Evaluation of Biological and Functional Changes in Healthy Smokers After Switching to THS 2.2 for 26 Weeks

• ClinicalTrials.gov Identifier: NCT02396381
• Recruitment Status: Completed
• First Posted: March 24, 2015
• Results First Posted: August 21, 2019
• Last Update Posted: January 26, 2023
• Sponsor: Philip Morris Products S.A.
• Information provided by (Responsible Party): Philip Morris Products S.A.

Tracking Information

• First Submitted Date: March 18, 2015
• First Posted Date: March 24, 2015
• Results First Submitted Date: July 27, 2018
• Results First Posted Date: August 21, 2019
• Last Update Posted Date: January 26, 2023
• Actual Study Start Date: March 12, 2015
• Actual Primary Completion Date: September 13, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 20, 2019)

• Levels of High Density Lipoprotein C (HDL-C). [ Time Frame: 26 Weeks ]
  Concentrations measured in serum. Geometric Least Squares means are provided as descriptive statistics.
• Levels of White Blood Cells (WBC). [ Time Frame: 26 Weeks ]
  Concentrations measured in blood. Geometric Least Squares means are provided as descriptive statistics.
• Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1). [ Time Frame: 26 Weeks ]
  FEV1 post-bronchodilator and expressed as percentage predicted (FEV1 %pred). Geometric Least Squares means are provided as descriptive statistics.
• Concentrations of Soluble Intercellular Adhesion Molecule 1 (sICAM-1). [ Time Frame: 26 Weeks ]
  Concentrations measured in serum. Geometric Least Squares means are provided as descriptive statistics.
• Concentrations of 11-dehydrothromboxane B2 (11-DTXB2). [ Time Frame: 26 Weeks ]
  Concentrations measured in urine and expressed as concentration adjusted for creatinine. Geometric Least Squares means are provided as descriptive statistics.
• Concentrations of 8-epi-prostaglandin F2α (8-epi-PGF2α). [ Time Frame: 26 Weeks ]
  Concentrations measured in urine and expressed as concentration adjusted for creatinine. Geometric Least Squares means are provided as descriptive statistics.
• Concentrations of Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (Total NNAL). [ Time Frame: 26 Weeks ]
  Concentrations measured in urine and expressed as concentration adjusted for creatinine. Geometric Least Squares means are provided as descriptive statistics.
• Percent Change From Baseline of Carboxyhemoglobin (COHb) [ Time Frame: 26 Weeks ]
  Carboxyhemoglobin (COHb) is assayed from whole blood. Geometric Least Squares means are provided as descriptive statistics. Expressed as % of saturation of hemoglobin.

Original Primary Outcome Measures (submitted: March 18, 2015)

Demonstration of changes of the "smoker's health profile" when switching from CC to THS 2.2 as compared to CC [ Time Frame: Week 26 ]

The following endpoints included in the "smoker's health profile" will be measured at week 26: high density lipoprotein cholesterol (HDL-C) in serum, white blood cell total count (WBC) in blood, soluble intercellular adhesion molecule-1 (sICAM-1) in serum, 11-dehydrothromboxane B2 (11-DTX-B2) in urine, 8-epi-prostaglandin F2α (8-epi-PGF2α) in urine, carboxyhemoglobin (COHb) in blood, forced expiratory volume in 1 second (FEV1 post-bronchodilator, total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (total NNAL) in urine.

• 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: Evaluation of Biological and Functional Changes in Healthy Smokers After Switching to THS 2.2 for 26 Weeks
• Official Title: A Randomized, Controlled, 2-arm Parallel Group, Multi-center Study, to Evaluate Biological and Functional Changes in Healthy Smokers Switching to Tobacco Heating System 2.2 (THS 2.2) Compared to Continuing Smoking Conventional Cigarettes for 26 Weeks in an Ambulatory Setting

Brief Summary

The aim of the study is to demonstrate clinical, biological and functional health changes in smokers switching to the candidate modified risk tobacco product: Tobacco Heating System 2.2 (THS 2.2) as compared to smokers continuing smoking their conventional cigarettes (CC) over a 26-week period.

To characterize the study as successful, at least 5 clinical risk endpoints should move in the direction of smoking cessation and these results would be statistically significant. The main analysis will be defined a priori (using the Hailperin-Ruger approach) and will be made between THS 2.2 use and CC use as "per actual product used" and product use categories.

Detailed Description

The clinical, biological and functional endpoints to be measured in this study ("smoker's health profile") may characterize the modification of risk of smoking-related diseases.

Clinical risk endpoint to be assessed are selected based on a) their association to smoking-related diseases b) their association to smoking status, c) their reversibility upon smoking cessation, and d) their suitability to be measured with valid and robust methods in clinical studies.

