Nicotine Pharmacokinetics and Pharmacodynamics, Safety and Tolerability of P3P

Not Applicable

Completed

Conditions: Pharmacokinetics

Interventions: Other: P3P 1
Other: P3P 2
Other: P3P 3
Other: P3P 4

Registration Number: NCT03369340

Lead Sponsor: Philip Morris Products S.A.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 19

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Product Sequence 1	P3P 1	Subjects will be exposed to P3P 3 on day 1 of the study, then randomized to follow a sequence of product exposure comprised of: P3P 2 on Day 2; P3P 4 on Day 3; P3P 1 on Day 4
Product Sequence 2	P3P 1	Subjects will be exposed to P3P 3 on day 1 of the study, then randomized to follow a sequence of product exposure comprised of: P3P 4 on Day 2; P3P 1 on Day 3; P3P 2 on Day 4
Product Sequence 3	P3P 3	Subjects will be exposed to P3P 3 on day 1 of the study, then randomized to follow a sequence of product exposure comprised of: P3P 1 on Day 2; P3P 2 on Day 3; P3P 4 on Day 4
Product Sequence 2	P3P 2	Subjects will be exposed to P3P 3 on day 1 of the study, then randomized to follow a sequence of product exposure comprised of: P3P 4 on Day 2; P3P 1 on Day 3; P3P 2 on Day 4
Product Sequence 6	P3P 4	Subjects will be exposed to P3P 3 on day 1 of the study, then randomized to follow a sequence of product exposure comprised of: P3P 4 on Day 2; P3P 2 on Day 3; P3P 1 on Day 4
Product Sequence 2	P3P 4	Subjects will be exposed to P3P 3 on day 1 of the study, then randomized to follow a sequence of product exposure comprised of: P3P 4 on Day 2; P3P 1 on Day 3; P3P 2 on Day 4
Product Sequence 5	P3P 1	Subjects will be exposed to P3P 3 on day 1 of the study, then randomized to follow a sequence of product exposure comprised of: P3P 2 on Day 2; P3P 1 on Day 3; P3P 4 on Day 4
Product Sequence 5	P3P 2	Subjects will be exposed to P3P 3 on day 1 of the study, then randomized to follow a sequence of product exposure comprised of: P3P 2 on Day 2; P3P 1 on Day 3; P3P 4 on Day 4
Product Sequence 1	P3P 2	Subjects will be exposed to P3P 3 on day 1 of the study, then randomized to follow a sequence of product exposure comprised of: P3P 2 on Day 2; P3P 4 on Day 3; P3P 1 on Day 4
Product Sequence 1	P3P 3	Subjects will be exposed to P3P 3 on day 1 of the study, then randomized to follow a sequence of product exposure comprised of: P3P 2 on Day 2; P3P 4 on Day 3; P3P 1 on Day 4
Product Sequence 3	P3P 1	Subjects will be exposed to P3P 3 on day 1 of the study, then randomized to follow a sequence of product exposure comprised of: P3P 1 on Day 2; P3P 2 on Day 3; P3P 4 on Day 4
Product Sequence 3	P3P 2	Subjects will be exposed to P3P 3 on day 1 of the study, then randomized to follow a sequence of product exposure comprised of: P3P 1 on Day 2; P3P 2 on Day 3; P3P 4 on Day 4
Product Sequence 6	P3P 1	Subjects will be exposed to P3P 3 on day 1 of the study, then randomized to follow a sequence of product exposure comprised of: P3P 4 on Day 2; P3P 2 on Day 3; P3P 1 on Day 4
Product Sequence 1	P3P 4	Subjects will be exposed to P3P 3 on day 1 of the study, then randomized to follow a sequence of product exposure comprised of: P3P 2 on Day 2; P3P 4 on Day 3; P3P 1 on Day 4
Product Sequence 2	P3P 3	Subjects will be exposed to P3P 3 on day 1 of the study, then randomized to follow a sequence of product exposure comprised of: P3P 4 on Day 2; P3P 1 on Day 3; P3P 2 on Day 4
Product Sequence 3	P3P 4	Subjects will be exposed to P3P 3 on day 1 of the study, then randomized to follow a sequence of product exposure comprised of: P3P 1 on Day 2; P3P 2 on Day 3; P3P 4 on Day 4
Product Sequence 5	P3P 3	Subjects will be exposed to P3P 3 on day 1 of the study, then randomized to follow a sequence of product exposure comprised of: P3P 2 on Day 2; P3P 1 on Day 3; P3P 4 on Day 4
Product Sequence 5	P3P 4	Subjects will be exposed to P3P 3 on day 1 of the study, then randomized to follow a sequence of product exposure comprised of: P3P 2 on Day 2; P3P 1 on Day 3; P3P 4 on Day 4
Product Sequence 4	P3P 1	Subjects will be exposed to P3P 3 on day 1 of the study, then randomized to follow a sequence of product exposure comprised of: P3P 1 on Day 2; P3P 4 on Day 3; P3P 2 on Day 4
Product Sequence 4	P3P 2	Subjects will be exposed to P3P 3 on day 1 of the study, then randomized to follow a sequence of product exposure comprised of: P3P 1 on Day 2; P3P 4 on Day 3; P3P 2 on Day 4
Product Sequence 4	P3P 3	Subjects will be exposed to P3P 3 on day 1 of the study, then randomized to follow a sequence of product exposure comprised of: P3P 1 on Day 2; P3P 4 on Day 3; P3P 2 on Day 4
Product Sequence 4	P3P 4	Subjects will be exposed to P3P 3 on day 1 of the study, then randomized to follow a sequence of product exposure comprised of: P3P 1 on Day 2; P3P 4 on Day 3; P3P 2 on Day 4
Product Sequence 6	P3P 2	Subjects will be exposed to P3P 3 on day 1 of the study, then randomized to follow a sequence of product exposure comprised of: P3P 4 on Day 2; P3P 2 on Day 3; P3P 1 on Day 4
Product Sequence 6	P3P 3	Subjects will be exposed to P3P 3 on day 1 of the study, then randomized to follow a sequence of product exposure comprised of: P3P 4 on Day 2; P3P 2 on Day 3; P3P 1 on Day 4

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.
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).
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.
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).
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).
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.