Nicotine Pharmacokinetics of THS Single Use of a Regular or a Menthol Stick Compared to CIG

Sponsor

Philip Morris Products S.A. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05789420

Collaborator

(none)

Enrollment

Location

Arms

4.4

Anticipated Duration (Months)

6.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to describe the nicotine pharmacokinetic (PK) profile during and after single use of THS (Induction heating technology, with either a regular or menthol stick) compared to singular CIG smoking in healthy adult subjects. In addition, pharmacodynamic effects (subjective effects) will be evaluated to provide further insights on product acceptance and likelihood to use the THS again. Safety will be assessed throughout the study.

Condition or Disease	Intervention/Treatment	Phase
Smoking, Tobacco	Other: P1R stick Other: P1M stick Other: CIG	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

A Single-center, Randomized, Controlled, Open-label Study in Smoking Healthy Subjects to Investigate the Nicotine Pharmacokinetic Profiles Following Single Use of Tobacco Heating System (THS) With a Regular or a Menthol Stick, Compared to Smoking of a Single Combustible Cigarette (CIG)

Actual Study Start Date :

Feb 16, 2023

Anticipated Primary Completion Date :

Apr 2, 2023

Anticipated Study Completion Date :

Jul 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Product Sequence 1 After at least 23 hours of abstinence from any Tobacco or Nicotine Product (TNP) on Day 1, and after at least 23 hrs of former IP use on Day 2 and Day 3 (nicotine wash-out), subjects will smoke a single CIG or perform a single use of a THS either with a regular or a menthol stick, according to randomized product use sequence. The list of possible sequences are: P1R; P1M; CIG / P1R; CIG; P1M / P1M; P1R; CIG / P1M; CIG; P1R / CIG; P1R; P1M / CIG; P1M; P1R	Other: P1R stick Regular flavor tobacco stick Other: P1M stick Mentholated flavor tobacco stick Other: CIG Subjects' preferred brand of commercially available, regular or mentholated cigarettes
Active Comparator: Product Sequence 2 After at least 23 hours of abstinence from any TNP on Day 1, and after at least 23 hrs of former IP use on Day 2 and Day 3 (nicotine wash-out), subjects will smoke a single CIG or perform a single use of a THS either with a regular or a menthol stick, according to randomized product use sequence. The list of possible sequences are: P1R; P1M; CIG / P1R; CIG; P1M / P1M; P1R; CIG / P1M; CIG; P1R / CIG; P1R; P1M / CIG; P1M; P1R	Other: P1R stick Regular flavor tobacco stick Other: P1M stick Mentholated flavor tobacco stick Other: CIG Subjects' preferred brand of commercially available, regular or mentholated cigarettes
Active Comparator: Product Sequence 3 After at least 23 hours of abstinence from any TNP on Day 1, and after at least 23 hrs of former IP use on Day 2 and Day 3 (nicotine wash-out), subjects will smoke a single CIG or perform a single use of a THS either with a regular or a menthol stick, according to randomized product use sequence. The list of possible sequences are: P1R; P1M; CIG / P1R; CIG; P1M / P1M; P1R; CIG / P1M; CIG; P1R / CIG; P1R; P1M / CIG; P1M; P1R	Other: P1R stick Regular flavor tobacco stick Other: P1M stick Mentholated flavor tobacco stick Other: CIG Subjects' preferred brand of commercially available, regular or mentholated cigarettes
Active Comparator: Product Sequence 4 After at least 23 hours of abstinence from any TNP on Day 1, and after at least 23 hrs of former IP use on Day 2 and Day 3 (nicotine wash-out), subjects will smoke a single CIG or perform a single use of a THS either with a regular or a menthol stick, according to randomized product use sequence. The list of possible sequences are: P1R; P1M; CIG / P1R; CIG; P1M / P1M; P1R; CIG / P1M; CIG; P1R / CIG; P1R; P1M / CIG; P1M; P1R	Other: P1R stick Regular flavor tobacco stick Other: P1M stick Mentholated flavor tobacco stick Other: CIG Subjects' preferred brand of commercially available, regular or mentholated cigarettes
Active Comparator: Product Sequence 5 After at least 23 hours of abstinence from any TNP on Day 1, and after at least 23 hrs of former IP use on Day 2 and Day 3 (nicotine wash-out), subjects will smoke a single CIG or perform a single use of a THS either with a regular or a menthol stick, according to randomized product use sequence. The list of possible sequences are: P1R; P1M; CIG / P1R; CIG; P1M / P1M; P1R; CIG / P1M; CIG; P1R / CIG; P1R; P1M / CIG; P1M; P1R	Other: P1R stick Regular flavor tobacco stick Other: P1M stick Mentholated flavor tobacco stick Other: CIG Subjects' preferred brand of commercially available, regular or mentholated cigarettes
Active Comparator: Product Sequence 6 After at least 23 hours of abstinence from any TNP on Day 1, and after at least 23 hrs of former IP use on Day 2 and Day 3 (nicotine wash-out), subjects will smoke a single CIG or perform a single use of a THS either with a regular or a menthol stick, according to randomized product use sequence. The list of possible sequences are: P1R; P1M; CIG / P1R; CIG; P1M / P1M; P1R; CIG / P1M; CIG; P1R / CIG; P1R; P1M / CIG; P1M; P1R	Other: P1R stick Regular flavor tobacco stick Other: P1M stick Mentholated flavor tobacco stick Other: CIG Subjects' preferred brand of commercially available, regular or mentholated cigarettes

