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CompletedNCT02649556Updated Dec 4, 2020Results posted

A 26-week Extension of the ZRHR-ERS-09-US Study Evaluating Biological and Functional Changes in Healthy Smokers After Switching to THS 2.2

An interventional study of THS 2.2 and CC in Smoking, sponsored by Philip Morris Products S.A.. Completed at 19 sites in United States. Open to participants aged 30 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2020-12-04.

Sponsored by Philip Morris Products S.A. · Not applicable, Interventional, and Other

From the registry’s dates

  • Registered 3 months after the study started (first participant enrolled Sep 2015, registered Jan 2016).
Phase
Not applicable
Study type
Interventional
Enrollment
672
Allocation
Randomized
Ages
30 Years and older
Sex
All
01

Study summary

The objective of the ZRHR-ERS-09-EXT-US study is to further assess the effect of the Tobacco Heating System 2.2 (THS 2.2), a candidate Modified Risk Tobacco Product, compared to conventional cigarettes (CC) on the components of the "smokers' health profile" for a prolonged period of 26 weeks, providing additional information to the results of the original study ZRHR-ERS-09-US of 26-week exposure (NCT02396381). In total, the ZRHR-ERS-09-EXT-US study will extend the exposure period to 52 weeks.

Read the detailed description

The ZRHR-ERS-09-EXT-US study is a 26-week extension of the original study ZRHR-ERS-09-US.

The subjects in the Full Analysis Set - As Exposed (FAS-EX) included subjects for combined analyses from the original six month study (ZRHR-ERS-09-US ) who did not enter the extension study (ZRHR-ERS-09-EXT-US).

This study was conducted as a separate investigation, as a follow-up of the randomized exposure period of the original study, extending the exposure from Week 26 (Visit 10 [V10]) to Week 52 (Visit 16 [V16]), and using the same sites.

Subjects continued to use the product they were randomized to in the original study ZRHR-ERS-09-US (THS 2.2 arm or CC arm).

02

Conditions studied

  • Smoking

Keywords

  • Modified risk tobacco product
  • Conventional cigarette
  • Exposure response
  • Smoking
  • Tobacco Heating System
03

In context

Lead sponsor

Philip Morris Products S.A. is the lead sponsor of 46 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
30 Years and older
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  • Subject completed V10 of the original study (ZRHR-ERS-09-US).
  • The subject is willing to comply to study procedures and to continue to use the product he/she was allocated to during the original study (THS 2.2 or CC) for an additional 26 weeks at V10.
  • Subject has given written informed consent to enter the 26-week extension study at V10.

Exclusion criteria

Exclusion Criteria:

  • Clinically relevant medical conditions that in the opinion of the investigators would jeopardize the safety of the participant.
  • As per judgment of the PI(s) or designee(s), the subject cannot participate in the study for any reason (e.g. medical, psychiatric and/or social reason).
  • Subject has made an attempt to quit using tobacco-containing products (e.g. CC and THS 2.2) during the original study.
  • Female subject is pregnant or breast feeding.
  • Female subject who does not agree to use an acceptable method of effective contraception.
05

Study design

Phase
Not applicable
Primary purpose
Other
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
672 participants (actual)

Study arms

  • Experimental
    THS 2.2

    Ad libitum use of THS 2.2

    Other: THS 2.2

  • Active comparator
    CC

    Ad libitum use of CC

    Other: CC

Interventions

  • OtherTHS 2.2

    Ad libitum use of THS 2.2 in an ambulatory setting for 26 weeks.

  • OtherCC

    Ad libitum use of CC in an ambulatory setting for 26 weeks. The subject's own preferred brands of CC (no brand restriction) continue to be used as the reference product.

06

What researchers measure

Primary outcomes

  1. Levels of High Density Lipoprotein C (HDL-C).

    Concentrations (mg/dL) measured in serum. Mean values are provided as descriptive statistics.

    Time frame: 52 weeks

  2. Levels of White Blood Cells (WBC).

    Total count in blood (GI/L). Mean values are provided as descriptive statistics.

    Time frame: 52 weeks

  3. Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1).

    FEV1 post-bronchodilator and expressed as percentage predicted (FEV1 %pred). Mean values are provided as descriptive statistics.

    Time frame: 52 weeks

  4. Concentrations of Soluble Intercellular Adhesion Molecule 1 (sICAM-1).

    Concentrations (ng/mL) measured in serum. Geometric Mean values are provided as descriptive statistics.

