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

A Two-arm, Open Label, Prefatory Study to Explore Changes in Nasal Mucociliary Clearance Between Smokers and Never Smokers and to Standardize Nasal Scraping Procedure

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.

Study Overview

• Status: Completed
• Conditions: Smokers; Never Smokers
• Intervention / Treatment: Other: Cigarette

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Neptune, New Jersey, United States, 07753
      • Inflamax Research - Neptune
    • Newark, New Jersey, United States, 07105
      • Inflamax Research - Newark

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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.	Other: 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.
No Intervention: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline
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.	Measured at 4 hours after product use.
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.	Measured at 8 hours after product use.
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.	Measured at 12 hours after product use.
Concentration of Plasma Nicotine at t0, Start of Product Use	Nicotine plasma concentrations will be measured using validated LC/MS/MS bioanalytical method.	Baseline
Concentration of Plasma Nicotine 4 Hours After Product Use	Nicotine plasma concentrations will be measured using validated LC/MS/MS bioanalytical method.	Measured at 4 hours after product use.
Concentration of Plasma Nicotine 8 Hours After Product Use	Nicotine plasma concentrations will be measured using validated LC/MS/MS bioanalytical method.	Measured at 8 hours after product use.
Concentration of Plasma Nicotine 12 Hours After Product Use	The Nicotine plasma concentrations will be measured using validated LC/MS/MS bioanalytical method.	Measured at 12 hours after product use.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ribonucleic Acid Quantity (Right Nostril)	Ribonucleic Acid quantity: concentration measured in the right nostril (RNA protect buffer) using two nasal scraping methods	Nasal scraping was performed at the final clinic visit, on Day 2, before checkout from the study.
Ribonucleic Acid Quantity (Left Nostril)	Ribonucleic Acid quantity: concentration measured in the left nostril (Qiazol buffer) using two nasal scraping methods	Nasal scraping was performed at the final clinic visit, on Day 2, before checkout from the study.
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.	Nasal scraping was performed at the final clinic visit, on Day 2, before checkout from the study.
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.	Nasal scraping was performed at the final clinic visit, on Day 2, before checkout from the study.

Collaborators and Investigators

• Sponsor: Philip Morris Products S.A.
• Investigators: Principal Investigator: Frank Lee, MD, Inflamax Research - Neptune

Publications and helpful links

General 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. doi: 10.1186/1471-2199-7-3.

Study record dates

Study Major Dates

• Study Start (Actual): January 21, 2017
• Primary Completion (Actual): August 14, 2017
• Study Completion (Actual): September 29, 2017

Study Registration Dates

• First Submitted: March 16, 2017
• First Submitted That Met QC Criteria: March 21, 2017
• First Posted (Actual): March 22, 2017

Study Record Updates

• Last Update Posted (Actual): November 20, 2020
• Last Update Submitted That Met QC Criteria: October 23, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: nasal mucociliary clearance; saccharine transit time
• Other Study ID Numbers: P1-CMS-01-US

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No individual participant data will be made available.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No