Reduced Exposure Study Using THS 2.2 Menthol With 5 Days in a Confinement Setting and 85 Days in an Ambulatory Setting

A Randomized, Controlled, Multi-center Study to Demonstrate Reductions in Exposure to Selected Smoke Constituents in Smokers Switching to THS 2.2 Menthol or Smoking Abstinence Compared to Smoking Menthol Conventional Cigarettes, for 90 Days

The main goal of the study is to evaluate if the ad libitum use of the THS 2.2 Menthol (mTHS 2.2) for 5 days in confinement and after 85 days of product use in an ambulatory setting, by Japanese adult healthy smokers results in a reduction in the levels of biomarkers of exposure for selected harmful and potentially harmful smoke constituents (HPHCs) compared to smokers continuing smoking their own preferred brand of menthol conventional cigarette (mCC) and smoking abstinence (SA). Smokers who remained abstinent from SA were used as a benchmark to provide context to the exposure reduction.

Study Overview

• Status: Completed
• Conditions: Smoking
• Intervention / Treatment: Other: THS 2.2 Menthol (mTHS 2.2); Other: Smoking Abstinence (SA); Other: Menthol Conventional Cigarette (mCC)

• Study Type: Interventional
• Enrollment (Actual): 160
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Japan
  • Tokyo, Japan
    • Osaki Hospital Tokyo Heart Center, 5-4-12, Kitashinagawa, Shinagawa-ku

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 23 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject is Japanese.
• Smoking, healthy subject as judged by the Investigator.
• Subject smokes at least 10 commercially available mCCs per day (no brand restrictions) for the last 4 weeks, based on self-reporting.
• Subject has smoked for at least the last 3 consecutive years.
• Subject does not plan to quit smoking in the next 3 months.

Exclusion Criteria:

• As per Investigator judgment, the subject cannot participate in the study for any reason (e.g., medical, psychiatric, and/or social reason).
• The subject has received medication within 14 days or within 5 half-lives of the medication (whichever is longer) which has an impact on cytochrome P450 1 A2 (CYP1A2) or cytochrome P450 2 A6 (CYP2A6) activity.
• For women: Subject is pregnant or is breast feeding.
• For women: Subject does not agree to use an acceptable method of effective contraception.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: THS 2.2 Menthol (mTHS 2.2); Ad libitum use of THS 2.2 Menthol for 5 Days in a Confinement Setting and 85 Days in an Ambulatory Setting	Other: THS 2.2 Menthol (mTHS 2.2); THS 2.2 Menthol ad libitum for 5 days in confinement prolonged by 85 days in an ambulatory setting
Active Comparator: Smoking abstinence (SA); Abstinence from smoking for 5 Days in a Confinement Setting and 85 Days in an Ambulatory Setting	Other: Smoking Abstinence (SA); SA for 5 days in confinement prolonged by 85 days in an ambulatory setting
Active Comparator: Menthol Conventional Cigarette (mCC); Ad libitum use of subject's own preferred brand of mCC for 5 Days in a Confinement Setting and 85 Days in an Ambulatory Setting	Other: Menthol Conventional Cigarette (mCC); Subject's own preferred brand of mCC ad libitum for 5 days in confinement prolonged by 85 days in an ambulatory setting

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Levels of Carboxyhemoglobin (COHb)	% COHb blood measurements performed in the evening of Day 5, expressed as % of saturation of hemoglobin. Geometric Least Squares means are provided as descriptive statistics.	5 days
Concentration of Monohydroxybutenyl Mercapturic Acid (MHBMA)	Concentrations measured at Day 5 in urine, adjusted for creatinine. Geometric Least Squares (LS) means are provided as descriptive statistics.	5 days
Concentration of 3-hydroxypropylmercapturic Acid (3-HPMA)	Concentrations measured at Day 5 in urine, adjusted for creatinine. Geometric Least Squares (LS) means are provided as descriptive statistics.	5 days
Concentration of S-phenylmercapturic Acid (S-PMA)	Concentrations measured at Day 5 in urine, adjusted for creatinine. Geometric Least Squares (LS) means are provided as descriptive statistics.	5 days
Concentration of Total 4-(Methylnitrosamino)-1-(3- Pyridyl)-1-butanol) (Total NNAL)	Concentrations measured at Day 90 in urine, adjusted for creatinine. Geometric Least Squares (LS) means are provided as descriptive statistics.	90 days

Collaborators and Investigators

• Sponsor: Philip Morris Products S.A.
• Investigators: Principal Investigator: Masahiro Endo, MD, Osaki Hospital Tokyo Heart Center

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: October 18, 2013
• First Submitted That Met QC Criteria: October 22, 2013
• First Posted (Estimate): October 28, 2013

Study Record Updates

• Last Update Posted (Actual): March 23, 2020
• Last Update Submitted That Met QC Criteria: March 11, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Candidate modified risk tobacco product; Ambulatory; Reduced exposure; HPHCs; Conventional cigarettes
• Additional Relevant MeSH Terms: Dermatologic Agents; Antipruritics; Menthol
• Other Study ID Numbers: ZRHM-REXA-07-JP (Other Identifier: Philip Morris Products S.A.)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO