SmokingNCT02396381

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

A study testing THS 2.2 and CC in people with Smoking, run by Philip Morris Products S.A. at 19 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial 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. Read more about this study

Who is it for?: Ages 30 years and olderHealthy volunteers can take part
Conditions the study is for: Smoking
What is being tested?: THS 2.2 and CC
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 1,039 participants
Where: 19 sitesUnited States
Study dates: 12 Mar 2015to 1 Aug 2017
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 30 years and older
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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

Who cannot join

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.

Trial locations and contacts

19 sites in 1 country.

City, postcode or hospital

19 sites in 1 country

United States19 sites

Benchmark
Austin, Texas, 78705
PMG Research of Bristol
Bristol, Tennessee, 37620
PMG Research of Cary
Cary, North Carolina, 27518
PMG Research of Charlotte
Charlotte, North Carolina, 28209
Clinical Research West Florida
Clearwater, Florida, 33765
Midwest Clinical Research Center
Dayton, Ohio, 45417
Covance, Inc
Daytona Beach, Florida, 32117
Benchmark
Fort Worth, Texas, 76135
NOCCR
Knoxville, Tennessee, 37920
Central Kentucky Research Associate
Lexington, Kentucky, 40509
Celerion Lincoln
Lincoln, Nebraska, 68502
Compass Research
Orlando, Florida, 32806
PMG Research of Raleigh
Raleigh, North Carolina, 27609
National Clinical Research
Richmond, Virginia, 23294
Benchmark
San Angelo, Texas, 76904
Clinical Research West Florida
Tampa, Florida, 33603
Celerion Arizona
Tempe, Arizona, 85283
Compass Research
The Villages, Florida, 32162
PMG Research of Wilmington
Wilmington, North Carolina, 28401

Other trials in United States

About this study

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

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.

Read the 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.

Conditions: Smoking
Being tested: THS 2.2, CC
Keywords: Candidate modified risk tobacco product, Conventional cigarette, Exposure response, Smoking, Tobacco Heating System
Medical subject headings: Smoking

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT02396381
Study group	Role	What they receive
THS 2.2	Experimental	Ad libitum use of THS 2.2 Receives: Other: THS 2.2
CC	Active comparator	Ad libitum use of CC Receives: Other: CC

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

12 Mar 20151 Aug 2017

First posted24 Mar 2015 (estimated)
Study start12 Mar 2015
Primary completion13 Sep 2016
Study completion1 Aug 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for SmokingStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Other
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 1,039 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02396381
Sponsor's protocol ID: ZRHR-ERS-09-US
Other IDs: ZRHR-ERS-09-US
Status last verified: Jan 2023
First submitted: 18 Mar 2015
Last updated: 26 Jan 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

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.
PubMed 31270101
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.
PubMed 30143474

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Smoking trials

Study at a glance

From the registry record, last updated by the sponsor on 26 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT02396381
Acronym / sponsor ID: ZRHR-ERS-09-US
Conditions: Smoking
Keywords: Candidate modified risk tobacco product, Conventional cigarette, Exposure response, Smoking, Tobacco Heating System
Study type: Interventional
Recruitment status: Completed
Enrolment: 1,039 participants (actual)
Lead sponsor: Philip Morris Products S.A.Industry (pharma, biotech, devices)
Study start: 12 Mar 2015 (actual)
Primary completion: 13 Sep 2016 (actual)
Study completion: 1 Aug 2017 (actual)
First posted: 24 Mar 2015 (estimated)
Results: Posted 21 Aug 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

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 design

Primary purpose: Other
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
THS 2.2	Experimental	Other: THS 2.2Ad libitum use of THS 2.2
CC	Active comparator	Other: CCAd libitum use of CC

Who may qualify

Ages: 30 years and older
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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

Key exclusion criteria (6 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
THS 2.2Ad libitum use of THS 2.2 in an ambulatory setting for 26 weeks	Other	THS 2.2
CCAd libitum use of CC in an ambulatory setting for 26 weeks	Other	CC

Primary outcome

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.

