL Labs
Address
660 Alabama Street, Second Floor,
San Francisco, CA 94110
USA
Country
United States of America
Secondary sponsor category [1] 297718 0
None
Name [1] 297718 0
Address [1] 297718 0
Country [1] 297718 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299534 0
Northern A Health & Disability Ethics Comiittee
Ethics committee address [1] 299534 0
Ministry of Health
133 Molsworth Street
PO Box 5013
Wellington 6011
Ethics committee country [1] 299534 0
New Zealand
Date submitted for ethics approval [1] 299534 0
01/06/2017
Approval date [1] 299534 0
01/07/2017
Ethics approval number [1] 299534 0
17/NTA/99

Summary
Brief summary
This is an open label, randomized, 6-sequence crossover study. The study will enrol 24 evaluable healthy adult smokers.
Subjects will be screened for participation up to 28 days before dosing. Subjects will be trained in the use of study product following completion of screening procedures. Subjects meeting all entry criteria at screening will be admitted to the clinic on Day 1. Eligible subjects will remain at the clinic until all study-related assessments are completed.
Subjects will receive a total of six “doses” of nicotine, delivered in a randomized order. ere will be a washout of at least 120 minutes between the first inhalation of each product. A product and its associated assessments will be referred to in this protocol as a “dosing period”. The use of the term “dose” in this protocol does not mean to imply that the products are intended as therapeutics or smoking cessation products.Treatments to be administered in the current study are:
A. Tobacco flavored JUUL 5% nicotine salt based ENDS product, consumed in 10 puffs.
B. Mint flavored JUUL 5% nicotine salt based ENDS product, consumed in 10 puffs.
C. Tobacco flavored traditional Pall Mall cigarette, consumed in 10 puffs.
D. Mint flavored traditional Newport 100s cigarette, consumed in 10 puffs.
E. Tobacco flavored JUUL 5% nicotine salt based ENDS product, consumed in ad libitum puffs.
F.Tobacco flavored traditional Pall Mall cigarette, consumed in ad libitum puffs (if the cigarette is completed in less than 4.5 minutes, another cigarette will be made available to be smoked until the end of the 4.5-minute period).
Treatments will be administered open label.
For Treatments A - D, the subject will be asked to inhale 10 times, with 30 seconds between inhalations, using the assigned product. With each inhalation procedure, subjects will be instructed to breathe in gently (“puff”) for 3 seconds, remove the JUUL from their mouth, and then inhale prior to exhaling. Total time for administration will be 4.5 minutes.
For Treatments E and F, the subject will be asked to consume the product using ad libitum puffs over a period of 4.5 minutes. For Treatment F, if the cigarette is completed in less than 4.5 minutes another cigarette will be made available to be smoked until the end of the 4.5-minute period.
PK samples will be collected up to 5 minutes prior to initiation of the first inhalation (- 5 min); 0.0, 1.5, 3.0, 5.0, 7, 10, 12, 15, 30 and 60 minutes after initiation of the first inhalation in each dosing period.
Carbon Monoxide levels in expired air will be measured 5-10 minutes prior to and 15-20 minutes after initiating each dose period. The CO measure may be conducted in a sub-set of subjects.
A product evaluation questionnaire will be completed after collection of the 30-minute PK sample in all dosing periods.
Subjects will be discharged after completion of safety and PK evaluations for the final dosing period.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 80758 0
Dr Chris Wynne
Address 80758 0
Christchurch Clinical Studies Trust
31 Tuam Street
Christchurch 8011
Country 80758 0
New Zealand
Phone 80758 0
+64 3 372 9477
Fax 80758 0
Email 80758 0
[email protected]
Contact person for public queries
Name 80759 0
Ms Jo Saunders
Address 80759 0
Christchurch Clinical Studies Trust
31 Tuam Street
Christchurch 8011
Country 80759 0
New Zealand
Phone 80759 0
+64 3 372 9477
Fax 80759 0
Email 80759 0
[email protected]
Contact person for scientific queries
Name 80760 0
Dr Chris Wynne
Address 80760 0
Christchurch Clinical Studies Trust
31 Tuam Street
Christchurch 8011
Country 80760 0
New Zealand
Phone 80760 0
+64 3 372 9477
Fax 80760 0
Email 80760 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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