Pharmacokinetics
Conditions
Keywords
Nicotine, Nicotine-containing product
Brief summary
This is a single-center, open-label, randomized, crossover study to evaluate the pharmacokinetic (PK) profiles of four P3P variants (differing in nicotine aerosol particle size, nicotine concentration and in the absence or presence of a flavoring system), following a fixed puffing regimen and an ad libitum use period. In addition, pharmacodynamic (PD) effects (subjective effects and related behavioral assessments), as well as human puffing topography, will be evaluated, to provide further insights on product safety, acceptance, and use.
Detailed description
The goal of the proposed study is to evaluate the pharmacokinetic profiles of four P3P variants. Variants with two different nicotine contents (1 mg/product and 2 mg/product), two different nicotine aersol particle sizes and presence/absence of a flavoring system will be tested to identify which one would yield plasma nicotine concentrations as close as possible to those achieved after smoking a single cigarette. All of the subjects will initially use the lowest nicotine content product (P3P 3). Subject will continue the study using the three remaining products (P3P 1, P3P 2 and P3P 4) containing 2 mg nicotine/product in a randomly assigned sequence. Two product use regimens: fixed puffing and ad libitum use will be applied to provide insight into nicotine absorption. The fixed puffing regimen with consistent use conditions across subjects will be applied in order to minimize variability. The 1 hour ad libitum use period will provide information on nicotine PK and product acceptance when subjects use the P3P according to their own puffing behavior which is closer to a real-world setting. Safety and tolerability will also be assessed throughout the study.
Interventions
OTHERP3P 1
2 mg of nicotine; no flavor; nicotine powder particle size of 2.25 ± 0.2 μm
OTHERP3P 2
2 mg of nicotine; flavor; nicotine powder particle size of 2.25 ± 0.2 μm
OTHERP3P 3
1 mg of nicotine; flavor; nicotine powder particle size of 2.25 ± 0.2 μm
OTHERP3P 4
2 mg of nicotine; flavor; nicotine powder particle size of 1.8 ± 0.2 μm
Sponsors
Philip Morris Products S.A.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Masking description
Sponsor staff, Investigator, the subjects and the investigational site will be blinded to the randomization sequences until they are assigned. Subjects will not be informed of the complete sequence to which they have been assigned.
Intervention model description
A single-center, open-label, randomized, crossover study.
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 between 21 and 65 years old. * Subject is Caucasian. * Smoking, healthy subject as judged by the Investigator or designee based on available assessments from the screening period. * Subject has been smoking at least 10 commercially available cigarettes per day at least for the last 4 weeks prior to Screening Visit. Smoking status will be verified based on a urinary cotinine test (cotinine ≥ 200 ng/mL). * Subject has been smoking for at least the last 3 years prior to Screening Visit. * Subject does not plan to quit smoking in the next 2 months after the Screening Visit.
Exclusion criteria
* Female subject is pregnant or breastfeeding. * Female subject uses estrogen-containing hormonal contraception or hormone replacement therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Nicotine Concentration-time Profile | Derived from multiple blood sampling (measured at 2 mins, 4 mins, 7 mins, 10 mins, 15 mins, 30 mins, 1 hour, 2 hours, and 4 hours post-product use) on Days 1, 2, 3 and 4 | To measure the plasma nicotine concentration-time profile of four P3P variants from the fixed puffing regimen, following correction of baseline nicotine levels. |
| Maximum Plasma Concentration [Cmax] | Derived from multiple blood sampling (measured at 2 mins, 4 mins, 7 mins, 10 mins, 15 mins, 30 mins, 1 hour, 2 hours, and 4 hours post-product use) on Days 1, 2, 3 and 4 | To measure the maximum nicotine plasma concentration \[Cmax\] of four P3P variants from the fixed puffing regimen, following correction of baseline nicotine levels. |
| Time to the Maximum Nicotine Concentration [Tmax] | Derived from multiple blood sampling (measured at 2 mins, 4 mins, 7 mins, 10 mins, 15 mins, 30 mins, 1 hour, 2 hours, and 4 hours post-product use) on Days 1, 2, 3 and 4 | To measure the time to maximum nicotine concentration \[Tmax\] of four P3P variants from the fixed puffing regimen, following correction of baseline nicotine levels. |
| Area Under the Concentration-time Curve From Start of Product Use (T0 Fix) to 4 Hours [AUCfix (0-4h)] | Derived from multiple blood sampling (measured at 2 mins, 4 mins, 7 mins, 10 mins, 15 mins, 30 mins, 1 hour, 2 hours, and 4 hours post-product use) on Days 1, 2, 3 and 4 | To measure the area under the plasma concentration-time curve of four P3P variants from the fixed puffing regimen, following correction of baseline nicotine levels. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average of Plasma Nicotine Concentration From T0 ad Lib to 1 Hour [Caverage] | Derived from multiple blood sampling (measured at 10 mins, 20 mins, 30 mins, 40 mins, 1 hour during ad libitum use) on Days 1, 2, 3 and 4 | To measure the average of plasma nicotine concentration \[Caverage\], of four P3P variants from the ad libitum use period, following correction of baseline nicotine levels |
