Reduced Exposure Study Using THS 2.2 Menthol With 5 Days in a Confinement Setting Followed by 86 Days in an Ambulatory Setting

A Randomized, Controlled, Open-label, 3-arm Parallel Group, Multi-center Study to Demonstrate Reductions in Exposure to Selected Smoke Constituents in Apparently Healthy Smokers Switching to the Tobacco Heating System 2.2 Menthol (THS 2.2 Menthol) or Observing Smoking Abstinence, Compared to Continuing to Use Menthol Conventional Cigarettes, for 5 Days in Confinement and Prolonged by 86 Days in an Ambulatory Setting

Evaluate if the ad libitum use of the THS 2.2 Menthol (mTHS), a candidate Modified Risk Tobacco Product, for 5 days in confinement, and after 86 days in an ambulatory setting, by apparently adult healthy smokers results in a reduction in the levels of biomarkers of exposure (BoExp) to selected harmful and potentially harmful constituents (HPHCs).

Study Overview

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

Detailed Description

The main goal of the study is to evaluate if the ad libitum use of the THS 2.2 Menthol (mTHS) for 5 days in confinement, and after 86 days in an ambulatory setting, by apparently adult healthy smokers results in a reduction in the levels of biomarkers of exposure (BoExp) to selected harmful and potentially harmful 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 Type: Interventional
• Enrollment (Actual): 160
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Florida
    • Daytona Beach, Florida, United States, 32117
      • Covance Daytona Beach, 1900 Mason Ave., Suite 140
  • Texas
    • Dallas, Texas, United States, 75247
      • Covance Dallas, 1341 W. Mockingbird Ln., Ste 400E

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Smoking, apparently 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 within the next 6 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 CYP1A2 or 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
• Masking: NONE

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 86 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 86 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 86 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 86 days in an ambulatory setting
SHAM_COMPARATOR: Smoking abstinence (SA); Abstinence from smoking for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting	Other: Smoking Abstinence (SA); SA for 5 days in confinement prolonged by 86 days in an ambulatory setting

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of Monohydroxybutenylmercapturic Acid (MHBMA)	Concentrations measured in urine, adjusted for creatinine, at Day 5 for the smokers of all arms (mTHS, mCC and SA). Geometric Least Squares means are provided as descriptive statistics.	5 days
Concentration of 3-hydroxypropylmercapturic Acid (3-HPMA)	Concentrations measured in urine, adjusted for creatinine, at Day 5 for the smokers of all arms (mTHS, mCC and SA). Geometric Least Squares means are provided as descriptive statistics.	5 days
Concentration of S-phenylmercapturic Acid (S-PMA)	Concentrations measured in urine, adjusted for creatinine, at Day 5 for the smokers of all arms (mTHS, mCC and SA). Geometric Least Squares means are provided as descriptive statistics.	5 days
Levels of Total 4-(Methylnitrosamino)-1-(3- Pyridyl)-1-butanol (Total NNAL)	Concentrations measured in urine, adjusted for creatinine, at Day 90 for the smokers of all arms (mTHS, mCC and SA). Geometric Least Squares means are provided as descriptive statistics.	90 days
Levels of Carboxyhemoglobin (COHb)	Carboxyhemoglobin (COHb) is assayed from whole blood. Expressed as % of saturation of hemoglobin. Blood measurements performed in the evening of Day 5, for the smokers of all arms (mTHS, mCC and SA). Geometric Least Squares means are provided as descriptive statistics.	5 days

Collaborators and Investigators

• Sponsor: Philip Morris Products S.A.
• Investigators: Principal Investigator: William Lewis, MD, Covance Dallas; Principal Investigator: Frank Farmer, MD, Covance Daytona Beach

Publications and helpful links

General Publications

• Haziza C, de La Bourdonnaye G, Donelli A, Skiada D, Poux V, Weitkunat R, Baker G, Picavet P, Ludicke F. Favorable Changes in Biomarkers of Potential Harm to Reduce the Adverse Health Effects of Smoking in Smokers Switching to the Menthol Tobacco Heating System 2.2 for 3 Months (Part 2). Nicotine Tob Res. 2020 Apr 17;22(4):549-559. doi: 10.1093/ntr/ntz084.
• Haziza C, de La Bourdonnaye G, Donelli A, Poux V, Skiada D, Weitkunat R, Baker G, Picavet P, Ludicke F. Reduction in Exposure to Selected Harmful and Potentially Harmful Constituents Approaching Those Observed Upon Smoking Abstinence in Smokers Switching to the Menthol Tobacco Heating System 2.2 for 3 Months (Part 1). Nicotine Tob Res. 2020 Apr 17;22(4):539-548. doi: 10.1093/ntr/ntz013.

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (ACTUAL): October 1, 2014
• Study Completion (ACTUAL): May 1, 2015

Study Registration Dates

• First Submitted: November 14, 2013
• First Submitted That Met QC Criteria: November 19, 2013
• First Posted (ESTIMATE): November 20, 2013

Study Record Updates

• Last Update Posted (ACTUAL): March 24, 2020
• Last Update Submitted That Met QC Criteria: March 11, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Smoking; Candidate modified risk tobacco product; Ambulatory; Reduced exposure; HPHCs; Menthol conventional cigarettes
• Additional Relevant MeSH Terms: Dermatologic Agents; Antipruritics; Menthol
• Other Study ID Numbers: ZRHM-REXA-08-US (OTHER: Philip Morris Products S.A.)

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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