Nicotine Pharmacokinetic and Pharmacodynamics Profile, Safety and Tolerability of P3L

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD, i.e., subjective effects) profiles, and the safety and tolerability of the nicotine-containing aerosol delivered by Platform 3 Liquid (P3L) system at three different nicotine levels in smoking healthy subjects in relation to Nicorette® inhalator.

Detailed Description
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The entire study will last between 16 to 49 days per subject. This includes : a screening period of up to 4 weeks prior to admission, 1 day of admission (Visit 2): after all inclusion/exclusion criteria are checked, all eligible subjects will be enrolled and perform a product test, first with P3L (at nicotine dose levels of approximately 50 μg/puff) and subsequently with Nicorette® inhalator (3 to 5 inhalations for each product). 4 days of on-site product use (one day with Nicorette® inhalator [Visit 3] and three days with P3L [Visit 4, Visit 5 and Visit 6]), 1 to 3 days between each product use and a 7-day safety follow-up period (discharge + 7 days), during which there are no scheduled investigational visits, and during which adverse events (AEs) and serious adverse events (SAEs) can be spontaneously reported by the subjects and the follow-up of AEs/SAEs will be conducted by the study investigational site. Subjects will come to the investigational site the night before each assessment day, at least 12 hours prior to the product use, on Visit 4, Visit 5, and Visit 6. Subjects will stay overnight at the investigational site between the admission visit (Visit 2) and Visit 3. Smoking or use of any tobacco/nicotine-containing products or electronic cigarettes, apart from product use assigned on the assessment days, will not be allowed during their stay at the investigational site. Smoking will be allowed once the subjects have left the investigational site. The maximum concentration of nicotine (Cmax) and the area under the concentration-time curve from start of product use to the last quantifiable time point (AUC0-last) will be derived from multiple blood sampling pre- and post-product use, and corrected for baseline nicotine concentration.

Official Title
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A Single-center, Open-label, Ascending Nicotine Levels Study to Investigate the Nicotine Pharmacokinetic and Pharmacodynamics Profiles, Safety and Tolerability of P3L in Smoking Healthy Subjects in Relation to Nicorette® Inhalator

Conditions
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Smoking

Intervention / Treatment
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* Other: Nicorette® inhalator
* Other: P3L