    Time frame: 52 weeks

  5. Concentrations of 11-dehydrothromboxane B2 (11-DTXB2).

    Concentrations measured in urine and expressed as concentration adjusted for creatinine (pg/mg creat). Geometric Mean values are provided as descriptive statistics.

    Time frame: 52 weeks

  6. Concentrations of 8-epi-prostaglandin F2α (8-epi-PGF2α).

    Concentrations measured in urine and expressed as concentration adjusted for creatinine (pg/mg creat). Geometric Mean values are provided as descriptive statistics.

    Time frame: 52 weeks

  7. Concentrations of Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (Total NNAL).

    Concentrations measured in urine and expressed as concentration adjusted for creatinine (pg/mg creat). Geometric Mean values are provided as descriptive statistics.

    Time frame: 52 weeks

  8. Levels of Carboxyhemoglobin (COHb).

    Carboxyhemoglobin (COHb) is assayed from whole blood. Expressed as % of saturation of hemoglobin. Geometric Mean values are provided as descriptive statistics.

    Time frame: 52 weeks

07

Results

Posted Dec 4, 2020

Participant flow

Of the 984 subjects (488 in the THS arm and 496 in the CC arm) who were enrolled and randomized into the original study, NCT02396381, 672 subjects were enrolled into the extension study (309 in the THS arm and 363 in the CC arm).

Participant flow — Overall Study
MilestoneTHS 2.2 UseCC UseDual UseOther Use
Started23042415251
Completed16731210228
Not completed631125023

Outcome measures

PrimaryLevels of High Density Lipoprotein C (HDL-C).

Concentrations (mg/dL) measured in serum. Mean values are provided as descriptive statistics.

Time frame:
52 weeks
Reported as:
Mean · mg/dL
Levels of High Density Lipoprotein C (HDL-C).
mg/dLTHS 2.2 UseCC UseDual UseOther Use
Levels of High Density Lipoprotein C (HDL-C).52.2 (49.5 to 54.8)50.6 (48.9 to 52.3)54.0 (49.7 to 58.4)54.7 (49.2 to 60.3)
Statistical analysis
  • THS 2.2 Use vs CC Use · Ls mean difference: 1.75 · 95% CI -0.160 to 3.65
PrimaryLevels of White Blood Cells (WBC).

Total count in blood (GI/L). Mean values are provided as descriptive statistics.

Time frame:
52 weeks
Reported as:
Mean · GI/L
Levels of White Blood Cells (WBC).
GI/LTHS 2.2 UseCC UseDual UseOther Use
Levels of White Blood Cells (WBC).6.73 (6.47 to 6.99)7.31 (7.07 to 7.54)7.28 (6.85 to 7.71)7.57 (6.85 to 8.29)
Statistical analysis
  • THS 2.2 Use vs CC Use · Ls mean difference: -0.413 · 95% CI -0.694 to -0.131
PrimaryPost-bronchodilator Forced Expiratory Volume in 1 Second (FEV1).

FEV1 post-bronchodilator and expressed as percentage predicted (FEV1 %pred). Mean values are provided as descriptive statistics.

Time frame:
52 weeks
Reported as:
Mean · Percent of predicted FEV1
Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1).
Percent of predicted FEV1THS 2.2 UseCC UseDual UseOther Use
Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1).93.2 (91.1 to 95.2)92.3 (90.7 to 94.0)91.1 (88.2 to 94.1)95.2 (90.1 to 100)
Statistical analysis
  • THS 2.2 Use vs CC Use · Ls mean difference: 0.914 · 95% CI -0.339 to 2.17
PrimaryConcentrations of Soluble Intercellular Adhesion Molecule 1 (sICAM-1).

Concentrations (ng/mL) measured in serum. Geometric Mean values are provided as descriptive statistics.

Time frame:
52 weeks
Reported as:
Geometric mean · ng/mL
Concentrations of Soluble Intercellular Adhesion Molecule 1 (sICAM-1).
ng/mLTHS 2.2 UseCC UseDual UseOther Use
Concentrations of Soluble Intercellular Adhesion Molecule 1 (sICAM-1).246 (230 to 263)258 (244 to 272)269 (252 to 286)255 (222 to 292)
Statistical analysis
  • THS 2.2 Use vs CC Use · % relative reduction: 3.11 · 95% CI 0.0231 to 6.10Derived as 100 x (1 - Geometric LS Mean Ratio)
PrimaryConcentrations of 11-dehydrothromboxane B2 (11-DTXB2).

