Smokers, Never Smokers
Conditions
Keywords
nasal mucociliary clearance, saccharine transit time
Brief summary
This study intends to evaluate the nasal mucociliary clearance (NMC) by determining the value obtained for saccharin transit time (STT) test over the course of 12 hours following a single cigarette use in adult smokers, to compare it relative to never smokers, and to examine the relationship between plasma nicotine levels and STT value in smokers and never smokers. Safety will also be monitored during the study. The planned maximum study duration for a single study participant from Screening through completion of study will be 33 days.
Interventions
OTHERCigarette
After enrollment, and between Visit 2 and Visit 3, the subjects will abstain from smoking for a period of 8 hours. At Visit 3, after the 8-hour smoking abstinence period, the subjects will smoke 1 single cigarette.
Sponsors
Philip Morris Products S.A.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
25 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
to be met at Visit 1 and Visit 2: * Male smokers aged ≥25 to ≤45 years old. * Male never smokers aged ≥25 to ≤45 years old. * Subject's BMI is comprised between 18.0 kg/m2 to 32.0 kg/m2, inclusive. * Subject is healthy, as judged by the Investigator. Additional Inclusion Criteria to allocate subjects in one of the two groups: * Non-menthol cigarette smokers: * A positive urine cotinine test (≥200 ng/mL). * Smoked at least 20 cigarettes per day for at least the past 5 years. * eCO levels \>10 parts per million (ppm). * No plans to quit smoking in the next 3 months. * Never smokers: * Subject who has smoked less than 100 cigarettes throughout their lifetime and no cigarettes in the past 3 years. * A negative urine cotinine test (\<200 ng/mL). * eCO levels ≤ 5 ppm.
Exclusion criteria
* As per the Investigator's judgment, the subject cannot participate in the study for any reason (e.g., medical, psychiatric, and/or social reason). * Inability to taste sweet within 60 minutes in the STT test. * Any condition the Principal Investigator or designee has cause to believe would interfere with the procedures for upper or lower airway function. This could include, but is not limited to, nasal/septum deviations, or nasal polyps or nasal allergies.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Concentration of Plasma Nicotine 12 Hours After Product Use | Measured at 12 hours after product use. | The Nicotine plasma concentrations will be measured using validated LC/MS/MS bioanalytical method. |
| Saccharin Transit Time 12 Hours After Product Use | Measured at 12 hours after product use. | Before performing the test, each subject will spend approximately 15 minutes acclimatizing to the environment of the clinic. A 1-2 mm particle of saccharin will be placed under direct vision, approximately 1 cm behind the anterior end of the inferior turbinate. The position of the subject's head should be flexed approximately 10° by visual assessment. The saccharin transit time will be determined as the elapsed time in minutes and seconds from placement of the saccharin until the time the subject perceives a sweet taste. |
| Concentration of Plasma Nicotine at t0, Start of Product Use | Baseline | Nicotine plasma concentrations will be measured using validated LC/MS/MS bioanalytical method. |
| Concentration of Plasma Nicotine 4 Hours After Product Use | Measured at 4 hours after product use. | Nicotine plasma concentrations will be measured using validated LC/MS/MS bioanalytical method. |
| Concentration of Plasma Nicotine 8 Hours After Product Use | Measured at 8 hours after product use. | Nicotine plasma concentrations will be measured using validated LC/MS/MS bioanalytical method. |
| Saccharin Transit Time at t0, Start of Product Use | Baseline | Before performing the test, each subject will spend approximately 15 minutes acclimatizing to the environment of the clinic. A 1-2 mm particle of saccharin will be placed under direct vision, approximately 1 cm behind the anterior end of the inferior turbinate. The position of the subject's head should be flexed approximately 10° by visual assessment. The saccharin transit time will be determined as the elapsed time in minutes and seconds from placement of the saccharin until the time the subject perceives a sweet taste. |