The biological markers, functional markers and biomarkers of exposure (BoExp) with the strongest scientific evidence will constitute the 'smoker's health profile' and will be measured as the primary objective of the study.

Additional endpoints involved in the mechanistic of smoking-related diseases will be studied to provide additional scientific evidence to strengthen the primary objective.

The study will provide a perspective of product usage in a "real world setting" where smoking CC in addition to THS 2.2 may be expected.

• 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
  Ad libitum use of THS 2.2 in an ambulatory setting for 26 weeks
• Other: CC
  Ad libitum use of CC in an ambulatory setting for 26 weeks

Study Arms

• Experimental: THS 2.2
  Ad libitum use of THS 2.2
  Intervention: Other: THS 2.2
• Active Comparator: CC
  Ad libitum use of CC
  Intervention: Other: CC

Publications *

• Ludicke F, Ansari SM, Lama N, Blanc N, Bosilkovska M, Donelli A, Picavet P, Baker G, Haziza C, Peitsch M, Weitkunat R. Effects of Switching to a Heat-Not-Burn Tobacco Product on Biologically Relevant Biomarkers to Assess a Candidate Modified Risk Tobacco Product: A Randomized Trial. Cancer Epidemiol Biomarkers Prev. 2019 Nov;28(11):1934-1943. doi: 10.1158/1055-9965.EPI-18-0915. Epub 2019 Jul 3.
• Ansari SM, Lama N, Blanc N, Bosilkovska M, Donelli A, Picavet P, Baker G, Haziza C, Ludicke F. Evaluation of Biological and Functional Changes in Healthy Smokers Switching to the Tobacco Heating System 2.2 Versus Continued Tobacco Smoking: Protocol for a Randomized, Controlled, Multicenter Study. JMIR Res Protoc. 2018 Aug 24;7(8):e11294. doi: 10.2196/11294.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 20, 2019): 1039
• Original Estimated Enrollment (submitted: March 18, 2015): 950
• Actual Study Completion Date: August 1, 2017
• Actual Primary Completion Date: September 13, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Current healthy smoker as judged by the Principal Investigator(s) or designee(s)
• Minimum age: 30 years old
• Have smoked for the last 10 years
• Have smoked more than 10 non menthol CC/day on average (no brand restriction) over the past year

Exclusion Criteria:

• Clinically relevant medical conditions that in the opinion of the investigators would jeopardize the safety of the participant.
• Subject who has (FEV1/FVC) < 0.7 and FEV1 < 80% predicted value at post-bronchodilator spirometry
• Subject with asthma condition (post-bronchodilator FEV1/FVC < 0.75 and reversibility in FEV1 ≥ 12% and > 200 mL from pre- to post-bronchodilator values)
• Subject who took or is taking concomitant medication which may have an impact on the "smoker's heath profile"
• Female subject is pregnant or breast feeding.
• Female subject who does not agree to use an acceptable method of effective contraception.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 30 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: NCT02396381
• Other Study ID Numbers: ZRHR-ERS-09-US; ZRHR-ERS-09-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

• Study Chair: Christelle Haziza, PhD; Philip Morris Products S.A.
• Principal Investigator: Danielle Armas, MD; Celerion Arizona
• Principal Investigator: Leonard Dunn, MD; Clinical Research West Florida
• Principal Investigator: Hugh Coleman, MD; Covance
• Principal Investigator: George Stoica, MD; Compass Research
• Principal Investigator: Mark Adams, MD; Central Kentucky Research Associate
• Principal Investigator: Peter Davidson, MD; Celerion Lincoln
• Principal Investigator: John Rubino, MD; PMG Research of Raleigh
• Principal Investigator: George Raad, MD; PMG Research of Charlotte
• Principal Investigator: Kevin Cannon, MD; PMG Research of Wilmington
• Principal Investigator: Derek Schroder, MD; PMG Research of Cary
• Principal Investigator: Stephanie Powell, MD; PMG Research of Bristol
• Principal Investigator: William Smith, MD; NOCCR
• Principal Investigator: Darrell Herrington, MD; Benchmark
• Principal Investigator: Laurence Chu, MD; Benchmark
• Principal Investigator: William Seger, MD; Benchmark
• Principal Investigator: Lon Lynn, MD; Clinical Research West Florida
• Principal Investigator: David Subich, MD; Compass Research
• Principal Investigator: Isabel Kuhare-Arcure, MD; Midwest Clinical Research
• Principal Investigator: Keith Scott, MD; National Clinical Research

• PRS Account: Philip Morris Products S.A.
• Verification Date: January 2023