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

• ClinicalTrials.gov Identifier: NCT01989156
• Recruitment Status: Completed
• First Posted: November 20, 2013
• Results First Posted: April 5, 2017
• Last Update Posted: March 24, 2020
• Sponsor: Philip Morris Products S.A.
• Information provided by (Responsible Party): Philip Morris Products S.A.

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Smoking	Other: THS 2.2 Menthol (mTHS 2.2); Other: Menthol Conventional Cigarette (mCC); Other: Smoking Abstinence (SA)	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 160 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: 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
• Study Start Date: December 2013
• Actual Primary Completion Date: October 2014
• Actual Study Completion Date: May 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Concentration of Monohydroxybutenylmercapturic Acid (MHBMA) [ Time Frame: 5 days ]
   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.
2. Concentration of 3-hydroxypropylmercapturic Acid (3-HPMA) [ Time Frame: 5 days ]
   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.
3. Concentration of S-phenylmercapturic Acid (S-PMA) [ Time Frame: 5 days ]
   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.
4. Levels of Total 4-(Methylnitrosamino)-1-(3- Pyridyl)-1-butanol (Total NNAL) [ Time Frame: 90 days ]
   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.
5. Levels of Carboxyhemoglobin (COHb) [ Time Frame: 5 days ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 22 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

United States, Florida

Covance Daytona Beach, 1900 Mason Ave., Suite 140

Daytona Beach, Florida, United States, 32117

United States, Texas

Covance Dallas, 1341 W. Mockingbird Ln., Ste 400E

Dallas, Texas, United States, 75247

Sponsors and Collaborators

Philip Morris Products S.A.

Investigators

• Principal Investigator: William Lewis, MD; Covance Dallas
• Principal Investigator: Frank Farmer, MD; Covance Daytona Beach
• Study Chair: Christelle Haziza, PhD; Philip Morris Products S.A.

  Study Documents (Full-Text)

Documents provided by Philip Morris Products S.A.:

Study Protocol  [PDF] April 14, 2014

Statistical Analysis Plan  [PDF] May 29, 2015

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Philip Morris Products S.A.
• ClinicalTrials.gov Identifier: NCT01989156
• Other Study ID Numbers: ZRHM-REXA-08-US; ZRHM-REXA-08-US ( Other Identifier: Philip Morris Products S.A. )
• First Posted: November 20, 2013
• Results First Posted: April 5, 2017
• Last Update Posted: March 24, 2020
• Last Verified: March 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Philip Morris Products S.A.:

Smoking; Candidate modified risk tobacco product; Menthol conventional cigarettes; Reduced exposure; HPHCs; Ambulatory

Additional relevant MeSH terms:

Menthol; Antipruritics; Dermatologic Agents