Nicotine Absorption, Vaping
Conditions
Keywords
Nicotine-containing product, Alternative to cigarettes
Brief summary
This is a single-center, open-label, concentration-ranging study to evaluate the nicotine PK profile and PD effects in healthy adult experienced users of closed tank/cartridge e-cigarettes using four different variants of P4M3 (nicotine concentration of 1.7%, 1.7% with 1.1% lactic acid \[LA\], 3% with 1.1% LA, and 4% with 2% LA) or their own e-cigarettes.
Detailed description
The goal of the study is to evaluate the nicotine concentration profiles and derived PK parameters, subjective effects, behavioral parameters, including puffing topography parameters of P4M3 with four different variants of P4M3, in experienced e-cigarette users after a single-use experience with fixed puffing regime and after ad libitum use of P4M3. Four variants of P4M3 will be evaluated together with subjects' own e-cigarettes to evaluate the relationship between the e-liquid composition (nicotine concentrations and presence of lactic acid) and the amount of nicotine absorbed, the speed of absorption, and the puffing topography.
Interventions
OTHERE-cigarette
Subject's own e-cigarette
OTHERP4M3-1.7%
P4M3 e-liquid concentration of 1.7% nicotine without lactic acid
OTHERP4M3-1.7%LA
P4M3 e-liquid concentration of 1.7% nicotine with lactic acid
OTHERP4M3-3%LA
P4M3 e-liquid concentration of 3% nicotine with lactic acid
OTHERP4M3-4%LA
P4M3 e-liquid concentration of 4% nicotine with lactic acid
Sponsors
Philip Morris Products S.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Masking description
This is an open-label study; however the site (except the pharmacy staff preparing the IPs for administration) will be masked to the randomization sequences until they are assigned. Subjects will not be informed of the complete sequence to which they have been assigned to receive the P4M3 products.
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Subject has signed the informed consent form (ICF) and is able to understand the information provided in the ICF. * Subject is 21 to 65 years of age, inclusive, at the Screening Visit. * Subject is a former daily cigarette smoker who smoked at least 100 cigarettes or more in his/her life and ceased smoking at least 3 months prior to the Screening Visit. * Subject has been using a commercially available, nicotine-containing closed tank/cartridge e-cigarette daily for at least 3 months prior to the Screening Visit. * Subject has a urine cotinine test ≥200 ng/mL at the Screening Visit and Admission.
Exclusion criteria
* Subject has a clinically relevant disease which requires medication which as per the judgment of the Investigator would jeopardize the safety of the subject. * Subject has abnormal renal function test result or subject with a creatinine clearance \<60 mL/minute at the Screening Visit, confirmed on repeat testing. * Subject has elevated liver function test results at the Screening Visit. * Subject has bilirubin \>1.5X ULN at the Screening Visit. * Subject has FEV1/FVC \<0.7 and FEV1 \<80% predicted value at post-bronchodilator spirometry at the Screening Visit. * Subject has asthma condition at the Screening Visit. * Subject has received medication within 14 days or within 5 half-lives of the drug (whichever is longer) prior to Admission, which has an impact on cytochrome P450 (CYP) 2A6 activity. * Subject has a carbon monoxide (CO) breath test ≥ 10 ppm at the Screening Visit or Admission. * Subject has a body mass index (BMI) \<18.5 kg/m2 or BMI ≥35 kg/m2 at the Screening Visit. * Subject has a positive serology test for human immunodeficiency virus (HIV) 1/2, hepatitis B, or hepatitis C at the Screening Visit. * Subject has clinically significant ECG findings at the Screening Visit. * Subject has participated in a clinical study within 3 months prior to the Screening Visit. * Subject smokes cigarettes or uses other tobacco products. * Female subject of childbearing potential who is pregnant or breastfeeding. * Female subject of childbearing potential who does not agree to use an acceptable method of effective contraception..
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Nicotine Concentration Versus Time Profile | From Day -1 (baseline) to Day 4 | To measure total and background-corrected plasma nicotine concentration versus time profiles from 60 minutes of ad libitum use. |
| Peak Plasma Nicotine Concentration [cCpeak] | From Day -1 (baseline) to Day 4 | To measure background-corrected peak plasma nicotine concentration \[cCpeak\] from 60 minutes of ad libitum use. |
| Time to Peak Plasma Nicotine Concentration [Tpeak] | From Day -1 (baseline) to Day 4 | To measure the time to peak plasma nicotine concentration \[tpeak\] from 60 minutes of ad libitum use. |
| Background-corrected Trough Plasma Nicotine Concentration [cCtrough] | From Day -1 (baseline) to Day 4 | To measure background-corrected trough plasma nicotine concentration \[cCtrough\] from 60 minutes of ad libitum use. |
| Background-corrected Average of Plasma Nicotine Concentration [cCaverage] | From Day -1 (baseline) to Day 4 | To measure background-corrected average of plasma nicotine concentration between 0 to 1 hour \[cCaverage\] from 60 minutes of ad libitum use. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve of Craving for an Electronic Cigarette | From Day -1 (baseline) to Day 4 | Measured on a Visual Analogue Scale (VAS) of 0 (no craving) to 100 (strong craving), before and after the fixed puffing regimen and ad libitum use period. (The VAS craving was measured from 0 to 100 on a 100 mm scale.) The data below present the Area under the VAS craving score-time curve from the start of product use to 4 hours. The area under the curve for VAS craving is an integrated measurement of the VAS craving taking into account several timepoints. AUC was calculated using a trapezoidal rule between timepoints without normalization. |
| Sensory Parameters (Fixed Puffing Regimen) | From Day 1 to Day 4 | Measured with a Sensory Questionnaire (SQ) within 60 minutes after each fixed puffing regimen use period. Response to each question is assessed on a 7-point scale, ranging from 1 (not at all) to 7 (extremely). |
| Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | From Day -1 (baseline) to Day 4 | To measure the total and background-corrected plasma nicotine concentration versus time profiles of the P4M3 variants and subjects' own e-cigarette from the fixed puffing regimen. |
| Human Puffing Topography (HPT) of the P4M3 Variants and the Subjects' Own E-cigarette | From Day -1 (baseline) to Day 4 | Total Puff Volume measured for the P4M3 variants and the subjects' own e-cigarette from the fixed puffing regimen and the 60 minutes ad libitum use. |
