Nicotine Pharmacokinetics Following Use of the P4M3 Gen 2.0 E-Cigarette Compared to Smoking Cigarettes

Study Overview
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Brief Summary
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This is a single-center, randomized, controlled, open-label, cross-over study with healthy adult smokers. The study will investigate the nicotine pharmacokinetic (PK) profiles of two e-liquid variants used with the P4M3 Gen 2.0 e-cigarette, compared to smoking combustible cigarettes. In addition, pharmacodynamic (PD) effects (subjective effects and related behavioral assessments), will be evaluated to provide further insights on product evaluation, craving, liking, puffing topography. The study will be conducted with three periods and six sequences in a cross-over design. This study is exploratory and there is no pre-specified hypothesis to be tested.

Detailed Description
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The purpose of the study is to evaluate the nicotine pharmacokinetics (PK) profiles of two e-liquid variants used with the P4M3 Gen 2.0 e-cigarette versus cigarettes following a six minutes ad libitum use period. In addition, pharmacodynamic effects (PD), including subjective effects and related behavioral assessments, as well as human puffing topography (HPT) will be evaluated, to provide further insights on P4M3 Gen 2.0 product acceptance and product use. Safety will be assessed throughout the study. The aim is to evaluate if P4M3 Gen 2.0 can provide an acceptable alternative to smoking cigarettes in terms of both, nicotine delivery and sensorial satisfaction for current adult smokers who would otherwise continue smoking cigarettes.

Official Title
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A Single-center, Randomized, Controlled, Open-label, Cross-over Study in Healthy Subjects to Investigate the Nicotine Pharmacokinetic Profiles of 2 Variants of P4M3 Gen 2.0, an Electronic Nicotine Delivery System, Compared to Cigarettes

Conditions
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Nicotine, Nicotine Vaping, Vaping

Intervention / Treatment
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* Other: CA35
* Other: CM35
* Other: Cig


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has signed the ICF and is able to understand the information provided in the ICF. Subject has smoked continuously for at least the last 3 years prior to the Screening visit. Subject has smoked ≥ 10 commercially available cigarettes per day for 4 weeks prior to Screening Visit and Admission. Subject does not plan to quit smoking cigarettes or using other nicotine or tobacco containing products in the next 3 months. Smoking, healthy subject as judged by the Investigator or designee based on available assessments from the Screening period. Exclusion Criteria: As per the Investigator's judgment, the subject cannot participate in the study for any reason other than medical. Subject has donated or received whole blood or blood products within 30 days prior to Screening Visit. BMI < 18.5 kg/m2 or > 35.0 kg/m2. Subject has received medication within 14 days or within 5 half-lives of the drug prior to Admission (whichever is longer), which has an impact on CYP2A6 activity. Subject has a positive serology test for HIV 1/2, Hepatitis B or Hepatitis C. Subject has a history of alcohol abuse that could interfere with the subject's participation in study. Subject has a positive urine drug test. Subject has a positive alcohol breath test. Subject has participated in another clinical study within 30 days prior to the Screening Visit. Subject is pregnant (does not have negative pregnancy tests at Screening Visit and at Admission) or is breastfeeding. For women of childbearing potential only: subject does not agree to use an acceptable method of effective contraception.