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is Caucasian Smoking, healthy subject as judged by the Investigator Subject smoked at least 10 commercially available non-menthol cigarettes (CCs) per day for the last 4 weeks Subject has smoked for at least the last 3 years prior to screening Subject does not plan to quit smoking in the next 3 months 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 Admission 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: 21 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nicorette® inhalator then P3L<br>Each subject will use the Nicorette® inhalator (15 mg) on Visit 3, and then use the P3L aerosol at nicotine dose levels of approximately 50 µg/puff, 80 µg/puff and 150 µg/puff on Visits 4, 5 and 6, respectively. | Other: Nicorette® inhalator<br>* Subjects will inhale the Nicorette® inhalator (15 mg) at the rate of one deep inhalation every 15 seconds on average, over approximately 20 minutes (80 inhalations in total).<br>Other: P3L<br>* Subjects will inhale P3L (50 µg/puff, 80 µg/puff and 150 µg/puff) at the rate of one inhalation every 30 seconds on average, over approximately 6 minutes (i.e., 12 inhalations in total).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Concentration (Cmax) of Nicotine Following Single Use of Nicorette® Inhalator | T0 = start of product use. Derived from multiple blood sampling pre- and post-product use on Visit 3 (over 240 minutes post-product use). Geometric Least Squares (geometric LS) means are provided. | Visit 3: blood taken at 45, 30 and 15 minutes prior to T0 and 2, 4, 7, 10, 15, 20, 30, 40, 50, 60, 120, and 240 minutes after T0. | 
| Maximum Concentration (Cmax) of Nicotine Following Single Use of P3L 50 µg/Puff | T0 = start of product use. Derived from multiple blood sampling pre- and post-product use on Visit 4 (over 240 minutes post-product use). Geometric Least Squares (geometric LS) means are provided. | Visit 4: blood taken at 45, 30 and 15 minutes prior to T0 and 2, 4, 7, 10, 15, 20, 30, 40, 50, 60, 120, and 240 minutes after T0. | 
| Maximum Concentration (Cmax) of Nicotine Following Single Use of P3L 80 µg/Puff | T0 = start of product use. Derived from multiple blood sampling pre- and post-product use on Visit 5 (over 240 minutes post-product use). Geometric Least Squares (geometric LS) means are provided. | Visit 5: blood taken at 45, 30 and 15 minutes prior to T0 and 2, 4, 7, 10, 15, 20, 30, 40, 50, 60, 120, and 240 minutes after T0. | 
| Maximum Concentration (Cmax) of Nicotine Following Single Use of P3L 150 µg/Puff | T0 = start of product use. Derived from multiple blood sampling pre- and post-product use on Visit 6 (over 240 minutes post-product use). Geometric Least Squares (geometric LS) means are provided. | Visit 6: blood taken at 45, 30 and 15 minutes prior to T0 and 2, 4, 7, 10, 15, 20, 30, 40, 50, 60, 120, and 240 minutes after T0. | 
| Time to the Maximum Concentration (Tmax) of Nicotine Following Single Use of Nicorette® Inhalator | T0 = start of product use. Derived from multiple blood sampling pre- and post-product use on Visit 3 (over 240 minutes post-product use). | Visit 3: blood taken at 45, 30 and 15 minutes prior to T0 and 2, 4, 7, 10, 15, 20, 30, 40, 50, 60, 120, and 240 minutes after T0. | 
| Time to the Maximum Concentration (Tmax) of Nicotine Following Single Use of P3L 50 µg/Puff | T0 = start of product use. Derived from multiple blood sampling pre- and post-product use on Visit 4 (over 240 minutes post-product use). | Visit 4: blood taken at 45, 30 and 15 minutes prior to T0 and 2, 4, 7, 10, 15, 20, 30, 40, 50, 60, 120, and 240 minutes after T0. | 
| Time to the Maximum Concentration (Tmax) of Nicotine Following Single Use of P3L 80 µg/Puff | T0 = start of product use. Derived from multiple blood sampling pre- and post-product use on Visit 5 (over 240 minutes post-product use). | Visit 5: blood taken at 45, 30 and 15 minutes prior to T0 and 2, 4, 7, 10, 15, 20, 30, 40, 50, 60, 120, and 240 minutes after T0. | 
| Time to the Maximum Concentration (Tmax) of Nicotine Following Single Use of P3L 150 µg/Puff | T0 = start of product use. Derived from multiple blood sampling pre- and post-product use on Visit 6 (over 240 minutes post-product use). | Visit 6: blood taken at 45, 30 and 15 minutes prior to T0 and 2, 4, 7, 10, 15, 20, 30, 40, 50, 60, 120, and 240 minutes after T0. | 
| Area Under the Concentration-time Curve From Start of Product Use to the Last Quantifiable Time Point (AUC0-last) of Nicotine Following Single Use of Nicorette® Inhalator | T0 = start of product use. Derived from multiple blood sampling pre- and post-product use on Visit 3 (over 240 minutes post-product use). Geometric Least Squares (geometric LS) means are provided. | Visit 3: blood taken at 45, 30 and 15 minutes prior to T0 and 2, 4, 7, 10, 15, 20, 30, 40, 50, 60, 120, and 240 minutes after T0. | 
| Area Under the Concentration-time Curve From Start of Product Use to the Last Quantifiable Time Point (AUC0-last) of Nicotine Following Single Use of P3L 50 µg/Puff | T0 = start of product use. Derived from multiple blood sampling pre- and post-product use on Visit 4 (over 240 minutes post-product use). Geometric Least Squares (geometric LS) means are provided. | Visit 4: blood taken at 45, 30 and 15 minutes prior to T0 and 2, 4, 7, 10, 15, 20, 30, 40, 50, 60, 120, and 240 minutes after T0. | 
| Area Under the Concentration-time Curve From Start of Product Use to the Last Quantifiable Time Point (AUC0-last) of Nicotine Following Single Use of P3L 80 µg/Puff | T0 = start of product use. Derived from multiple blood sampling pre- and post-product use on Visit 5 (over 240 minutes post-product use). Geometric Least Squares (geometric LS) means are provided. | Visit 5: blood taken at 45, 30 and 15 minutes prior to T0 and 2, 4, 7, 10, 15, 20, 30, 40, 50, 60, 120, and 240 minutes after T0. | 
| Area Under the Concentration-time Curve From Start of Product Use to the Last Quantifiable Time Point (AUC0-last) of Nicotine Following Single Use of P3L 150 µg/Puff | T0 = start of product use. Derived from multiple blood sampling pre- and post-product use on Visit 6 (over 240 minutes post-product use). Geometric Least Squares (geometric LS) means are provided. | Visit 6: blood taken at 45, 30 and 15 minutes prior to T0 and 2, 4, 7, 10, 15, 20, 30, 40, 50, 60, 120, and 240 minutes after T0. | 
| Area Under the Concentration-time Curve From Start of Product Use to 10 Minutes After Start of Product Use (AUC0-10) of Nicotine Following Single Use of Nicorette® Inhalator | T0 = start of product use. Derived from multiple blood sampling pre- and post-product use on Visit 3 (over 240 minutes post-product use). Geometric Least Squares (geometric LS) means are provided. | Visit 3: blood taken at 45, 30 and 15 minutes prior to T0 and 2, 4, 7, and 10 minutes after T0. | 
| Area Under the Concentration-time Curve From Start of Product Use to 10 Minutes After Start of Product Use (AUC0-10) of Nicotine Following Single Use of P3L 50 µg/Puff | T0 = start of product use. Derived from multiple blood sampling pre- and post-product use on Visit 4 (over 240 minutes post-product use). Geometric Least Squares (geometric LS) means are provided. | Visit 4: blood taken at 45, 30 and 15 minutes prior to T0 and 2, 4, 7, and 10 minutes after T0. | 
| Area Under the Concentration-time Curve From Start of Product Use to 10 Minutes After Start of Product Use (AUC0-10) of Nicotine Following Single Use of P3L 80 µg/Puff | T0 = start of product use. Derived from multiple blood sampling pre- and post-product use on Visit 5 (over 240 minutes post-product use). Geometric Least Squares (geometric LS) means are provided. | Visit 5: blood taken at 45, 30 and 15 minutes prior to T0 and 2, 4, 7, and 10 minutes after T0. | 
| Area Under the Concentration-time Curve From Start of Product Use to 10 Minutes After Start of Product Use (AUC0-10) of Nicotine Following Single Use of P3L 150 µg/Puff | T0 = start of product use. Derived from multiple blood sampling pre- and post-product use on Visit 6 (over 240 minutes post-product use). Geometric Least Squares (geometric LS) means are provided. | Visit 6: blood taken at 45, 30 and 15 minutes prior to T0 and 2, 4, 7, and 10 minutes after T0. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nicotine absorption, nicotine containing product, adult smoker, Nicorette, nicotine delivery system