| Sensory Parameters (ad Libitum Use) | From Day 1 to Day 4 | Measured with a Sensory Questionnaire (SQ) within 60 minutes after each ad libitum use period. Response to each question is assessed on a 7-point scale, ranging from 1 (not at all) to 7 (extremely). |
| Background-corrected Maximum Plasma Concentration [cCmax] | From Day -1 (baseline) to Day 4 | To measure the background-corrected maximum plasma concentration \[cCmax\] of the P4M3 variants and subjects' own e-cigarette from the fixed puffing regimen. |
| Time to the Maximum Concentration [Tmax] | From Day -1 (baseline) to Day 4 | To measure the time to the maximum concentration \[tmax\] of the P4M3 variants and subjects' own e-cigarette from the fixed puffing regimen. |
| Background-corrected Area Under the Concentration-time Curve [cAUC(0-4h)] | From Day -1 (baseline) to Day 4 | To measure the background-corrected area under the concentration-time curve, which is above the corrected baseline from the start of product use to 4 hours \[cAUC(0-4h)\], of the P4M3 variants and subjects' own e-cigarette from the fixed puffing regimen. |
| Subjective Effects of P4M3 Use | From Day -1 (baseline) to Day 4 | Measured with an adapted version of the modified Cigarette Evaluation Questionnaire (adapted mCEQ) within 60 minutes after the ad libitum use session. Assessed on a 7-point scale, ranging from 1 (not at all) to 7 (extremely). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Product Exposure Sequence 1 Subjects will be randomized to follow a sequence of product exposure comprised of :
E-cigarette; P4M3-1.7%; P4M3-1.7%LA; P4M3-3%LA; and P4M3-4%LA
E-cigarette: Subject's own e-cigarette
P4M3-1.7%: P4M3 e-liquid concentration of 1.7% nicotine without lactic acid
P4M3-1.7%LA: P4M3 e-liquid concentration of 1.7% nicotine with lactic acid
P4M3-3%LA: P4M3 e-liquid concentration of 3% nicotine with lactic acid
P4M3-4%LA: P4M3 e-liquid concentration of 4% nicotine with lactic acid | 8 |
| Product Exposure Sequence 2 Subjects will be randomized to follow a sequence of product exposure comprised of :
E-cigarette; P4M3-1.7%LA; P4M3-1.7%; P4M3-3%LA; and P4M3-4%LA
E-cigarette: Subject's own e-cigarette
P4M3-1.7%: P4M3 e-liquid concentration of 1.7% nicotine without lactic acid
P4M3-1.7%LA: P4M3 e-liquid concentration of 1.7% nicotine with lactic acid
P4M3-3%LA: P4M3 e-liquid concentration of 3% nicotine with lactic acid
P4M3-4%LA: P4M3 e-liquid concentration of 4% nicotine with lactic acid | 7 |
| Total | 15 |
Baseline characteristics
| Characteristic | Product Exposure Sequence 1 | Product Exposure Sequence 2 | Total |
|---|---|---|---|
| Age, Continuous | 38.3 years | 42.0 years | 40.0 years |
| BMI (kg/m^2) | 26.361 kg/m^2 | 26.174 kg/m^2 | 26.274 kg/m^2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 7 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Height (cm) | 178.2 cm | 165.0 cm | 172.1 cm |
| 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 | 8 Participants | 7 Participants | 15 Participants |
| Sex: Female, Male Female | 1 Participants | 4 Participants | 5 Participants |
| Sex: Female, Male Male | 7 Participants | 3 Participants | 10 Participants |
| Weight (kg) | 83.95 kg | 70.41 kg | 77.63 kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 1 / 15 | 1 / 15 | 2 / 15 | 0 / 15 | 4 / 15 | 2 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 15 |
Outcome results
Primary
Background-corrected Average of Plasma Nicotine Concentration [cCaverage]
To measure background-corrected average of plasma nicotine concentration between 0 to 1 hour \[cCaverage\] from 60 minutes of ad libitum use.
Time frame: From Day -1 (baseline) to Day 4
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Subject's Own E-cigarette | Background-corrected Average of Plasma Nicotine Concentration [cCaverage] | 8.548 ng/mL | Geometric Coefficient of Variation 95.38 |
| P4M3-1.7% | Background-corrected Average of Plasma Nicotine Concentration [cCaverage] | 7.302 ng/mL | Geometric Coefficient of Variation 55.95 |
| P4M3-1.7%LA | Background-corrected Average of Plasma Nicotine Concentration [cCaverage] | 7.870 ng/mL | Geometric Coefficient of Variation 101.89 |
| P4M3-3%LA | Background-corrected Average of Plasma Nicotine Concentration [cCaverage] | 16.03 ng/mL | Geometric Coefficient of Variation 62.01 |
| P4M3-4%LA | Background-corrected Average of Plasma Nicotine Concentration [cCaverage] | 14.48 ng/mL | Geometric Coefficient of Variation 55.31 |
Primary
Background-corrected Trough Plasma Nicotine Concentration [cCtrough]
To measure background-corrected trough plasma nicotine concentration \[cCtrough\] from 60 minutes of ad libitum use.
Time frame: From Day -1 (baseline) to Day 4
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Subject's Own E-cigarette | Background-corrected Trough Plasma Nicotine Concentration [cCtrough] | 3.492 ng/mL | Geometric Coefficient of Variation 98.26 |
| P4M3-1.7% | Background-corrected Trough Plasma Nicotine Concentration [cCtrough] | 2.819 ng/mL | Geometric Coefficient of Variation 74.17 |
| P4M3-1.7%LA | Background-corrected Trough Plasma Nicotine Concentration [cCtrough] | 2.905 ng/mL | Geometric Coefficient of Variation 101.32 |
| P4M3-3%LA | Background-corrected Trough Plasma Nicotine Concentration [cCtrough] | 6.032 ng/mL | Geometric Coefficient of Variation 73.4 |
| P4M3-4%LA | Background-corrected Trough Plasma Nicotine Concentration [cCtrough] | 4.845 ng/mL | Geometric Coefficient of Variation 59.4 |
Primary
Peak Plasma Nicotine Concentration [cCpeak]
To measure background-corrected peak plasma nicotine concentration \[cCpeak\] from 60 minutes of ad libitum use.
Time frame: From Day -1 (baseline) to Day 4
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Subject's Own E-cigarette | Peak Plasma Nicotine Concentration [cCpeak] | 14.87 ng/mL | Geometric Coefficient of Variation 83.01 |
| P4M3-1.7% | Peak Plasma Nicotine Concentration [cCpeak] | 13.32 ng/mL | Geometric Coefficient of Variation 55.65 |
| P4M3-1.7%LA | Peak Plasma Nicotine Concentration [cCpeak] | 13.05 ng/mL | Geometric Coefficient of Variation 98.16 |
| P4M3-3%LA | Peak Plasma Nicotine Concentration [cCpeak] | 26.47 ng/mL | Geometric Coefficient of Variation 63.68 |
| P4M3-4%LA | Peak Plasma Nicotine Concentration [cCpeak] | 26.57 ng/mL | Geometric Coefficient of Variation 57.34 |
Primary
Plasma Nicotine Concentration Versus Time Profile
To measure total and background-corrected plasma nicotine concentration versus time profiles from 60 minutes of ad libitum use.
