Trial Outcomes & Findings for Prefatory Study to Explore Changes in Nasal Mucociliary Clearance and to Standardize Nasal Scraping Procedure (NCT NCT03086707)

NCT ID: NCT03086707

Last Updated: 2020-11-20

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 14 participants
• Primary outcome timeframe: Baseline
• Results posted on: 2020-11-20

Participant Flow

Participant milestones

Measure	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.	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.
Overall Study STARTED	7	7
Overall Study COMPLETED	7	7
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Prefatory Study to Explore Changes in Nasal Mucociliary Clearance and to Standardize Nasal Scraping Procedure

Baseline characteristics by cohort

Measure	Cigarette Smokers n=7 Participants 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.	Never Smokers n=7 Participants 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.	Total n=14 Participants Total of all reporting groups
Age, Continuous	33.9 years STANDARD_DEVIATION 7.20 • n=5 Participants	32.1 years STANDARD_DEVIATION 4.30 • n=7 Participants	33.0 years STANDARD_DEVIATION 5.76 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=5 Participants	3 Participants n=7 Participants	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	7 participants n=5 Participants	7 participants n=7 Participants	14 participants n=5 Participants
Weight (kg)	73.3 kg STANDARD_DEVIATION 7.18 • n=5 Participants	85.9 kg STANDARD_DEVIATION 11.60 • n=7 Participants	79.6 kg STANDARD_DEVIATION 11.35 • n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Cigarette Smokers n=7 Participants 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.	Never Smokers n=7 Participants 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.
Saccharin Transit Time at t0, Start of Product Use	8.4 minutes Interval 4.81 to 11.89	10.1 minutes Interval 4.05 to 16.21

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Cigarette Smokers n=7 Participants 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.	Never Smokers n=7 Participants 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.
Saccharin Transit Time 4 Hours After Product Use	8.0 minutes Interval 5.83 to 10.12	7.1 minutes Interval 1.98 to 12.28

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Cigarette Smokers n=7 Participants 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.	Never Smokers n=7 Participants 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.
Saccharin Transit Time 8 Hours After Product Use	9.9 minutes Interval 3.25 to 16.57	10.1 minutes Interval 3.03 to 17.11

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Cigarette Smokers n=7 Participants 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.	Never Smokers n=7 Participants 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.
Saccharin Transit Time 12 Hours After Product Use	8.6 minutes Interval 5.34 to 11.78	9.0 minutes Interval 2.61 to 15.47

PRIMARY outcome

Timeframe: Baseline

Nicotine plasma concentrations will be measured using validated LC/MS/MS bioanalytical method.

Outcome measures

Measure	Cigarette Smokers n=7 Participants 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.	Never Smokers n=7 Participants 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.
Concentration of Plasma Nicotine at t0, Start of Product Use	18.8 ng/mL Interval 13.83 to 23.8	0.0 ng/mL Interval 0.0 to 0.0

PRIMARY outcome

Timeframe: Measured at 4 hours after product use.

Nicotine plasma concentrations will be measured using validated LC/MS/MS bioanalytical method.

Outcome measures

Measure	Cigarette Smokers n=7 Participants 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.	Never Smokers n=7 Participants 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.
Concentration of Plasma Nicotine 4 Hours After Product Use	4.6 ng/mL Interval 1.25 to 7.9	0.2 ng/mL All subjects in the never smoker group presented a plasma value below the Lower Limit of Quantification at the study timepoints.

PRIMARY outcome

Timeframe: Measured at 8 hours after product use.

Nicotine plasma concentrations will be measured using validated LC/MS/MS bioanalytical method.

Outcome measures

Measure	Cigarette Smokers n=7 Participants 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.	Never Smokers n=7 Participants 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.
Concentration of Plasma Nicotine 8 Hours After Product Use	2.8 ng/mL Interval 0.35 to 5.26	0.2 ng/mL All subjects in the never smoker group presented a plasma value below the Lower Limit of Quantification at the study timepoints.

PRIMARY outcome

Timeframe: Measured at 12 hours after product use.

The Nicotine plasma concentrations will be measured using validated LC/MS/MS bioanalytical method.

Outcome measures

Measure	Cigarette Smokers n=7 Participants 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.	Never Smokers n=7 Participants 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.
Concentration of Plasma Nicotine 12 Hours After Product Use	3.9 ng/mL Interval -2.24 to 9.96	0.2 ng/mL All subjects in the never smoker group presented a plasma value below the Lower Limit of Quantification at the study timepoints.

SECONDARY outcome

Timeframe: 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.

Ribonucleic Acid quantity: concentration measured in the right nostril (RNA protect buffer) using two nasal scraping methods

Outcome measures

Measure	Cigarette Smokers n=5 Participants 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.	Never Smokers n=5 Participants 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.
Ribonucleic Acid Quantity (Right Nostril)	47.5 ng/uL Standard Deviation 23.83	44.0 ng/uL Standard Deviation 43.77

SECONDARY outcome

Timeframe: 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.

Ribonucleic Acid quantity: concentration measured in the left nostril (Qiazol buffer) using two nasal scraping methods

Outcome measures

Measure	Cigarette Smokers n=5 Participants 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.	Never Smokers n=5 Participants 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.
Ribonucleic Acid Quantity (Left Nostril)	46.2 ng/uL Standard Deviation 36.64	57.9 ng/uL Standard Deviation 39.94

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Cigarette Smokers n=5 Participants 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.	Never Smokers n=5 Participants 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.
Ribonucleic Acid Quality (Right Nostril)	8.6 RNA Integrity Number Standard Deviation 1.13	7.1 RNA Integrity Number Standard Deviation 1.91

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Cigarette Smokers n=5 Participants 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.	Never Smokers n=5 Participants 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.
Ribonucleic Acid Quality (Left Nostril)	2.4 RNA Integrity Number Standard Deviation 0.54	2.3 RNA Integrity Number Standard Deviation 0.41

Adverse Events

Cigarette Smokers

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Never Smokers

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Cigarette Smokers n=7 participants at risk 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.	Never Smokers n=7 participants at risk 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.
Investigations Blood glucose decreased	14.3% 1/7 • Number of events 1 • Adverse events were collected over the entire study duration of up to 7 months, with individual subject participation of a maximum of 33 days from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period.	0.00% 0/7 • Adverse events were collected over the entire study duration of up to 7 months, with individual subject participation of a maximum of 33 days from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period.

Additional Information

Julia Hoeng, PhD

Philip Morris Products S.A.

Phone: +41 (58) 242 11 11

Email: ClinicalTrials.PMI@pmi.com

Results disclosure agreements

• Principal investigator is a sponsor employee We confirm we have the contractual provisions in place which specify that in no event will the study site be allowed to disclose to any third party (or publicly release) any information obtained through the study without the CRO's prior written consent which in turn cannot provide such consent without Sponsor's approval unless such publication is made to satisfy regulatory requirements. The Intellectual Property rights and research results from the present study belong to the Sponsor.
• Publication restrictions are in place

Restriction type: OTHER