Pharmacokinetics
Conditions
Keywords
Nicotine
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.
Interventions
OTHERP3P-1mg
P3P-1mg (P3P product containing 1mg of nicotine.)
OTHERP3P-2mg
P3P-2mg (P3P product containing 2mg of nicotine.)
Sponsors
Philip Morris Products S.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Masking description
Neither the site staff nor the subject will be informed about the product variant the subjects have been randomized to.
Intervention model description
A randomized, double-blinded, 2-arm parallel groups, single center study
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 |
| 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. |
| 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. |
| 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. |
| 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). |
| 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. |
| 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. |
| 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. |
| 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). |
| 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 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). |
Countries
Russia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| P3P-1mg Subjects randomized to exclusive use of P3P-1mg
P3P-1mg: P3P-1mg (P3P product containing 1mg of nicotine.) | 30 |
| P3P-2mg Subjects randomized to exclusive use of P3P-2mg
P3P-2mg: P3P-2mg (P3P product containing 2mg of nicotine.) | 30 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | P3P-1mg | P3P-2mg | Total |
|---|---|---|---|
| Age, Continuous | 26.3 years STANDARD_DEVIATION 4.82 | 30.0 years STANDARD_DEVIATION 8.36 | 28.2 years STANDARD_DEVIATION 7.02 |
| BMI | 23.3 kg/m^2 STANDARD_DEVIATION 3.69 | 24.0 kg/m^2 STANDARD_DEVIATION 3.48 | 23.7 kg/m^2 STANDARD_DEVIATION 3.58 |
| Height | 174 cm STANDARD_DEVIATION 9.49 | 172 cm STANDARD_DEVIATION 12.5 | 173 cm STANDARD_DEVIATION 11 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 30 Participants | 30 Participants | 60 Participants |
| Sex: Female, Male Female | 13 Participants | 13 Participants | 26 Participants |
| Sex: Female, Male Male | 17 Participants | 17 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 30 |
| other Total, other adverse events | 7 / 30 | 5 / 30 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 |
Outcome results
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.
Time frame: Derived from multiple blood sampling pre- and post-product use (over 4 hours post-product use), on day 1 and day 30.
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| P3P-1mg | Area Under the Concentration-time Curve From Start of Product Use (T0) to 4 Hours [cAUC(0-4h)] | Day 1 | 3.03 ng*hour/mL |
| P3P-1mg | Area Under the Concentration-time Curve From Start of Product Use (T0) to 4 Hours [cAUC(0-4h)] | Day 30 | 3.96 ng*hour/mL |
| P3P-2mg | Area Under the Concentration-time Curve From Start of Product Use (T0) to 4 Hours [cAUC(0-4h)] | Day 1 | 4.74 ng*hour/mL |
| P3P-2mg | Area Under the Concentration-time Curve From Start of Product Use (T0) to 4 Hours [cAUC(0-4h)] | Day 30 | 5.35 ng*hour/mL |
Primary
Maximum Nicotine Concentration [cCmax]
To measure the maximum plasma nicotine concentration \[cCmax\] following correction of baseline nicotine levels.
Time frame: Derived from multiple blood sampling pre- and post-product use (over 4 hours post-product use), on day 1 and day 30.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| P3P-1mg | Maximum Nicotine Concentration [cCmax] | Day 1 | 1.46 ng/mL |
| P3P-1mg | Maximum Nicotine Concentration [cCmax] | Day 30 | 2.05 ng/mL |
| P3P-2mg | Maximum Nicotine Concentration [cCmax] | Day 1 | 2.11 ng/mL |
| P3P-2mg | Maximum Nicotine Concentration [cCmax] | Day 30 | 2.39 ng/mL |
Primary
Plasma Nicotine Concentration-time Profile
To measure the plasma nicotine concentration-time profile following correction of baseline nicotine levels.
Time frame: Derived from multiple blood sampling pre- and post-product use (over 4 hours post-product use), on day 1 and day 30.