| Saccharin Transit Time 4 Hours After Product Use | Measured at 4 hours after product use. | Before performing the test, each subject will spend approximately 15 minutes acclimatizing to the environment of the clinic. A 1-2 mm particle of saccharin will be placed under direct vision, approximately 1 cm behind the anterior end of the inferior turbinate. The position of the subject's head should be flexed approximately 10° by visual assessment. The saccharin transit time will be determined as the elapsed time in minutes and seconds from placement of the saccharin until the time the subject perceives a sweet taste. |
| Saccharin Transit Time 8 Hours After Product Use | Measured at 8 hours after product use. | Before performing the test, each subject will spend approximately 15 minutes acclimatizing to the environment of the clinic. A 1-2 mm particle of saccharin will be placed under direct vision, approximately 1 cm behind the anterior end of the inferior turbinate. The position of the subject's head should be flexed approximately 10° by visual assessment. The saccharin transit time will be determined as the elapsed time in minutes and seconds from placement of the saccharin until the time the subject perceives a sweet taste. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ribonucleic Acid Quantity (Left Nostril) | Nasal scraping was performed at the final clinic visit, on Day 2, before checkout from the study. | Ribonucleic Acid quantity: concentration measured in the left nostril (Qiazol buffer) using two nasal scraping methods |
| Ribonucleic Acid Quality (Right Nostril) | Nasal scraping was performed at the final clinic visit, on Day 2, before checkout from the study. | Ribonucleic Acid quality assessed using the RNA integrity number: measured in the right nostril (RNA protect buffer) using two nasal scraping methods. RNA integrity Number is an algorithm for assessing RNA integrity and based on a numbering system from 1 to 10, with 1 being the most degraded profile and 10 being the most intact. |
| Ribonucleic Acid Quality (Left Nostril) | Nasal scraping was performed at the final clinic visit, on Day 2, before checkout from the study. | Ribonucleic Acid quality assessed using the RNA integrity number: measured in the left nostril (Qiazol buffer) using two nasal scraping methods. RNA integrity Number is an algorithm for assessing RNA integrity and based on a numbering system from 1 to 10, with 1 being the most degraded profile and 10 being the most intact. |
| Ribonucleic Acid Quantity (Right Nostril) | Nasal scraping was performed at the final clinic visit, on Day 2, before checkout from the study. | Ribonucleic Acid quantity: concentration measured in the right nostril (RNA protect buffer) using two nasal scraping methods |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cigarette Smokers Subjects who have smoked at least 20 cigarettes per day for at least the past 5 years.
Subjects will be allowed to use their own brand of non-menthol cigarettes. There will be no smoking restriction after the discharge at Visit 3 and during the 1 day follow-up period.
Cigarette: After enrollment, and between Visit 2 and Visit 3, the subjects will abstain from smoking for a period of 8 hours. At Visit 3, after the 8-hour smoking abstinence period, the subjects will smoke 1 single cigarette. | 7 |
| Never Smokers Subjects who have smoked less than 100 cigarettes throughout their lifetime and no cigarettes in the past 3 years.
Subjects will not be allowed to smoke until discharge at Visit 3. | 7 |
| Total | 14 |
Baseline characteristics
| Characteristic | Cigarette Smokers | Total | Never Smokers |
|---|---|---|---|
| Age, Continuous | 33.9 years STANDARD_DEVIATION 7.2 | 33.0 years STANDARD_DEVIATION 5.76 | 32.1 years STANDARD_DEVIATION 4.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 4 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 10 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 7 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 6 Participants | 3 Participants |
| Region of Enrollment United States | 7 participants | 14 participants | 7 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 7 Participants | 14 Participants | 7 Participants |
| Weight (kg) | 73.3 kg STANDARD_DEVIATION 7.18 | 79.6 kg STANDARD_DEVIATION 11.35 | 85.9 kg STANDARD_DEVIATION 11.6 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 7 |
| other Total, other adverse events | 1 / 7 | 0 / 7 |
| serious Total, serious adverse events | 0 / 7 | 0 / 7 |
Outcome results
Primary
Concentration of Plasma Nicotine 12 Hours After Product Use
The Nicotine plasma concentrations will be measured using validated LC/MS/MS bioanalytical method.
