Pharmacokinetics and Pharmacodynamics of THS With LEVIA Compared to THS With TEREA and to Cigarettes

NCT07459712 | Completed

• 1 other identifier: P1-LEV-PK-01
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

A single-center, randomized, controlled, open-label, crossover study in currently smoking adult participants to investigate the nicotine pharmacokinetics and pharmacodynamics of Tobacco Heating System (THS) with LEVIA, a tobacco-free nicotine-containing consumable, compared to THS with TEREA, a tobacco-containing consumable, and cigarettes. The study will use a 2-period, 2-sequence design for the ad libitum use days, and a 3-period, 6-sequence Williams design for the single-use days. Across the ad libitum use and single-use period, this is a design with 5 periods and 12 sequences.

Conditions

Nicotine

Keywords

Heated Tobacco

Outcome Measures

Primary Outcomes (6)

• Background-corrected plasma nicotine concentrations (cC0h) to (cC12h)

  To measure the background-corrected plasma nicotine concentrations (cC0h) to (cC12h)

  Measured from Day 3 to Day 5

• Background-corrected maximum plasma nicotine concentration (Cmax)

  To measure the background-corrected maximum plasma nicotine concentration \[Cmax\]

  Measured from Day 3 to Day 5

• Area under the background-corrected plasma nicotine concentration-time curve (AUC) (AUC) from the start of product use (T0) to the timepoint of last quantifiable concentration (AUC0-last) and extrapolated to infinity (AUC0-infinity)

  To measure the area under the background-corrected plasma nicotine concentration-time curve (AUC)

  Measured from Day 3 to Day 5

• Time to the background-corrected maximum concentration (Tmax)

  To measure the time to the background-corrected maximum concentration \[Tmax\]

  Measured from Day 3 to Day 5

• Terminal elimination rate constant (λz)

  To measure the terminal elimination rate constant (λz)

  Measured from Day 3 to Day 5

• Half-life of nicotine (t1/2)

  To measure the half-life of nicotine (t1/2)

  Measured from Day 3 to Day 5

Secondary Outcomes (7)

• Product consumption

  Measured from Day 1 to Day 2

• NEQ in Plasma

  Measured from Day 1 to Day 2

• NEQ in Urine

  Measured from Day 1 to Day 3

• Craving for using a tobacco or nicotine product

  Measured from Day 3 to Day 5

• Product Liking

  Measured from Day 3 to Day 5

Study Arms (2)

Ad libitum product use (day 1; day 2)

ACTIVE COMPARATOR

Participants will be simultaneously randomized to product use sequences for ad libitum use. The list of possible sequences are: * THS with LEVIA; THS with TEREA * THS with TEREA; THS with LEVIA

Other: THS with LEVIA (ad libitum); Other: THS with TEREA (ad libitum)

Single product use (day 3; day 4; day 5)

ACTIVE COMPARATOR

Participants will be simultaneously randomized to product use sequences for single product use. The list of possible sequences are: * Cigarette; THS with LEVIA; THS with TEREA * Cigarette; THS with TEREA; THS with LEVIA * THS with LEVIA; Cigarette; THS with TEREA * THS with LEVIA; THS with TEREA; Cigarette * THS with TEREA; Cigarette; THS with LEVIA * THS with TEREA; THS with LEVIA; Cigarette

Other: THS with LEVIA; Other: THS with TEREA; Other: Cigarette

Interventions

THS with LEVIA (ad libitum) OTHER

On Day 1 through Day 2, after at least 10 hours of abstinence from any tobacco and nicotine-containing products, participants will use THS with LEVIA ad libitum in the randomized product-use sequence. The ad libitum use period will last approximately 12 hours.

Ad libitum product use (day 1; day 2)

THS with TEREA (ad libitum) OTHER

On Day 1 through Day 2, after at least 10 hours of abstinence from any tobacco and nicotine-containing products, participants will use THS with TEREA ad libitum in the randomized product-use sequence. The ad libitum use period will last approximately 12 hours.

Ad libitum product use (day 1; day 2)

THS with LEVIA OTHER

On Day 3 through Day 5, after at least 10 hours of abstinence from any tobacco and nicotine-containing products, participants will use a single THS with LEVIA in the randomized product-use sequence, as instructed by the investigational site staff.