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| P3P-1mg | Plasma Nicotine Concentration-time Profile | 4 mins after start of product use (Day 1) | 0.563 ng/ml |
| P3P-1mg | Plasma Nicotine Concentration-time Profile | 7 mins after start of product use (Day 1) | 0.928 ng/ml |
| P3P-1mg | Plasma Nicotine Concentration-time Profile | 10 mins after start of product use (Day 1) | 0.982 ng/ml |
| P3P-1mg | Plasma Nicotine Concentration-time Profile | 15 mins after start of product use (Day 1) | 1.18 ng/ml |
| P3P-1mg | Plasma Nicotine Concentration-time Profile | 30 mins after start of product use (Day 1) | 1.24 ng/ml |
| P3P-1mg | Plasma Nicotine Concentration-time Profile | 1 hr after start of product use (Day 1) | 1.07 ng/ml |
| P3P-1mg | Plasma Nicotine Concentration-time Profile | 2 hr after start of product use (Day 1) | 0.702 ng/ml |
| P3P-1mg | Plasma Nicotine Concentration-time Profile | 4 hr after start of product use (Day 1) | 0.353 ng/ml |
| P3P-1mg | Plasma Nicotine Concentration-time Profile | 4 mins after start of product use (Day 30) | 1.01 ng/ml |
| P3P-1mg | Plasma Nicotine Concentration-time Profile | 7 mins after start of product use (Day 30) | 1.28 ng/ml |
| P3P-1mg | Plasma Nicotine Concentration-time Profile | 10 mins after start of product use (Day 30) | 1.46 ng/ml |
| P3P-1mg | Plasma Nicotine Concentration-time Profile | 15 mins after start of product use (Day 30) | 1.45 ng/ml |
| P3P-1mg | Plasma Nicotine Concentration-time Profile | 30 mins after start of product use (Day 30) | 1.29 ng/ml |
| P3P-1mg | Plasma Nicotine Concentration-time Profile | 1 hr after start of product use (Day 30) | 1.16 ng/ml |
| P3P-1mg | Plasma Nicotine Concentration-time Profile | 2 hr after start of product use (Day 30) | 0.927 ng/ml |
| P3P-1mg | Plasma Nicotine Concentration-time Profile | 4 hr after start of product use (Day 30) | 0.530 ng/ml |
| P3P-2mg | Plasma Nicotine Concentration-time Profile | 4 hr after start of product use (Day 30) | 0.551 ng/ml |
| P3P-2mg | Plasma Nicotine Concentration-time Profile | 4 mins after start of product use (Day 1) | 0.563 ng/ml |
| P3P-2mg | Plasma Nicotine Concentration-time Profile | 4 mins after start of product use (Day 30) | 0.990 ng/ml |
| P3P-2mg | Plasma Nicotine Concentration-time Profile | 7 mins after start of product use (Day 1) | 1.02 ng/ml |
| P3P-2mg | Plasma Nicotine Concentration-time Profile | 30 mins after start of product use (Day 30) | 1.76 ng/ml |
| P3P-2mg | Plasma Nicotine Concentration-time Profile | 10 mins after start of product use (Day 1) | 1.39 ng/ml |
| P3P-2mg | Plasma Nicotine Concentration-time Profile | 7 mins after start of product use (Day 30) | 1.34 ng/ml |
| P3P-2mg | Plasma Nicotine Concentration-time Profile | 15 mins after start of product use (Day 1) | 1.58 ng/ml |
| P3P-2mg | Plasma Nicotine Concentration-time Profile | 2 hr after start of product use (Day 30) | 1.16 ng/ml |
| P3P-2mg | Plasma Nicotine Concentration-time Profile | 30 mins after start of product use (Day 1) | 1.59 ng/ml |
| P3P-2mg | Plasma Nicotine Concentration-time Profile | 10 mins after start of product use (Day 30) | 1.62 ng/ml |
| P3P-2mg | Plasma Nicotine Concentration-time Profile | 1 hr after start of product use (Day 1) | 1.45 ng/ml |
| P3P-2mg | Plasma Nicotine Concentration-time Profile | 1 hr after start of product use (Day 30) | 1.71 ng/ml |
| P3P-2mg | Plasma Nicotine Concentration-time Profile | 2 hr after start of product use (Day 1) | 1.08 ng/ml |
| P3P-2mg | Plasma Nicotine Concentration-time Profile | 15 mins after start of product use (Day 30) | 1.67 ng/ml |
| P3P-2mg | Plasma Nicotine Concentration-time Profile | 4 hr after start of product use (Day 1) | 0.570 ng/ml |
Primary
Time to the Maximum Nicotine Concentration [cTmax]
To measure the time to maximum nicotine concentration \[cTmax\] following correction of baseline nicotine levels.
