SmokingZRHX-EX-01NCT01780714
Exploratory THS 2.1 Biomarkers of Exposure Study
A study testing Conventional cigarettes (CC) and THS 2.1 in people with Smoking, run by Philip Morris Products S.A. at 1 site in Poland.
Trial summary
The goal of this exploratory study is to evaluate the effect of a candidate modified risk tobacco product (MRTP), THS 2.1, on selected biomarkers of exposure to harmful and potentially harmful smoke constituents (HPHCs), compared to conventional cigarettes (CC). Read more about this study
- Who is it for?
- Ages 23 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Smoking
- What is being tested?
- Conventional cigarettes (CC) and THS 2.1
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 sitePoland
- Study dates
- Jun 2012to Dec 2012
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 23 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Subject has signed an informed consent form before commencement of study procedures
- Healthy Caucasian aged between 23 to 65 years
- Subject is a current smoker for at least 3 years (based on self-reporting and biochemically verified), who, for the last 4 weeks, had smoked at least 10 commercially available non-mentholated CC per day, and is not planning to make a quit attempt within the next 3 months
- Main Exclusion Criteria:
- As per Investigator judgment, the subject should not participate in the study for any reason (e.g. medical, psychiatric and/or social reason)
- The subject has a medical condition requiring smoking cessation, or has a clinically relevant disease / condition which could interfere with the study participation and/or study results
- The subject has participated in a clinical study within 3 months prior to the Screening Visit
- Pregnant or lactating woman, and for woman of childbearing potential, absence / refusal to use an acceptable method of effective contraception
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Single-center, Open-label, Randomized, Controlled, 2-arm Parallel Group Study to Evaluate the Exposure to Selected Smoke Constituents in Smoking, But Otherwise Healthy Subjects Switching From Conventional Cigarettes to the Tobacco Heating System (THS) 2.1
The goal of this exploratory study is to evaluate the effect of a candidate modified risk tobacco product (MRTP), THS 2.1, on selected biomarkers of exposure to harmful and potentially harmful smoke constituents (HPHCs), compared to conventional cigarettes (CC). The subjective effects (urge to smoke and withdrawal symptoms) which are related to the use of this product will be explored. Initial information on safety and on some biological effects when using THS 2.1 will be collected. Human Smoking Topography (HST) will be explored.
Read the detailed description
This study intends to evaluate the levels of selected biomarkers of exposure to selected HPHC and of cytochrome P450 1A2 (CYP1A2) enzymatic activity, as compared to smokers continuing smoking CC ad libitum, after 5 days of ad libitum use.
Additional parameters will be explored, such as: cytochrome P450 2A6 (CYP2A6) enzymatic activity, nicotine pharmacokinetics, product evaluation and safety, marker of platelet function, and HST.
After screening, subjects will be admitted to the clinic for 9 days, including the Day of Admission, 2 days of baseline during which all subjects will continue to smoke their usual CC for a 5-day exposure after randomization. After leaving the clinic on the Day of Discharge, the subjects will be followed up for safety over a period of 7 days. All subjects will receive smoking cessation advice at screening, at Day of Admission and at Day of Discharge.
This clinical study will be conducted in compliance with International Conference on Harmonisation of technical requirements for registration of pharmaceuticals for human use (ICH Good Clinical Practice), the Declaration of Helsinki as amended in 2008, and the applicable regulatory requirements.
- Conditions
- Smoking
- Being tested
- Conventional cigarettes (CC), THS 2.1
- Keywords
- smoking, cigarette, exposure, biomarker, human smoking topography (HST), modified risk tobacco product (MRTP), THS 2.1
- Medical subject headings
- Smoking
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Conventional cigarettes (CC)Other
Subjects are randomized in a 1:1 fashion to be assigned either A) continuing CC, or B) switching to THS 2.1
THS 2.1Other
Subjects are randomized in a 1:1 fashion to be assigned either A) continuing CC, or B) switching to THS 2.1
| Study group | Role | What they receive |
|---|---|---|
| Conventional cigarettes (CC) | Active comparator | Smokers are continuing to smoke exclusively their usual own brand of CC, for 5 days, ad libitum, under highly controlled conditions Receives: Other: Conventional cigarettes (CC) |
| Tobacco Heating System 2.1 (THS 2.1) | Experimental | Smokers are switching to the exclusive and ad-libitum use of THS 2.1 for 5 days, under highly controlled conditions Receives: Other: THS 2.1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of carboxyhemoglobin (COHb) levels in blood, and evaluation of excretion of 3-hydroxypropyl mercapturic acid (3-HPMA), monohydroxybutenyl mercapturic acid (MHBMA), and S-phenyl mercapturic acid (S-PMA) in 24-hour urine on switching to THS 2.1
Biomarkers of exposure to carbon monoxide (CO), acrolein, 1,3-butadiene, and benzene
Measured: 5 days
Secondary outcomes (10)
Selected secondary biomarkers of exposure to HPHCs
Evaluation of the levels of total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (total NNAL),1-hydroxypyrene , total N-nitrosonornicotine (NNN), 4-aminobiphenyl (4-ABP), 2- aminonaphthalene (2-NA), o-toluidine, nicotine equivalents and 2-cyanoethylmercapturic acid, biomarkers of exposure to the HPHCs 4-(methylnitrosamino)-1- (3-pyridyl)-1-butanone, NNN, 4-ABP, 2-NA, o-toluidine, nicotine and acrylonitrile, respectively, as excreted in urine.