Time frame: From Day -1 (baseline) to Day 4
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Subject's Own E-cigarette | Plasma Nicotine Concentration Versus Time Profile | 10 mins | 4.546 ng/mL | Geometric Coefficient of Variation 99.52 |
| Subject's Own E-cigarette | Plasma Nicotine Concentration Versus Time Profile | 240 mins | 4.297 ng/mL | Geometric Coefficient of Variation 91.97 |
| Subject's Own E-cigarette | Plasma Nicotine Concentration Versus Time Profile | 120 mins | 8.809 ng/mL | Geometric Coefficient of Variation 90.18 |
| Subject's Own E-cigarette | Plasma Nicotine Concentration Versus Time Profile | 30 mins | 8.852 ng/mL | Geometric Coefficient of Variation 113.8 |
| Subject's Own E-cigarette | Plasma Nicotine Concentration Versus Time Profile | 20 mins | 7.235 ng/mL | Geometric Coefficient of Variation 103.89 |
| Subject's Own E-cigarette | Plasma Nicotine Concentration Versus Time Profile | 40 mins | 10.25 ng/mL | Geometric Coefficient of Variation 111.09 |
| Subject's Own E-cigarette | Plasma Nicotine Concentration Versus Time Profile | 60 mins | 14.46 ng/mL | Geometric Coefficient of Variation 80.78 |
| P4M3-1.7% | Plasma Nicotine Concentration Versus Time Profile | 60 mins | 13.24 ng/mL | Geometric Coefficient of Variation 55.46 |
| P4M3-1.7% | Plasma Nicotine Concentration Versus Time Profile | 40 mins | 9.338 ng/mL | Geometric Coefficient of Variation 61 |
| P4M3-1.7% | Plasma Nicotine Concentration Versus Time Profile | 20 mins | 5.237 ng/mL | Geometric Coefficient of Variation 65.2 |
| P4M3-1.7% | Plasma Nicotine Concentration Versus Time Profile | 10 mins | 3.165 ng/mL | Geometric Coefficient of Variation 77.27 |
| P4M3-1.7% | Plasma Nicotine Concentration Versus Time Profile | 120 mins | 9.356 ng/mL | Geometric Coefficient of Variation 69.35 |
| P4M3-1.7% | Plasma Nicotine Concentration Versus Time Profile | 30 mins | 7.808 ng/mL | Geometric Coefficient of Variation 62.57 |
| P4M3-1.7% | Plasma Nicotine Concentration Versus Time Profile | 240 mins | 4.524 ng/mL | Geometric Coefficient of Variation 76.68 |
| P4M3-1.7%LA | Plasma Nicotine Concentration Versus Time Profile | 40 mins | 9.852 ng/mL | Geometric Coefficient of Variation 99.6 |
| P4M3-1.7%LA | Plasma Nicotine Concentration Versus Time Profile | 10 mins | 4.167 ng/mL | Geometric Coefficient of Variation 119.38 |
| P4M3-1.7%LA | Plasma Nicotine Concentration Versus Time Profile | 20 mins | 6.990 ng/mL | Geometric Coefficient of Variation 121.67 |
| P4M3-1.7%LA | Plasma Nicotine Concentration Versus Time Profile | 30 mins | 8.165 ng/mL | Geometric Coefficient of Variation 111.02 |
| P4M3-1.7%LA | Plasma Nicotine Concentration Versus Time Profile | 60 mins | 12.64 ng/mL | Geometric Coefficient of Variation 96.63 |
| P4M3-1.7%LA | Plasma Nicotine Concentration Versus Time Profile | 120 mins | 7.157 ng/mL | Geometric Coefficient of Variation 102.04 |
| P4M3-1.7%LA | Plasma Nicotine Concentration Versus Time Profile | 240 mins | 3.311 ng/mL | Geometric Coefficient of Variation 91.7 |
| P4M3-3%LA | Plasma Nicotine Concentration Versus Time Profile | 30 mins | 17.85 ng/mL | Geometric Coefficient of Variation 66.05 |
| P4M3-3%LA | Plasma Nicotine Concentration Versus Time Profile | 60 mins | 25.53 ng/mL | Geometric Coefficient of Variation 62.65 |
| P4M3-3%LA | Plasma Nicotine Concentration Versus Time Profile | 20 mins | 11.92 ng/mL | Geometric Coefficient of Variation 65.52 |
| P4M3-3%LA | Plasma Nicotine Concentration Versus Time Profile | 240 mins | 7.490 ng/mL | Geometric Coefficient of Variation 53.81 |
| P4M3-3%LA | Plasma Nicotine Concentration Versus Time Profile | 120 mins | 15.52 ng/mL | Geometric Coefficient of Variation 52.34 |
| P4M3-3%LA | Plasma Nicotine Concentration Versus Time Profile | 10 mins | 7.518 ng/mL | Geometric Coefficient of Variation 93.39 |
| P4M3-3%LA | Plasma Nicotine Concentration Versus Time Profile | 40 mins | 20.72 ng/mL | Geometric Coefficient of Variation 63.01 |
| P4M3-4%LA | Plasma Nicotine Concentration Versus Time Profile | 30 mins | 14.65 ng/mL | Geometric Coefficient of Variation 60.02 |
| P4M3-4%LA | Plasma Nicotine Concentration Versus Time Profile | 240 mins | 5.681 ng/mL | Geometric Coefficient of Variation 45.33 |
| P4M3-4%LA | Plasma Nicotine Concentration Versus Time Profile | 120 mins | 12.76 ng/mL | Geometric Coefficient of Variation 50.27 |
| P4M3-4%LA | Plasma Nicotine Concentration Versus Time Profile | 60 mins | 25.77 ng/mL | Geometric Coefficient of Variation 55.6 |
| P4M3-4%LA | Plasma Nicotine Concentration Versus Time Profile | 20 mins | 9.942 ng/mL | Geometric Coefficient of Variation 65.34 |
| P4M3-4%LA | Plasma Nicotine Concentration Versus Time Profile | 10 mins | 6.782 ng/mL | Geometric Coefficient of Variation 95.57 |
| P4M3-4%LA | Plasma Nicotine Concentration Versus Time Profile | 40 mins | 19.17 ng/mL | Geometric Coefficient of Variation 56.21 |
Primary
Time to Peak Plasma Nicotine Concentration [Tpeak]
To measure the time to peak plasma nicotine concentration \[tpeak\] from 60 minutes of ad libitum use.
Time frame: From Day -1 (baseline) to Day 4
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Subject's Own E-cigarette | Time to Peak Plasma Nicotine Concentration [Tpeak] | 60.000 minutes |
| P4M3-1.7% | Time to Peak Plasma Nicotine Concentration [Tpeak] | 60.000 minutes |
| P4M3-1.7%LA | Time to Peak Plasma Nicotine Concentration [Tpeak] | 60.000 minutes |
| P4M3-3%LA | Time to Peak Plasma Nicotine Concentration [Tpeak] | 60.000 minutes |
| P4M3-4%LA | Time to Peak Plasma Nicotine Concentration [Tpeak] | 60.000 minutes |
Secondary
Area Under the Curve of Craving for an Electronic Cigarette
Measured on a Visual Analogue Scale (VAS) of 0 (no craving) to 100 (strong craving), before and after the fixed puffing regimen and ad libitum use period. (The VAS craving was measured from 0 to 100 on a 100 mm scale.) The data below present the Area under the VAS craving score-time curve from the start of product use to 4 hours. The area under the curve for VAS craving is an integrated measurement of the VAS craving taking into account several timepoints. AUC was calculated using a trapezoidal rule between timepoints without normalization.
Time frame: From Day -1 (baseline) to Day 4
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Subject's Own E-cigarette | Area Under the Curve of Craving for an Electronic Cigarette | Fixed Puffing | 154.8 score*hr | Standard Deviation 120.9 |
| Subject's Own E-cigarette | Area Under the Curve of Craving for an Electronic Cigarette | Ad Libitum | 143.2 score*hr | Standard Deviation 87.05 |
| P4M3-1.7% | Area Under the Curve of Craving for an Electronic Cigarette | Fixed Puffing | 134.4 score*hr | Standard Deviation 117.02 |
| P4M3-1.7% | Area Under the Curve of Craving for an Electronic Cigarette | Ad Libitum | 117.9 score*hr | Standard Deviation 84.65 |
| P4M3-1.7%LA | Area Under the Curve of Craving for an Electronic Cigarette | Fixed Puffing | 135.5 score*hr | Standard Deviation 120.61 |
| P4M3-1.7%LA | Area Under the Curve of Craving for an Electronic Cigarette | Ad Libitum | 119.5 score*hr | Standard Deviation 100.03 |
| P4M3-3%LA | Area Under the Curve of Craving for an Electronic Cigarette | Ad Libitum | 108.0 score*hr | Standard Deviation 89.93 |
| P4M3-3%LA | Area Under the Curve of Craving for an Electronic Cigarette | Fixed Puffing | 141.8 score*hr | Standard Deviation 105.87 |
| P4M3-4%LA | Area Under the Curve of Craving for an Electronic Cigarette | Fixed Puffing | 124.9 score*hr | Standard Deviation 106.8 |
| P4M3-4%LA | Area Under the Curve of Craving for an Electronic Cigarette | Ad Libitum | 96.9 score*hr | Standard Deviation 90.26 |
Secondary
Background-corrected Area Under the Concentration-time Curve [cAUC(0-4h)]
To measure the background-corrected area under the concentration-time curve, which is above the corrected baseline from the start of product use to 4 hours \[cAUC(0-4h)\], of the P4M3 variants and subjects' own e-cigarette from the fixed puffing regimen.
Time frame: From Day -1 (baseline) to Day 4
Population: Values below the Lower Limit of Quantification were set to missing.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Subject's Own E-cigarette | Background-corrected Area Under the Concentration-time Curve [cAUC(0-4h)] | Fixed Regimen | 7.796 ng*h/mL | Geometric Coefficient of Variation 81.19 |
| Subject's Own E-cigarette | Background-corrected Area Under the Concentration-time Curve [cAUC(0-4h)] | Ad libitum | 33.77 ng*h/mL | Geometric Coefficient of Variation 86.94 |
| P4M3-1.7% | Background-corrected Area Under the Concentration-time Curve [cAUC(0-4h)] | Fixed Regimen | 6.969 ng*h/mL | Geometric Coefficient of Variation 50.19 |
| P4M3-1.7% | Background-corrected Area Under the Concentration-time Curve [cAUC(0-4h)] | Ad libitum | 33.03 ng*h/mL | Geometric Coefficient of Variation 61.44 |
| P4M3-1.7%LA | Background-corrected Area Under the Concentration-time Curve [cAUC(0-4h)] | Fixed Regimen | 7.679 ng*h/mL | Geometric Coefficient of Variation 66.36 |
| P4M3-1.7%LA | Background-corrected Area Under the Concentration-time Curve [cAUC(0-4h)] | Ad libitum | 28.64 ng*h/mL | Geometric Coefficient of Variation 96.87 |
| P4M3-3%LA | Background-corrected Area Under the Concentration-time Curve [cAUC(0-4h)] | Ad libitum | 60.21 ng*h/mL | Geometric Coefficient of Variation 55.29 |
| P4M3-3%LA | Background-corrected Area Under the Concentration-time Curve [cAUC(0-4h)] | Fixed Regimen | 11.55 ng*h/mL | Geometric Coefficient of Variation 56 |
| P4M3-4%LA | Background-corrected Area Under the Concentration-time Curve [cAUC(0-4h)] | Fixed Regimen | 13.570 ng*h/mL | Geometric Coefficient of Variation 67.1 |
| P4M3-4%LA | Background-corrected Area Under the Concentration-time Curve [cAUC(0-4h)] | Ad libitum | 52.79 ng*h/mL | Geometric Coefficient of Variation 50.19 |
Secondary
Background-corrected Maximum Plasma Concentration [cCmax]
To measure the background-corrected maximum plasma concentration \[cCmax\] of the P4M3 variants and subjects' own e-cigarette from the fixed puffing regimen.
Time frame: From Day -1 (baseline) to Day 4
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Subject's Own E-cigarette | Background-corrected Maximum Plasma Concentration [cCmax] | 5.402 ng/mL | Geometric Coefficient of Variation 78.06 |
| P4M3-1.7% | Background-corrected Maximum Plasma Concentration [cCmax] | 5.074 ng/mL | Geometric Coefficient of Variation 77.64 |
| P4M3-1.7%LA | Background-corrected Maximum Plasma Concentration [cCmax] | 6.735 ng/mL | Geometric Coefficient of Variation 83.39 |
| P4M3-3%LA | Background-corrected Maximum Plasma Concentration [cCmax] | 9.437 ng/mL | Geometric Coefficient of Variation 63.11 |
| P4M3-4%LA | Background-corrected Maximum Plasma Concentration [cCmax] | 11.990 ng/mL | Geometric Coefficient of Variation 78.62 |
Secondary
Human Puffing Topography (HPT) of the P4M3 Variants and the Subjects' Own E-cigarette
Total Puff Volume measured for the P4M3 variants and the subjects' own e-cigarette from the fixed puffing regimen and the 60 minutes ad libitum use.