Time frame: Measured at 12 hours after product use.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cigarette Smokers | Concentration of Plasma Nicotine 12 Hours After Product Use | 3.9 ng/mL |
| Never Smokers | Concentration of Plasma Nicotine 12 Hours After Product Use | 0.2 ng/mL |
Primary
Concentration of Plasma Nicotine 4 Hours After Product Use
Nicotine plasma concentrations will be measured using validated LC/MS/MS bioanalytical method.
Time frame: Measured at 4 hours after product use.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cigarette Smokers | Concentration of Plasma Nicotine 4 Hours After Product Use | 4.6 ng/mL |
| Never Smokers | Concentration of Plasma Nicotine 4 Hours After Product Use | 0.2 ng/mL |
Primary
Concentration of Plasma Nicotine 8 Hours After Product Use
Nicotine plasma concentrations will be measured using validated LC/MS/MS bioanalytical method.
Time frame: Measured at 8 hours after product use.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cigarette Smokers | Concentration of Plasma Nicotine 8 Hours After Product Use | 2.8 ng/mL |
| Never Smokers | Concentration of Plasma Nicotine 8 Hours After Product Use | 0.2 ng/mL |
Primary
Concentration of Plasma Nicotine at t0, Start of Product Use
Nicotine plasma concentrations will be measured using validated LC/MS/MS bioanalytical method.
Time frame: Baseline
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cigarette Smokers | Concentration of Plasma Nicotine at t0, Start of Product Use | 18.8 ng/mL |
| Never Smokers | Concentration of Plasma Nicotine at t0, Start of Product Use | 0.0 ng/mL |
Primary
Saccharin Transit Time 12 Hours After Product Use
Before performing the test, each subject will spend approximately 15 minutes acclimatizing to the environment of the clinic. A 1-2 mm particle of saccharin will be placed under direct vision, approximately 1 cm behind the anterior end of the inferior turbinate. The position of the subject's head should be flexed approximately 10° by visual assessment. The saccharin transit time will be determined as the elapsed time in minutes and seconds from placement of the saccharin until the time the subject perceives a sweet taste.
Time frame: Measured at 12 hours after product use.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cigarette Smokers | Saccharin Transit Time 12 Hours After Product Use | 8.6 minutes |
| Never Smokers | Saccharin Transit Time 12 Hours After Product Use | 9.0 minutes |
Primary
Saccharin Transit Time 4 Hours After Product Use
Before performing the test, each subject will spend approximately 15 minutes acclimatizing to the environment of the clinic. A 1-2 mm particle of saccharin will be placed under direct vision, approximately 1 cm behind the anterior end of the inferior turbinate. The position of the subject's head should be flexed approximately 10° by visual assessment. The saccharin transit time will be determined as the elapsed time in minutes and seconds from placement of the saccharin until the time the subject perceives a sweet taste.
Time frame: Measured at 4 hours after product use.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cigarette Smokers | Saccharin Transit Time 4 Hours After Product Use | 8.0 minutes |
| Never Smokers | Saccharin Transit Time 4 Hours After Product Use | 7.1 minutes |
Primary
Saccharin Transit Time 8 Hours After Product Use
Before performing the test, each subject will spend approximately 15 minutes acclimatizing to the environment of the clinic. A 1-2 mm particle of saccharin will be placed under direct vision, approximately 1 cm behind the anterior end of the inferior turbinate. The position of the subject's head should be flexed approximately 10° by visual assessment. The saccharin transit time will be determined as the elapsed time in minutes and seconds from placement of the saccharin until the time the subject perceives a sweet taste.
