Nicotine Pharmacokinetics and Pharmacodynamics, Safety and Tolerability of P3P

Philip Morris

Status: Completed

Conditions: Pharmacokinetics

Treatments: Other: P3P 3; Other: P3P 2; Other: P3P 1; Other: P3P 4

Study type: Interventional

Funder types: Industry

Identifiers

NCT03369340

P3P-PK-01-CH

Details and patient eligibility

About

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.

Full 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.

Enrollment: 19 patients

Sex: All

Ages: 21 to 65 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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19 participants in 6 patient groups

Product Sequence 1

Active Comparator group

Description:

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

Treatment:

Other: P3P 2

Other: P3P 1

Other: P3P 4

Other: P3P 3

Product Sequence 2

Active Comparator group

Description:

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

Treatment:

Other: P3P 2

Other: P3P 1

Other: P3P 4

Other: P3P 3

Product Sequence 3

Active Comparator group

Description:

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

Treatment:

Other: P3P 2

Other: P3P 1

Other: P3P 4

Other: P3P 3

Product Sequence 4

Active Comparator group

Description:

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

Treatment:

Other: P3P 2

Other: P3P 1

Other: P3P 4

Other: P3P 3

Product Sequence 5

Active Comparator group

Description:

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

Treatment:

Other: P3P 2

Other: P3P 1

Other: P3P 4

Other: P3P 3

Product Sequence 6

Active Comparator group

Description:

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

Treatment:

Other: P3P 2

Other: P3P 1

Other: P3P 4

Other: P3P 3