Time frame: From Day -1 (baseline) to Day 4
Population: HPT raw data were reviewed for recording errors by personnel independent from the study and accepted or rejected prior to analysis. HPT data with the 'Rejected' status were excluded from the analysis. Consequently, the number of subjects analyzed differ from the overall number of subjects analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Subject's Own E-cigarette | Human Puffing Topography (HPT) of the P4M3 Variants and the Subjects' Own E-cigarette | Fixed Puffing | 1103.2913 mL (Total Puff Volume) |
| Subject's Own E-cigarette | Human Puffing Topography (HPT) of the P4M3 Variants and the Subjects' Own E-cigarette | Ad Libitum | 2054.8081 mL (Total Puff Volume) |
| P4M3-1.7% | Human Puffing Topography (HPT) of the P4M3 Variants and the Subjects' Own E-cigarette | Fixed Puffing | 1133.2255 mL (Total Puff Volume) |
| P4M3-1.7% | Human Puffing Topography (HPT) of the P4M3 Variants and the Subjects' Own E-cigarette | Ad Libitum | 2752.3456 mL (Total Puff Volume) |
| P4M3-1.7%LA | Human Puffing Topography (HPT) of the P4M3 Variants and the Subjects' Own E-cigarette | Fixed Puffing | 1235.2367 mL (Total Puff Volume) |
| P4M3-1.7%LA | Human Puffing Topography (HPT) of the P4M3 Variants and the Subjects' Own E-cigarette | Ad Libitum | 2945.8303 mL (Total Puff Volume) |
| P4M3-3%LA | Human Puffing Topography (HPT) of the P4M3 Variants and the Subjects' Own E-cigarette | Ad Libitum | 2601.0945 mL (Total Puff Volume) |
| P4M3-3%LA | Human Puffing Topography (HPT) of the P4M3 Variants and the Subjects' Own E-cigarette | Fixed Puffing | 1139.8381 mL (Total Puff Volume) |
| P4M3-4%LA | Human Puffing Topography (HPT) of the P4M3 Variants and the Subjects' Own E-cigarette | Fixed Puffing | 935.8970 mL (Total Puff Volume) |
| P4M3-4%LA | Human Puffing Topography (HPT) of the P4M3 Variants and the Subjects' Own E-cigarette | Ad Libitum | 1934.8479 mL (Total Puff Volume) |
Secondary
Sensory Parameters (ad Libitum Use)
Measured with a Sensory Questionnaire (SQ) within 60 minutes after each ad libitum use period. Response to each question is assessed on a 7-point scale, ranging from 1 (not at all) to 7 (extremely).
Time frame: From Day 1 to Day 4
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Subject's Own E-cigarette | Sensory Parameters (ad Libitum Use) | Strength of puffs on tongue? | 3.0 score on a scale | Standard Deviation 1.2 |
| Subject's Own E-cigarette | Sensory Parameters (ad Libitum Use) | How much did you like the puffs you took? | 4.7 score on a scale | Standard Deviation 1.23 |
| Subject's Own E-cigarette | Sensory Parameters (ad Libitum Use) | How harsh were the puffs you took? | 3.1 score on a scale | Standard Deviation 1.28 |
| Subject's Own E-cigarette | Sensory Parameters (ad Libitum Use) | How similar to your own brand were the puffs? | 3.8 score on a scale | Standard Deviation 2.05 |
| Subject's Own E-cigarette | Sensory Parameters (ad Libitum Use) | Strength of puffs in nose? | 2.1 score on a scale | Standard Deviation 1.04 |
| Subject's Own E-cigarette | Sensory Parameters (ad Libitum Use) | Strength of puffs in back of mouth & throat? | 3.5 score on a scale | Standard Deviation 0.92 |
| Subject's Own E-cigarette | Sensory Parameters (ad Libitum Use) | Strength of puffs in windpipe? | 3.5 score on a scale | Standard Deviation 1 |
| Subject's Own E-cigarette | Sensory Parameters (ad Libitum Use) | Strength puffs in chest? | 3.1 score on a scale | Standard Deviation 1.04 |
| P4M3-1.7% | Sensory Parameters (ad Libitum Use) | Strength of puffs on tongue? | 2.7 score on a scale | Standard Deviation 1.05 |
| P4M3-1.7% | Sensory Parameters (ad Libitum Use) | How much did you like the puffs you took? | 3.9 score on a scale | Standard Deviation 1.69 |
| P4M3-1.7% | Sensory Parameters (ad Libitum Use) | Strength puffs in chest? | 3.3 score on a scale | Standard Deviation 1.55 |
| P4M3-1.7% | Sensory Parameters (ad Libitum Use) | Strength of puffs in windpipe? | 3.9 score on a scale | Standard Deviation 1.63 |
| P4M3-1.7% | Sensory Parameters (ad Libitum Use) | How similar to your own brand were the puffs? | 2.2 score on a scale | Standard Deviation 1.09 |
| P4M3-1.7% | Sensory Parameters (ad Libitum Use) | How harsh were the puffs you took? | 3.9 score on a scale | Standard Deviation 1.44 |
| P4M3-1.7% | Sensory Parameters (ad Libitum Use) | Strength of puffs in back of mouth & throat? | 3.5 score on a scale | Standard Deviation 1.46 |
| P4M3-1.7% | Sensory Parameters (ad Libitum Use) | Strength of puffs in nose? | 2.0 score on a scale | Standard Deviation 0.93 |
| P4M3-1.7%LA | Sensory Parameters (ad Libitum Use) | How harsh were the puffs you took? | 3.3 score on a scale | Standard Deviation 1.45 |
| P4M3-1.7%LA | Sensory Parameters (ad Libitum Use) | How similar to your own brand were the puffs? | 2.1 score on a scale | Standard Deviation 1.34 |
| P4M3-1.7%LA | Sensory Parameters (ad Libitum Use) | Strength of puffs on tongue? | 2.5 score on a scale | Standard Deviation 1.07 |
| P4M3-1.7%LA | Sensory Parameters (ad Libitum Use) | Strength of puffs in nose? | 2.0 score on a scale | Standard Deviation 1.07 |
| P4M3-1.7%LA | Sensory Parameters (ad Libitum Use) | Strength puffs in chest? | 2.9 score on a scale | Standard Deviation 1.07 |
| P4M3-1.7%LA | Sensory Parameters (ad Libitum Use) | Strength of puffs in back of mouth & throat? | 2.7 score on a scale | Standard Deviation 1.17 |
| P4M3-1.7%LA | Sensory Parameters (ad Libitum Use) | Strength of puffs in windpipe? | 2.9 score on a scale | Standard Deviation 0.89 |
| P4M3-1.7%LA | Sensory Parameters (ad Libitum Use) | How much did you like the puffs you took? | 3.4 score on a scale | Standard Deviation 1.64 |
| P4M3-3%LA | Sensory Parameters (ad Libitum Use) | Strength of puffs in back of mouth & throat? | 3.4 score on a scale | Standard Deviation 1.25 |
| P4M3-3%LA | Sensory Parameters (ad Libitum Use) | Strength of puffs in windpipe? | 3.5 score on a scale | Standard Deviation 1.31 |