Time frame: Derived from multiple blood sampling pre- and post-product use (over 4 hours post-product use), on day 1 and day 30.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| P3P-1mg | Time to the Maximum Nicotine Concentration [cTmax] | Day 1 | 30.0 minutes |
| P3P-1mg | Time to the Maximum Nicotine Concentration [cTmax] | Day 30 | 15.0 minutes |
| P3P-2mg | Time to the Maximum Nicotine Concentration [cTmax] | Day 1 | 30.0 minutes |
| P3P-2mg | Time to the Maximum Nicotine Concentration [cTmax] | Day 30 | 30.0 minutes |
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.
Time frame: Before and after product use, on day 1 and day 30.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| P3P-1mg | Amount of Powder Extracted From P3P Used for PK Assessment. | Day 1 | 24.1 mg |
| P3P-1mg | Amount of Powder Extracted From P3P Used for PK Assessment. | Day 30 | 28.9 mg |
| P3P-2mg | Amount of Powder Extracted From P3P Used for PK Assessment. | Day 30 | 24.2 mg |
| P3P-2mg | Amount of Powder Extracted From P3P Used for PK Assessment. | Day 1 | 22.4 mg |
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).
Time frame: Measured at baseline, day 7, day 15, day 22, and day 29.
Population: Some participants were excluded from analysis for protocol deviations.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| P3P-1mg | CEMA | Day 7 | -41.1 Percent change from baseline |
| P3P-1mg | CEMA | Day 15 | -38.5 Percent change from baseline |
| P3P-1mg | CEMA | Day 22 | -18.9 Percent change from baseline |
| P3P-1mg | CEMA | Day 29 | -28.3 Percent change from baseline |
| P3P-2mg | CEMA | Day 29 | -30.8 Percent change from baseline |
| P3P-2mg | CEMA | Day 7 | -27.3 Percent change from baseline |
| P3P-2mg | CEMA | Day 22 | -23.6 Percent change from baseline |
| P3P-2mg | CEMA | Day 15 | -26.0 Percent change from baseline |
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.
Time frame: Before, during and up to 4 hours post-product use on day 1 and day 30
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| P3P-1mg | Craving for a Cigarette | Day 1 | 138 score on a scale (millimetres*hour) |
| P3P-1mg | Craving for a Cigarette | Day 30 | 130 score on a scale (millimetres*hour) |
| P3P-2mg | Craving for a Cigarette | Day 1 | 111 score on a scale (millimetres*hour) |
| P3P-2mg | Craving for a Cigarette | Day 30 | 109 score on a scale (millimetres*hour) |
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.
Time frame: Measured before product use, on day 1 and day 30.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| P3P-1mg | CYP2A6 Activity | 15.5 Percent change from baseline |
| P3P-2mg | CYP2A6 Activity | 3.19 Percent change from baseline |
Secondary
NEQ
To measure percent changes from baseline in Nicotine equivalents (NEQ) concentrations, measured in spot urine and expressed as concentration adjusted for creatinine.
Time frame: Measured at baseline, day 7, day 15, day 22, and day 29.
Population: Some participants were excluded from analysis for protocol deviations.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| P3P-1mg | NEQ | Day 7 | 20.3 Percent change from baseline |
| P3P-1mg | NEQ | Day 15 | 44.6 Percent change from baseline |
| P3P-1mg | NEQ | Day 22 | 41.7 Percent change from baseline |
| P3P-1mg | NEQ | Day 29 | 26.4 Percent change from baseline |
| P3P-2mg | NEQ | Day 29 | 22.9 Percent change from baseline |
| P3P-2mg | NEQ | Day 7 | 30.1 Percent change from baseline |
| P3P-2mg | NEQ | Day 22 | 18.8 Percent change from baseline |
| P3P-2mg | NEQ | Day 15 | 30.4 Percent change from baseline |
Secondary
Overall Product Use
To assess the number of any nicotine/tobacco products used overall on a daily basis.
Time frame: Recorded daily by subject, in product use diary, from day 1 until day 30.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| P3P-1mg | Overall Product Use | Cigarettes | 2.64 products used per day |
| P3P-1mg | Overall Product Use | Other tobacco products | 0.02 products used per day |
| P3P-1mg | Overall Product Use | Heat not burn and/or smokeless tobacco | 0.26 products used per day |
| P3P-1mg | Overall Product Use | Electronic cigarettes | 0.00 products used per day |
| P3P-1mg | Overall Product Use | P3P | 6.54 products used per day |
| P3P-2mg | Overall Product Use | Electronic cigarettes | 0.02 products used per day |
| P3P-2mg | Overall Product Use | P3P | 6.37 products used per day |
| P3P-2mg | Overall Product Use | Cigarettes | 2.68 products used per day |
| P3P-2mg | Overall Product Use | Heat not burn and/or smokeless tobacco | 0.25 products used per day |
| P3P-2mg | Overall Product Use | Other tobacco products | 0.01 products used per day |
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.