| Area Under the Concentration-time Curve From Start of Product Use (T0 ad Lib) to 4 Hours [AUCad Lib (0-4h)] | Derived from multiple blood sampling (measured at 10 mins, 20 mins, 30 mins, 40 mins, 1 hour, 2 hours, and 4 hours during and post-ad libitum use) on Days 1, 2, 3 and 4 | To measure the area under the plasma concentration-time curve of four P3P variants from the ad libitum use period, following correction of baseline nicotine levels. |
| AUC of Craving for a Cigarette During and After the Fixed Puffing Regimen | During and up to 4 hours post-product use on days 1, 2, 3 and 4 | Measured on a Visual Analogue Scale (VAS) of 0 (no craving) to 100 (strong craving). |
| AUC Craving for a Cigarette During and After the ad Libitum Use Period | During and up to 4 hours post-product use on days 1, 2, 3 and 4 | Measured on a Visual Analogue Scale (VAS) of 0 (no craving) to 100 (strong craving). |
| Product Evaluation | Within 60 minutes after the ad libitum use session on days 1, 2, 3 and 4 | Measured with an adapted version of the modified Cigarette Evaluation Questionnaire (adapted mCEQ) following the ad libitum use period. Assessed on a 7-point scale, ranging from 1 (not at all) to 7 (extremely). |
| Plasma Nicotine Concentration-time Profile | Derived from multiple blood sampling (measured at 10 mins, 20 mins, 30 mins, 40 mins, 1 hour, 2 hours, and 4 hours during and post-ad libitum use) on Days 1, 2, 3 and 4 | To measure the plasma nicotine concentration-time profile of four P3P variants from the ad libitum use period, following correction of baseline nicotine levels. |
| Human Puffing Topography (HPT) Parameters (Puff Volume) of Four P3P Variants During the Fixed Puffing Regimen Period. | During fixed puffing product use on days 1, 2, 3 and 4 | Descriptive statistics of total puff volume and average puff volume, of four P3P variants, during the fixed puffing regimen period. |
| Human Puffing Topography (HPT) Parameters (Puff Volume) of Four P3P Variants During the ad Libitum Use Period. | During ad libitum product use on days 1, 2, 3 and 4 | Descriptive statistics of total puff volume and average puff volume, of four P3P variants, during the ad libitum use period. |
| Amount of Powder Aerosolized From P3P From the Fixed Puffing Regimen. | Before and after fixed puffing product use on days 1, 2, 3 and 4 | Descriptive statistics of P3P weight before use, and after use, for the fixed puffing regimen. |
| Amount of Powder Aerosolized From P3P From the ad Libitum Use Period (Per Product Used). | Before and after ad libitum product use on days 1, 2, 3 and 4 | P3P weight before use, and after use, to determine the amount of powder aerosolized from P3P during Ad Libitum use (per product used). |
| Sensory Parameters | Within 60 minutes after the ad libitum use session on days 1, 2, 3 and 4 | Measured with a Sensory Questionnaire (SQ) following the ad libitum use period. Response to each question is assessed on a 7-point scale, ranging from 1 (not at all) to 7 (extremely). |
| Peak Plasma Nicotine Concentration [Cpeak] | Derived from multiple blood sampling (measured at 10 mins, 20 mins, 30 mins, 40 mins, 1 hour, 2 hours, and 4 hours during and post-ad libitum use) on Days 1, 2, 3 and 4 | To measure the Peak plasma nicotine concentration \[Cpeak\] of four P3P variants from the ad libitum use period, following correction of baseline nicotine levels. |
| Time to Peak Plasma Nicotine Concentration [Tpeak] | Derived from multiple blood sampling (measured at 10 mins, 20 mins, 30 mins, 40 mins, 1 hour, 2 hours, and 4 hours during and post-ad libitum use) on Days 1, 2, 3 and 4 | To measure the time to peak plasma nicotine concentration \[Tpeak\] of four P3P variants from the ad libitum use period, following correction of baseline nicotine levels. |
| Trough Plasma Nicotine Concentration [Ctrough] | Derived from multiple blood sampling (measured at 10 mins, 20 mins, 30 mins, 40 mins, 1 hour, 2 hours, and 4 hours during and post-ad libitum use) on Days 1, 2, 3 and 4 | To measure the trough plasma nicotine concentration \[Ctrough\] of four P3P variants from the ad libitum use period, following correction of baseline nicotine levels. |
Countries
Switzerland
Participant flow
Recruitment details
40 subjects were screened for eligibility. 21 subjects were screen failures (10 reserve subjects were not enrolled, 9 subjects did not meet eligibility criteria, and 2 subjects withdrew.)
Pre-assignment details
On Day 1, 19 subjects were enrolled and exposed to P3P 3 before randomization. One enrolled subject withdrew after P3P 3 use before randomization. 18 subjects were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Safety Population The safety population comprised all enrolled subjects who were exposed to P3P during the study. | 19 |
| Total | 19 |
Baseline characteristics
| Characteristic | Safety Population |
|---|---|
| Age, Continuous | 35.4 years STANDARD_DEVIATION 9.03 |
| BMI (kg/m^2) | 24.6 kg/m^2 STANDARD_DEVIATION 2.72 |
| Body weight (kg) | 72.3 kilograms STANDARD_DEVIATION 12.4 |
| Height (cm) | 171 centimetres STANDARD_DEVIATION 12.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 19 Participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 18 | 0 / 19 | 0 / 18 |
| other Total, other adverse events | 4 / 18 | 5 / 18 | 4 / 19 | 3 / 18 |
| serious Total, serious adverse events | 0 / 18 | 0 / 18 | 0 / 19 | 0 / 18 |
Outcome results
Primary
Area Under the Concentration-time Curve From Start of Product Use (T0 Fix) to 4 Hours [AUCfix (0-4h)]
To measure the area under the plasma concentration-time curve of four P3P variants from the fixed puffing regimen, following correction of baseline nicotine levels.
