A Single-center, Open-label, Randomized, Crossover Study to Investigate the Nicotine Pharmacokinetic Profile, Pharmacodynamics, Safety and Tolerability of Four P3P Variants in Smoking Healthy Adult Subjects
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Pharmacokinetics
- Sponsor
- Philip Morris Products S.A.
- Enrollment
- 19
- Locations
- 1
- Primary Endpoint
- Plasma Nicotine Concentration-time Profile
- Status
- Completed
- Last Updated
- 6 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
Plasma Nicotine Concentration-time Profile
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
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]
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
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]
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
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)]
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
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 Outcomes
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- Product Evaluation(Within 60 minutes after the ad libitum use session on days 1, 2, 3 and 4)
- Sensory Parameters(Within 60 minutes after the ad libitum use session on days 1, 2, 3 and 4)
- 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)
- 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)