| P4M3-3%LA | Sensory Parameters (ad Libitum Use) | How similar to your own brand were the puffs? | 2.1 score on a scale | Standard Deviation 1.04 |
| P4M3-3%LA | Sensory Parameters (ad Libitum Use) | Strength puffs in chest? | 3.3 score on a scale | Standard Deviation 1.45 |
| P4M3-3%LA | Sensory Parameters (ad Libitum Use) | Strength of puffs on tongue? | 2.8 score on a scale | Standard Deviation 1.15 |
| P4M3-3%LA | Sensory Parameters (ad Libitum Use) | How much did you like the puffs you took? | 3.6 score on a scale | Standard Deviation 1.3 |
| P4M3-3%LA | Sensory Parameters (ad Libitum Use) | How harsh were the puffs you took? | 3.3 score on a scale | Standard Deviation 1.8 |
| P4M3-3%LA | Sensory Parameters (ad Libitum Use) | Strength of puffs in nose? | 2.1 score on a scale | Standard Deviation 0.89 |
| P4M3-4%LA | Sensory Parameters (ad Libitum Use) | Strength of puffs in windpipe? | 3.7 score on a scale | Standard Deviation 1.59 |
| P4M3-4%LA | Sensory Parameters (ad Libitum Use) | How much did you like the puffs you took? | 3.1 score on a scale | Standard Deviation 1.21 |
| P4M3-4%LA | Sensory Parameters (ad Libitum Use) | Strength of puffs in back of mouth & throat? | 3.7 score on a scale | Standard Deviation 1.59 |
| P4M3-4%LA | Sensory Parameters (ad Libitum Use) | Strength puffs in chest? | 3.2 score on a scale | Standard Deviation 1.58 |
| P4M3-4%LA | Sensory Parameters (ad Libitum Use) | Strength of puffs in nose? | 1.8 score on a scale | Standard Deviation 0.7 |
| P4M3-4%LA | Sensory Parameters (ad Libitum Use) | How harsh were the puffs you took? | 3.9 score on a scale | Standard Deviation 1.57 |
| P4M3-4%LA | Sensory Parameters (ad Libitum Use) | Strength of puffs on tongue? | 2.5 score on a scale | Standard Deviation 1.17 |
| P4M3-4%LA | Sensory Parameters (ad Libitum Use) | How similar to your own brand were the puffs? | 2.1 score on a scale | Standard Deviation 1 |
Secondary
Sensory Parameters (Fixed Puffing Regimen)
Measured with a Sensory Questionnaire (SQ) within 60 minutes after each fixed puffing regimen use period. Response to each question is assessed on a 7-point scale, ranging from 1 (not at all) to 7 (extremely).
Time frame: From Day 1 to Day 4
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Subject's Own E-cigarette | Sensory Parameters (Fixed Puffing Regimen) | Strength of puffs in nose? | 1.9 score on a scale | Standard Deviation 0.92 |
| Subject's Own E-cigarette | Sensory Parameters (Fixed Puffing Regimen) | Strength of puffs on tongue? | 2.5 score on a scale | Standard Deviation 1.13 |
| Subject's Own E-cigarette | Sensory Parameters (Fixed Puffing Regimen) | Strength puffs in chest? | 2.9 score on a scale | Standard Deviation 1.13 |
| Subject's Own E-cigarette | Sensory Parameters (Fixed Puffing Regimen) | How similar to your own brand were the puffs? | 3.6 score on a scale | Standard Deviation 1.81 |
| Subject's Own E-cigarette | Sensory Parameters (Fixed Puffing Regimen) | Strength of puffs in windpipe? | 3.3 score on a scale | Standard Deviation 1.44 |
| Subject's Own E-cigarette | Sensory Parameters (Fixed Puffing Regimen) | How harsh were the puffs you took? | 3.6 score on a scale | Standard Deviation 1.41 |
| Subject's Own E-cigarette | Sensory Parameters (Fixed Puffing Regimen) | Strength of puffs in back of mouth & throat? | 3.7 score on a scale | Standard Deviation 1.3 |
| Subject's Own E-cigarette | Sensory Parameters (Fixed Puffing Regimen) | How much did you like the puffs you took? | 4.9 score on a scale | Standard Deviation 1.41 |
| P4M3-1.7% | Sensory Parameters (Fixed Puffing Regimen) | Strength of puffs in windpipe? | 4.1 score on a scale | Standard Deviation 1.1 |
| P4M3-1.7% | Sensory Parameters (Fixed Puffing Regimen) | How harsh were the puffs you took? | 4.4 score on a scale | Standard Deviation 1.3 |
| P4M3-1.7% | Sensory Parameters (Fixed Puffing Regimen) | Strength puffs in chest? | 3.5 score on a scale | Standard Deviation 1.41 |
| P4M3-1.7% | Sensory Parameters (Fixed Puffing Regimen) | How much did you like the puffs you took? | 3.7 score on a scale | Standard Deviation 1.34 |
| P4M3-1.7% | Sensory Parameters (Fixed Puffing Regimen) | How similar to your own brand were the puffs? | 2.3 score on a scale | Standard Deviation 1.18 |
| P4M3-1.7% | Sensory Parameters (Fixed Puffing Regimen) | Strength of puffs on tongue? | 2.8 score on a scale | Standard Deviation 1.09 |
| P4M3-1.7% | Sensory Parameters (Fixed Puffing Regimen) | Strength of puffs in nose? | 2.2 score on a scale | Standard Deviation 1.02 |
| P4M3-1.7% | Sensory Parameters (Fixed Puffing Regimen) | Strength of puffs in back of mouth & throat? | 4.1 score on a scale | Standard Deviation 1.19 |
| P4M3-1.7%LA | Sensory Parameters (Fixed Puffing Regimen) | Strength of puffs on tongue? | 2.5 score on a scale | Standard Deviation 1.1 |
| P4M3-1.7%LA | Sensory Parameters (Fixed Puffing Regimen) | How harsh were the puffs you took? | 3.2 score on a scale | Standard Deviation 1.53 |
| P4M3-1.7%LA | Sensory Parameters (Fixed Puffing Regimen) | Strength of puffs in windpipe? | 3.1 score on a scale | Standard Deviation 1.08 |
| P4M3-1.7%LA | Sensory Parameters (Fixed Puffing Regimen) | Strength of puffs in back of mouth & throat? | 2.9 score on a scale | Standard Deviation 1.1 |
| P4M3-1.7%LA | Sensory Parameters (Fixed Puffing Regimen) | Strength puffs in chest? | 2.2 score on a scale | Standard Deviation 1.13 |
| P4M3-1.7%LA | Sensory Parameters (Fixed Puffing Regimen) | How similar to your own brand were the puffs? | 2.3 score on a scale | Standard Deviation 1.64 |
| P4M3-1.7%LA | Sensory Parameters (Fixed Puffing Regimen) | Strength of puffs in nose? | 1.8 score on a scale | Standard Deviation 0.81 |
| P4M3-1.7%LA | Sensory Parameters (Fixed Puffing Regimen) | How much did you like the puffs you took? | 3.7 score on a scale | Standard Deviation 1.86 |
