Clinical trial NCT03953183: Product Use and Adaptation, Safety and Tolerability of P3P in Adult Healthy Smokers Switching to it
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pharmacokinetics
Keywords: Nicotine
Lead sponsor: Philip Morris Products S.A.
Sponsor class: INDUSTRY
First posted: 2019-05-16
Enrollment: 60
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A randomized, double-blinded, 2-arm parallel groups, single center study
Primary purpose: BASIC_SCIENCE

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.

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.

Eligibility 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.

Primary outcomes:
measure: Plasma Nicotine Concentration-time Profile
timeFrame: Derived from multiple blood sampling pre- and post-product use (over 4 hours post-product use), on day 1 and day 30.
measure: Maximum Nicotine Concentration [cCmax]
timeFrame: Derived from multiple blood sampling pre- and post-product use (over 4 hours post-product use), on day 1 and day 30.
measure: Time to the Maximum Nicotine Concentration [cTmax]
timeFrame: Derived from multiple blood sampling pre- and post-product use (over 4 hours post-product use), on day 1 and day 30.
measure: Area Under the Concentration-time Curve From Start of Product Use (T0) to 4 Hours [cAUC(0-4h)]
timeFrame: Derived from multiple blood sampling pre- and post-product use (over 4 hours post-product use), on day 1 and day 30.
Secondary outcomes:
measure: Craving for a Cigarette
timeFrame: Before, during and up to 4 hours post-product use on day 1 and day 30
measure: Sensory Parameters
timeFrame: Within 60 minutes after product use on day 1 and day 30.
measure: Product Experience
timeFrame: Within 60 minutes after product use on day 1 and day 30.
measure: Product Dependence
timeFrame: Within 60 minutes after product use on day 1 and day 30.
measure: Product Acceptance
timeFrame: Within 60 minutes after product use on day 1 and day 30.
measure: Puffing Behavior of Subject
timeFrame: 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.
measure: Overall Product Use
timeFrame: Recorded daily by subject, in product use diary, from day 1 until day 30.
measure: NEQ
timeFrame: Measured at baseline, day 7, day 15, day 22, and day 29.
measure: Total NNAL
timeFrame: Measured at baseline, day 7, day 15, day 22, and day 29.
measure: CEMA
timeFrame: Measured at baseline, day 7, day 15, day 22, and day 29.
measure: CYP2A6 Activity
timeFrame: Measured before product use, on day 1 and day 30.
measure: Amount of Powder Extracted From P3P Used for PK Assessment.
timeFrame: Before and after product use, on day 1 and day 30.
Other outcomes:
Locations:
city: St. Petersburg
country: Russian Federation
facility: LLC Scientific Research Center Eco-Safety
Study officials:
affiliation: Philip Morris Products SA
name: Christelle Haziza, PhD
role: STUDY_CHAIR
affiliation: LLC Scientific Research Center Eco-Safety
name: Vasilyuk V Bogdanovich, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.