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

• ClinicalTrials.gov Identifier: NCT03086707
• Recruitment Status: Completed
• First Posted: March 22, 2017
• Results First Posted: October 23, 2020
• Last Update Posted: November 20, 2020
• Sponsor: Philip Morris Products S.A.
• Information provided by (Responsible Party): Philip Morris Products S.A.

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Other
• Conditions: Smokers; Never Smokers
• Intervention: Other: Cigarette
• Enrollment: 14

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Cigarette Smokers	Never Smokers
Arm/Group Description	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.	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.
Period Title: Overall Study
Started	7	7
Completed	7	7
Not Completed	0	0

Baseline Characteristics

Arm/Group Title		Cigarette Smokers	Never Smokers	Total
Arm/Group Description		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.	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 of all reporting groups
Overall Number of Baseline Participants		7	7	14
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	7 participants	7 participants	14 participants
		33.9 (7.20)	32.1 (4.30)	33.0 (5.76)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	7 participants	7 participants	14 participants
	Female	0 0.0%	0 0.0%	0 0.0%
	Male	7 100.0%	7 100.0%	14 100.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	7 participants	7 participants	14 participants
	Hispanic or Latino	0 0.0%	4 57.1%	4 28.6%
	Not Hispanic or Latino	7 100.0%	3 42.9%	10 71.4%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	7 participants	7 participants	14 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	1 14.3%	1 7.1%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	4 57.1%	3 42.9%	7 50.0%
	White	3 42.9%	3 42.9%	6 42.9%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	7 participants	7 participants	14 participants
		7	7	14
Weight (kg); Mean (Standard Deviation); Unit of measure: Kg
	Number Analyzed	7 participants	7 participants	14 participants
		73.3 (7.18)	85.9 (11.60)	79.6 (11.35)

Outcome Measures

1. Primary Outcome

Title	Saccharin Transit Time at t0, Start of Product Use
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cigarette Smokers	Never Smokers
Arm/Group Description:	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.	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 Number of Participants Analyzed	7	7
Mean (95% Confidence Interval); Unit of Measure: minutes
	8.4; (4.81 to 11.89)	10.1; (4.05 to 16.21)

2. Primary Outcome

Title	Saccharin Transit Time 4 Hours After Product Use
Description	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cigarette Smokers	Never Smokers
Arm/Group Description:	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.	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 Number of Participants Analyzed	7	7
Mean (95% Confidence Interval); Unit of Measure: minutes
	8.0; (5.83 to 10.12)	7.1; (1.98 to 12.28)

3. Primary Outcome

Title	Saccharin Transit Time 8 Hours After Product Use
Description	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cigarette Smokers	Never Smokers
Arm/Group Description:	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.	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 Number of Participants Analyzed	7	7
Mean (95% Confidence Interval); Unit of Measure: minutes
	9.9; (3.25 to 16.57)	10.1; (3.03 to 17.11)

4. Primary Outcome

Title	Saccharin Transit Time 12 Hours After Product Use
Description	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cigarette Smokers	Never Smokers
Arm/Group Description:	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.	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 Number of Participants Analyzed	7	7
Mean (95% Confidence Interval); Unit of Measure: minutes
	8.6; (5.34 to 11.78)	9.0; (2.61 to 15.47)

5. Primary Outcome

Title	Concentration of Plasma Nicotine at t0, Start of Product Use
Description	Nicotine plasma concentrations will be measured using validated LC/MS/MS bioanalytical method.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cigarette Smokers	Never Smokers
Arm/Group Description:	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.	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 Number of Participants Analyzed	7	7
Mean (95% Confidence Interval); Unit of Measure: ng/mL
	18.8; (13.83 to 23.80)	0.0; (0.00 to 0.00)

6. Primary Outcome

Title	Concentration of Plasma Nicotine 4 Hours After Product Use
Description	Nicotine plasma concentrations will be measured using validated LC/MS/MS bioanalytical method.
Time Frame	Measured at 4 hours after product use.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cigarette Smokers	Never Smokers
Arm/Group Description:	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.	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 Number of Participants Analyzed	7	7
Mean (95% Confidence Interval); Unit of Measure: ng/mL
	4.6; (1.25 to 7.90)	0.2 [1]; (NA to NA)

[1]

All subjects in the never smoker group presented a plasma value below the Lower Limit of Quantification at the study timepoints.

7. Primary Outcome

Title	Concentration of Plasma Nicotine 8 Hours After Product Use
Description	Nicotine plasma concentrations will be measured using validated LC/MS/MS bioanalytical method.
Time Frame	Measured at 8 hours after product use.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cigarette Smokers	Never Smokers
Arm/Group Description:	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.	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 Number of Participants Analyzed	7	7
Mean (95% Confidence Interval); Unit of Measure: ng/mL
	2.8; (0.35 to 5.26)	0.2 [1]; (NA to NA)

[1]

All subjects in the never smoker group presented a plasma value below the Lower Limit of Quantification at the study timepoints.