| P4M3-3%LA | Sensory Parameters (Fixed Puffing Regimen) | Strength of puffs in nose? | 2.2 score on a scale | Standard Deviation 0.87 |
| P4M3-3%LA | Sensory Parameters (Fixed Puffing Regimen) | Strength of puffs on tongue? | 2.8 score on a scale | Standard Deviation 1.21 |
| P4M3-3%LA | Sensory Parameters (Fixed Puffing Regimen) | How much did you like the puffs you took? | 3.5 score on a scale | Standard Deviation 1.73 |
| P4M3-3%LA | Sensory Parameters (Fixed Puffing Regimen) | Strength of puffs in windpipe? | 4.1 score on a scale | Standard Deviation 1.49 |
| P4M3-3%LA | Sensory Parameters (Fixed Puffing Regimen) | How harsh were the puffs you took? | 4.1 score on a scale | Standard Deviation 1.19 |
| P4M3-3%LA | Sensory Parameters (Fixed Puffing Regimen) | Strength puffs in chest? | 3.5 score on a scale | Standard Deviation 1.83 |
| P4M3-3%LA | Sensory Parameters (Fixed Puffing Regimen) | Strength of puffs in back of mouth & throat? | 3.9 score on a scale | Standard Deviation 1.34 |
| P4M3-3%LA | Sensory Parameters (Fixed Puffing Regimen) | How similar to your own brand were the puffs? | 2.1 score on a scale | Standard Deviation 1.07 |
| P4M3-4%LA | Sensory Parameters (Fixed Puffing Regimen) | Strength puffs in chest? | 3.2 score on a scale | Standard Deviation 1.66 |
| P4M3-4%LA | Sensory Parameters (Fixed Puffing Regimen) | How much did you like the puffs you took? | 3.5 score on a scale | Standard Deviation 1.25 |
| P4M3-4%LA | Sensory Parameters (Fixed Puffing Regimen) | How harsh were the puffs you took? | 3.7 score on a scale | Standard Deviation 1.54 |
| P4M3-4%LA | Sensory Parameters (Fixed Puffing Regimen) | How similar to your own brand were the puffs? | 2.3 score on a scale | Standard Deviation 1.12 |
| P4M3-4%LA | Sensory Parameters (Fixed Puffing Regimen) | Strength of puffs on tongue? | 3.0 score on a scale | Standard Deviation 1.26 |
| P4M3-4%LA | Sensory Parameters (Fixed Puffing Regimen) | Strength of puffs in nose? | 2.3 score on a scale | Standard Deviation 1.23 |
| P4M3-4%LA | Sensory Parameters (Fixed Puffing Regimen) | Strength of puffs in back of mouth & throat? | 3.9 score on a scale | Standard Deviation 1.51 |
| P4M3-4%LA | Sensory Parameters (Fixed Puffing Regimen) | Strength of puffs in windpipe? | 3.8 score on a scale | Standard Deviation 1.57 |
Secondary
Subjective Effects of P4M3 Use
Measured with an adapted version of the modified Cigarette Evaluation Questionnaire (adapted mCEQ) within 60 minutes after the ad libitum use session. Assessed on a 7-point scale, ranging from 1 (not at all) to 7 (extremely).
Time frame: From Day -1 (baseline) to Day 4
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Subject's Own E-cigarette | Subjective Effects of P4M3 Use | Enjoyment of Respiratory Tract Sensations | 4.3 score on a scale | Standard Deviation 1.23 |
| Subject's Own E-cigarette | Subjective Effects of P4M3 Use | Product Satisfaction | 4.76 score on a scale | Standard Deviation 1.058 |
| Subject's Own E-cigarette | Subjective Effects of P4M3 Use | Craving Reduction | 4.3 score on a scale | Standard Deviation 1.67 |
| Subject's Own E-cigarette | Subjective Effects of P4M3 Use | Psychological Reward | 3.88 score on a scale | Standard Deviation 1.242 |
| Subject's Own E-cigarette | Subjective Effects of P4M3 Use | Aversion | 1.77 score on a scale | Standard Deviation 0.864 |
| P4M3-1.7% | Subjective Effects of P4M3 Use | Enjoyment of Respiratory Tract Sensations | 3.2 score on a scale | Standard Deviation 1.02 |
| P4M3-1.7% | Subjective Effects of P4M3 Use | Aversion | 1.57 score on a scale | Standard Deviation 0.843 |
| P4M3-1.7% | Subjective Effects of P4M3 Use | Psychological Reward | 3.49 score on a scale | Standard Deviation 1.396 |
| P4M3-1.7% | Subjective Effects of P4M3 Use | Craving Reduction | 3.9 score on a scale | Standard Deviation 1.25 |
| P4M3-1.7% | Subjective Effects of P4M3 Use | Product Satisfaction | 3.62 score on a scale | Standard Deviation 1.425 |
| P4M3-1.7%LA | Subjective Effects of P4M3 Use | Aversion | 2.00 score on a scale | Standard Deviation 1.036 |
| P4M3-1.7%LA | Subjective Effects of P4M3 Use | Product Satisfaction | 3.49 score on a scale | Standard Deviation 1.667 |
| P4M3-1.7%LA | Subjective Effects of P4M3 Use | Psychological Reward | 3.13 score on a scale | Standard Deviation 1.529 |
| P4M3-1.7%LA | Subjective Effects of P4M3 Use | Enjoyment of Respiratory Tract Sensations | 3.1 score on a scale | Standard Deviation 1.23 |
| P4M3-1.7%LA | Subjective Effects of P4M3 Use | Craving Reduction | 3.7 score on a scale | Standard Deviation 1.8 |
| P4M3-3%LA | Subjective Effects of P4M3 Use | Craving Reduction | 3.6 score on a scale | Standard Deviation 1.51 |
| P4M3-3%LA | Subjective Effects of P4M3 Use | Product Satisfaction | 3.24 score on a scale | Standard Deviation 1.165 |
| P4M3-3%LA | Subjective Effects of P4M3 Use | Enjoyment of Respiratory Tract Sensations | 3.0 score on a scale | Standard Deviation 0.93 |
| P4M3-3%LA | Subjective Effects of P4M3 Use | Aversion | 2.37 score on a scale | Standard Deviation 1.518 |
| P4M3-3%LA | Subjective Effects of P4M3 Use | Psychological Reward | 3.01 score on a scale | Standard Deviation 1.06 |
| P4M3-4%LA | Subjective Effects of P4M3 Use | Aversion | 2.53 score on a scale | Standard Deviation 1.788 |
| P4M3-4%LA | Subjective Effects of P4M3 Use | Enjoyment of Respiratory Tract Sensations | 2.9 score on a scale | Standard Deviation 1.28 |
| P4M3-4%LA | Subjective Effects of P4M3 Use | Product Satisfaction | 3.04 score on a scale | Standard Deviation 1.469 |
| P4M3-4%LA | Subjective Effects of P4M3 Use | Craving Reduction | 3.5 score on a scale | Standard Deviation 1.85 |
| P4M3-4%LA | Subjective Effects of P4M3 Use | Psychological Reward | 2.88 score on a scale | Standard Deviation 1.207 |
Secondary
Time to the Maximum Concentration [Tmax]
To measure the time to the maximum concentration \[tmax\] of the P4M3 variants and subjects' own e-cigarette from the fixed puffing regimen.