Time frame: Derived from multiple blood sampling (measured at 2 mins, 4 mins, 7 mins, 10 mins, 15 mins, 30 mins, 1 hour, 2 hours, and 4 hours post-product use) on Days 1, 2, 3 and 4
Population: Baseline correction of nicotine concentrations could be performed for 16 out of the 18 randomized subjects.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| P3P 1 | Area Under the Concentration-time Curve From Start of Product Use (T0 Fix) to 4 Hours [AUCfix (0-4h)] | 5.84 ng/mL*h |
| P3P 2 | Area Under the Concentration-time Curve From Start of Product Use (T0 Fix) to 4 Hours [AUCfix (0-4h)] | 5.08 ng/mL*h |
| P3P 3 | Area Under the Concentration-time Curve From Start of Product Use (T0 Fix) to 4 Hours [AUCfix (0-4h)] | 2.37 ng/mL*h |
| P3P 4 | Area Under the Concentration-time Curve From Start of Product Use (T0 Fix) to 4 Hours [AUCfix (0-4h)] | 5.73 ng/mL*h |
Primary
Maximum Plasma Concentration [Cmax]
To measure the maximum nicotine plasma concentration \[Cmax\] of four P3P variants from the fixed puffing regimen, following correction of baseline nicotine levels.
Time frame: Derived from multiple blood sampling (measured at 2 mins, 4 mins, 7 mins, 10 mins, 15 mins, 30 mins, 1 hour, 2 hours, and 4 hours post-product use) on Days 1, 2, 3 and 4
Population: Baseline correction of nicotine concentrations could be performed for 16 out of the 18 randomized subjects
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| P3P 1 | Maximum Plasma Concentration [Cmax] | 3.08 ng/mL |
| P3P 2 | Maximum Plasma Concentration [Cmax] | 2.13 ng/mL |
| P3P 3 | Maximum Plasma Concentration [Cmax] | 1.14 ng/mL |
| P3P 4 | Maximum Plasma Concentration [Cmax] | 2.79 ng/mL |
Primary
Plasma Nicotine Concentration-time Profile
To measure the plasma nicotine concentration-time profile of four P3P variants from the fixed puffing regimen, following correction of baseline nicotine levels.
Time frame: Derived from multiple blood sampling (measured at 2 mins, 4 mins, 7 mins, 10 mins, 15 mins, 30 mins, 1 hour, 2 hours, and 4 hours post-product use) on Days 1, 2, 3 and 4
Population: Baseline correction of nicotine concentrations could be performed for 16 out of the 18 randomized subjects.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| P3P 1 | Plasma Nicotine Concentration-time Profile | 1 hour after start of fixed puffing product use | 1.97 ng/mL |
| P3P 1 | Plasma Nicotine Concentration-time Profile | 30 mins after start of fixed puffing product use | 2.40 ng/mL |
| P3P 1 | Plasma Nicotine Concentration-time Profile | 4 hours after start of fixed puffing product use | 0.553 ng/mL |
| P3P 1 | Plasma Nicotine Concentration-time Profile | 10 mins after start of fixed puffing product use | 2.33 ng/mL |
| P3P 1 | Plasma Nicotine Concentration-time Profile | 7 mins after start of fixed puffing product use | 2.01 ng/mL |
| P3P 1 | Plasma Nicotine Concentration-time Profile | 4 mins after start of fixed puffing product use | 1.56 ng/mL |
| P3P 1 | Plasma Nicotine Concentration-time Profile | 2 hours after start of fixed puffing product use | 1.20 ng/mL |
| P3P 1 | Plasma Nicotine Concentration-time Profile | 15 mins after start of fixed puffing product use | 2.62 ng/mL |
| P3P 1 | Plasma Nicotine Concentration-time Profile | 2 mins after start of fixed puffing product use | 0.751 ng/mL |
| P3P 2 | Plasma Nicotine Concentration-time Profile | 15 mins after start of fixed puffing product use | 1.78 ng/mL |
| P3P 2 | Plasma Nicotine Concentration-time Profile | 1 hour after start of fixed puffing product use | 1.71 ng/mL |
| P3P 2 | Plasma Nicotine Concentration-time Profile | 30 mins after start of fixed puffing product use | 1.98 ng/mL |
| P3P 2 | Plasma Nicotine Concentration-time Profile | 4 mins after start of fixed puffing product use | 0.740 ng/mL |
| P3P 2 | Plasma Nicotine Concentration-time Profile | 2 mins after start of fixed puffing product use | 0.336 ng/mL |
| P3P 2 | Plasma Nicotine Concentration-time Profile | 7 mins after start of fixed puffing product use | 1.20 ng/mL |
| P3P 2 | Plasma Nicotine Concentration-time Profile | 4 hours after start of fixed puffing product use | 0.568 ng/mL |
| P3P 2 | Plasma Nicotine Concentration-time Profile | 2 hours after start of fixed puffing product use | 1.17 ng/mL |
| P3P 2 | Plasma Nicotine Concentration-time Profile | 10 mins after start of fixed puffing product use | 1.54 ng/mL |
| P3P 3 | Plasma Nicotine Concentration-time Profile | 15 mins after start of fixed puffing product use | 0.947 ng/mL |
| P3P 3 | Plasma Nicotine Concentration-time Profile | 2 mins after start of fixed puffing product use | 0.205 ng/mL |
| P3P 3 | Plasma Nicotine Concentration-time Profile | 4 mins after start of fixed puffing product use | 0.394 ng/mL |
| P3P 3 | Plasma Nicotine Concentration-time Profile | 7 mins after start of fixed puffing product use | 0.547 ng/mL |
| P3P 3 | Plasma Nicotine Concentration-time Profile | 10 mins after start of fixed puffing product use | 0.701 ng/mL |
| P3P 3 | Plasma Nicotine Concentration-time Profile | 30 mins after start of fixed puffing product use | 0.931 ng/mL |
| P3P 3 | Plasma Nicotine Concentration-time Profile | 1 hour after start of fixed puffing product use | 0.758 ng/mL |
| P3P 3 | Plasma Nicotine Concentration-time Profile | 2 hours after start of fixed puffing product use | 0.383 ng/mL |
| P3P 3 | Plasma Nicotine Concentration-time Profile | 4 hours after start of fixed puffing product use | 0.219 ng/mL |
| P3P 4 | Plasma Nicotine Concentration-time Profile | 1 hour after start of fixed puffing product use | 1.85 ng/mL |
| P3P 4 | Plasma Nicotine Concentration-time Profile | 10 mins after start of fixed puffing product use | 1.92 ng/mL |
| P3P 4 | Plasma Nicotine Concentration-time Profile | 7 mins after start of fixed puffing product use | 1.66 ng/mL |
| P3P 4 | Plasma Nicotine Concentration-time Profile | 4 hours after start of fixed puffing product use | 0.623 ng/mL |
| P3P 4 | Plasma Nicotine Concentration-time Profile | 2 hours after start of fixed puffing product use | 1.23 ng/mL |
| P3P 4 | Plasma Nicotine Concentration-time Profile | 4 mins after start of fixed puffing product use | 1.20 ng/mL |
| P3P 4 | Plasma Nicotine Concentration-time Profile | 30 mins after start of fixed puffing product use | 2.25 ng/mL |
| P3P 4 | Plasma Nicotine Concentration-time Profile | 15 mins after start of fixed puffing product use | 2.31 ng/mL |
| P3P 4 | Plasma Nicotine Concentration-time Profile | 2 mins after start of fixed puffing product use | 0.478 ng/mL |
Primary
Time to the Maximum Nicotine Concentration [Tmax]
To measure the time to maximum nicotine concentration \[Tmax\] of four P3P variants from the fixed puffing regimen, following correction of baseline nicotine levels.
