Clinical trial NCT03369340: Nicotine Pharmacokinetics and Pharmacodynamics, Safety and Tolerability of P3P
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pharmacokinetics
Keywords: Nicotine
Nicotine-containing product
Lead sponsor: Philip Morris Products S.A.
Sponsor class: INDUSTRY
First posted: 2017-12-12
Enrollment: 19
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: A single-center, open-label, randomized, crossover study.
Primary purpose: OTHER

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Plasma Nicotine Concentration-time Profile
timeFrame: 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
measure: Maximum Plasma Concentration [Cmax]
timeFrame: 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
measure: Time to the Maximum Nicotine Concentration [Tmax]
timeFrame: 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
measure: Area Under the Concentration-time Curve From Start of Product Use (T0 Fix) to 4 Hours [AUCfix (0-4h)]
timeFrame: 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
Secondary outcomes:
measure: Plasma Nicotine Concentration-time Profile
timeFrame: 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
measure: Peak Plasma Nicotine Concentration [Cpeak]
timeFrame: 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
measure: Time to Peak Plasma Nicotine Concentration [Tpeak]
timeFrame: 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
measure: Trough Plasma Nicotine Concentration [Ctrough]
timeFrame: 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
measure: Average of Plasma Nicotine Concentration From T0 ad Lib to 1 Hour [Caverage]
timeFrame: 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
measure: Area Under the Concentration-time Curve From Start of Product Use (T0 ad Lib) to 4 Hours [AUCad Lib (0-4h)]
timeFrame: 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
measure: AUC of Craving for a Cigarette During and After the Fixed Puffing Regimen
timeFrame: During and up to 4 hours post-product use on days 1, 2, 3 and 4
measure: AUC Craving for a Cigarette During and After the ad Libitum Use Period
timeFrame: During and up to 4 hours post-product use on days 1, 2, 3 and 4
measure: Product Evaluation
timeFrame: Within 60 minutes after the ad libitum use session on days 1, 2, 3 and 4
measure: Sensory Parameters
timeFrame: Within 60 minutes after the ad libitum use session on days 1, 2, 3 and 4
measure: Human Puffing Topography (HPT) Parameters (Puff Volume) of Four P3P Variants During the Fixed Puffing Regimen Period.
timeFrame: During fixed puffing product use on days 1, 2, 3 and 4
measure: Human Puffing Topography (HPT) Parameters (Puff Volume) of Four P3P Variants During the ad Libitum Use Period.
timeFrame: During ad libitum product use on days 1, 2, 3 and 4
measure: Amount of Powder Aerosolized From P3P From the Fixed Puffing Regimen.
timeFrame: Before and after fixed puffing product use on days 1, 2, 3 and 4
measure: Amount of Powder Aerosolized From P3P From the ad Libitum Use Period (Per Product Used).
timeFrame: Before and after ad libitum product use on days 1, 2, 3 and 4
Other outcomes:
Locations:
city: Arzo
country: Switzerland
facility: CROSS Research
state: Ticino
Study officials:
affiliation: Philip Morris Products S.A.
name: Christelle Haziza, PhD
role: STUDY_CHAIR
affiliation: CROSS Research, Arzo, Ticino, Switzerland
name: Milko Radicioni, MD
role: PRINCIPAL_INVESTIGATOR
References: