Product Use and Adaptation, Safety and Tolerability of P3P in Adult Healthy Smokers Switching to it

• ClinicalTrials.gov Identifier: NCT03953183
• Recruitment Status: Completed
• First Posted: May 16, 2019
• Results First Posted: December 14, 2020
• Last Update Posted: December 14, 2020
• Sponsor: Philip Morris Products S.A.
• Information provided by (Responsible Party): Philip Morris Products S.A.

Study Description

Brief Summary:

The purpose of the study is to evaluate the product use and adaptation in adult, current cigarette smoking subjects between baseline and after one month of use of one of two P3P variants. The effect of P3P use behavior on nicotine pharmacokinetic (PK) profile, acceptability, as well as the safety and tolerability of P3P over a period of 1 month will be investigated.

Condition or disease	Intervention/treatment	Phase
Pharmacokinetics	Other: P3P-1mg; Other: P3P-2mg	Not Applicable

Detailed Description:

This is a study of daily use of up to 15 P3P products over one month, including 2 confinement periods (2 overnight stays at the beginning of the study and 1 overnight stay at the end of the exposure period). During the confinement visits, nicotine PK from P3P exposure will be assessed as well as pharmacodynamic effects related to craving, sensory parameters, product experience, and product acceptance.

Between the two confinement periods, subjects will return to the investigational site for weekly ambulatory visits during which P3P will be resupplied and selected safety and other study assessments will be performed.

From the start of the exposure period onwards, subjects will be instructed not to smoke or use other tobacco or nicotine containing products and to use P3P exclusively.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: A randomized, double-blinded, 2-arm parallel groups, single center study
• Masking: Double (Participant, Investigator)
• Masking Description: Neither the site staff nor the subject will be informed about the product variant the subjects have been randomized to.
• Primary Purpose: Basic Science
• Official Title: A Randomized, Double-blinded, 2-arm Parallel Groups, Single Center Study to Assess Product Use and Adaptation, Safety and Tolerability of P3P, a Novel Nicotine-containing Product, in Adult Healthy Cigarette Smokers Switching to One of Two P3P Variants for One Month
• Actual Study Start Date: April 23, 2019
• Actual Primary Completion Date: August 14, 2019
• Actual Study Completion Date: October 25, 2019

Arms and Interventions

Arm	Intervention/treatment
P3P-1mg; Subjects randomized to exclusive use of P3P-1mg	Other: P3P-1mg; P3P-1mg (P3P product containing 1mg of nicotine.)
P3P-2mg; Subjects randomized to exclusive use of P3P-2mg	Other: P3P-2mg; P3P-2mg (P3P product containing 2mg of nicotine.)

Outcome Measures

Primary Outcome Measures :

1. Plasma Nicotine Concentration-time Profile [ Time Frame: Derived from multiple blood sampling pre- and post-product use (over 4 hours post-product use), on day 1 and day 30. ]
   To measure the plasma nicotine concentration-time profile following correction of baseline nicotine levels.
2. Maximum Nicotine Concentration [cCmax] [ Time Frame: Derived from multiple blood sampling pre- and post-product use (over 4 hours post-product use), on day 1 and day 30. ]
   To measure the maximum plasma nicotine concentration [cCmax] following correction of baseline nicotine levels.
3. Time to the Maximum Nicotine Concentration [cTmax] [ Time Frame: Derived from multiple blood sampling pre- and post-product use (over 4 hours post-product use), on day 1 and day 30. ]
   To measure the time to maximum nicotine concentration [cTmax] following correction of baseline nicotine levels.
4. Area Under the Concentration-time Curve From Start of Product Use (T0) to 4 Hours [cAUC(0-4h)] [ Time Frame: Derived from multiple blood sampling pre- and post-product use (over 4 hours post-product use), on day 1 and day 30. ]
   To measure the area under the plasma concentration-time curve [cAUC(0-4h)] following correction of baseline nicotine levels.

Secondary Outcome Measures :

1. Craving for a Cigarette [ Time Frame: Before, during and up to 4 hours post-product use on day 1 and day 30 ]
   Measured on a Visual Analogue Scale (VAS) of 0 (no craving) to 100 (strong craving). Over time results calculated as area under curve mm*hour.
2. Sensory Parameters [ Time Frame: Within 60 minutes after product use on day 1 and day 30. ]
   Measured with a Sensory Questionnaire. Response to each question is assessed on a 7-point scale, ranging from 1 (not at all) to 7 (extremely).
3. Product Experience [ Time Frame: Within 60 minutes after product use on day 1 and day 30. ]
   Measured with ABOUT[TM]-Product Experience questionnaire. Response to each question is assessed on a 7-point scale, ranging from 1 (not at all) to 7 (extremely).
4. Product Dependence [ Time Frame: Within 60 minutes after product use on day 1 and day 30. ]
   Measured with ABOUT[TM]-Dependence questionnaire. Response to each question is assessed on a 5-point scale, ranging from 1 (not at all/never) to 5 (extremely/all the time) or a 6-point scale ranging from 0 (more than 3 hours) to 5 (0-5 minutes).
5. Product Acceptance [ Time Frame: Within 60 minutes after product use on day 1 and day 30. ]
   Measured with a Product Acceptance questionnaire. Response to each question is assessed on a 7-point scale, ranging from 1 (most negative) to 7 (most positive) or as multiple choice questions.
6. Puffing Behavior of Subject [ Time Frame: Evaluated by site staff on day 1 and day 30. Self-evaluated by subject on day 2, day 7, day 15, day 22, and day 29. ]

   To measure changes in subject puffing behavior. Evaluated by selection of one puffing behavior response out of three possible responses.