Time frame: Derived from multiple blood sampling (measured at 2 mins, 4 mins, 7 mins, 10 mins, 15 mins, 30 mins, 1 hour, 2 hours, and 4 hours post-product use) on Days 1, 2, 3 and 4
Population: Baseline correction of nicotine concentrations could be performed for 16 out of the 18 randomized subjects.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| P3P 1 | Time to the Maximum Nicotine Concentration [Tmax] | 15.0 minutes |
| P3P 2 | Time to the Maximum Nicotine Concentration [Tmax] | 22.5 minutes |
| P3P 3 | Time to the Maximum Nicotine Concentration [Tmax] | 15.0 minutes |
| P3P 4 | Time to the Maximum Nicotine Concentration [Tmax] | 15.0 minutes |
Secondary
Amount of Powder Aerosolized From P3P From the ad Libitum Use Period (Per Product Used).
P3P weight before use, and after use, to determine the amount of powder aerosolized from P3P during Ad Libitum use (per product used).
Time frame: Before and after ad libitum product use on days 1, 2, 3 and 4
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| P3P 1 | Amount of Powder Aerosolized From P3P From the ad Libitum Use Period (Per Product Used). | Average Weight before use | 954 mg | Standard Deviation 1.83 |
| P3P 1 | Amount of Powder Aerosolized From P3P From the ad Libitum Use Period (Per Product Used). | Average Difference of Weight (Before/After Use) | 17.0 mg | Standard Deviation 4.17 |
| P3P 1 | Amount of Powder Aerosolized From P3P From the ad Libitum Use Period (Per Product Used). | Average Weight after use | 937 mg | Standard Deviation 4.69 |
| P3P 2 | Amount of Powder Aerosolized From P3P From the ad Libitum Use Period (Per Product Used). | Average Weight before use | 964 mg | Standard Deviation 1.36 |
| P3P 2 | Amount of Powder Aerosolized From P3P From the ad Libitum Use Period (Per Product Used). | Average Difference of Weight (Before/After Use) | 25.9 mg | Standard Deviation 4.63 |
| P3P 2 | Amount of Powder Aerosolized From P3P From the ad Libitum Use Period (Per Product Used). | Average Weight after use | 938 mg | Standard Deviation 4.9 |
| P3P 3 | Amount of Powder Aerosolized From P3P From the ad Libitum Use Period (Per Product Used). | Average Weight after use | 939 mg | Standard Deviation 4.19 |
| P3P 3 | Amount of Powder Aerosolized From P3P From the ad Libitum Use Period (Per Product Used). | Average Weight before use | 964 mg | Standard Deviation 1.94 |
| P3P 3 | Amount of Powder Aerosolized From P3P From the ad Libitum Use Period (Per Product Used). | Average Difference of Weight (Before/After Use) | 25.6 mg | Standard Deviation 3.92 |
| P3P 4 | Amount of Powder Aerosolized From P3P From the ad Libitum Use Period (Per Product Used). | Average Weight before use | 964 mg | Standard Deviation 1.59 |
| P3P 4 | Amount of Powder Aerosolized From P3P From the ad Libitum Use Period (Per Product Used). | Average Difference of Weight (Before/After Use) | 23.9 mg | Standard Deviation 2.66 |
| P3P 4 | Amount of Powder Aerosolized From P3P From the ad Libitum Use Period (Per Product Used). | Average Weight after use | 940 mg | Standard Deviation 2.28 |
Secondary
Amount of Powder Aerosolized From P3P From the Fixed Puffing Regimen.
Descriptive statistics of P3P weight before use, and after use, for the fixed puffing regimen.
