Reduced Exposure Study Using the CHTP 1.2 With 5 Days in a Confinement Setting Followed by 85 Days in an Ambulatory Setting.

• ClinicalTrials.gov Identifier: NCT02641587
• Recruitment Status: Completed
• First Posted: December 29, 2015
• Results First Posted: March 6, 2019
• Last Update Posted: March 27, 2020
• Sponsor: Philip Morris Products S.A.
• Information provided by (Responsible Party): Philip Morris Products S.A.

Tracking Information

• First Submitted Date: December 23, 2015
• First Posted Date: December 29, 2015
• Results First Submitted Date: October 2, 2018
• Results First Posted Date: March 6, 2019
• Last Update Posted Date: March 27, 2020
• Actual Study Start Date: January 2016
• Actual Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 5, 2019)

• Concentrations of Monohydroxybutenylmercapturic Acid (MHBMA) [ Time Frame: 5 days ]
  Concentrations measured at Day 5 in urine, adjusted for creatinine. Geometric least squares (LS) means and confidence intervals (Cls) from a generalized linear model conducted on log-transformed Day 5 values with log-transformed baseline value, study arm, sex and CC consumption reported at admission as fixed effect factors.
• 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 and confidence intervals (Cls) from a generalized linear model conducted on log-transformed Day 5 values with log-transformed baseline value, study arm, sex and CC consumption reported at admission as fixed effect factors.
• 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 and confidence intervals (Cls) from a generalized linear model conducted on log-transformed Day 5 values with log-transformed baseline value, study arm, sex and CC consumption reported at admission as fixed effect factors.
• 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 (LS) means and confidence intervals (Cls) from a generalized linear model conducted on log-transformed Day 5 values with log-transformed baseline value, study arm, sex and CC consumption reported at admission as fixed effect factors.
• Concentrations 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 and confidence intervals (Cls) from a generalized linear model conducted on log-transformed Day 90 values with log-transformed baseline value, study arm, sex and CC consumption reported at admission as fixed effect factors.

Original Primary Outcome Measures (submitted: December 23, 2015)

• Ratio of the concentrations of monohydroxybutenylmercapturic acid (MHBMA) in smokers switching from CC to CHTP 1.2 as compared to smokers continuing to use CC for 5 days. [ Time Frame: 5 days ]
  Concentrations measured in urine, adjusted for creatinine.
• Ratio of the concentrations of 3-hydroxypropylmercapturic acid (3-HPMA) in smokers switching from CC to CHTP 1.2 as compared to smokers continuing to use CC for 5 days. [ Time Frame: 5 days ]
  Concentrations measured in urine, adjusted for creatinine.
• Ratio of the concentrations of S-phenylmercapturic acid (S-PMA) in smokers switching from CC to CHTP 1.2 as compared to smokers continuing to use CC for 5 days. [ Time Frame: 5 days ]
  Concentrations measured in urine, adjusted for creatinine.
• Levels of carboxyhemoglobin (COHb) in smokers switching from CC to CHTP 1.2 as compared to smokers continuing to use CC for 5 days. [ Time Frame: 5 days ]
  Expressed as % of saturation of hemoglobin.
• Ratio of the concentrations of total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (total NNAL) in smokers switching from CC to CHTP 1.2 as compared to smokers continuing to use CC for 90 days. [ Time Frame: 90 days ]
  Concentrations measured in urine, adjusted for creatinine.

• 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 the CHTP 1.2 With 5 Days in a Confinement Setting Followed by 85 Days in an Ambulatory Setting.
• Official Title: A Randomized, Controlled, Open-label, 2-arm Parallel Group, Single Center Study to Demonstrate Reductions in Exposure to Selected Smoke Constituents in Healthy Smokers Switching to the Carbon Heated Tobacco Product 1.2 (CHTP 1.2), Compared to Continuing to Use Combustible Cigarettes, for 5 Days in Confinement Followed by 85 Days in an Ambulatory Setting.
• Brief Summary: The overall goal of the study is to demonstrate reduction in the levels of biomarkers of exposure (BoExp) to selected harmful and potentially harmful constituents (HPHCs) identified in cigarettes and to obtain safety information in healthy adult smokers switching to the Carbon Heated Tobacco Product 1.2 (CHTP 1.2) as compared to subjects continuing smoking cigarettes (CC) in a confinement setting for 5 days (exclusive use) followed by an ambulatory setting of 85 days.
• 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: CHTP 1.2
  Ad libitum use of the CHTP 1.2 for 5 days in confinement followed by 85 days in an ambulatory setting.
• Other: CC
  Ad libitum use of subject's own preferred non-menthol brand of CC for 5 days in confinement followed by 85 days in an ambulatory setting.

Study Arms

• Experimental: CHTP 1.2
  Ad libitum use of the CHTP 1.2
  Intervention: Other: CHTP 1.2
• Active Comparator: CC
  Ad libitum use of subject's own preferred non-menthol brand of CC
  Intervention: Other: CC

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 29, 2016): 121
• Original Estimated Enrollment (submitted: December 23, 2015): 120
• Actual Study Completion Date: July 2017
• Actual Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Subject is aged ≥ 28 years.
• Subject is Caucasian.
• Subject is healthy, as judged by the Investigator.
• Subject has smoked at least 10 commercially available non-menthol CCs per day (no brand restrictions) at least for the last 6 weeks prior to the screening visit and admission.
• Subject has smoked at least for the last 10 years.
• Subject does not plan to quit smoking in 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).
• 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 1A2 (CYP1A2) or cytochrome P450 2A6 (CYP2A6) activity.
• Female subject is pregnant or breast feeding.
• Female subject does not agree to use an acceptable method of effective contraception.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 28 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: Poland

Administrative Information

• NCT Number: NCT02641587
• Other Study ID Numbers: P2R-REXA-07-EU
• 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

• Study Chair: Christelle Haziza, PhD; Philip Morris Products S.A.
• Principal Investigator: Monika Tomaszewska-Kiecana, MD; BioVirtus Research Site

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