Clinical trial NCT02396381: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Smoking
Keywords: Candidate modified risk tobacco product
Conventional cigarette
Exposure response
Smoking
Tobacco Heating System
Lead sponsor: Philip Morris Products S.A.
Sponsor class: INDUSTRY
First posted: 2015-03-24
Enrollment: 1039
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

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.

Primary outcomes:
measure: Levels of High Density Lipoprotein C (HDL-C).
timeFrame: 26 Weeks
measure: Levels of White Blood Cells (WBC).
timeFrame: 26 Weeks
measure: Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1).
timeFrame: 26 Weeks
measure: Concentrations of Soluble Intercellular Adhesion Molecule 1 (sICAM-1).
timeFrame: 26 Weeks
measure: Concentrations of 11-dehydrothromboxane B2 (11-DTXB2).
timeFrame: 26 Weeks
measure: Concentrations of 8-epi-prostaglandin F2α (8-epi-PGF2α).
timeFrame: 26 Weeks
measure: Concentrations of Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (Total NNAL).
timeFrame: 26 Weeks
measure: Percent Change From Baseline of Carboxyhemoglobin (COHb)
timeFrame: 26 Weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Tempe
country: United States
facility: Celerion Arizona
state: Arizona
city: Clearwater
country: United States
facility: Clinical Research West Florida
state: Florida
city: Daytona Beach
country: United States
facility: Covance, Inc
state: Florida
city: Orlando
country: United States
facility: Compass Research
state: Florida
city: Tampa
country: United States
facility: Clinical Research West Florida
state: Florida
city: The Villages
country: United States
facility: Compass Research
state: Florida
city: Lexington
country: United States
facility: Central Kentucky Research Associate
state: Kentucky
city: Lincoln
country: United States
facility: Celerion Lincoln
state: Nebraska
city: Cary
country: United States
facility: PMG Research of Cary
state: North Carolina
city: Charlotte
country: United States
facility: PMG Research of Charlotte
state: North Carolina
city: Raleigh
country: United States
facility: PMG Research of Raleigh
state: North Carolina
city: Wilmington
country: United States
facility: PMG Research of Wilmington
state: North Carolina
city: Dayton
country: United States
facility: Midwest Clinical Research Center
state: Ohio
city: Bristol
country: United States
facility: PMG Research of Bristol
state: Tennessee
city: Knoxville
country: United States
facility: NOCCR
state: Tennessee
city: Austin
country: United States
facility: Benchmark
state: Texas
city: Fort Worth
country: United States
facility: Benchmark
state: Texas
city: San Angelo
country: United States
facility: Benchmark
state: Texas
city: Richmond
country: United States
facility: National Clinical Research
state: Virginia
Study officials:
affiliation: Philip Morris Products S.A.
name: Christelle Haziza, PhD
role: STUDY_CHAIR
affiliation: Celerion Arizona
name: Danielle Armas, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinical Research West Florida
name: Leonard Dunn, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Covance
name: Hugh Coleman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Compass Research
name: George Stoica, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Central Kentucky Research Associate
name: Mark Adams, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Celerion Lincoln
name: Peter Davidson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: PMG Research of Raleigh
name: John Rubino, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: PMG Research of Charlotte
name: George Raad, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: PMG Research of Wilmington
name: Kevin Cannon, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: PMG Research of Cary
name: Derek Schroder, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: PMG Research of Bristol
name: Stephanie Powell, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: NOCCR
name: William Smith, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Benchmark
name: Darrell Herrington, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Benchmark
name: Laurence Chu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Benchmark
name: William Seger, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinical Research West Florida
name: Lon Lynn, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Compass Research
name: David Subich, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Midwest Clinical Research
name: Isabel Kuhare-Arcure, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Clinical Research
name: Keith Scott, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.