Time frame: Before and after fixed puffing product use on days 1, 2, 3 and 4
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| P3P 1 | Amount of Powder Aerosolized From P3P From the Fixed Puffing Regimen. | Weight before use | 954 mg | Standard Deviation 2.7 |
| P3P 1 | Amount of Powder Aerosolized From P3P From the Fixed Puffing Regimen. | Difference of Weight (Before/After Use) | 15.6 mg | Standard Deviation 6.16 |
| P3P 1 | Amount of Powder Aerosolized From P3P From the Fixed Puffing Regimen. | Weight after use | 938 mg | Standard Deviation 6.01 |
| P3P 2 | Amount of Powder Aerosolized From P3P From the Fixed Puffing Regimen. | Weight before use | 965 mg | Standard Deviation 2.11 |
| P3P 2 | Amount of Powder Aerosolized From P3P From the Fixed Puffing Regimen. | Difference of Weight (Before/After Use) | 21.6 mg | Standard Deviation 5.89 |
| P3P 2 | Amount of Powder Aerosolized From P3P From the Fixed Puffing Regimen. | Weight after use | 944 mg | Standard Deviation 6.46 |
| P3P 3 | Amount of Powder Aerosolized From P3P From the Fixed Puffing Regimen. | Weight after use | 943 mg | Standard Deviation 6.46 |
| P3P 3 | Amount of Powder Aerosolized From P3P From the Fixed Puffing Regimen. | Weight before use | 966 mg | Standard Deviation 2.48 |
| P3P 3 | Amount of Powder Aerosolized From P3P From the Fixed Puffing Regimen. | Difference of Weight (Before/After Use) | 22.6 mg | Standard Deviation 6.07 |
| P3P 4 | Amount of Powder Aerosolized From P3P From the Fixed Puffing Regimen. | Weight before use | 965 mg | Standard Deviation 2.95 |
| P3P 4 | Amount of Powder Aerosolized From P3P From the Fixed Puffing Regimen. | Difference of Weight (Before/After Use) | 22.2 mg | Standard Deviation 3.14 |
| P3P 4 | Amount of Powder Aerosolized From P3P From the Fixed Puffing Regimen. | Weight after use | 942 mg | Standard Deviation 4.51 |
Secondary
Area Under the Concentration-time Curve From Start of Product Use (T0 ad Lib) to 4 Hours [AUCad Lib (0-4h)]
To measure the area under the plasma concentration-time curve of four P3P variants from the ad libitum use period, following correction of baseline nicotine levels.
Time frame: Derived from multiple blood sampling (measured at 10 mins, 20 mins, 30 mins, 40 mins, 1 hour, 2 hours, and 4 hours during and post-ad libitum use) on Days 1, 2, 3 and 4
Population: Baseline correction of nicotine concentrations could be performed for 16 out of the 18 randomized subjects.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| P3P 1 | Area Under the Concentration-time Curve From Start of Product Use (T0 ad Lib) to 4 Hours [AUCad Lib (0-4h)] | 13.6 ng/mL*h |
| P3P 2 | Area Under the Concentration-time Curve From Start of Product Use (T0 ad Lib) to 4 Hours [AUCad Lib (0-4h)] | 14.5 ng/mL*h |
| P3P 3 | Area Under the Concentration-time Curve From Start of Product Use (T0 ad Lib) to 4 Hours [AUCad Lib (0-4h)] | 6.32 ng/mL*h |
| P3P 4 | Area Under the Concentration-time Curve From Start of Product Use (T0 ad Lib) to 4 Hours [AUCad Lib (0-4h)] | 12.1 ng/mL*h |
Secondary
AUC Craving for a Cigarette During and After the ad Libitum Use Period
Measured on a Visual Analogue Scale (VAS) of 0 (no craving) to 100 (strong craving).
Time frame: During and up to 4 hours post-product use on days 1, 2, 3 and 4
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| P3P 1 | AUC Craving for a Cigarette During and After the ad Libitum Use Period | 76.4 score on a scale (millimetres)*h |
| P3P 2 | AUC Craving for a Cigarette During and After the ad Libitum Use Period | 72.4 score on a scale (millimetres)*h |
| P3P 3 | AUC Craving for a Cigarette During and After the ad Libitum Use Period | 89.6 score on a scale (millimetres)*h |
| P3P 4 | AUC Craving for a Cigarette During and After the ad Libitum Use Period | 66.8 score on a scale (millimetres)*h |
Secondary
AUC of Craving for a Cigarette During and After the Fixed Puffing Regimen
Measured on a Visual Analogue Scale (VAS) of 0 (no craving) to 100 (strong craving).
Time frame: During and up to 4 hours post-product use on days 1, 2, 3 and 4
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| P3P 1 | AUC of Craving for a Cigarette During and After the Fixed Puffing Regimen | 40.1 score on a scale (millimetres)*h |
| P3P 2 | AUC of Craving for a Cigarette During and After the Fixed Puffing Regimen | 57.6 score on a scale (millimetres)*h |
| P3P 3 | AUC of Craving for a Cigarette During and After the Fixed Puffing Regimen | 116 score on a scale (millimetres)*h |
| P3P 4 | AUC of Craving for a Cigarette During and After the Fixed Puffing Regimen | 64.8 score on a scale (millimetres)*h |
Secondary
Average of Plasma Nicotine Concentration From T0 ad Lib to 1 Hour [Caverage]
To measure the average of plasma nicotine concentration \[Caverage\], of four P3P variants from the ad libitum use period, following correction of baseline nicotine levels
Time frame: Derived from multiple blood sampling (measured at 10 mins, 20 mins, 30 mins, 40 mins, 1 hour during ad libitum use) on Days 1, 2, 3 and 4
Population: Baseline correction of nicotine concentrations could be performed for 16 out of the 18 randomized subjects.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| P3P 1 | Average of Plasma Nicotine Concentration From T0 ad Lib to 1 Hour [Caverage] | 3.19 ng/mL |
| P3P 2 | Average of Plasma Nicotine Concentration From T0 ad Lib to 1 Hour [Caverage] | 3.13 ng/mL |
| P3P 3 | Average of Plasma Nicotine Concentration From T0 ad Lib to 1 Hour [Caverage] | 1.69 ng/mL |
| P3P 4 | Average of Plasma Nicotine Concentration From T0 ad Lib to 1 Hour [Caverage] | 2.87 ng/mL |
Secondary
Human Puffing Topography (HPT) Parameters (Puff Volume) of Four P3P Variants During the ad Libitum Use Period.
