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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| P3P-1mg | Other | Subjects randomized to exclusive use of P3P-1mg |
|
| P3P-2mg | Other | Subjects randomized to exclusive use of P3P-2mg |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| P3P-1mg | Other | P3P-1mg (P3P product containing 1mg of nicotine.) |
| |
| 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. |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Christelle Haziza, PhD | Philip Morris Products SA | Study Chair |
| Vasilyuk V Bogdanovich, MD | LLC Scientific Research Center Eco-Safety | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| LLC Scientific Research Center Eco-Safety | Saint Petersburg | 196143 | Russia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30906527 | Background | Chrea C, Acquadro C, Afolalu EF, Spies E, Salzberger T, Abetz-Webb L, Cano S, Arnould B, Mainy N, Rose J, Weitkunat R. Developing fit-for-purpose self-report instruments for assessing consumer responses to tobacco and nicotine products: the ABOUT Toolbox initiative. F1000Res. 2018 Dec 2;7:1878. doi: 10.12688/f1000research.16810.1. eCollection 2018. |
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| ID | Title | Description |
|---|---|---|
| FG000 | P3P-1mg | Subjects randomized to exclusive use of P3P-1mg P3P-1mg: P3P-1mg (P3P product containing 1mg of nicotine.) |
| FG001 | P3P-2mg | Subjects randomized to exclusive use of P3P-2mg P3P-2mg: P3P-2mg (P3P product containing 2mg of nicotine.) |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | P3P-1mg | Subjects randomized to exclusive use of P3P-1mg P3P-1mg: P3P-1mg (P3P product containing 1mg of nicotine.) |
| BG001 | P3P-2mg | Subjects randomized to exclusive use of P3P-2mg P3P-2mg: P3P-2mg (P3P product containing 2mg of nicotine.) |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Plasma Nicotine Concentration-time Profile | To measure the plasma nicotine concentration-time profile following correction of baseline nicotine levels. | Some participants were excluded from analysis for protocol deviations. For participants in whom the elimination rate constant could not be calculated for any of the visits, background-corrected nicotine concentrations were considered as missing. | Posted | Geometric Mean | 95% Confidence Interval | ng/ml | Derived from multiple blood sampling pre- and post-product use (over 4 hours post-product use), on day 1 and day 30. |
|
Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a total study duration of up to 45 days for each subject.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | P3P-1mg | Subjects randomized to exclusive use of P3P-1mg P3P-1mg: P3P-1mg (P3P product containing 1mg of nicotine.) |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Blood Bilirubin Increased | Investigations | MedDRA (22.0) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Christelle Haziza | Philip Morris Products S.A. | +41 58 242 11 11 | ClinicalTrials.PMI@pmi.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 12, 2019 | Sep 24, 2020 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 24, 2019 | Sep 24, 2020 | SAP_001.pdf |
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A randomized, double-blinded, 2-arm parallel groups, single center study
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Neither the site staff nor the subject will be informed about the product variant the subjects have been randomized to.
| P3P-2mg |
| Other |
P3P-2mg (P3P product containing 2mg of nicotine.) |
|
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.
| 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. |
| BG002 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Height | Mean | Standard Deviation | cm |
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| BMI | Mean | Standard Deviation | kg/m^2 |
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Subjects randomized to exclusive use of P3P-2mg P3P-2mg: P3P-2mg (P3P product containing 2mg of nicotine.) |
|
|
| Primary | Maximum Nicotine Concentration [cCmax] | To measure the maximum plasma nicotine concentration [cCmax] following correction of baseline nicotine levels. | Posted | Geometric Mean | 95% Confidence Interval | ng/mL | Derived from multiple blood sampling pre- and post-product use (over 4 hours post-product use), on day 1 and day 30. |
|
|
|
| Primary | Time to the Maximum Nicotine Concentration [cTmax] | To measure the time to maximum nicotine concentration [cTmax] following correction of baseline nicotine levels. | Posted | Median | 95% Confidence Interval | minutes | Derived from multiple blood sampling pre- and post-product use (over 4 hours post-product use), on day 1 and day 30. |
|
|
|
| Primary | 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. | Some participants were excluded from analysis for protocol deviations. For participants in whom the elimination rate constant could not be calculated for any of the visits, background-corrected nicotine concentrations were considered as missing. | Posted | Geometric Mean | 95% Confidence Interval | ng*hour/mL | Derived from multiple blood sampling pre- and post-product use (over 4 hours post-product use), on day 1 and day 30. |
|
|
|
| Secondary | 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. | Posted | Mean | 95% Confidence Interval | score on a scale (millimetres*hour) | Before, during and up to 4 hours post-product use on day 1 and day 30 |
|
|
|
| Secondary | 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). | Posted | Mean | 95% Confidence Interval | score on a scale | Within 60 minutes after product use on day 1 and day 30. |
|
|
|
| Secondary | 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). | Posted | Mean | 95% Confidence Interval | score | Within 60 minutes after product use on day 1 and day 30. |
|
|
|
| Secondary | 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). | Posted | Mean | 95% Confidence Interval | score | Within 60 minutes after product use on day 1 and day 30. |
|
|
|
| Secondary | 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. | Posted | Mean | 95% Confidence Interval | score on a scale | Within 60 minutes after product use on day 1 and day 30. |
|
|
|
| Secondary | Puffing Behavior of Subject | To measure changes in subject puffing behavior. Evaluated by selection of one puffing behavior response out of three possible responses.