Time frame: From Day -1 (baseline) to Day 4
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Subject's Own E-cigarette | Time to the Maximum Concentration [Tmax] | 10.002 minutes |
| P4M3-1.7% | Time to the Maximum Concentration [Tmax] | 10.002 minutes |
| P4M3-1.7%LA | Time to the Maximum Concentration [Tmax] | 7.002 minutes |
| P4M3-3%LA | Time to the Maximum Concentration [Tmax] | 10.002 minutes |
| P4M3-4%LA | Time to the Maximum Concentration [Tmax] | 7.002 minutes |
Secondary
Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles
To measure the total and background-corrected plasma nicotine concentration versus time profiles of the P4M3 variants and subjects' own e-cigarette from the fixed puffing regimen.
Time frame: From Day -1 (baseline) to Day 4
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Subject's Own E-cigarette | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 240 mins | 0.8435 ng/mL | Geometric Coefficient of Variation 81.99 |
| Subject's Own E-cigarette | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 15 mins | 3.810 ng/mL | Geometric Coefficient of Variation 71.38 |
| Subject's Own E-cigarette | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 4 mins | 3.158 ng/mL | Geometric Coefficient of Variation 107.95 |
| Subject's Own E-cigarette | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 30 mins | 3.209 ng/mL | Geometric Coefficient of Variation 83.26 |
| Subject's Own E-cigarette | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 120 mins | 1.579 ng/mL | Geometric Coefficient of Variation 96.29 |
| Subject's Own E-cigarette | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 7 mins | 4.960 ng/mL | Geometric Coefficient of Variation 81.41 |
| Subject's Own E-cigarette | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 60 mins | 2.365 ng/mL | Geometric Coefficient of Variation 93.3 |
| Subject's Own E-cigarette | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 10 mins | 4.443 ng/mL | Geometric Coefficient of Variation 80.92 |
| Subject's Own E-cigarette | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 2 mins | 1.228 ng/mL | Geometric Coefficient of Variation 138.63 |
| P4M3-1.7% | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 60 mins | 2.300 ng/mL | Geometric Coefficient of Variation 52.26 |
| P4M3-1.7% | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 30 mins | 2.704 ng/mL | Geometric Coefficient of Variation 98.56 |
| P4M3-1.7% | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 10 mins | 4.386 ng/mL | Geometric Coefficient of Variation 66.4 |
| P4M3-1.7% | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 15 mins | 3.788 ng/mL | Geometric Coefficient of Variation 60.59 |
| P4M3-1.7% | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 7 mins | 3.992 ng/mL | Geometric Coefficient of Variation 77.63 |
| P4M3-1.7% | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 240 mins | 0.6550 ng/mL | Geometric Coefficient of Variation 50.33 |
| P4M3-1.7% | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 4 mins | 1.915 ng/mL | Geometric Coefficient of Variation 120.88 |
| P4M3-1.7% | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 2 mins | 0.7868 ng/mL | Geometric Coefficient of Variation 268.65 |
| P4M3-1.7% | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 120 mins | 1.292 ng/mL | Geometric Coefficient of Variation 52.31 |
| P4M3-1.7%LA | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 30 mins | 3.202 ng/mL | Geometric Coefficient of Variation 73.14 |
| P4M3-1.7%LA | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 2 mins | 1.620 ng/mL | Geometric Coefficient of Variation 117.19 |
| P4M3-1.7%LA | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 4 mins | 4.048 ng/mL | Geometric Coefficient of Variation 126.28 |
| P4M3-1.7%LA | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 7 mins | 5.869 ng/mL | Geometric Coefficient of Variation 83.79 |
| P4M3-1.7%LA | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 10 mins | 5.232 ng/mL | Geometric Coefficient of Variation 72.58 |
| P4M3-1.7%LA | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 15 mins | 4.250 ng/mL | Geometric Coefficient of Variation 74.72 |
| P4M3-1.7%LA | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 60 mins | 2.352 ng/mL | Geometric Coefficient of Variation 71.13 |
| P4M3-1.7%LA | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 120 mins | 1.479 ng/mL | Geometric Coefficient of Variation 68.44 |
| P4M3-1.7%LA | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 240 mins | 0.6794 ng/mL | Geometric Coefficient of Variation 84.09 |
| P4M3-3%LA | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 10 mins | 7.793 ng/mL | Geometric Coefficient of Variation 57.17 |
| P4M3-3%LA | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 30 mins | 5.232 ng/mL | Geometric Coefficient of Variation 57.79 |
| P4M3-3%LA | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 7 mins | 8.162 ng/mL | Geometric Coefficient of Variation 67.2 |
| P4M3-3%LA | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 60 mins | 3.646 ng/mL | Geometric Coefficient of Variation 62.22 |
| P4M3-3%LA | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 4 mins | 4.817 ng/mL | Geometric Coefficient of Variation 113.35 |
| P4M3-3%LA | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 240 mins | 1.038 ng/mL | Geometric Coefficient of Variation 54.59 |
| P4M3-3%LA | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 120 mins | 2.074 ng/mL | Geometric Coefficient of Variation 65.23 |
| P4M3-3%LA | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 2 mins | 2.025 ng/mL | Geometric Coefficient of Variation 165.36 |
| P4M3-3%LA | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 15 mins | 7.251 ng/mL | Geometric Coefficient of Variation 57.53 |
| P4M3-4%LA | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 2 mins | 3.634 ng/mL | Geometric Coefficient of Variation 143.44 |
| P4M3-4%LA | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 10 mins | 9.480 ng/mL | Geometric Coefficient of Variation 68.97 |
| P4M3-4%LA | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 30 mins | 6.203 ng/mL | Geometric Coefficient of Variation 66.86 |
| P4M3-4%LA | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 7 mins | 9.905 ng/mL | Geometric Coefficient of Variation 69.36 |
| P4M3-4%LA | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 15 mins | 8.152 ng/mL | Geometric Coefficient of Variation 57.85 |
| P4M3-4%LA | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 240 mins | 1.183 ng/mL | Geometric Coefficient of Variation 74.31 |
| P4M3-4%LA | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 120 mins | 2.398 ng/mL | Geometric Coefficient of Variation 79.9 |
| P4M3-4%LA | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 60 mins | 4.238 ng/mL | Geometric Coefficient of Variation 74.41 |
| P4M3-4%LA | Total and Background-corrected Plasma Nicotine Concentration Versus Time Profiles | 4 mins | 7.356 ng/mL | Geometric Coefficient of Variation 65.15 |