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Nicotine Pharmacokinetics and Pharmacodynamics, Safety and Tolerability of P3P

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ClinicalTrials.gov Identifier: NCT03369340
Recruitment Status : Completed
First Posted : December 12, 2017
Results First Posted : January 31, 2020
Last Update Posted : January 31, 2020
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Pharmacokinetics Other: P3P 1 Other: P3P 2 Other: P3P 3 Other: P3P 4 Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: A single-center, open-label, randomized, crossover study.
Masking: None (Open Label)
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.
Primary Purpose: Other
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
Actual Study Start Date : November 7, 2017
Actual Primary Completion Date : February 1, 2018
Actual Study Completion Date : May 2, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Product Sequence 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

Other: P3P 1
2 mg of nicotine; no flavor; nicotine powder particle size of 2.25 ± 0.2 μm

Other: P3P 2
2 mg of nicotine; flavor; nicotine powder particle size of 2.25 ± 0.2 μm

Other: P3P 3
1 mg of nicotine; flavor; nicotine powder particle size of 2.25 ± 0.2 μm

Other: P3P 4
2 mg of nicotine; flavor; nicotine powder particle size of 1.8 ± 0.2 μm

Active Comparator: Product Sequence 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

Other: P3P 1
2 mg of nicotine; no flavor; nicotine powder particle size of 2.25 ± 0.2 μm

Other: P3P 2
2 mg of nicotine; flavor; nicotine powder particle size of 2.25 ± 0.2 μm

Other: P3P 3
1 mg of nicotine; flavor; nicotine powder particle size of 2.25 ± 0.2 μm

Other: P3P 4
2 mg of nicotine; flavor; nicotine powder particle size of 1.8 ± 0.2 μm

Active Comparator: Product Sequence 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

Other: P3P 1
2 mg of nicotine; no flavor; nicotine powder particle size of 2.25 ± 0.2 μm

Other: P3P 2
2 mg of nicotine; flavor; nicotine powder particle size of 2.25 ± 0.2 μm

Other: P3P 3
1 mg of nicotine; flavor; nicotine powder particle size of 2.25 ± 0.2 μm

Other: P3P 4
2 mg of nicotine; flavor; nicotine powder particle size of 1.8 ± 0.2 μm

Active Comparator: Product Sequence 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

Other: P3P 1
2 mg of nicotine; no flavor; nicotine powder particle size of 2.25 ± 0.2 μm

Other: P3P 2
2 mg of nicotine; flavor; nicotine powder particle size of 2.25 ± 0.2 μm

Other: P3P 3
1 mg of nicotine; flavor; nicotine powder particle size of 2.25 ± 0.2 μm

Other: P3P 4
2 mg of nicotine; flavor; nicotine powder particle size of 1.8 ± 0.2 μm

Active Comparator: Product Sequence 5

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

Other: P3P 1
2 mg of nicotine; no flavor; nicotine powder particle size of 2.25 ± 0.2 μm

Other: P3P 2
2 mg of nicotine; flavor; nicotine powder particle size of 2.25 ± 0.2 μm

Other: P3P 3
1 mg of nicotine; flavor; nicotine powder particle size of 2.25 ± 0.2 μm

Other: P3P 4
2 mg of nicotine; flavor; nicotine powder particle size of 1.8 ± 0.2 μm

Active Comparator: Product Sequence 6

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

Other: P3P 1
2 mg of nicotine; no flavor; nicotine powder particle size of 2.25 ± 0.2 μm

Other: P3P 2
2 mg of nicotine; flavor; nicotine powder particle size of 2.25 ± 0.2 μm

Other: P3P 3
1 mg of nicotine; flavor; nicotine powder particle size of 2.25 ± 0.2 μm

Other: P3P 4
2 mg of nicotine; flavor; nicotine powder particle size of 1.8 ± 0.2 μm




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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 Outcome Measures :
  1. Plasma Nicotine Concentration-time Profile [ 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 ]
    To measure the plasma nicotine concentration-time profile of four P3P variants from the ad libitum use period, following correction of baseline nicotine levels.

  2. Peak Plasma Nicotine Concentration [Cpeak] [ 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 ]
    To measure the Peak plasma nicotine concentration [Cpeak] of four P3P variants from the ad libitum use period, following correction of baseline nicotine levels.

  3. Time to Peak Plasma Nicotine Concentration [Tpeak] [ 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 ]
    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.

  4. Trough Plasma Nicotine Concentration [Ctrough] [ 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 ]
    To measure the trough plasma nicotine concentration [Ctrough] of four P3P variants from the ad libitum use period, following correction of baseline nicotine levels.

  5. Average of Plasma Nicotine Concentration From T0 ad Lib to 1 Hour [Caverage] [ 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 ]
    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

  6. Area Under the Concentration-time Curve From Start of Product Use (T0 ad Lib) to 4 Hours [AUCad Lib (0-4h)] [ 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 ]
    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.

  7. AUC of Craving for a Cigarette During and After the Fixed Puffing Regimen [ Time Frame: 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).

  8. AUC Craving for a Cigarette During and After the ad Libitum Use Period [ Time Frame: 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).

  9. Product Evaluation [ Time Frame: 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).

  10. Sensory Parameters [ Time Frame: 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).

  11. Human Puffing Topography (HPT) Parameters (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 ]
    Descriptive statistics of total puff volume and average puff volume, of four P3P variants, during the fixed puffing regimen period.

  12. Human Puffing Topography (HPT) Parameters (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 ]
    Descriptive statistics of total puff volume and average puff volume, of four P3P variants, during the ad libitum use period.

  13. Amount of Powder Aerosolized From P3P From the Fixed Puffing Regimen. [ Time Frame: 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.

  14. Amount of Powder Aerosolized From P3P From the ad Libitum Use Period (Per Product Used). [ Time Frame: 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).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   21 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03369340


Locations
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Switzerland
CROSS Research
Arzo, Ticino, Switzerland, 6864
Sponsors and Collaborators
Philip Morris Products S.A.
Investigators
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Study Chair: Christelle Haziza, PhD Philip Morris Products S.A.
Principal Investigator: Milko Radicioni, MD CROSS Research, Arzo, Ticino, Switzerland
  Study Documents (Full-Text)

Documents provided by Philip Morris Products S.A.:
Study Protocol  [PDF] July 24, 2017
Statistical Analysis Plan  [PDF] April 30, 2018

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Responsible Party: Philip Morris Products S.A.
ClinicalTrials.gov Identifier: NCT03369340    
Other Study ID Numbers: P3P-PK-01-CH
First Posted: December 12, 2017    Key Record Dates
Results First Posted: January 31, 2020
Last Update Posted: January 31, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Philip Morris Products S.A.:
Nicotine
Nicotine-containing product