Time frame: Within 60 minutes after product use on day 1 and day 30.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| P3P-1mg | Product Acceptance | Overall opinion about P3P (day 1) | 3.63 score on a scale |
| P3P-1mg | Product Acceptance | Overall opinion about P3P (day 30) | 3.80 score on a scale |
| P3P-1mg | Product Acceptance | Taste intensity (day 1) | 5.27 score on a scale |
| P3P-1mg | Product Acceptance | Taste intensity (day 30) | 5.03 score on a scale |
| P3P-1mg | Product Acceptance | Consistency of sensation (day 1) | 4.23 score on a scale |
| P3P-1mg | Product Acceptance | Consistency of sensation (day 30) | 3.93 score on a scale |
| P3P-1mg | Product Acceptance | Compared to pipe (day 1) | 4.00 score on a scale |
| P3P-1mg | Product Acceptance | Compared to pipe (day 30) | 3.77 score on a scale |
| P3P-1mg | Product Acceptance | Compared to hookah (day 1) | 3.28 score on a scale |
| P3P-1mg | Product Acceptance | Compared to hookah (day 30) | 3.40 score on a scale |
| P3P-1mg | Product Acceptance | Compared to heat-not-burn (day 1) | 3.27 score on a scale |
| P3P-1mg | Product Acceptance | Compared to heat-not-burn (day 30) | 3.06 score on a scale |
| P3P-1mg | Product Acceptance | Compared to e-cigarette (day 1) | 4.17 score on a scale |
| P3P-1mg | Product Acceptance | Compared to e-cigarette (day 30) | 3.71 score on a scale |
| P3P-1mg | Product Acceptance | Compared to snuff/chewing tobacco (day 1) | 5.00 score on a scale |
| P3P-1mg | Product Acceptance | Compared to snuff/chewing tobacco (day 30) | 3.56 score on a scale |
| P3P-1mg | Product Acceptance | Compared to NRT (day 1) | 6.40 score on a scale |
| P3P-1mg | Product Acceptance | Compared to NRT (day 30) | 4.86 score on a scale |
| P3P-2mg | Product Acceptance | Compared to e-cigarette (day 30) | 3.07 score on a scale |
| P3P-2mg | Product Acceptance | Overall opinion about P3P (day 1) | 3.46 score on a scale |
| P3P-2mg | Product Acceptance | Compared to hookah (day 30) | 2.88 score on a scale |
| P3P-2mg | Product Acceptance | Overall opinion about P3P (day 30) | 3.61 score on a scale |
| P3P-2mg | Product Acceptance | Compared to NRT (day 30) | 4.20 score on a scale |
| P3P-2mg | Product Acceptance | Taste intensity (day 1) | 5.36 score on a scale |
| P3P-2mg | Product Acceptance | Compared to heat-not-burn (day 1) | 3.19 score on a scale |
| P3P-2mg | Product Acceptance | Taste intensity (day 30) | 5.25 score on a scale |
| P3P-2mg | Product Acceptance | Compared to snuff/chewing tobacco (day 1) | 5.00 score on a scale |
| P3P-2mg | Product Acceptance | Consistency of sensation (day 1) | 3.93 score on a scale |
| P3P-2mg | Product Acceptance | Compared to heat-not-burn (day 30) | 4.13 score on a scale |
| P3P-2mg | Product Acceptance | Consistency of sensation (day 30) | 4.29 score on a scale |
| P3P-2mg | Product Acceptance | Compared to NRT (day 1) | 5.67 score on a scale |
| P3P-2mg | Product Acceptance | Compared to pipe (day 1) | 3.25 score on a scale |
| P3P-2mg | Product Acceptance | Compared to e-cigarette (day 1) | 3.76 score on a scale |
| P3P-2mg | Product Acceptance | Compared to pipe (day 30) | 3.90 score on a scale |
| P3P-2mg | Product Acceptance | Compared to snuff/chewing tobacco (day 30) | 4.83 score on a scale |
| P3P-2mg | Product Acceptance | Compared to hookah (day 1) | 3.24 score on a scale |
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).