   • 1. Puffing and holding the aerosol in the mouth for a short time and then inhaling (i.e. like a cigarette)
   • 2. Puffing and immediately inhaling (without holding the aerosol in the mouth)
   • 3. Puffing and immediately exhaling, without inhalation
7. Overall Product Use [ Time Frame: Recorded daily by subject, in product use diary, from day 1 until day 30. ]
   To assess the number of any nicotine/tobacco products used overall on a daily basis.
8. NEQ [ Time Frame: Measured at baseline, day 7, day 15, day 22, and day 29. ]
   To measure percent changes from baseline in Nicotine equivalents (NEQ) concentrations, measured in spot urine and expressed as concentration adjusted for creatinine.
9. Total NNAL [ Time Frame: Measured at baseline, day 7, day 15, day 22, and day 29. ]
   To measure percent changes from baseline in total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) concentrations, measured in spot urine and expressed as concentration adjusted for creatinine.
10. CEMA [ Time Frame: Measured at baseline, day 7, day 15, day 22, and day 29. ]
    To measure percent changes from baseline in 2-cyanoethylmercapturic acid (CEMA) concentrations, measured in spot urine and expressed as concentration adjusted for creatinine (ng/mg creat).
11. CYP2A6 Activity [ Time Frame: Measured before product use, on day 1 and day 30. ]
    To measure percent change from baseline in CYP2A6 enzymatic activity, on day 30, as measured by molar metabolic ratio of trans-3-hydroxy-cotinine/cotinine in plasma.
12. Amount of Powder Extracted From P3P Used for PK Assessment. [ Time Frame: Before and after product use, on day 1 and day 30. ]
    Weight difference (mg) of P3P before and after use, to determine the amount of powder extracted from P3P.

Eligibility Criteria

• 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 and dated the ICF and is able to understand the information provided in it.
• Subject has been a smoker for at least the last 3 years prior to the Screening Visit and has smoked 5 to 15 commercially available cigarettes per day for the last 3 months prior to Screening.
• Subject has a positive urinary cotinine test (cotinine ≥ 200 ng/mL).
• Subject does not plan to quit smoking within 2 months.
• Smoking, healthy subject as judged by the Investigator or designee based on available assessments from the Screening period.
• Ready to switch from smoking cigarettes to using P3P for the duration of the study.

Exclusion Criteria:

• As per the Investigator's judgment, the subject cannot participate in the study for any reason other than medical (e.g., psychological and/or social reason).
• Subject has a clinically relevant disease which requires medication or any other clinically significant medical condition, which as per the judgment of the Investigator would jeopardize the safety of the subject.
• Subject has asthma condition (post-bronchodilator FEV1/FVC < 0.75 and reversibility in FEV1 ≥ 12% and > 200 mL from pre- to post-bronchodilator values).
• Subject has (FEV1/FVC) < 0.7 and FEV1 < 80% predicted value at post-bronchodilator spirometry.
• Subject has a BMI < 18.5 kg/m2 or > 32.0 kg/m2.
• Subject has received medication within 14 days or within 5 half-lives of the drug prior to Admission (whichever is longer) which has an impact on CYP2A6 activity.
• Subject has a positive serology test for HIV 1/2, Hepatitis B, or Hepatitis C.
• Subject has a positive alcohol breath test and/or a history of alcohol disorder within the past 2 years.
• Subject has a positive urine drug test.
• Subject has participated in another clinical study within 3 months prior to the Screening Visit.
• Subject has been previously screened or enrolled in this study.
• For women only: subject is pregnant or is breastfeeding.
• For women of childbearing potential only: subject does not agree to use an acceptable method of effective contraception.

Contacts and Locations

Locations

Russian Federation

LLC Scientific Research Center Eco-Safety

St. Petersburg, Russian Federation, 196143

Sponsors and Collaborators

Philip Morris Products S.A.

Investigators

• Study Chair: Christelle Haziza, PhD; Philip Morris Products SA
• Principal Investigator: Vasilyuk V Bogdanovich, MD; LLC Scientific Research Center Eco-Safety

  Study Documents (Full-Text)

Documents provided by Philip Morris Products S.A.:

Study Protocol  [PDF] June 12, 2019

Statistical Analysis Plan  [PDF] October 24, 2019

More Information

Publications:

Chrea C, Acquadro C, Afolalu EF, Spies E, Salzberger T, Abetz-Webb L, Cano S, Arnould B, Mainy N, Rose J, Weitkunat R. Developing fit-for-purpose self-report instruments for assessing consumer responses to tobacco and nicotine products: the ABOUT Toolbox initiative. F1000Res. 2018 Dec 2;7:1878. doi: 10.12688/f1000research.16810.1. eCollection 2018.

• Responsible Party: Philip Morris Products S.A.
• ClinicalTrials.gov Identifier: NCT03953183
• Other Study ID Numbers: P3P-SE-02-RU
• First Posted: May 16, 2019
• Results First Posted: December 14, 2020
• Last Update Posted: December 14, 2020
• Last Verified: November 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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