Product Use and Adaptation, Safety and Tolerability of P3P in Adult Healthy Smokers Switching to it

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the product use and adaptation in adult, current cigarette smoking subjects between baseline and after one month of use of one of two P3P variants. The effect of P3P use behavior on nicotine pharmacokinetic (PK) profile, acceptability, as well as the safety and tolerability of P3P over a period of 1 month will be investigated.

Detailed Description
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This is a study of daily use of up to 15 P3P products over one month, including 2 confinement periods (2 overnight stays at the beginning of the study and 1 overnight stay at the end of the exposure period). During the confinement visits, nicotine PK from P3P exposure will be assessed as well as pharmacodynamic effects related to craving, sensory parameters, product experience, and product acceptance. Between the two confinement periods, subjects will return to the investigational site for weekly ambulatory visits during which P3P will be resupplied and selected safety and other study assessments will be performed. From the start of the exposure period onwards, subjects will be instructed not to smoke or use other tobacco or nicotine containing products and to use P3P exclusively.

Official Title
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A Randomized, Double-blinded, 2-arm Parallel Groups, Single Center Study to Assess Product Use and Adaptation, Safety and Tolerability of P3P, a Novel Nicotine-containing Product, in Adult Healthy Cigarette Smokers Switching to One of Two P3P Variants for One Month

Conditions
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Pharmacokinetics

Intervention / Treatment
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* Other: P3P-1mg
* Other: P3P-2mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has signed and dated the ICF and is able to understand the information provided in it. Subject has been a smoker for at least the last 3 years prior to the Screening Visit and has smoked 5 to 15 commercially available cigarettes per day for the last 3 months prior to Screening. Subject has a positive urinary cotinine test (cotinine ≥ 200 ng/mL). Subject does not plan to quit smoking within 2 months. Smoking, healthy subject as judged by the Investigator or designee based on available assessments from the Screening period. Ready to switch from smoking cigarettes to using P3P for the duration of the study. Exclusion Criteria: As per the Investigator's judgment, the subject cannot participate in the study for any reason other than medical (e.g., psychological and/or social reason). Subject has a clinically relevant disease which requires medication or any other clinically significant medical condition, which as per the judgment of the Investigator would jeopardize the safety of the subject. Subject has asthma condition (post-bronchodilator FEV1/FVC < 0.75 and reversibility in FEV1 ≥ 12% and > 200 mL from pre- to post-bronchodilator values). Subject has (FEV1/FVC) < 0.7 and FEV1 < 80% predicted value at post-bronchodilator spirometry. Subject has a BMI < 18.5 kg/m2 or > 32.0 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 positive alcohol breath test and/or a history of alcohol disorder within the past 2 years. Subject has a positive urine drug test. Subject has participated in another clinical study within 3 months prior to the Screening Visit. Subject has been previously screened or enrolled in this study. For women only: subject is pregnant 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: 21 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A randomized, double-blinded, 2-arm parallel groups, single center study
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: P3P-1mg<br>Subjects randomized to exclusive use of P3P-1mg | Other: P3P-1mg<br>* P3P-1mg (P3P product containing 1mg of nicotine.)<br>|
| Other: P3P-2mg<br>Subjects randomized to exclusive use of P3P-2mg | Other: P3P-2mg<br>* P3P-2mg (P3P product containing 2mg of nicotine.)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Nicotine Concentration-time Profile | To measure the plasma nicotine concentration-time profile following correction of baseline nicotine levels. | Derived from multiple blood sampling pre- and post-product use (over 4 hours post-product use), on day 1 and day 30. | 
| Maximum Nicotine Concentration [cCmax] | To measure the maximum plasma nicotine concentration [cCmax] following correction of baseline nicotine levels. | Derived from multiple blood sampling pre- and post-product use (over 4 hours post-product use), on day 1 and day 30. | 
| Time to the Maximum Nicotine Concentration [cTmax] | To measure the time to maximum nicotine concentration [cTmax] following correction of baseline nicotine levels. | Derived from multiple blood sampling pre- and post-product use (over 4 hours post-product use), on day 1 and day 30. | 
| Area Under the Concentration-time Curve From Start of Product Use (T0) to 4 Hours [cAUC(0-4h)] | To measure the area under the plasma concentration-time curve [cAUC(0-4h)] following correction of baseline nicotine levels. | Derived from multiple blood sampling pre- and post-product use (over 4 hours post-product use), on day 1 and day 30. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Craving for a Cigarette | Measured on a Visual Analogue Scale (VAS) of 0 (no craving) to 100 (strong craving). Over time results calculated as area under curve mm*hour. | Before, during and up to 4 hours post-product use on day 1 and day 30 | 
| Sensory Parameters | Measured with a Sensory Questionnaire. Response to each question is assessed on a 7-point scale, ranging from 1 (not at all) to 7 (extremely). | Within 60 minutes after product use on day 1 and day 30. | 
| Product Experience | Measured with ABOUT[TM]-Product Experience questionnaire. Response to each question is assessed on a 7-point scale, ranging from 1 (not at all) to 7 (extremely). | Within 60 minutes after product use on day 1 and day 30. | 
| Product Dependence | Measured with ABOUT[TM]-Dependence questionnaire. Response to each question is assessed on a 5-point scale, ranging from 1 (not at all/never) to 5 (extremely/all the time) or a 6-point scale ranging from 0 (more than 3 hours) to 5 (0-5 minutes). | Within 60 minutes after product use on day 1 and day 30. | 
| Product Acceptance | Measured with a Product Acceptance questionnaire. Response to each question is assessed on a 7-point scale, ranging from 1 (most negative) to 7 (most positive) or as multiple choice questions. | Within 60 minutes after product use on day 1 and day 30. | 
| Puffing Behavior of Subject | To measure changes in subject puffing behavior. Evaluated by selection of one puffing behavior response out of three possible responses. 1. Puffing and holding the aerosol in the mouth for a short time and then inhaling (i.e. like a cigarette) 2. Puffing and immediately inhaling (without holding the aerosol in the mouth) 3. Puffing and immediately exhaling, without inhalation | Evaluated by site staff on day 1 and day 30. Self-evaluated by subject on day 2, day 7, day 15, day 22, and day 29. | 
| Overall Product Use | To assess the number of any nicotine/tobacco products used overall on a daily basis. | Recorded daily by subject, in product use diary, from day 1 until day 30. | 
| NEQ | To measure percent changes from baseline in Nicotine equivalents (NEQ) concentrations, measured in spot urine and expressed as concentration adjusted for creatinine. | Measured at baseline, day 7, day 15, day 22, and day 29. | 
| Total NNAL | To measure percent changes from baseline in total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) concentrations, measured in spot urine and expressed as concentration adjusted for creatinine. | Measured at baseline, day 7, day 15, day 22, and day 29. | 
| CEMA | To measure percent changes from baseline in 2-cyanoethylmercapturic acid (CEMA) concentrations, measured in spot urine and expressed as concentration adjusted for creatinine (ng/mg creat). | Measured at baseline, day 7, day 15, day 22, and day 29. | 
| CYP2A6 Activity | To measure percent change from baseline in CYP2A6 enzymatic activity, on day 30, as measured by molar metabolic ratio of trans-3-hydroxy-cotinine/cotinine in plasma. | Measured before product use, on day 1 and day 30. | 
| Amount of Powder Extracted From P3P Used for PK Assessment. | Weight difference (mg) of P3P before and after use, to determine the amount of powder extracted from P3P. | Before and after product use, on day 1 and day 30. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nicotine