| Posted | Count of Participants | Participants | 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. |
|
|
|
| Secondary | Overall Product Use | To assess the number of any nicotine/tobacco products used overall on a daily basis. | Posted | Mean | 95% Confidence Interval | products used per day | Recorded daily by subject, in product use diary, from day 1 until day 30. |
|
|
|
| Secondary | NEQ | To measure percent changes from baseline in Nicotine equivalents (NEQ) concentrations, measured in spot urine and expressed as concentration adjusted for creatinine. | Some participants were excluded from analysis for protocol deviations. | Posted | Geometric Mean | 95% Confidence Interval | Percent change from baseline | Measured at baseline, day 7, day 15, day 22, and day 29. |
|
|
|
| Secondary | 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. | Some participants were excluded from analysis for protocol deviations. | Posted | Geometric Mean | 95% Confidence Interval | Percent change from baseline | Measured at baseline, day 7, day 15, day 22, and day 29. |
|
|
|
| Secondary | 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). | Some participants were excluded from analysis for protocol deviations. | Posted | Geometric Mean | 95% Confidence Interval | Percent change from baseline | Measured at baseline, day 7, day 15, day 22, and day 29. |
|
|
|
| Secondary | 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. | Posted | Geometric Mean | 95% Confidence Interval | Percent change from baseline | Measured before product use, on day 1 and day 30. |
|
|
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| Secondary | 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. | Posted | Mean | 95% Confidence Interval | mg | Before and after product use, on day 1 and day 30. |
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| 0 |
| 30 |
| 0 |
| 30 |
| 7 |
| 30 |
| EG001 | P3P-2mg | Subjects randomized to exclusive use of P3P-2mg P3P-2mg: P3P-2mg (P3P product containing 2mg of nicotine.) | 0 | 30 | 0 | 30 | 5 | 30 |
| Headache | Nervous system disorders | MedDRA (22.0) | Non-systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (22.0) | Non-systematic Assessment |
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| Throat Irritation | Respiratory, thoracic and mediastinal disorders | MedDRA (22.0) | Non-systematic Assessment |
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We confirm we have the contractual provisions in place which specify that in no event will the study site be allowed to disclose to any third party (or publicly release) any information obtained through the study without the CRO's prior written consent which in turn cannot provide such consent without Sponsor's approval unless such publication is made to satisfy regulatory requirements.
The Intellectual Property rights and research results from the present study belong to the Sponsor.
| Puffs Similar to Own Brand (day 1) |
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| Puffs Strength on Tongue (day 1) |
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| Puffs Strength in Nose (day 1) |
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| Puffs Strength in Back of Mouth/Throat (day 1) |
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| Puff Strength in Windpipe (day 1) |
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| Puff Strength in Chest (day 1) |
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| Puffs Evaluation/Liking (day 30) |
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| Puffs Harshness (day 30) |
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| Puffs Similar to Own Brand (day 30) |
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| Puffs Strength on Tongue (day 30) |
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| Puffs Strength in Nose (day 30) |
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| Puffs Strength in Back of Mouth/Throat (day 30) |
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| Puff Strength in Windpipe (day 30) |
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| Puff Strength in Chest (day 30) |
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| Craving reduction (day 1) |
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| Craving reduction (day 30) |
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| Psychological reward (day 1) |
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| Psychological reward (day 30) |
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| Enjoyment of respiratory tract sensations (day 1) |
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| Enjoyment of respiratory tract sensations (day 30) |
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| Product satisfaction (day 1) |
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| Product satisfaction (day 30) |
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| Signs and symptoms (day 1) |
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| Signs and symptoms (day 30) |
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| Behavioral impact (day 1) |
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| Behavioral impact (day 30) |
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| Taste intensity (day 1) |
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| Taste intensity (day 30) |
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| Consistency of sensation (day 1) |
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| Consistency of sensation (day 30) |
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| Compared to pipe (day 1) |
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| Compared to pipe (day 30) |
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| Compared to hookah (day 1) |
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| Compared to hookah (day 30) |
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| Compared to heat-not-burn (day 1) |
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| Compared to heat-not-burn (day 30) |
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| Compared to e-cigarette (day 1) |
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| Compared to e-cigarette (day 30) |
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| Compared to snuff/chewing tobacco (day 1) |
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| Compared to snuff/chewing tobacco (day 30) |
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| Compared to NRT (day 1) |
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| Compared to NRT (day 30) |
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| Day 2: Behavior #3 |
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| Day 29: Behavior #1 |
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| Day 29: Behavior #2 |
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| Day 29: Behavior #3 |
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| Heat not burn and/or smokeless tobacco |
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| Other tobacco products |
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| Electronic cigarettes |
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| Day 22 |
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| Day 29 |
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| Day 22 |
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| Day 29 |
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| Day 22 |
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| Day 29 |
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