Nicotine
Conditions
Keywords
Heated Tobacco
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.
Interventions
OTHERTHS with LEVIA (ad libitum)
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.
OTHERTHS with TEREA (ad libitum)
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.
OTHERTHS with LEVIA
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.
OTHERTHS with TEREA
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.
OTHERCigarette
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.
Sponsors
Philip Morris Products S.A.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* 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.
Exclusion criteria
* 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. * Participant or one of their family members is a current or former employee of the tobacco industry. * Participant or one of their family members is an employee of the investigational site or of any other parties involved in the study. * Participant has participated in a clinical research study involving the administration of an investigational or marketed drug or device within 30 days prior to investigational product use, the administration of a biological product in the context of a clinical research study within 90 days prior to the Screening visit, or concomitant participation in an investigational study involving no drug or device administration. * Participant has been previously screened or enrolled in this study (except overenrolled participants). * For women only: participant with positive urine pregnancy tests at the Screening visit or at Admission, or is a lactating female. * For women of childbearing potential only: participant does not agree to use an acceptable method of effective contraception throughout study participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Background-corrected maximum plasma nicotine concentration (Cmax) | Measured from Day 3 to Day 5 | To measure the background-corrected maximum plasma nicotine concentration \[Cmax\] |
| Background-corrected plasma nicotine concentrations (cC0h) to (cC12h) | Measured from Day 3 to Day 5 | To measure the background-corrected plasma nicotine concentrations (cC0h) to (cC12h) |
| 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) | Measured from Day 3 to Day 5 | To measure the area under the background-corrected plasma nicotine concentration-time curve (AUC) |
| Time to the background-corrected maximum concentration (Tmax) | Measured from Day 3 to Day 5 | To measure the time to the background-corrected maximum concentration \[Tmax\] |
| Terminal elimination rate constant (λz) | Measured from Day 3 to Day 5 | To measure the terminal elimination rate constant (λz) |
| Half-life of nicotine (t1/2) | Measured from Day 3 to Day 5 | To measure the half-life of nicotine (t1/2) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Product consumption | Measured from Day 1 to Day 2 | Product consumption expressed as number of LEVIA or TEREA sticks (N sticks) |
| NEQ in Plasma | Measured from Day 1 to Day 2 | Nicotine, cotinine and trans-3'-hydroxycotinine concentrations expressed as nicotine equivalents in plasma (NEQplasma) |
| NEQ in Urine | Measured from Day 1 to Day 3 | Nicotine and metabolites concentrations expressed as nicotine equivalents adjusted to creatinine (NEQcreate) in first void urine |
| Craving for using a tobacco or nicotine product | Measured from Day 3 to Day 5 | Craving will be self-reported on a Visual Analogue Scale, asking participants to rate their craving for using a tobacco or nicotine product on a 100 mm unipolar scale, ranging from 0 (no craving) to 100 (strong craving). |
| Product Liking | Measured from Day 3 to Day 5 | Product liking will be self-reported on a Visual Analogue Scale, stating "Overall, my liking for this product is:" which participants will complete on a 100 mm bipolar scale, ranging from 0 (strong disliking) to 100 (strong liking) with a neutral middle point. |
| Nicotine Satisfaction | Measured from Day 3 to Day 5 | Satisfaction with the perceived nicotine content will be self-reported on a Visual Analogue Scale, stating "Overall, the nicotine level in this product is:" which participants will complete on a 100 mm bipolar scale, ranging from 0 (not enough) to 100 (too much) with a middle point (just right). |
| Product Experience | Measured from Day 3 to Day 5 | The 12-item self-report measure consists of three multi-item scales and two single-item scales: * Aversion (e.g., dizziness, nausea), * Craving reduction, Enjoyment of sensation in the mouth (single-item assessment), * Product satisfaction (e.g., satisfying, tastes good), and * Psychological rewards (e.g., helps concentrate, reduces hunger). Participants rate each item on a 7-point scale, ranging from 1 (not at all) to 7 (extremely). A score is computed for each of the five scales. For each scale, the mean of the individual item responses is calculated. Higher scores indicate higher perceived intensity of the effect. |
Countries
Poland
Contacts
STUDY_CHAIRChristelle Haziza, PhD
Philip Morris Products S.A.
Outcome results
None listed