Concentrations measured in urine and expressed as concentration adjusted for creatinine (pg/mg creat). Geometric Mean values are provided as descriptive statistics.

Time frame:
52 weeks
Reported as:
Geometric mean · pg/mg creat
Concentrations of 11-dehydrothromboxane B2 (11-DTXB2).
pg/mg creatTHS 2.2 UseCC UseDual UseOther Use
Concentrations of 11-dehydrothromboxane B2 (11-DTXB2).582 (518 to 654)586 (538 to 638)595 (510 to 693)536 (396 to 727)
Statistical analysis
  • THS 2.2 Use vs CC Use · % relative reduction: 3.44 · 95% CI -8.74 to 14.3Derived as 100 x (1-Geometric LS Mean Ratio)
PrimaryConcentrations of 8-epi-prostaglandin F2α (8-epi-PGF2α).

Concentrations measured in urine and expressed as concentration adjusted for creatinine (pg/mg creat). Geometric Mean values are provided as descriptive statistics.

Time frame:
52 weeks
Reported as:
Geometric mean · pg/mg creat
Concentrations of 8-epi-prostaglandin F2α (8-epi-PGF2α).
pg/mg creatTHS 2.2 UseCC UseDual UseOther Use
Concentrations of 8-epi-prostaglandin F2α (8-epi-PGF2α).307 (279 to 338)327 (307 to 348)326 (293 to 362)364 (289 to 458)
Statistical analysis
  • THS 2.2 Use vs CC Use · % relative reduction: 7.15 · 95% CI -1.03 to 14.7Derived as 100 x (1 - Geometric LS Mean Ratio)
PrimaryConcentrations of Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (Total NNAL).

Concentrations measured in urine and expressed as concentration adjusted for creatinine (pg/mg creat). Geometric Mean values are provided as descriptive statistics.

Time frame:
52 weeks
Reported as:
Geometric mean · pg/mg creat
Concentrations of Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (Total NNAL).
pg/mg creatTHS 2.2 UseCC UseDual UseOther Use
Concentrations of Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (Total NNAL).133 (105 to 168)269 (238 to 305)253 (207 to 309)304 (214 to 431)
Statistical analysis
  • THS 2.2 Use vs CC Use · % relative reduction: 46.3 · 95% CI 36.2 to 54.8Derived as 100 x (1 - Geometric LS Mean Ratio)
PrimaryLevels of Carboxyhemoglobin (COHb).

Carboxyhemoglobin (COHb) is assayed from whole blood. Expressed as % of saturation of hemoglobin. Geometric Mean values are provided as descriptive statistics.

Time frame:
52 weeks
Reported as:
Geometric mean · percent change
Levels of Carboxyhemoglobin (COHb).
percent changeTHS 2.2 UseCC UseDual UseOther Use
Levels of Carboxyhemoglobin (COHb).2.59 (2.24 to 3.01)4.06 (3.77 to 4.38)3.92 (3.44 to 4.46)5.22 (4.47 to 6.11)
Statistical analysis
  • THS 2.2 Use vs CC Use · % relative reduction: 31.7 · 95% CI 23.3 to 39.1Derived as 100 x (1 - Geometric LS Mean Ratio)

Adverse events

Collected over 18 months (from March 2015 to September 2016). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
THS 2.2 Use1/241 (0.4%)12/241 (5%)40/241 (16.6%)
CC Use1/434 (0.2%)15/434 (3.5%)87/434 (20%)
Dual Use0/159 (0%)1/159 (0.6%)26/159 (16.4%)
Other Use1/106 (0.9%)1/106 (0.9%)13/106 (12.3%)
Most frequent serious events
Showing 10 of 31
Most frequent serious events
EventTHS 2.2 UseCC UseDual UseOther Use
Alchohol abusePsychiatric disorders0/2410/4340/1591/106
Metastases to small intestine with AnaemiaNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/2410/4340/1591/106
Bereavement and Adjustment Disorder with Depressed MoodSocial circumstances0/2410/4340/1591/106
Multiple fracturesInjury, poisoning and procedural complications0/2410/4341/1590/106
Pyelonephritis AcuteInfections and infestations0/2411/4341/1590/106
Appendicitis with PeritonitisInfections and infestations1/2410/4340/1590/106
EpiglottitisInfections and infestations1/2410/4340/1590/106
InfluenzaInfections and infestations1/2410/4340/1590/106
Pneumonia mycoplasmalInfections and infestations1/2410/4340/1590/106
Head injury with SeizureInjury, poisoning and procedural complications1/2410/4340/1590/106
Most frequent other events
Most frequent other events
EventTHS 2.2 UseCC UseDual UseOther Use
Upper respiratory tract infectionInfections and infestations21/24140/43411/1598/106
HypertensionVascular disorders9/24126/4349/1594/106
Blood triglycerides increasedInvestigations10/24126/4346/1591/106

