Assessment of HPHC Exposure in Smokers Switching to THS/TP18 With Different Device Variants

NCT07443631 | Recruiting

• 1 other identifier: P1-REX_PK-22
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, controlled, open-label, 6 parallel arms study to assess reduced exposure of biomarkers of exposure (BoE) of selected HPHC in smokers switching to TP18 (a prototype heated tobacco device) or THS relative to smokers who continue smoking CIG after 5 days of confinement period, followed by 2 days of pharmacokinetic (PK) period of single use of THS/TP18 and CIG, and followed by an ambulatory period.

Conditions

Smoking

Keywords

HPHC

Outcome Measures

Primary Outcomes (6)

• 3-hydroxypropyl mercapturic acid (3-HPMA) in Urine (confinement period)

  Concentrations of 3-HPMA measured in 24-hour urine and expressed as concentration adjusted for creatinine.

  Measured from Day -1 to Day 5.

• 2-cyanoethyl mercapturic acid N-acetyl-S-(2-cyanoethyl)-L-cysteine (2-CyEMA) in Urine (confinement period)

  Concentrations of 2-CyEMA measured in 24-hour urine and expressed as concentration adjusted for creatinine.

  Measured from Day -1 to Day 5.

• Monohydroxybutenyl mercapturic acid (MHBMA) in Urine (confinement period)

  Concentrations of MHBMA measured in 24-hour urine and expressed as concentration adjusted for creatinine.

  Measured from Day -1 to Day 5.

• Total N-nitrosonornicotine (total NNN) in Urine (confinement period)

  Concentrations of total NNN measured in 24-hour urine and expressed as concentration adjusted for creatinine.

  Measured from Day -1 to Day 5.

• Total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (total NNAL) in Urine (confinement period)

  Concentrations of total NNAL measured in 24-hour urine and expressed as concentration adjusted for creatinine.

  Measured from Day -1 to Day 5.

• Carboxyhemoglobin (COHb) in Blood (confinement period)

  Carboxyhemoglobin (COHb) is assayed from whole blood and expressed as percentage of the total hemoglobin saturated with carbon monoxide.

  Measured from Day -1 to Day 5.

Secondary Outcomes (6)

• S-phenylmercapturic acid (S-PMA) in Urine (confinement period)

  Measured from Day -1 to Day 5.

• 2-hydroxyethylmercapturic acid (2-HEMA) in Urine (confinement period)

  Measured from Day -1 to Day 5.

• 3-hydroxy-1-methylpropylmercapturic acid (3-HMPMA) in Urine (confinement period)

  Measured from Day -1 to Day 5.

• Total 3-hydroxybenzo(a)pyrene (3-OH-B[a]P) in Urine (confinement period)

  Measured from Day -1 to Day 5.

• 4-aminobiphenyl (4-ABP) in Urine (confinement period)

  Measured from Day -1 to Day 5.

Other Outcomes (16)

• Plasma nicotine concentrations [C0h] to [C6h] (pharmacokinetic period)

  Measured from Day 6 to Day 7.

• Maximum plasma nicotine concentration [Cmax] (pharmacokinetic period)

  Measured from Day 6 to Day 7.

• Area under the plasma nicotine concentration-time curve (pharmacokinetic period)

  Measured from Day 6 to Day 7.

Study Arms (6)

THS1

OTHER

During the confinement period, participants will use only their assigned product THS 1 (with the corresponding sticks) ad libitum. During the PK period, they will complete a four-way single-product crossover using THS/TP18 and CIG, according to randomized product sequences. During the ambulatory period, they may choose any variant (THS1, THS2, THS3, or THS4) at any time, ad libitum.

Other: THS1 (TP18 variant 1)

THS2

OTHER

During the confinement period, participants will use only their assigned product THS 2 (with the corresponding sticks) ad libitum. During the PK period, they will complete a four-way single-product crossover using THS/TP18 and CIG, according to randomized product sequences. During the ambulatory period, they may choose any variant (THS1, THS2, THS3, or THS4) at any time, ad libitum.

Other: THS2 (TP18 variant 2)

THS3

OTHER

During the confinement period, participants will use only their assigned product THS 3 (with the corresponding sticks) ad libitum. During the PK period, they will complete a four-way single-product crossover using THS/TP18 and CIG, according to randomized product sequences. During the ambulatory period, they may choose any variant (THS1, THS2, THS3, or THS4) at any time, ad libitum.

Other: THS3 (TP18 variant 3)

THS4

OTHER

During the confinement period, participants will use only their assigned product THS 4 (with the corresponding sticks) ad libitum. During the PK period, they will complete a four-way single-product crossover using THS/TP18 and CIG, according to randomized product sequences. During the ambulatory period, they may choose any variant (THS1, THS2, THS3, or THS4) at any time, ad libitum.

Other: THS4 (TP18 variant 4)

THS5

OTHER

During the confinement period, participants will use only their assigned product THS 5 (with the corresponding sticks) ad libitum. During the PK period, they will complete a four-way single-product crossover using THS/TP18 and CIG, according to randomized product sequences. During the ambulatory period, they will be continue to use THS5 ad libitum.