8. Primary Outcome

Title	Concentration of Plasma Nicotine 12 Hours After Product Use
Description	The Nicotine plasma concentrations will be measured using validated LC/MS/MS bioanalytical method.
Time Frame	Measured at 12 hours after product use.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cigarette Smokers	Never Smokers
Arm/Group Description:	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.	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 Number of Participants Analyzed	7	7
Mean (95% Confidence Interval); Unit of Measure: ng/mL
	3.9; (-2.24 to 9.96)	0.2 [1]; (NA to NA)

[1]

All subjects in the never smoker group presented a plasma value below the Lower Limit of Quantification at the study timepoints.

9. Secondary Outcome

Title	Ribonucleic Acid Quantity (Right Nostril)
Description	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.

Outcome Measure Data

Analysis Population Description

10 study participants underwent nasal scraping using either method 1 or method 2.

Arm/Group Title	Nasal Scraping Method 1	Nasal Scraping Method 2
Arm/Group Description:	Five study participants underwent nasal scraping using method 1.	Five study participants underwent nasal scraping using method 2.
Overall Number of Participants Analyzed	5	5
Mean (Standard Deviation); Unit of Measure: ng/uL
	47.5 (23.83)	44.0 (43.77)

10. Secondary Outcome

Title	Ribonucleic Acid Quantity (Left Nostril)
Description	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.

Outcome Measure Data

Analysis Population Description

10 study participants underwent nasal scraping using either method 1 or method 2.

Arm/Group Title	Nasal Scraping Method 1	Nasal Scraping Method 2
Arm/Group Description:	Five study participants underwent nasal scraping using method 1.	Five study participants underwent nasal scraping using method 2.
Overall Number of Participants Analyzed	5	5
Mean (Standard Deviation); Unit of Measure: ng/uL
	46.2 (36.64)	57.9 (39.94)

11. Secondary Outcome

Title	Ribonucleic Acid Quality (Right Nostril)
Description	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.

Outcome Measure Data

Analysis Population Description

10 study participants underwent nasal scraping using either method 1 or method 2.

Arm/Group Title	Nasal Scraping Method 1	Nasal Scraping Method 2
Arm/Group Description:	Five study participants underwent nasal scraping using method 1.	Five study participants underwent nasal scraping using method 2.
Overall Number of Participants Analyzed	5	5
Mean (Standard Deviation); Unit of Measure: RNA Integrity Number
	8.6 (1.13)	7.1 (1.91)

12. Secondary Outcome

Title	Ribonucleic Acid Quality (Left Nostril)
Description	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.

Outcome Measure Data

Analysis Population Description

10 study participants underwent nasal scraping using either method 1 or method 2.

Arm/Group Title	Nasal Scraping Method 1	Nasal Scraping Method 2
Arm/Group Description:	Five study participants underwent nasal scraping using method 1.	Five study participants underwent nasal scraping using method 2.
Overall Number of Participants Analyzed	5	5
Mean (Standard Deviation); Unit of Measure: RNA Integrity Number
	2.4 (0.54)	2.3 (0.41)

Adverse Events

Time Frame	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.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Cigarette Smokers		Never Smokers
Arm/Group Description	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.		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.
All-Cause Mortality
	Cigarette Smokers		Never Smokers
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/7 (0.00%)		0/7 (0.00%)
Serious Adverse Events
	Cigarette Smokers		Never Smokers
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0.00%)		0/7 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Cigarette Smokers		Never Smokers
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/7 (14.29%)		0/7 (0.00%)
Investigations
Blood glucose decreased * 1	1/7 (14.29%)	1	0/7 (0.00%)	0
1 Term from vocabulary, MedDRA; * Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: Julia Hoeng, PhD
• Organization: Philip Morris Products S.A.
• Phone: +41 (58) 242 11 11
• EMail: ClinicalTrials.PMI@pmi.com

Publications:

Schroeder A, Mueller O, Stocker S, Salowsky R, Leiber M, Gassmann M, Lightfoot S, Menzel W, Granzow M, Ragg T. The RIN: an RNA integrity number for assigning integrity values to RNA measurements. BMC Mol Biol. 2006 Jan 31;7:3.

• Responsible Party: Philip Morris Products S.A.
• ClinicalTrials.gov Identifier: NCT03086707
• Other Study ID Numbers: P1-CMS-01-US
• First Submitted: March 16, 2017
• First Posted: March 22, 2017
• Results First Submitted: October 21, 2019
• Results First Posted: October 23, 2020
• Last Update Posted: November 20, 2020