Results and safety

Results posted to the registry on 21 Aug 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
THS 2.2 Group	488	381
CC Group	496	422

Primary outcome: Levels of High Density Lipoprotein C (HDL-C).

Time frame: 26 Weeks. Geometric mean (95% Confidence Interval). Unit: mg/dL

Measure	THS 2.2 Use n = 245	CC Use n = 428	Dual Use n = 142	Other Use n = 42
Value	54.1 (51.4 to 56.7)	50.9 (49.4 to 52.4)	56.3 (52.7 to 59.9)	52.8 (47.4 to 58.1)

THS 2.2 Use vs CC Use: LS Mean Difference: 3.09 (96.875% CI 1.10 to 5.09), p <0.001, Hailperin-Rüger

Population analysed: Full Analysis Set - As Exposed (FAS-EX)

Primary outcome: Levels of White Blood Cells (WBC).

Time frame: 26 Weeks. Geometric mean (95% Confidence Interval). Unit: GI/L

Measure	THS 2.2 Use n = 245	CC Use n = 428	Dual Use n = 142	Other Use n = 42
Value	6.98 (6.70 to 7.25)	7.48 (7.28 to 7.69)	7.41 (7.00 to 7.82)	8.71 (7.80 to 9.62)

THS 2.2 Use vs CC Use: LS Mean Difference: -0.420 (96.875% CI -0.717 to -0.123), p = 0.001, Hailperin-Rüger

Population analysed: Full Analysis Set - As Exposed (FAS-EX)

Primary outcome: Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1).

Time frame: 26 Weeks. Geometric mean (95% Confidence Interval). Unit: Percent of predicted FEV1

Measure	THS 2.2 Use n = 245	CC Use n = 428	Dual Use n = 142	Other Use n = 42
Value	95.4 (93.7 to 97.1)	93.4 (92.0 to 94.8)	93.7 (91.3 to 96.0)	94.3 (89.3 to 99.4)

THS 2.2 Use vs CC Use: LS Mean Difference: 1.28 (96.875% CI 0.145 to 2.42), p = 0.008, Hailperin-Rüger

Population analysed: Full Analysis Set - As Exposed (FAS-EX)

Primary outcome: Concentrations of Soluble Intercellular Adhesion Molecule 1 (sICAM-1).

Time frame: 26 Weeks. Geometric mean (95% Confidence Interval). Unit: ng/mL

Measure	THS 2.2 Use n = 245	CC Use n = 428	Dual Use n = 142	Other Use n = 42
Value	252 (239 to 266)	266 (253 to 279)	270 (253 to 288)	273 (234 to 317)

THS 2.2 Use vs CC Use: % Reduction: 2.86 (96.875% CI -0.426 to 6.04), p = 0.030, Hailperin-Rüger

Population analysed: Full Analysis Set - As Exposed (FAS-EX)

Adverse events

Time frame: The entire study duration per subject was between 32 to 38 weeks, including a Screening period of up to 42 days prior to enrollment, a 6 to 10-day run-in period prior to randomization, followed by a 26 week randomized exposure period. The end of study for a subject was defined as the check-out or the date of early termination of the subject plus the 28 day Safety Follow-up period, unless the subject was lost to follow-up.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
THS 2.2 Group	6 of 477 (1.3%)	23 of 477 (4.8%)	2 of 477
CC Group	7 of 483 (1.4%)	29 of 483 (6%)	0 of 483
Product Test	0 of 52 (0%)	0 of 52 (0%)	0 of 52

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Jan 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 31270101Ludicke 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.
Derived from this study: PubMed 30143474Ansari 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.
Individual participant dataSharing planned: No

Related trials for Smoking

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Christelle Haziza, PhD study chair

Philip Morris Products S.A.

Danielle Armas, MD principal investigator

Celerion Arizona

Leonard Dunn, MD principal investigator

Clinical Research West Florida

19 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing THS 2.2 and CC in people with Smoking, run by Philip Morris Products S.A. at 19 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Levels of High Density Lipoprotein C (HDL-C). (time frame: 26 Weeks). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02396381, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jan 2023.