Time frame: Within 60 minutes after product use on day 1 and day 30.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| P3P-1mg | Product Dependence | Extent of use (day 1) | 57.9 score |
| P3P-1mg | Product Dependence | Extent of use (day 30) | 52.8 score |
| P3P-1mg | Product Dependence | Signs and symptoms (day 1) | 45.2 score |
| P3P-1mg | Product Dependence | Signs and symptoms (day 30) | 38.3 score |
| P3P-1mg | Product Dependence | Behavioral impact (day 1) | 32.3 score |
| P3P-1mg | Product Dependence | Behavioral impact (day 30) | 23.5 score |
| P3P-2mg | Product Dependence | Behavioral impact (day 1) | 35.7 score |
| P3P-2mg | Product Dependence | Extent of use (day 1) | 59.1 score |
| P3P-2mg | Product Dependence | Signs and symptoms (day 30) | 41.1 score |
| P3P-2mg | Product Dependence | Extent of use (day 30) | 53.0 score |
| P3P-2mg | Product Dependence | Behavioral impact (day 30) | 26.8 score |
| P3P-2mg | Product Dependence | Signs and symptoms (day 1) | 49.5 score |
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).
Time frame: Within 60 minutes after product use on day 1 and day 30.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| P3P-1mg | Product Experience | Aversion (day 1) | 1.25 score |
| P3P-1mg | Product Experience | Aversion (day 30) | 1.35 score |
| P3P-1mg | Product Experience | Craving reduction (day 1) | 4.23 score |
| P3P-1mg | Product Experience | Craving reduction (day 30) | 4.07 score |
| P3P-1mg | Product Experience | Psychological reward (day 1) | 3.00 score |
| P3P-1mg | Product Experience | Psychological reward (day 30) | 3.11 score |
| P3P-1mg | Product Experience | Enjoyment of respiratory tract sensations (day 1) | 2.13 score |
| P3P-1mg | Product Experience | Enjoyment of respiratory tract sensations (day 30) | 2.33 score |
| P3P-1mg | Product Experience | Product satisfaction (day 1) | 3.70 score |
| P3P-1mg | Product Experience | Product satisfaction (day 30) | 3.50 score |
| P3P-2mg | Product Experience | Enjoyment of respiratory tract sensations (day 30) | 2.29 score |
| P3P-2mg | Product Experience | Aversion (day 1) | 1.32 score |
| P3P-2mg | Product Experience | Psychological reward (day 30) | 2.93 score |
| P3P-2mg | Product Experience | Aversion (day 30) | 1.45 score |
| P3P-2mg | Product Experience | Product satisfaction (day 30) | 3.42 score |
| P3P-2mg | Product Experience | Craving reduction (day 1) | 4.04 score |
| P3P-2mg | Product Experience | Enjoyment of respiratory tract sensations (day 1) | 2.29 score |
| P3P-2mg | Product Experience | Craving reduction (day 30) | 4.14 score |
| P3P-2mg | Product Experience | Product satisfaction (day 1) | 3.62 score |
| P3P-2mg | Product Experience | Psychological reward (day 1) | 3.16 score |
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. * 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
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| P3P-1mg | Puffing Behavior of Subject | Day 2: Inhalation Behavior #1 | 18 Participants |
| P3P-1mg | Puffing Behavior of Subject | Day 2: Behavior #2 | 12 Participants |
| P3P-1mg | Puffing Behavior of Subject | Day 2: Behavior #3 | 0 Participants |
| P3P-1mg | Puffing Behavior of Subject | Day 29: Behavior #1 | 20 Participants |
| P3P-1mg | Puffing Behavior of Subject | Day 29: Behavior #2 | 10 Participants |
| P3P-1mg | Puffing Behavior of Subject | Day 29: Behavior #3 | 0 Participants |
| P3P-2mg | Puffing Behavior of Subject | Day 29: Behavior #2 | 7 Participants |
| P3P-2mg | Puffing Behavior of Subject | Day 2: Inhalation Behavior #1 | 17 Participants |
| P3P-2mg | Puffing Behavior of Subject | Day 29: Behavior #1 | 21 Participants |
| P3P-2mg | Puffing Behavior of Subject | Day 2: Behavior #2 | 11 Participants |
| P3P-2mg | Puffing Behavior of Subject | Day 29: Behavior #3 | 0 Participants |
| P3P-2mg | Puffing Behavior of Subject | Day 2: Behavior #3 | 0 Participants |
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).