Other: THS5 (THS 3.0 reference device)

CIG

OTHER

During the confinement period, participants will use only their usual brand of commercially available CIG ad libitum. This arm will not participate in the PK period and will move directly to the ambulatory period. During the ambulatory period, participants will smoke only cigarettes, ad libitum.

Other: CIG (Cigarette)

Interventions

THS1 (TP18 variant 1) OTHER

TP18 prototype variant "1" (THS1) and associated tobacco sticks. The Sponsor will supply two types of sticks: regular (tobacco flavor) and non-characterizing menthol flavor. Participants can choose either or both variants.

THS1

THS2 (TP18 variant 2) OTHER

TP18 prototype variant "2" (THS2) and associated tobacco sticks. The Sponsor will supply two types of sticks: regular (tobacco flavor) and non-characterizing menthol flavor. Participants can choose either or both variants.

THS2

THS3 (TP18 variant 3) OTHER

TP18 prototype variant "3" (THS3) and associated tobacco sticks. The Sponsor will supply two types of sticks: regular (tobacco flavor) and non-characterizing menthol flavor. Participants can choose either or both variants.

THS3

THS4 (TP18 variant 4) OTHER

TP18 prototype variant "4" (THS4) and associated tobacco sticks. The Sponsor will supply two types of sticks: regular (tobacco flavor) and non-characterizing menthol flavor. Participants can choose either or both variants.

THS4

THS5 (THS 3.0 reference device) OTHER

THS 3.0 device (reference) and the corresponding tobacco sticks will be provided by the Sponsor. There are two variants of the sticks: regular (tobacco flavor) and non-characterizing menthol flavor. Participants may choose either variant or both.

THS5

CIG (Cigarette) OTHER

Current cigarette smokers will use their usual brand of commercially available CIG.

CIG

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant has signed the ICF and understands the information provided in it.
• Participant is male or female and between 21 and 65 years old (inclusive).
• Participant has been a smoker for at least 2 years prior to the screening visit and is willing to switch to THS and TP18.
• Participant has smoked on average ≥10 commercially available CIGs/day over the last 30 days. Smoking status will be verified based on a urinary cotinine test (cotinine ≥200 ng/mL).
• Participant does not plan to quit smoking within the next three months.
• Participant is available for the entire study period and willing to comply with the study procedures, including product use assignments and periods of abstinence from any nicotine/tobacco-containing products, and willing to adhere to a standardized diet (during confinement period and during overnight stays on Day 30 and Day 60).

You may not qualify if:

• As per the Investigator's judgment, the participant cannot participate in the study for any reason other than medical (e.g., psychological, social reason).
• Participant is legally incompetent, or physically or mentally incapable of giving consent (e.g., in emergency situations, under guardianship, prisoners).
• Participant has a health condition which requires medication or any other clinically relevant finding based on available assessments from the Screening period (e.g., safety panel, pulmonary function test, vital signs, physical examination, ECG, and medical history), as determined by the Principal Investigator or designee.
• Participant experienced within 30 days prior to screening/admission a body temperature \>37.9°C or an acute illness (e.g., upper respiratory-tract infection, viral infection, etc.).
• According to the Investigator's judgment, the participant has medical conditions that require or will require medical intervention (e.g., initiation of treatment, surgery, hospitalization) during the study period, which may interfere with study participation and/or study results.
• Participant uses medication that aids in smoking cessation.
• Participant experiences difficulty with venipuncture and/or poor venous access.
• Participant has a hemoglobin level \< 11.0 g/dL for females and \< 12.0 g/dL for males at the Screening visit.
• Participant has a positive nitrite urinary test at screening or on admission day (Day -2)
• Participant has donated blood or received whole blood or blood products within the past 3 months.
• BMI \< 18.5 kg/m2 or ≥ 32.0 kg/m2.
• Positive serology test for HIV 1/2, HBV, or HCVa.
• Participant has a positive alcohol breath test and/or has a history of alcohol disorder that could interfere with their participation in the study.
• The participant has a positive urine drug test.
• Participant or one of their family members is a current or former employee of the tobacco industry, manufacturing or distributing e-cigarettes or other nicotine/tobacco-containing products.

Sponsors & Collaborators

• Philip Morris Products S.A.: lead

Study Sites (1)

Celerion

Belfast, BT9 6AD, United Kingdom

RECRUITING

MeSH Terms

Conditions

Smoking

Interventions

Tobacco Products

Condition Hierarchy (Ancestors)

Behavior

Intervention Hierarchy (Ancestors)

Smoking Devices; Manufactured Materials; Technology, Industry, and Agriculture

Study Officials

• Christelle Haziza, PhD

  Philip Morris Products S.A.

  STUDY CHAIR

Central Study Contacts

Christelle Haziza, PhD

CONTACT

+41 58 242 11 11; christelle.haziza@pmi.com

Sandrine Pouly, PhD

CONTACT

+41 58 242 11 11

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2026
• First Posted: March 2, 2026
• Study Start: February 19, 2026
• Primary Completion (Estimated): May 28, 2026
• Study Completion (Estimated): December 18, 2026
• Last Updated: May 1, 2026

Record last verified: 2026-02

Locations

GB (1)