Descriptive statistics of total puff volume and average puff volume, of four P3P variants, during the ad libitum use period.
Time frame: During ad libitum product use on days 1, 2, 3 and 4
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| P3P 1 | Human Puffing Topography (HPT) Parameters (Puff Volume) of Four P3P Variants During the ad Libitum Use Period. | Total Puff Volume (per product) | 1485 mL |
| P3P 1 | Human Puffing Topography (HPT) Parameters (Puff Volume) of Four P3P Variants During the ad Libitum Use Period. | Average Puff Volume (per product) | 57.5 mL |
| P3P 2 | Human Puffing Topography (HPT) Parameters (Puff Volume) of Four P3P Variants During the ad Libitum Use Period. | Average Puff Volume (per product) | 62.3 mL |
| P3P 2 | Human Puffing Topography (HPT) Parameters (Puff Volume) of Four P3P Variants During the ad Libitum Use Period. | Total Puff Volume (per product) | 1559 mL |
| P3P 3 | Human Puffing Topography (HPT) Parameters (Puff Volume) of Four P3P Variants During the ad Libitum Use Period. | Total Puff Volume (per product) | 1598 mL |
| P3P 3 | Human Puffing Topography (HPT) Parameters (Puff Volume) of Four P3P Variants During the ad Libitum Use Period. | Average Puff Volume (per product) | 65.4 mL |
| P3P 4 | Human Puffing Topography (HPT) Parameters (Puff Volume) of Four P3P Variants During the ad Libitum Use Period. | Total Puff Volume (per product) | 1512 mL |
| P3P 4 | Human Puffing Topography (HPT) Parameters (Puff Volume) of Four P3P Variants During the ad Libitum Use Period. | Average Puff Volume (per product) | 62.7 mL |
Secondary
Human Puffing Topography (HPT) Parameters (Puff Volume) of Four P3P Variants During the Fixed Puffing Regimen Period.
Descriptive statistics of total puff volume and average puff volume, of four P3P variants, during the fixed puffing regimen period.
Time frame: During fixed puffing product use on days 1, 2, 3 and 4
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| P3P 1 | Human Puffing Topography (HPT) Parameters (Puff Volume) of Four P3P Variants During the Fixed Puffing Regimen Period. | Total Puff Volume (per product) | 732 mL |
| P3P 1 | Human Puffing Topography (HPT) Parameters (Puff Volume) of Four P3P Variants During the Fixed Puffing Regimen Period. | Average Puff Volume (per product) | 61.0 mL |
| P3P 2 | Human Puffing Topography (HPT) Parameters (Puff Volume) of Four P3P Variants During the Fixed Puffing Regimen Period. | Average Puff Volume (per product) | 66.9 mL |
| P3P 2 | Human Puffing Topography (HPT) Parameters (Puff Volume) of Four P3P Variants During the Fixed Puffing Regimen Period. | Total Puff Volume (per product) | 806 mL |
| P3P 3 | Human Puffing Topography (HPT) Parameters (Puff Volume) of Four P3P Variants During the Fixed Puffing Regimen Period. | Total Puff Volume (per product) | 878 mL |
| P3P 3 | Human Puffing Topography (HPT) Parameters (Puff Volume) of Four P3P Variants During the Fixed Puffing Regimen Period. | Average Puff Volume (per product) | 72.8 mL |
| P3P 4 | Human Puffing Topography (HPT) Parameters (Puff Volume) of Four P3P Variants During the Fixed Puffing Regimen Period. | Total Puff Volume (per product) | 845 mL |
| P3P 4 | Human Puffing Topography (HPT) Parameters (Puff Volume) of Four P3P Variants During the Fixed Puffing Regimen Period. | Average Puff Volume (per product) | 70.4 mL |
Secondary
Peak Plasma Nicotine Concentration [Cpeak]
To measure the Peak plasma nicotine concentration \[Cpeak\] of four P3P variants from the ad libitum use period, following correction of baseline nicotine levels.
Time frame: Derived from multiple blood sampling (measured at 10 mins, 20 mins, 30 mins, 40 mins, 1 hour, 2 hours, and 4 hours during and post-ad libitum use) on Days 1, 2, 3 and 4
Population: Baseline correction of nicotine concentrations could be performed for 16 out of the 18 randomized subjects.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| P3P 1 | Peak Plasma Nicotine Concentration [Cpeak] | 5.38 ng/mL |
| P3P 2 | Peak Plasma Nicotine Concentration [Cpeak] | 5.41 ng/mL |
| P3P 3 | Peak Plasma Nicotine Concentration [Cpeak] | 2.63 ng/mL |
| P3P 4 | Peak Plasma Nicotine Concentration [Cpeak] | 4.67 ng/mL |
Secondary
Plasma Nicotine Concentration-time Profile
To measure the plasma nicotine concentration-time profile of four P3P variants from the ad libitum use period, following correction of baseline nicotine levels.
