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.

Tracking Information

• First Submitted Date: November 14, 2013
• First Posted Date: November 20, 2013
• Results First Submitted Date: December 21, 2016
• Results First Posted Date: April 5, 2017
• Last Update Posted Date: March 24, 2020
• Study Start Date: December 2013
• Actual Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 21, 2017)

• 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.
• 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.
• 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.
• 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.
• 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.

Original Primary Outcome Measures (submitted: November 19, 2013)

• The evaluation of the total levels of monohydroxybutenyl mercapturic acid (MHBMA); 3-hydroxypropylmercapturic acid (3-HPMA); S-phenylmercapturic acid (S-PMA); total4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (total NNAL) in 24 hours urine. [ Time Frame: MHBMA, 3-HPMA, S-PMA at 5 days; total NNAL at 91 days ]
  To demonstrate the reduction of exposure to respectively 1,3-butadiene; acrolein; benzene HPHCs) after 5 days and to 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) after 91 days of switching from mCC to THS 2.2 Menthol as compared to mCC.
• The evaluation of the total levels of carboxyhemoglobin (COHb) in blood. [ Time Frame: 91 days ]
  To demonstrate the reduction of exposure to carbon monoxide (CO) after 5 days of switching from mCC to THS 2.2 Menthol as compared to mCC.

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Reduced Exposure Study Using THS 2.2 Menthol With 5 Days in a Confinement Setting Followed by 86 Days in an Ambulatory Setting
• 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
• 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).
• 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
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Other
• Condition: Smoking

Intervention

• 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
• 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
• Other: Smoking Abstinence (SA)
  SA for 5 days in confinement prolonged by 86 days in an ambulatory setting

Study Arms

• 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
  Intervention: Other: THS 2.2 Menthol (mTHS 2.2)
• 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
  Intervention: Other: Menthol Conventional Cigarette (mCC)
• Sham Comparator: Smoking abstinence (SA)
  Abstinence from smoking for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting
  Intervention: Other: Smoking Abstinence (SA)

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 19, 2014): 160
• Original Estimated Enrollment (submitted: November 19, 2013): 190
• Actual Study Completion Date: May 2015
• Actual Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 22 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01989156
• Other Study ID Numbers: ZRHM-REXA-08-US; ZRHM-REXA-08-US ( Other Identifier: Philip Morris Products S.A. )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Philip Morris Products S.A.
• Original Responsible Party: Same as current
• Current Study Sponsor: Philip Morris Products S.A.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

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.

• PRS Account: Philip Morris Products S.A.
• Verification Date: March 2020