Outcome Measures

Primary Outcome Measures

Maximum plasma concentration [Cmax] [Measured from start of product use to 24 hours]
To measure Cmax from the single use of THS with either a regular or a menthol stick or of a single cigarette.
Time to the maximum concentration [Tmax] [Measured from start of product use to 24 hours]
To measure Tmax from the single use of THS with either a regular or a menthol stick or of a single cigarette.
Area under the curve of nicotine plasma concentration-time computed from T0 to T=24 hours [AUC0-24h] [Measured from start of product use to 24 hours]
To measure AUC0-24h from the single use of THS with either a regular or a menthol stick or of a single cigarette.
Area under the curve of nicotine plasma concentration-time computed from T0 to the subject-specific time of maximum nicotine concentration [AUC0-t'] [Measured from start of product use to 24 hours]
To measure AUC0-t' from the single use of THS with either a regular or a menthol stick or of a single cigarette.

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Subject has signed the ICF and is able to understand the information provided in the ICF.
Subject has been a smoker for ≥3 years prior to the screening visit (smoking cessation attempts during this period, if any, did not last > 6 months in total).
Subject has continuously smoked on average ≥10 commercially available regular CIG/day over the last 4 weeks. Smoking status will be verified based on a urinary cotinine test (cotinine ≥200 ng/mL).
Subject is healthy as judged by the Investigator based on available assessments from the screening period (e.g., safety laboratory, spirometry, vital signs, physical examination, ECG, and medical history).
Subject does not plan to quit smoking within the next three months.

Exclusion Criteria:

As per the Investigator's judgment, the subject cannot participate in the study for any reason other than medical (e.g., psychological, social reason).
Subject is legally incompetent, or physically or mentally incapable of giving consent (e.g., in emergency situations, under guardianship, prisoners).
Subject has a clinically relevant disease which requires medication (including but not limited to gastrointestinal, renal, hepatic, neurological, hematological, endocrine, oncological, urological, immunological, pulmonary, and cardiovascular disease) or any other medical condition (including safety laboratory), which as per the judgment of the Investigator would jeopardize the safety of the subject.
Subject experienced within 30 days prior to screening/admission a body temperature

37.5°C or an acute illness (e.g., upper respiratory-tract infection, viral infection, etc.) or the subject has a confirmed or suspected active COVID-19 infection (based on the signs and symptoms observed at the time of assessment)

As per the Investigator's judgment, the subject has medical conditions which do or will require a medical intervention (e.g., start of treatment, surgery, hospitalization) during the study participation, which may interfere with the study participation and/or study results.
Subject has relevant history of, or current asthma condition or COPD condition, and/or clinically significant findings.
Subject has donated blood or received whole blood or blood products within 3 months.
BMI < 18.5 kg/m2 or ≥ 32.0 kg/m2.
Positive serology test for HIV 1/2, HBV, or HCV.
Subject has a positive alcohol breath test and/or has a history of alcohol disorder that could interfere with their participation in the study.
The subject has a positive urine drug test.
Subject or one of their family members is a current or former employee of the tobacco or e-cigarette industry.
Subject or one of their family members is an employee of the investigational site or of any other parties involved in the study.
Subject has participated in another clinical study within 3 months.
Subject has been previously screened or enrolled in this study.
Subject is pregnant (does not have negative pregnancy tests at Screening and at Baseline) or is breastfeeding.
For women of childbearing potential only: subject does not agree to use an acceptable method of effective contraception.