Time frame: Derived from multiple blood sampling (measured at 10 mins, 20 mins, 30 mins, 40 mins, 1 hour, 2 hours, and 4 hours during and post-ad libitum use) on Days 1, 2, 3 and 4
Population: Baseline correction of nicotine concentrations could be performed for 16 out of the 18 randomized subjects.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| P3P 1 | Plasma Nicotine Concentration-time Profile | 10 minutes after start of ad libitum product use | 1.78 ng/mL |
| P3P 1 | Plasma Nicotine Concentration-time Profile | 2 hours after start of ad libitum product use | 3.91 ng/mL |
| P3P 1 | Plasma Nicotine Concentration-time Profile | 1 hour after start of ad libitum product use | 5.28 ng/mL |
| P3P 1 | Plasma Nicotine Concentration-time Profile | 20 minutes after start of ad libitum product use | 2.31 ng/mL |
| P3P 1 | Plasma Nicotine Concentration-time Profile | 4 hours after start of ad libitum product use | 2.07 ng/mL |
| P3P 1 | Plasma Nicotine Concentration-time Profile | 30 minutes after start of ad libitum product use | 3.23 ng/mL |
| P3P 1 | Plasma Nicotine Concentration-time Profile | 40 minutes after start of ad libitum product use | 3.96 ng/mL |
| P3P 2 | Plasma Nicotine Concentration-time Profile | 2 hours after start of ad libitum product use | 4.42 ng/mL |
| P3P 2 | Plasma Nicotine Concentration-time Profile | 40 minutes after start of ad libitum product use | 4.05 ng/mL |
| P3P 2 | Plasma Nicotine Concentration-time Profile | 30 minutes after start of ad libitum product use | 3.17 ng/mL |
| P3P 2 | Plasma Nicotine Concentration-time Profile | 1 hour after start of ad libitum product use | 5.23 ng/mL |
| P3P 2 | Plasma Nicotine Concentration-time Profile | 4 hours after start of ad libitum product use | 2.35 ng/mL |
| P3P 2 | Plasma Nicotine Concentration-time Profile | 20 minutes after start of ad libitum product use | 2.27 ng/mL |
| P3P 2 | Plasma Nicotine Concentration-time Profile | 10 minutes after start of ad libitum product use | 1.48 ng/mL |
| P3P 3 | Plasma Nicotine Concentration-time Profile | 40 minutes after start of ad libitum product use | 1.98 ng/mL |
| P3P 3 | Plasma Nicotine Concentration-time Profile | 10 minutes after start of ad libitum product use | 0.945 ng/mL |
| P3P 3 | Plasma Nicotine Concentration-time Profile | 20 minutes after start of ad libitum product use | 1.21 ng/mL |
| P3P 3 | Plasma Nicotine Concentration-time Profile | 30 minutes after start of ad libitum product use | 1.68 ng/mL |
| P3P 3 | Plasma Nicotine Concentration-time Profile | 1 hour after start of ad libitum product use | 2.67 ng/mL |
| P3P 3 | Plasma Nicotine Concentration-time Profile | 2 hours after start of ad libitum product use | 1.84 ng/mL |
| P3P 3 | Plasma Nicotine Concentration-time Profile | 4 hours after start of ad libitum product use | 0.917 ng/mL |
| P3P 4 | Plasma Nicotine Concentration-time Profile | 30 minutes after start of ad libitum product use | 2.87 ng/mL |
| P3P 4 | Plasma Nicotine Concentration-time Profile | 4 hours after start of ad libitum product use | 1.81 ng/mL |
| P3P 4 | Plasma Nicotine Concentration-time Profile | 2 hours after start of ad libitum product use | 3.61 ng/mL |
| P3P 4 | Plasma Nicotine Concentration-time Profile | 20 minutes after start of ad libitum product use | 2.06 ng/mL |
| P3P 4 | Plasma Nicotine Concentration-time Profile | 10 minutes after start of ad libitum product use | 1.49 ng/mL |
| P3P 4 | Plasma Nicotine Concentration-time Profile | 1 hour after start of ad libitum product use | 4.42 ng/mL |
| P3P 4 | Plasma Nicotine Concentration-time Profile | 40 minutes after start of ad libitum product use | 3.86 ng/mL |
Secondary
Product Evaluation
Measured with an adapted version of the modified Cigarette Evaluation Questionnaire (adapted mCEQ) following the ad libitum use period. Assessed on a 7-point scale, ranging from 1 (not at all) to 7 (extremely).
Time frame: Within 60 minutes after the ad libitum use session on days 1, 2, 3 and 4
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| P3P 1 | Product Evaluation | Aversion | 1.23 score on a scale |
| P3P 1 | Product Evaluation | Enjoyment of Respiratory Tract Sensations | 2.60 score on a scale |
| P3P 1 | Product Evaluation | Craving Reduction | 4.42 score on a scale |
| P3P 1 | Product Evaluation | Psychological Reward | 3.12 score on a scale |
| P3P 1 | Product Evaluation | Product Satisfaction | 3.22 score on a scale |
| P3P 2 | Product Evaluation | Psychological Reward | 3.38 score on a scale |
| P3P 2 | Product Evaluation | Aversion | 1.20 score on a scale |
| P3P 2 | Product Evaluation | Craving Reduction | 4.58 score on a scale |
| P3P 2 | Product Evaluation | Enjoyment of Respiratory Tract Sensations | 3.88 score on a scale |
| P3P 2 | Product Evaluation | Product Satisfaction | 4.40 score on a scale |
| P3P 3 | Product Evaluation | Psychological Reward | 3.21 score on a scale |
| P3P 3 | Product Evaluation | Product Satisfaction | 4.42 score on a scale |
| P3P 3 | Product Evaluation | Enjoyment of Respiratory Tract Sensations | 3.75 score on a scale |
| P3P 3 | Product Evaluation | Aversion | 1.10 score on a scale |
| P3P 3 | Product Evaluation | Craving Reduction | 4.14 score on a scale |
| P3P 4 | Product Evaluation | Aversion | 1.03 score on a scale |
| P3P 4 | Product Evaluation | Enjoyment of Respiratory Tract Sensations | 3.60 score on a scale |
| P3P 4 | Product Evaluation | Product Satisfaction | 4.13 score on a scale |
| P3P 4 | Product Evaluation | Psychological Reward | 3.25 score on a scale |
| P3P 4 | Product Evaluation | Craving Reduction | 4.58 score on a scale |
Secondary
Sensory Parameters
Measured with a Sensory Questionnaire (SQ) following the 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: Within 60 minutes after the ad libitum use session on days 1, 2, 3 and 4
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| P3P 1 | Sensory Parameters | Puff Strength in Windpipe | 4.38 score on a scale |
| P3P 1 | Sensory Parameters | Puffs Strength on Tongue | 3.44 score on a scale |
| P3P 1 | Sensory Parameters | Puffs Similarity to Own Brand | 2.57 score on a scale |
| P3P 1 | Sensory Parameters | Puffs Evaluation/Liking | 3.17 score on a scale |
| P3P 1 | Sensory Parameters | Puff Strength in Chest | 3.48 score on a scale |
| P3P 1 | Sensory Parameters | Puffs Strength in Back of Mouth/Throat | 4.40 score on a scale |
| P3P 1 | Sensory Parameters | Puffs Strength in Nose | 1.89 score on a scale |
| P3P 1 | Sensory Parameters | Puffs Harshness | 4.67 score on a scale |
| P3P 2 | Sensory Parameters | Puffs Strength in Nose | 1.56 score on a scale |
| P3P 2 | Sensory Parameters | Puffs Evaluation/Liking | 4.22 score on a scale |
| P3P 2 | Sensory Parameters | Puffs Harshness | 3.61 score on a scale |
| P3P 2 | Sensory Parameters | Puffs Similarity to Own Brand | 2.63 score on a scale |
| P3P 2 | Sensory Parameters | Puffs Strength on Tongue | 3.10 score on a scale |
| P3P 2 | Sensory Parameters | Puffs Strength in Back of Mouth/Throat | 3.56 score on a scale |
| P3P 2 | Sensory Parameters | Puff Strength in Windpipe | 3.44 score on a scale |
| P3P 2 | Sensory Parameters | Puff Strength in Chest | 2.81 score on a scale |
| P3P 3 | Sensory Parameters | Puffs Strength in Nose | 1.89 score on a scale |
| P3P 3 | Sensory Parameters | Puffs Strength on Tongue | 3.53 score on a scale |
| P3P 3 | Sensory Parameters | Puffs Evaluation/Liking | 4.22 score on a scale |
| P3P 3 | Sensory Parameters | Puffs Strength in Back of Mouth/Throat | 3.69 score on a scale |
| P3P 3 | Sensory Parameters | Puff Strength in Chest | 2.39 score on a scale |
| P3P 3 | Sensory Parameters | Puff Strength in Windpipe | 3.14 score on a scale |
| P3P 3 | Sensory Parameters | Puffs Similarity to Own Brand | 2.78 score on a scale |
| P3P 3 | Sensory Parameters | Puffs Harshness | 3.67 score on a scale |
| P3P 4 | Sensory Parameters | Puffs Strength in Nose | 1.72 score on a scale |
| P3P 4 | Sensory Parameters | Puff Strength in Windpipe | 3.77 score on a scale |
| P3P 4 | Sensory Parameters | Puffs Strength on Tongue | 2.88 score on a scale |
| P3P 4 | Sensory Parameters | Puffs Evaluation/Liking | 3.78 score on a scale |
| P3P 4 | Sensory Parameters | Puffs Similarity to Own Brand | 2.30 score on a scale |
| P3P 4 | Sensory Parameters | Puff Strength in Chest | 3.37 score on a scale |
| P3P 4 | Sensory Parameters | Puffs Harshness | 3.72 score on a scale |
| P3P 4 | Sensory Parameters | Puffs Strength in Back of Mouth/Throat | 3.79 score on a scale |
Secondary
Time to Peak Plasma Nicotine Concentration [Tpeak]
To measure the time to peak plasma nicotine concentration \[Tpeak\] of four P3P variants from the ad libitum use period, following correction of baseline nicotine levels.
Time frame: Derived from multiple blood sampling (measured at 10 mins, 20 mins, 30 mins, 40 mins, 1 hour, 2 hours, and 4 hours during and post-ad libitum use) on Days 1, 2, 3 and 4
Population: Baseline correction of nicotine concentrations could be performed for 16 out of the 18 randomized subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| P3P 1 | Time to Peak Plasma Nicotine Concentration [Tpeak] | 65.0 minutes | Standard Deviation 22.5 |
| P3P 2 | Time to Peak Plasma Nicotine Concentration [Tpeak] | 82.4 minutes | Standard Deviation 52.1 |
| P3P 3 | Time to Peak Plasma Nicotine Concentration [Tpeak] | 68.0 minutes | Standard Deviation 27.2 |
| P3P 4 | Time to Peak Plasma Nicotine Concentration [Tpeak] | 61.9 minutes | Standard Deviation 24.8 |
Secondary
Trough Plasma Nicotine Concentration [Ctrough]
To measure the trough plasma nicotine concentration \[Ctrough\] of four P3P variants from the ad libitum use period, following correction of baseline nicotine levels.
Time frame: Derived from multiple blood sampling (measured at 10 mins, 20 mins, 30 mins, 40 mins, 1 hour, 2 hours, and 4 hours during and post-ad libitum use) on Days 1, 2, 3 and 4
Population: Baseline correction of nicotine concentrations could be performed for 16 out of the 18 randomized subjects.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| P3P 1 | Trough Plasma Nicotine Concentration [Ctrough] | 1.80 ng/mL |
| P3P 2 | Trough Plasma Nicotine Concentration [Ctrough] | 1.58 ng/mL |
| P3P 3 | Trough Plasma Nicotine Concentration [Ctrough] | 1.13 ng/mL |
| P3P 4 | Trough Plasma Nicotine Concentration [Ctrough] | 1.56 ng/mL |