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

• ClinicalTrials.gov Identifier: NCT01970995
• Recruitment Status: Completed
• First Posted: October 28, 2013
• Results First Posted: February 7, 2017
• Last Update Posted: March 23, 2020
• Sponsor: Philip Morris Products S.A.
• Information provided by (Responsible Party): Philip Morris Products S.A.

Tracking Information

• First Submitted Date: October 18, 2013
• First Posted Date: October 28, 2013
• Results First Submitted Date: December 14, 2016
• Results First Posted Date: February 7, 2017
• Last Update Posted Date: March 23, 2020
• Study Start Date: August 2013
• Actual Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 14, 2016)

• Concentration of Monohydroxybutenyl Mercapturic Acid (MHBMA) [ Time Frame: 5 days ]
  Concentrations measured at Day 5 in urine, adjusted for creatinine. Geometric Least Squares (LS) means are provided as descriptive statistics.
• Concentration of 3-hydroxypropylmercapturic Acid (3-HPMA) [ Time Frame: 5 days ]
  Concentrations measured at Day 5 in urine, adjusted for creatinine. Geometric Least Squares (LS) means are provided as descriptive statistics.
• Concentration of S-phenylmercapturic Acid (S-PMA) [ Time Frame: 5 days ]
  Concentrations measured at Day 5 in urine, adjusted for creatinine. Geometric Least Squares (LS) means are provided as descriptive statistics.
• Levels of Carboxyhemoglobin (COHb) [ Time Frame: 5 days ]
  % 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.
• Concentration of Total 4-(Methylnitrosamino)-1-(3- Pyridyl)-1-butanol) (Total NNAL) [ Time Frame: 90 days ]
  Concentrations measured at Day 90 in urine, adjusted for creatinine. Geometric Least Squares (LS) means are provided as descriptive statistics.

Original Primary Outcome Measures (submitted: October 22, 2013)

• To demonstrate the levels of monohydroxybutenyl mercapturic acid (MHBMA); 3-hydroxypropylmercapturic acid (3-HPMA); S-phenylmercapturic acid (S-PMA) expressed as concentration adjusted to creatinine in 24-hour urine and carboxyhemoglobin (COHb) in blood. [ Time Frame: 5 days ]
  To demonstrate the reduction of exposure to respectively 1,3-butadiene; acrolein; benzene and carbon monoxide (HPHCs) after 5 days of switching from mCC to THS 2.2 Menthol as compared to mCC.
• To demonstrate the levels of Total 4-(methylnitrosamino)-1-(3- pyridyl)-1-butanol) (Total NNAL) [ Time Frame: 90 days ]
  To demonstrate the reduction of exposure to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone after 90 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 and 85 Days in an Ambulatory Setting
• Official Title: 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• 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 85 days in an ambulatory setting
• Other: Smoking Abstinence (SA)
  SA for 5 days in confinement prolonged by 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

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 85 Days in an Ambulatory Setting
  Intervention: Other: THS 2.2 Menthol (mTHS 2.2)
• Active Comparator: Smoking abstinence (SA)
  Abstinence from smoking for 5 Days in a Confinement Setting and 85 Days in an Ambulatory Setting
  Intervention: Other: Smoking Abstinence (SA)
• 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
  Intervention: Other: Menthol Conventional Cigarette (mCC)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 27, 2014): 160
• Original Estimated Enrollment (submitted: October 22, 2013): 350
• Actual Study Completion Date: November 2014
• Actual Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 23 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT01970995
• Other Study ID Numbers: ZRHM-REXA-07-JP; ZRHM-REXA-07-JP ( Other Identifier: Philip Morris Products S.A. )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

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: Masahiro Endo, MD; Osaki Hospital Tokyo Heart Center
• Study Chair: Christelle Haziza, PhD; Philip Morris Products S.A.

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