Single product use (day 3; day 4; day 5)

THS with TEREA OTHER

On Day 3 through Day 5, after at least 10 hours of abstinence from any tobacco and nicotine-containing products, participants will use a single THS with TEREA in the randomized product-use sequence, as instructed by the investigational site staff.

Single product use (day 3; day 4; day 5)

Cigarette OTHER

On Day 3 through Day 5, after at least 10 hours of abstinence from any tobacco and nicotine-containing products, participants will use their usual brand of cigarettes according to the randomized product-use sequence and as instructed by the investigational site staff.

Single product use (day 3; day 4; day 5)

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 Informed Consent Form (ICF) and is able to understand the information provided in the ICF.
• Male or female current (past 30 days) daily users of heated tobacco products and concomitantly smoking cigarettes aged between 21 and 65 years inclusive.
• Participant has used heated tobacco products (no brand restriction) for at least the last 6 months prior to the Screening visit.
• Participant has smoked commercially available or roll-your own cigarettes (no brand restrictions) for at least the last 12 months prior to the Screening visit.
• Participant has used at least 10 heated tobacco products and/or commercially available cigarettes without any brand restriction or roll-your own cigarettes per day in the past 30 days prior to Screening visit and Admission.
• Participant has a urinary cotinine concentration of ≥ 200 ng/mL.
• Participant has a BMI \>18.5 and \<30.0 kg/m2 and body weight ≥50.0 kg for males and ≥45.0 kg for females.
• Participant is available for the entire study period and willing to comply with study procedures, including product use assignments and periods of abstinence from any nicotine/tobacco containing products and willing to adhere to a standardized diet.

You may not qualify if:

• Participant has reasons other than medical (e.g., psychological, social reason) not to be part of the study, as determined by the Principal Investigator or designee.
• Participant is legally incompetent, or physically or mentally incapable of giving consent (e.g., emergency situation, under guardianship, prisoner).
• Participant has a health condition that requires medication or any other clinically relevant finding based on the assessment from the Screening visit (e.g., safety laboratory, pulmonary function test, vital signs, physical examination, ECG, and medical history) as determined by the Principal Investigator or designee.
• Participant experiences difficulty with venipuncture and/or poor venous access.
• Participant has medical conditions which require, or will require during the study, a medical intervention (e.g., start of treatment, surgery, hospitalization).
• Presence of fever (body temperature \>37.5°C), e.g., a fever associated with a symptomatic viral or bacterial infection.
• Participant has a hemoglobin level \< 11.0 g/dL for females and \< 12.0 g/dL for males at the Screening visit.
• Participant uses medication that aids in smoking cessation.
• Participant previously attempted to quit using tobacco- or nicotine-containing products within 28 days prior to the first investigational product use.
• Participant has donated plasma within seven days prior to the Screening visit or has donated or lost 450 mL or more of whole blood within 8 weeks prior to the Screening visit for males, and in the 12 weeks prior to the Screening visit for females.
• Participant has a known sensitivity or allergy to LEVIA or TEREA investigational products.
• Participant has a positive serology test for HIV 1/2, hepatitis B or C.
• Participant has a medical history of alcohol abuse within one year prior to the Screening visit or regular use of alcohol within six months prior to the Screening visit that exceeds 10 units for women or 15 units for men of alcohol per week.
• Participant has a positive urine drug screen test. The Principal Investigator will assess whether THC-positive participants are eligible for study participation.
• Participant has a positive alcohol breath test.

Sponsors & Collaborators

• Philip Morris Products S.A.: lead

Study Sites (1)

BioResearch Group Sp. z o.o.

Nadarzyn, 05-830, Poland

Location

MeSH Terms

Interventions

Tobacco Products

Intervention Hierarchy (Ancestors)

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

Study Officials

• Christelle Haziza, PhD

  Philip Morris Products S.A.

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: March 5, 2026
• First Posted: March 10, 2026
• Study Start: February 1, 2026
• Primary Completion: February 9, 2026
• Study Completion: April 14, 2026
• Last Updated: May 5, 2026

Record last verified: 2026-05

Locations

PL (1)