Ages Eligible for Study
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Minimum Age: 24 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 |
| --- | --- |
| Active Comparator: Product Sequence 1<br>After at least 12 hours of abstinence from the use of any nicotine/tobacco containing products (referred to as nicotine wash-out), subjects will smoke a cigarette or use one of the e-liquid variants with P4M3 Gen 2.0 according to randomized product use sequence ad libitum for 6 minutes (± 30 seconds). CA35 on Day 1; Cig on Day 2; CM35 on Day 3 | Other: CA35<br>* Nicotine concentration: 3.5 % e-liquid flavor: Tobacco<br>* Other names: P4M3 variant CA35;Other: CM35<br>* Nicotine concentration: 3.5 % e-liquid flavor: Menthol<br>* Other names: P4M3 variant CM35;Other: Cig<br>* Subjects' preferred brand of commercially available, regular or mentholated cigarettes<br>|
| Active Comparator: Product Sequence 2<br>After at least 12 hours of abstinence from the use of any nicotine/tobacco containing products (referred to as nicotine wash-out), subjects will smoke a cigarette or use one of the e-liquid variants with P4M3 Gen 2.0 according to randomized product use sequence ad libitum for 6 minutes (± 30 seconds). CA35 on Day 1; CM35 on Day 2; Cig on Day 3 | Other: CA35<br>* Nicotine concentration: 3.5 % e-liquid flavor: Tobacco<br>* Other names: P4M3 variant CA35;Other: CM35<br>* Nicotine concentration: 3.5 % e-liquid flavor: Menthol<br>* Other names: P4M3 variant CM35;Other: Cig<br>* Subjects' preferred brand of commercially available, regular or mentholated cigarettes<br>|
| Active Comparator: Product Sequence 3<br>After at least 12 hours of abstinence from the use of any nicotine/tobacco containing products (referred to as nicotine wash-out), subjects will smoke a cigarette or use one of the e-liquid variants with P4M3 Gen 2.0 according to randomized product use sequence ad libitum for 6 minutes (± 30 seconds). Cig on Day 1; CA35 on Day 2; CM35 on Day 3 | Other: CA35<br>* Nicotine concentration: 3.5 % e-liquid flavor: Tobacco<br>* Other names: P4M3 variant CA35;Other: CM35<br>* Nicotine concentration: 3.5 % e-liquid flavor: Menthol<br>* Other names: P4M3 variant CM35;Other: Cig<br>* Subjects' preferred brand of commercially available, regular or mentholated cigarettes<br>|
| Active Comparator: Product Sequence 4<br>After at least 12 hours of abstinence from the use of any nicotine/tobacco containing products (referred to as nicotine wash-out), subjects will smoke a cigarette or use one of the e-liquid variants with P4M3 Gen 2.0 according to randomized product use sequence ad libitum for 6 minutes (± 30 seconds). Cig on Day 1; CM35 on Day 2; CA35 on Day 3 | Other: CA35<br>* Nicotine concentration: 3.5 % e-liquid flavor: Tobacco<br>* Other names: P4M3 variant CA35;Other: CM35<br>* Nicotine concentration: 3.5 % e-liquid flavor: Menthol<br>* Other names: P4M3 variant CM35;Other: Cig<br>* Subjects' preferred brand of commercially available, regular or mentholated cigarettes<br>|
| Active Comparator: Product Sequence 5<br>After at least 12 hours of abstinence from the use of any nicotine/tobacco containing products (referred to as nicotine wash-out), subjects will smoke a cigarette or use one of the e-liquid variants with P4M3 Gen 2.0 according to randomized product use sequence ad libitum for 6 minutes (± 30 seconds). CM35 on Day 1; Cig on Day 2; CA35 on Day 3 | Other: CA35<br>* Nicotine concentration: 3.5 % e-liquid flavor: Tobacco<br>* Other names: P4M3 variant CA35;Other: CM35<br>* Nicotine concentration: 3.5 % e-liquid flavor: Menthol<br>* Other names: P4M3 variant CM35;Other: Cig<br>* Subjects' preferred brand of commercially available, regular or mentholated cigarettes<br>|
| Active Comparator: Product Sequence 6<br>After at least 12 hours of abstinence from the use of any nicotine/tobacco containing products (referred to as nicotine wash-out), subjects will smoke a cigarette or use one of the e-liquid variants with P4M3 Gen 2.0 according to randomized product use sequence ad libitum for 6 minutes (± 30 seconds). CM35 on Day 1; CA35 on Day 2; Cig on Day 3 | Other: CA35<br>* Nicotine concentration: 3.5 % e-liquid flavor: Tobacco<br>* Other names: P4M3 variant CA35;Other: CM35<br>* Nicotine concentration: 3.5 % e-liquid flavor: Menthol<br>* Other names: P4M3 variant CM35;Other: Cig<br>* Subjects' preferred brand of commercially available, regular or mentholated cigarettes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Background-corrected maximum plasma concentration [Cmax] | To measure Cmax from 6 minutes ad libitum use for two e-liquid variants used with the P4M3 Gen 2.0 e-cigarette and for subjects smoking cigarettes. | Measured at start of product use to 6 minutes | 
| Background-corrected time to the maximum concentration [Tmax] | To measure Tmax from 6 minutes ad libitum use for two e-liquid variants used with the P4M3 Gen 2.0 e-cigarette and for subjects smoking cigarettes. | Measured at start of product use to 6 minutes | 
| Area under the background-corrected concentration-time curve (AUC) | To measure AUC from 6 minutes ad libitum use for two e-liquid variants used with the P4M3 Gen 2.0 e-cigarette and for subjects smoking cigarettes. | Measured from start of product use to 2 minutes, to 4 minutes, to 10 hours, and then to time of last quantifiable concentration | 
| Maximum ratio of background-corrected concentration over time | To measure the maximum ratio of background-corrected concentration over time, from T0 (excluded) to Tmax (included) | Measured at start of product use to 6 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nicotine, Pharmacokinetics, Smoking, Cigarette, E-Cigarette