User Acceptability of a Nicotine Lactate Delivery System (P3L)

Study Overview
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Brief Summary
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This study will provide an initial assessment of the acceptability of the Nicotine Lactate Delivery System (P3L) after ad libitum use and the ability of combustible cigarette (CC) smokers to use P3L to maintain their customary nicotine intake, in a manner comparable with their own brand of CC or the VUSE e-cigarette system.

Detailed Description
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The total duration of the study for an individual subject will be between 3 and 8 weeks, including 1 day for the screening visit, 3 days for the ad libitum use sessions (P3L, VUSE e-cigarette system and subjects' own commercially available non-menthol CC), 1 day for the preference evaluation session (subjects will be given the choice of using ad libitum the P3L or the VUSE), the 2 to 10 days of interval between each visit, and 7 days for the passive safety follow-up period. The pharmacokinetics (PK) and pharmacodynamics (PD, i.e., subjective effects) profiles, will be evaluated as well as the safety and tolerability of the P3L.

Official Title
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User Acceptability of a Nicotine Lactate Delivery System Relative to the VUSE e-Cigarette System and Combustible Cigarette Comparators

Conditions
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Smoking

Intervention / Treatment
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* Other: P3L
* Other: VUSE
* Other: CC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Smoking, healthy subject as judged by the Investigator Subject smoked at least 10 commercially available non-menthol CCs per day for the last 12 months Subject does not plan to quit smoking in the next 60 days Exclusion Criteria: As per Investigator judgment, the subject cannot participate in the study for any reason (e.g., medical, psychiatric, and/or social reason) Subject has donated or been in receipt of whole blood or blood products within 3 months prior to the screening visit Subject has used tobacco products or nicotine containing products other than CCs within 30 days prior to the screening visit Female subject is pregnant or breast feeding Female subject does not agree to use an acceptable method of effective contraception Female subject uses estrogen-containing hormonal contraception or hormone replacement therapy

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: P3L Product use<br>Subject product use was randomly assigned for each ad libitum use session, following a sequence of product exposure comprised of the three products (P3L, VUSE, and CC). | Other: P3L<br>* Ad libitum use for a maximum of three hours. P3L delivers, on average, 80 µg of nicotine per puff under Health Canada Intense smoking regime.<br>|
| Experimental: VUSE Product Use<br>Subject product use was randomly assigned for each ad libitum use session, following a sequence of product exposure comprised of the three products (P3L, VUSE, and CC). | Other: VUSE<br>* Ad libitum use for a maximum of three hours. VUSE delivers, on average, 80 µg of nicotine per puff based on the CORESTA e-cigarette recommended smoking regime.<br>|
| Experimental: CC Product Use<br>Subject product use was randomly assigned for each ad libitum use session, following a sequence of product exposure comprised of the three products (P3L, VUSE, and CC). | Other: CC<br>* Ad libitum use of the subject's own brand of non-menthol CC for a maximum of three hours.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline Plasma Concentration of Nicotine/Cotinine After Each ad Libitum Use Session. | For each ad libitum use session (P3L, VUSE, and CC), change from baseline plasma concentration of Nicotine/Cotinine was measured from two blood samples collected before product use (to provide baseline measures) and from two blood samples collected following product use (to show change from baseline). | Measured at 15 minutes and 5 minutes prior to each 3 hour product use to provide baseline measures, then at 15 minutes and 30 minutes after product use period to show change from baseline. | 
| Overall Score of the Short Version of the Questionnaire of Smoking Urges (QSU-brief). Total Score; Factor 1 (Reward); Factor 2 (Relief) | The QSU-Brief questionnaire is an instrument used to measure urge to smoke. Subjects were asked to respond to 10 questions, scored from 1 to 7 on a 7-point scale. A score of 1 on this scale indicates a very low urge to smoke, while a score of 7 indicates a very high urge to smoke. Subjects were asked to complete the questionnaire before, during, and after each ad libitum product use session. (P3L, VUSE, and Subjects' Own Brand of Non-menthol CC). Two factor scores and a total score were derived. Factor 1 represents the desire and intention to smoke with smoking perceived as rewarding, while Factor 2 represents an anticipation of relief from negative effect with an urgent desire to smoke. Products were compared over all timepoints using a repeated measure model using values after t0. The model adjusted for baseline value, sequence, and period with repeated measure over time and a random effect in subjects. Adjusted mean over all timepoints, for each timepoint, were estimated. | QSU-brief questionnaire completed before product use session, then at 60 mins, 120 mins, and 180 mins after starting each product use session. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Conventional cigarette, Nicotine lactate delivery system, e-cigarette, VUSE, Combustible cigarette