A cross-sectional study to demonstrate favorable differences in Biomarkers of Potential Harm following at least one year of Tobacco Heating System (THS) use compared to cigarette smoking.
Demonstration of favorable differences in Biomarkers of Potential Harm following at least one year of switching to THS.
12F JP Tower, 2-7-2 Marunouchi, Chiyoda-ku, Tokyo Japan
+81-3-3516-8590
JPN_RWLP_Register@syneoshealth.com
Complete
Nov. 25, 2022
Oct. 06, 2022
900
Interventional
non-randomized controlled trial
open(masking not used)
active control
parallel assignment
other
Inclusion Criteria:
1. Subject is able to understand the information provided in the main ICF and has signed the main ICF.
2. Subject is 30-60 years old.
3. Subject is healthy based on ECG, spirometry, vital signs, physical examination, medical history and Investigator's assessment.
Cigarette smokers:
4. Has smoked >= 10 cigarettes/day on average (no brand restriction) over the past 2 years prior to screening.
5. Has smoked >= 10 cigarettes/day on average (no brand restriction) for at least 10 years.
6. Has not used other tobacco and nicotine products apart from cigarettes on a daily basis over the past 2 years prior to screening.
7. Smoking status will be verified by urinary cotinine test (>= 200 ng/mL) and CO breath test (>= 10 ppm (1)).
THS users:
8. Has used >= 10 HeatSticks/day on average over the past 2 years prior to screening.
9. Has smoked >= 10 cigarettes/day on average (no brand restriction) for at least 8 years prior to switching to THS.
10.Has smoked < 30 cigarettes/month and used other tobacco products or e-cigarettes < daily over the past 2 years prior to screening.
11. Product use will be verified by urinary cotinine test (>= 200 ng/mL) and CO breath test (< 10 ppm).
Former cigarette smokers:
12. Has not smoked cigarettes or used any tobacco or nicotine-containing products on a daily basis over the past 2 years prior to screening.
13. Has smoked >= 10 cigarettes/day on average (no brand restriction) for at least 8 years prior to stopping smoking.
14. Smoking status will be verified by urinary cotinine test (< 100 ng/mL) and CO breath test (< 10 ppm).
Exclusion criteria:
1. As per the judgment of the Investigator, subject cannot participate in the study for any
reason (e.g., medical, psychiatric and/or social reason). The Investigator should
specifically evaluate the subject eligibility in light of COVID-19 risk factors and local
situation.
2. Subject has/had clinically relevant diseases (including but not limited to gastrointestinal,
renal, hepatic, neurological, hematological, endocrine, oncological, urological,
immunological, pulmonary, and cardiovascular disease) or conditions that in the opinion
of the investigator would jeopardize the safety of the subject or affect the validity of the
study results.
3. Subject has/had within 30 days prior to screening a body temperature > 37.5 or an
acute illness (e.g., upper-respiratory-tract infection, viral infection, etc.) or the subject
is confirmed or suspected of having active COVID-19 infection (based on the signs and
symptoms observed at the time of assessment) at screening.
4. Subject has used any prescribed or over-the-counter systemic medication with an impact
on WBC or 8-epi-PGF2alfa within 5 half-lives of the medication prior to enrollment in the
study (please refer to Appendix B).
5. Subject has high blood pressure (hypertension), defined as > 139 mmHg systolic and/or
> 89 mmHg diastolic or is currently treated with medication controlling high blood
pressure.
6. Subject who has (FEV1/FVC) < 0.7 and FEV1 < 80% predicted value at postbronchodilator
(BD) spirometry.
7. Subject who has (FEV1/FVC) < 0.75 (pre-BD) and reversibility in FEV1 (that is both >
12% and > 200 mL from pre- to post-BD values).
8. Subject who has a body mass index (BMI) < 18.5 or >= 30 kg/m2.
9. Subject with positive alcohol and/or drug screening test results.
10. Pregnant or breast-feeding female subject.
- A target of 300 current cigarette smokers
- A target of 300 THS users with a minimum of 2 years of THS use
- A target of 300 former cigarette smokers with minimum of 2 years of smoking abstinence.
To demonstrate beneficial differences in inflammation, oxidative stress, and exposure to
Harmful and Potentially Harmful Constituents (HPHCs) in THS users compared with
current cigarette smokers.
Endpoints:
Biomarkers of Exposure (BoExp) to HPHCs:
- Carboxyhemoglobin (COHb) in blood.
- Total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (total NNAL) in urine
(expressed as concentration adjusted to creatinine),
Biomarkers of Potential Harm (BoPH) for core pathophysiological pathways
underlying the main smoking-related diseases:
- Inflammation: White Blood Cell total count (WBC) in blood,
- Oxidative stress: 8-epi-Prostaglandin-F2alfa (8-epi-PGF2alfa) in urine (expressed as
concentration adjusted to creatinine).
1. To determine the differences in BoPH between THS users and former cigarette smokers
compared to current cigarette smokers.
Endpoints:
Inflammation:
- Neutrophil to Lymphocyte Ratio (NLR),
- High-sensitivity C-Reactive Protein (hs-CRP),
- Homocysteine (HCY).
Oxidative stress:
- Myeloperoxidase (MPO).
Lipid metabolism:
- Triglycerides (TG).
Platelet Activation:
- Fibrinogen.
Glycemic Control:
- Glycated Hemoglobin (HbA1c).
Lung function (spirometry with and without bronchodilator, absolute and % predicted
values, where applicable):
- FEV1/FVC.
2. To determine the differences in the levels of BoExp to nicotine between THS users and
former cigarette smokers compared to current cigarette smokers.
Endpoints:
BoExp to nicotine:
- Nicotine Equivalents (NEQ) in urine (expressed as concentration adjusted to
creatinine),
- 2-Cyanoethyl Mercapturic Acid N-Acetyl-S-(2-cyanoethyl)-L-cysteine
(2CyEMA) in urine (expressed as concentrations adjusted to creatinine).
3. To determine the differences in self-reported health perceptions between THS users and
former cigarette smokers compared to current cigarette smokers.
Endpoints:
Short Form Health Survey (SF-36) domain scores (Physical Functioning and Mental
Health),
ABOUT - Health and Functioning domain scores (between THS users and cigarette
smokers only).
4. To evaluate the safety during the study.
Endpoints:
Adverse events (AEs),
Serious adverse events (SAEs).
Philip Morris International Inc.
Japan Conference of Clinical Research IRB
1-13-23 Minami-Ikebukuro, Toshima-ku, Tokyo, Tokyo