Measured: 5 days
CYP1A2 activity and CYP2A6 activity
Evaluation of the CYP1A2 activity, as measured by the plasma caffeine molar metabolic ratio (paraxanthine / caffeine) and in CYP2A6 activity, as measured by nicotine molar metabolic ratio (3-hydroxy-cotinine / cotinine) in plasma and in urine
Measured: 5 days
Plasma nicotine
Time course of nicotine plasma concentrations and derived pharmacokinetic parameters
Measured: 5 days
11-dehydro-thromboxane B2 (11-DTX-B2)
To describe the 11-DTX-B2 levels in urine as a marker of platelet function
Measured: 5 days
Product use and smoking topography
Monitoring of daily product use and human smoking topography
Measured: Up to 5 days
Safety monitoring
Monitoring of adverse events, based on clinical and laboratory evaluation
Measured: 8 days + 7 days follow-up
Cough Visual Analog Scale (Cough VAS)
Visual Analog Scale on cough
Measured: 7 days
Modified Cigarette Evaluation Questionnaire (MCEQ)
MCEQ measuring subjective effects of smoking
Measured: 5 days
Questionnaire on Smoking Urges (brief version) (QSU-brief)
QSU-brief measuring subjective effects of smoking
Measured: 5 days
Minnesota Withdrawal Scale-Revised (MNSWS-R)
MNWS-R questionnaire measuring subjective effects of smoking
Measured: 5 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2013 (estimated)
- Study startJun 2012
- Primary completionJul 2012
- Study completionDec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)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
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Philip Morris Products S.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Katarzyna Jarus-Dziedzic, MD PhD, Principal investigator, MTZ Clinical Research Sp. z o.o., Warsaw, Poland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01780714
- Sponsor's protocol ID
- ZRHX-EX-01
- Acronym
- ZRHX-EX-01
- Status last verified
- Nov 2019
- First submitted
- 15 Jan 2013
- Last updated
- 20 Nov 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
Ludicke F, Baker G, Magnette J, Picavet P, Weitkunat R. Reduced Exposure to Harmful and Potentially Harmful Smoke Constituents With the Tobacco Heating System 2.1. Nicotine Tob Res. 2017 Feb;19(2):168-175. doi: 10.1093/ntr/ntw164. Epub 2016 Jul 1.
PubMed 27613951
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-center, Open-label, Randomized, Controlled, 2-arm Parallel Group Study to Evaluate the Exposure to Selected Smoke Constituents in Smoking, But Otherwise Healthy Subjects Switching From Conventional Cigarettes to the Tobacco Heating System (THS) 2.1
- ClinicalTrials.gov ID
- NCT01780714
- Acronym / sponsor ID
- ZRHX-EX-01 / ZRHX-EX-01
- Conditions
- Smoking
- Keywords
- smoking, cigarette, exposure, biomarker, human smoking topography (HST), modified risk tobacco product (MRTP), THS 2.1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Philip Morris Products S.A.Industry (pharma, biotech, devices)
- Study start
- Jun 2012
- Primary completion
- Jul 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 31 Jan 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this exploratory study is to evaluate the effect of a candidate modified risk tobacco product (MRTP), THS 2.1, on selected biomarkers of exposure to harmful and potentially harmful smoke constituents (HPHCs), compared to conventional cigarettes (CC). The subjective effects (urge to smoke and withdrawal symptoms) which are related to the use of this product will be explored. Initial information on safety and on some biological effects when using THS 2.1 will be collected. Human Smoking Topography (HST) will be explored.
Detailed description
This study intends to evaluate the levels of selected biomarkers of exposure to selected HPHC and of cytochrome P450 1A2 (CYP1A2) enzymatic activity, as compared to smokers continuing smoking CC ad libitum, after 5 days of ad libitum use.