Time frame: Measured at 8 hours after product use.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cigarette Smokers | Saccharin Transit Time 8 Hours After Product Use | 9.9 minutes |
| Never Smokers | Saccharin Transit Time 8 Hours After Product Use | 10.1 minutes |
Primary
Saccharin Transit Time at t0, Start of Product Use
Before performing the test, each subject will spend approximately 15 minutes acclimatizing to the environment of the clinic. A 1-2 mm particle of saccharin will be placed under direct vision, approximately 1 cm behind the anterior end of the inferior turbinate. The position of the subject's head should be flexed approximately 10° by visual assessment. The saccharin transit time will be determined as the elapsed time in minutes and seconds from placement of the saccharin until the time the subject perceives a sweet taste.
Time frame: Baseline
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cigarette Smokers | Saccharin Transit Time at t0, Start of Product Use | 8.4 minutes |
| Never Smokers | Saccharin Transit Time at t0, Start of Product Use | 10.1 minutes |
Secondary
Ribonucleic Acid Quality (Left Nostril)
Ribonucleic Acid quality assessed using the RNA integrity number: measured in the left nostril (Qiazol buffer) using two nasal scraping methods. RNA integrity Number is an algorithm for assessing RNA integrity and based on a numbering system from 1 to 10, with 1 being the most degraded profile and 10 being the most intact.
Time frame: Nasal scraping was performed at the final clinic visit, on Day 2, before checkout from the study.
Population: 10 study participants underwent nasal scraping using either method 1 or method 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cigarette Smokers | Ribonucleic Acid Quality (Left Nostril) | 2.4 RNA Integrity Number | Standard Deviation 0.54 |
| Never Smokers | Ribonucleic Acid Quality (Left Nostril) | 2.3 RNA Integrity Number | Standard Deviation 0.41 |
Secondary
Ribonucleic Acid Quality (Right Nostril)
Ribonucleic Acid quality assessed using the RNA integrity number: measured in the right nostril (RNA protect buffer) using two nasal scraping methods. RNA integrity Number is an algorithm for assessing RNA integrity and based on a numbering system from 1 to 10, with 1 being the most degraded profile and 10 being the most intact.
Time frame: Nasal scraping was performed at the final clinic visit, on Day 2, before checkout from the study.
Population: 10 study participants underwent nasal scraping using either method 1 or method 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cigarette Smokers | Ribonucleic Acid Quality (Right Nostril) | 8.6 RNA Integrity Number | Standard Deviation 1.13 |
| Never Smokers | Ribonucleic Acid Quality (Right Nostril) | 7.1 RNA Integrity Number | Standard Deviation 1.91 |
Secondary
Ribonucleic Acid Quantity (Left Nostril)
Ribonucleic Acid quantity: concentration measured in the left nostril (Qiazol buffer) using two nasal scraping methods
Time frame: Nasal scraping was performed at the final clinic visit, on Day 2, before checkout from the study.
Population: 10 study participants underwent nasal scraping using either method 1 or method 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cigarette Smokers | Ribonucleic Acid Quantity (Left Nostril) | 46.2 ng/uL | Standard Deviation 36.64 |
| Never Smokers | Ribonucleic Acid Quantity (Left Nostril) | 57.9 ng/uL | Standard Deviation 39.94 |
Secondary
Ribonucleic Acid Quantity (Right Nostril)
Ribonucleic Acid quantity: concentration measured in the right nostril (RNA protect buffer) using two nasal scraping methods
Time frame: Nasal scraping was performed at the final clinic visit, on Day 2, before checkout from the study.
Population: 10 study participants underwent nasal scraping using either method 1 or method 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cigarette Smokers | Ribonucleic Acid Quantity (Right Nostril) | 47.5 ng/uL | Standard Deviation 23.83 |
| Never Smokers | Ribonucleic Acid Quantity (Right Nostril) | 44.0 ng/uL | Standard Deviation 43.77 |