Baseline characteristics

Age, Continuous
Age, Continuous(years)THS 2.2 UseCC UseDual UseOther UseTotal
Mean43.8 ± 9.6845.2 ± 9.5444.2 ± 9.7644.5 ± 8.2144.6 ± 9.55
Sex: Female, Male
Sex: Female, Male(Participants)THS 2.2 UseCC UseDual UseOther UseTotal
Female871806719353
Male1432448532504
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)THS 2.2 UseCC UseDual UseOther UseTotal
Hispanic or Latino17286253
Not Hispanic or Latino21339614649804
Unknown or Not Reported00000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)THS 2.2 UseCC UseDual UseOther UseTotal
American Indian or Alaska Native12216
Asian25018
Native Hawaiian or Other Pacific Islander12003
Black or African American41732512151
White18233812336679
More than one race00000
Unknown or Not Reported342110
BMI
BMI(kg/m^2)THS 2.2 UseCC UseDual UseOther UseTotal
Mean27.0 ± 4.0627.1 ± 4.1326.9 ± 4.2526.6 ± 4.9127.0 ± 4.18
08

Study locations

19 sites
  • Celerion Arizona
    Tempe, Arizona 85283, United States
  • Clinical Research West Florida
    Clearwater, Florida 33765, United States
  • Covance, Inc
    Daytona Beach, Florida 32117, United States
  • Compass Research
    Orlando, Florida 32806, United States
  • Clinical Research West Florida
    Tampa, Florida 33603, United States
  • Compass Research
    The Villages, Florida 32162, United States
  • Central Kentucky Research Associate
    Lexington, Kentucky 40509, United States
  • Celerion Lincoln
    Lincoln, Nebraska 68502, United States
  • PMG Research of Cary
    Cary, North Carolina 27518, United States
  • PMG Research of Charlotte
    Charlotte, North Carolina 28209, United States
  • PMG Research of Raleigh
    Raleigh, North Carolina 27609, United States
  • PMG Research of Wilmington
    Wilmington, North Carolina 28401, United States
  • Midwest Clinical Research
    Dayton, Ohio 45417, United States
  • PMG Research of Bristol
    Bristol, Tennessee 37620, United States
  • NOCCR
    Knoxville, Tennessee 37920, United States
  • Benchmark
    Austin, Texas 78705, United States
  • Benchmark
    Fort Worth, Texas 76135, United States
  • Benchmark
    San Angelo, Texas 76904, United States
  • National Clinical Research
    Richmond, Virginia 23294, United States
09

References and documents

Study documents

  • Study protocol · Aug 23, 2016
  • Statistical analysis plan · Dec 8, 2017

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Dec 4, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02649556
Lead sponsor
Philip Morris Products S.A.
Responsible party
Sponsor
First posted
Jan 7, 2016
Start date
Sep 30, 2015
Primary completion
Mar 13, 2017
Completion
Dec 20, 2017
Results posted
Dec 4, 2020
Last update
Dec 4, 2020

Study contacts

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
Hugh Coleman, MD
principal investigator · Covance
George Stoica, MD
principal investigator · Compass Research
Mark Adams, MD
principal investigator · Central Kentucky Research Associate
Peter Davidson, MD
principal investigator · Celerion Lincoln
John Rubino, MD
principal investigator · PMG Research of Raleigh
George Raad, MD
principal investigator · PMG Research of Charlotte
Kevin Cannon, MD
principal investigator · PMG Research of Wilmington
Derek Schroder, MD
principal investigator · PMG Research of Cary
Stephanie Powell, MD
principal investigator · PMG Research of Bristol
William Smith, MD
principal investigator · NOCCR
Darrell Herrington, MD
principal investigator · Benchmark
Laurence Chu, MD
principal investigator · Benchmark
William Seger, MD
principal investigator · Benchmark
David Subich, MD
principal investigator · Compass Research
Lon Lynn, MD
principal investigator · Clinical Research West Florida
Isabel Kuhare-Arcure, MD
principal investigator · Midwest Clinical Research
Keith Scott, MD
principal investigator · National Clinical Research

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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