Additional parameters will be explored, such as: cytochrome P450 2A6 (CYP2A6) enzymatic activity, nicotine pharmacokinetics, product evaluation and safety, marker of platelet function, and HST.
After screening, subjects will be admitted to the clinic for 9 days, including the Day of Admission, 2 days of baseline during which all subjects will continue to smoke their usual CC for a 5-day exposure after randomization. After leaving the clinic on the Day of Discharge, the subjects will be followed up for safety over a period of 7 days. All subjects will receive smoking cessation advice at screening, at Day of Admission and at Day of Discharge.
This clinical study will be conducted in compliance with International Conference on Harmonisation of technical requirements for registration of pharmaceuticals for human use (ICH Good Clinical Practice), the Declaration of Helsinki as amended in 2008, and the applicable regulatory requirements.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Conventional cigarettes (CC) | Active comparator | Other: Conventional cigarettes (CC)Smokers are continuing to smoke exclusively their usual own brand of CC, for 5 days, ad libitum, under highly controlled conditions |
| Tobacco Heating System 2.1 (THS 2.1) | Experimental | Other: THS 2.1Smokers are switching to the exclusive and ad-libitum use of THS 2.1 for 5 days, under highly controlled conditions |
Who may qualify
- Ages
- 23 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Subject has signed an informed consent form before commencement of study procedures
- Healthy Caucasian aged between 23 to 65 years
- Subject is a current smoker for at least 3 years (based on self-reporting and biochemically verified), who, for the last 4 weeks, had smoked at least 10 commercially available non-mentholated CC per day, and is not planning to make a quit attempt within the next 3 months
- As per Investigator judgment, the subject should not participate in the study for any reason (e.g. medical, psychiatric and/or social reason)
- The subject has a medical condition requiring smoking cessation, or has a clinically relevant disease / condition which could interfere with the study participation and/or study results
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| Conventional cigarettes (CC)Subjects are randomized in a 1:1 fashion to be assigned either A) continuing CC, or B) switching to THS 2.1 | Other | Conventional cigarettes (CC) |
| THS 2.1Subjects are randomized in a 1:1 fashion to be assigned either A) continuing CC, or B) switching to THS 2.1 | Other | Tobacco Heating System 2.1 (THS 2.1) |
Primary outcome
Evaluation of carboxyhemoglobin (COHb) levels in blood, and evaluation of excretion of 3-hydroxypropyl mercapturic acid (3-HPMA), monohydroxybutenyl mercapturic acid (MHBMA), and S-phenyl mercapturic acid (S-PMA) in 24-hour urine on switching to THS 2.1
Time frame: 5 days
Biomarkers of exposure to carbon monoxide (CO), acrolein, 1,3-butadiene, and benzene
10 secondary outcomes
Selected secondary biomarkers of exposure to HPHCs
Time frame: 5 days
CYP1A2 activity and CYP2A6 activity
Time frame: 5 days
Plasma nicotine
Time frame: 5 days
11-dehydro-thromboxane B2 (11-DTX-B2)
Time frame: 5 days
Product use and smoking topography
Time frame: Up to 5 days
Safety monitoring
Time frame: 8 days + 7 days follow-up
Cough Visual Analog Scale (Cough VAS)
Time frame: 7 days
Modified Cigarette Evaluation Questionnaire (MCEQ)
Time frame: 5 days
Questionnaire on Smoking Urges (brief version) (QSU-brief)
Time frame: 5 days
Minnesota Withdrawal Scale-Revised (MNSWS-R)
Time frame: 5 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2019.
- Results publication: PubMed 27613951Ludicke F, Baker G, Magnette J, Picavet P, Weitkunat R. Reduced Exposure to Harmful and Potentially Harmful Smoke Constituents With the Tobacco Heating System 2.1. Nicotine Tob Res. 2017 Feb;19(2):168-175. doi: 10.1093/ntr/ntw164. Epub 2016 Jul 1.
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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.
Katarzyna Jarus-Dziedzic, MD PhD principal investigator
MTZ Clinical Research Sp. z o.o., Warsaw, Poland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Conventional cigarettes (CC) and THS 2.1 in people with Smoking, run by Philip Morris Products S.A. at 1 site in Poland.
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 8 inclusion and 0 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 20 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Poland. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Evaluation of carboxyhemoglobin (COHb) levels in blood, and evaluation of excretion of 3-hydroxypropyl mercapturic acid (3-HPMA), monohydroxybutenyl mercapturic acid (MHBMA), and S-phenyl mercapturic acid (S-PMA) in 24-hour urine on switching to THS 2.1 (time frame: 5 days). 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 NCT01780714, which also lists 1 linked publication.
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 20 Nov 2019.