Product Use and Adaptation, Safety and Tolerability of P3P in Adult Healthy Smokers Switching to it
- Conditions
- Pharmacokinetics
- Interventions
- Other: P3P-1mgOther: P3P-2mg
- Registration Number
- NCT03953183
- Lead Sponsor
- Philip Morris Products S.A.
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 60
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description P3P-1mg P3P-1mg Subjects randomized to exclusive use of P3P-1mg P3P-2mg P3P-2mg Subjects randomized to exclusive use of P3P-2mg
- Primary Outcome Measures
Name Time Method Plasma Nicotine Concentration-time Profile Derived from multiple blood sampling pre- and post-product use (over 4 hours post-product use), on day 1 and day 30. To measure the plasma nicotine concentration-time profile following correction of baseline nicotine levels.
Maximum Nicotine Concentration [cCmax] Derived from multiple blood sampling pre- and post-product use (over 4 hours post-product use), on day 1 and day 30. To measure the maximum plasma nicotine concentration \[cCmax\] following correction of baseline nicotine levels.
Time to the Maximum Nicotine Concentration [cTmax] Derived from multiple blood sampling pre- and post-product use (over 4 hours post-product use), on day 1 and day 30. To measure the time to maximum nicotine concentration \[cTmax\] following correction of baseline nicotine levels.
Area Under the Concentration-time Curve From Start of Product Use (T0) to 4 Hours [cAUC(0-4h)] Derived from multiple blood sampling pre- and post-product use (over 4 hours post-product use), on day 1 and day 30. To measure the area under the plasma concentration-time curve \[cAUC(0-4h)\] following correction of baseline nicotine levels.
- Secondary Outcome Measures
Name Time Method Craving for a Cigarette Before, during and up to 4 hours post-product use on day 1 and day 30 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.
Product Dependence Within 60 minutes after product use on day 1 and day 30. 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).
Total NNAL Measured at baseline, day 7, day 15, day 22, and day 29. 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.
Product Experience Within 60 minutes after product use on day 1 and day 30. 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).
Product Acceptance Within 60 minutes after product use on day 1 and day 30. 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.
CEMA Measured at baseline, day 7, day 15, day 22, and day 29. 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).
Amount of Powder Extracted From P3P Used for PK Assessment. Before and after product use, on day 1 and day 30. Weight difference (mg) of P3P before and after use, to determine the amount of powder extracted from P3P.
NEQ Measured at baseline, day 7, day 15, day 22, and day 29. To measure percent changes from baseline in Nicotine equivalents (NEQ) concentrations, measured in spot urine and expressed as concentration adjusted for creatinine.
Sensory Parameters Within 60 minutes after product use on day 1 and day 30. 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).
Overall Product Use Recorded daily by subject, in product use diary, from day 1 until day 30. To assess the number of any nicotine/tobacco products used overall on a daily basis.
CYP2A6 Activity Measured before product use, on day 1 and day 30. 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.
Puffing Behavior of Subject 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. 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
Trial Locations
- Locations (1)
LLC Scientific Research Center Eco-Safety
🇷🇺St. Petersburg, Russian Federation