Time frame: Within 60 minutes after product use on day 1 and day 30.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| P3P-1mg | Sensory Parameters | Puffs Evaluation/Liking (day 1) | 3.33 score on a scale |
| P3P-1mg | Sensory Parameters | Puffs Harshness (day 1) | 4.60 score on a scale |
| P3P-1mg | Sensory Parameters | Puffs Similar to Own Brand (day 1) | 2.33 score on a scale |
| P3P-1mg | Sensory Parameters | Puffs Strength on Tongue (day 1) | 3.00 score on a scale |
| P3P-1mg | Sensory Parameters | Puffs Strength in Nose (day 1) | 1.80 score on a scale |
| P3P-1mg | Sensory Parameters | Puffs Strength in Back of Mouth/Throat (day 1) | 4.83 score on a scale |
| P3P-1mg | Sensory Parameters | Puff Strength in Windpipe (day 1) | 4.50 score on a scale |
| P3P-1mg | Sensory Parameters | Puff Strength in Chest (day 1) | 3.40 score on a scale |
| P3P-1mg | Sensory Parameters | Puffs Evaluation/Liking (day 30) | 3.43 score on a scale |
| P3P-1mg | Sensory Parameters | Puffs Harshness (day 30) | 4.20 score on a scale |
| P3P-1mg | Sensory Parameters | Puffs Similar to Own Brand (day 30) | 2.93 score on a scale |
| P3P-1mg | Sensory Parameters | Puffs Strength on Tongue (day 30) | 2.83 score on a scale |
| P3P-1mg | Sensory Parameters | Puffs Strength in Nose (day 30) | 1.80 score on a scale |
| P3P-1mg | Sensory Parameters | Puffs Strength in Back of Mouth/Throat (day 30) | 4.87 score on a scale |
| P3P-1mg | Sensory Parameters | Puff Strength in Windpipe (day 30) | 4.20 score on a scale |
| P3P-1mg | Sensory Parameters | Puff Strength in Chest (day 30) | 3.53 score on a scale |
| P3P-2mg | Sensory Parameters | Puff Strength in Chest (day 30) | 4.07 score on a scale |
| P3P-2mg | Sensory Parameters | Puffs Evaluation/Liking (day 1) | 3.50 score on a scale |
| P3P-2mg | Sensory Parameters | Puffs Evaluation/Liking (day 30) | 3.46 score on a scale |
| P3P-2mg | Sensory Parameters | Puffs Harshness (day 1) | 5.18 score on a scale |
| P3P-2mg | Sensory Parameters | Puffs Strength in Nose (day 30) | 1.93 score on a scale |
| P3P-2mg | Sensory Parameters | Puffs Similar to Own Brand (day 1) | 3.04 score on a scale |
| P3P-2mg | Sensory Parameters | Puffs Harshness (day 30) | 4.68 score on a scale |
| P3P-2mg | Sensory Parameters | Puffs Strength on Tongue (day 1) | 3.57 score on a scale |
| P3P-2mg | Sensory Parameters | Puff Strength in Windpipe (day 30) | 4.93 score on a scale |
| P3P-2mg | Sensory Parameters | Puffs Strength in Nose (day 1) | 2.07 score on a scale |
| P3P-2mg | Sensory Parameters | Puffs Similar to Own Brand (day 30) | 2.64 score on a scale |
| P3P-2mg | Sensory Parameters | Puffs Strength in Back of Mouth/Throat (day 1) | 5.07 score on a scale |
| P3P-2mg | Sensory Parameters | Puffs Strength in Back of Mouth/Throat (day 30) | 4.86 score on a scale |
| P3P-2mg | Sensory Parameters | Puff Strength in Windpipe (day 1) | 4.89 score on a scale |
| P3P-2mg | Sensory Parameters | Puffs Strength on Tongue (day 30) | 3.36 score on a scale |
| P3P-2mg | Sensory Parameters | Puff Strength in Chest (day 1) | 3.86 score on a scale |
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.
Time frame: Measured at baseline, day 7, day 15, day 22, and day 29.
Population: Some participants were excluded from analysis for protocol deviations.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| P3P-1mg | Total NNAL | Day 7 | -7.07 Percent change from baseline |
| P3P-1mg | Total NNAL | Day 15 | -8.05 Percent change from baseline |
| P3P-1mg | Total NNAL | Day 22 | 14.3 Percent change from baseline |
| P3P-1mg | Total NNAL | Day 29 | -6.10 Percent change from baseline |
| P3P-2mg | Total NNAL | Day 29 | -11.8 Percent change from baseline |
| P3P-2mg | Total NNAL | Day 7 | -17.1 Percent change from baseline |
| P3P-2mg | Total NNAL | Day 22 | -14.4 Percent change from baseline |
| P3P-2mg | Total NNAL | Day 15 | -5.75 Percent change from baseline |