SmokingNCT01989156

Reduced Exposure Study Using THS 2.2 Menthol With 5 Days in a Confinement Setting Followed by 86 Days in an Ambulatory Setting

A study testing THS 2.2 Menthol (mTHS 2.2), Menthol Conventional Cigarette (mCC) and Smoking Abstinence (SA) in people with Smoking, run by Philip Morris Products S.A. at 2 sites in United States.

Completed

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

Official record

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Trial summary

Evaluate if the ad libitum use of the THS 2.2 Menthol (mTHS), a candidate Modified Risk Tobacco Product, for 5 days in confinement, and after 86 days in an ambulatory setting, by apparently adult healthy smokers results in a reduction in the levels of biomarkers of exposure (BoExp) to selected harmful and potentially… Read more about this study

Who is it for?: Ages 22 years and olderHealthy volunteers can take part
Conditions the study is for: Smoking
What is being tested?: THS 2.2 Menthol (mTHS 2.2), Menthol Conventional Cigarette (mCC) and Smoking Abstinence (SA)
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 160 participants
Where: 2 sitesUnited States
Study dates: Dec 2013to May 2015
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 22 years and older
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

Smoking, apparently healthy subject as judged by the Investigator.
Subject smokes at least 10 commercially available mCCs per day (no brand restrictions) for the last 4 weeks, based on self-reporting.
Subject has smoked for at least the last 3 consecutive years.
Subject does not plan to quit smoking within the next 6 months.

Who cannot join

As per Investigator judgment, the subject cannot participate in the study for any reason (e.g., medical, psychiatric, and/or social reason).
The subject has received medication within 14 days or within 5 half-lives of the medication (whichever is longer), which has an impact on CYP1A2 or CYP2A6 activity.
For women: Subject is pregnant or is breast feeding.
For women: Subject does not agree to use an acceptable method of effective contraception.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

Covance Dallas, 1341 W. Mockingbird Ln., Ste 400E
Dallas, Texas, 75247
Covance Daytona Beach, 1900 Mason Ave., Suite 140
Daytona Beach, Florida, 32117

Other trials in United States

About this study

Official title: A Randomized, Controlled, Open-label, 3-arm Parallel Group, Multi-center Study to Demonstrate Reductions in Exposure to Selected Smoke Constituents in Apparently Healthy Smokers Switching to the Tobacco Heating System 2.2 Menthol (THS 2.2 Menthol) or Observing Smoking Abstinence, Compared to Continuing to Use Menthol Conventional Cigarettes, for 5 Days in Confinement and Prolonged by 86 Days in an Ambulatory Setting

Read the detailed description

The main goal of the study is to evaluate if the ad libitum use of the THS 2.2 Menthol (mTHS) for 5 days in confinement, and after 86 days in an ambulatory setting, by apparently adult healthy smokers results in a reduction in the levels of biomarkers of exposure (BoExp) to selected harmful and potentially harmful constituents (HPHCs) compared to smokers continuing smoking their own preferred brand of menthol conventional cigarette (mCC) and smoking abstinence (SA). Smokers who remained abstinent from SA were used as a benchmark to provide context to the exposure reduction.

Conditions: Smoking
Being tested: THS 2.2 Menthol (mTHS 2.2), Menthol Conventional Cigarette (mCC), Smoking Abstinence (SA)
Keywords: Smoking, Candidate modified risk tobacco product, Menthol conventional cigarettes, Reduced exposure, HPHCs, Ambulatory
Medical subject headings: Smoking

What participants receive

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

THS 2.2 Menthol (mTHS 2.2)Other
THS 2.2 Menthol ad libitum for 5 days in confinement prolonged by 86 days in an ambulatory setting
Menthol Conventional Cigarette (mCC)Other
Subject's own preferred brand of mCC ad libitum for 5 days in confinement prolonged by 86 days in an ambulatory setting
Smoking Abstinence (SA)Other
SA for 5 days in confinement prolonged by 86 days in an ambulatory setting

Study groups in NCT01989156
Study group	Role	What they receive
THS 2.2 Menthol (mTHS 2.2)	Experimental	Ad libitum use of THS 2.2 Menthol for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting Receives: Other: THS 2.2 Menthol (mTHS 2.2)
Menthol Conventional Cigarette (mCC)	Active comparator	Ad libitum use of subject's own preferred brand of mCC for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting Receives: Other: Menthol Conventional Cigarette (mCC)
Smoking abstinence (SA)	Sham comparator	Abstinence from smoking for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting Receives: Other: Smoking Abstinence (SA)

What is being measured

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

Concentration of Monohydroxybutenylmercapturic Acid (MHBMA)
Concentrations measured in urine, adjusted for creatinine, at Day 5 for the smokers of all arms (mTHS, mCC and SA). Geometric Least Squares means are provided as descriptive statistics.
Measured: 5 days
Concentration of 3-hydroxypropylmercapturic Acid (3-HPMA)
Concentrations measured in urine, adjusted for creatinine, at Day 5 for the smokers of all arms (mTHS, mCC and SA). Geometric Least Squares means are provided as descriptive statistics.
Measured: 5 days
Concentration of S-phenylmercapturic Acid (S-PMA)
Concentrations measured in urine, adjusted for creatinine, at Day 5 for the smokers of all arms (mTHS, mCC and SA). Geometric Least Squares means are provided as descriptive statistics.
Measured: 5 days
Levels of Total 4-(Methylnitrosamino)-1-(3- Pyridyl)-1-butanol (Total NNAL)
Concentrations measured in urine, adjusted for creatinine, at Day 90 for the smokers of all arms (mTHS, mCC and SA). Geometric Least Squares means are provided as descriptive statistics.
Measured: 90 days
Levels of Carboxyhemoglobin (COHb)
Carboxyhemoglobin (COHb) is assayed from whole blood. Expressed as % of saturation of hemoglobin. Blood measurements performed in the evening of Day 5, for the smokers of all arms (mTHS, mCC and SA). Geometric Least Squares means are provided as descriptive statistics.
Measured: 5 days

Timeline

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

Dec 2013May 2015

First posted20 Nov 2013 (estimated)
Study startDec 2013
Primary completionOct 2014
Study completionMay 2015

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: 160 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01989156
Sponsor's protocol ID: ZRHM-REXA-08-US
Other IDs: ZRHM-REXA-08-US
Status last verified: Mar 2020
First submitted: 14 Nov 2013
Last updated: 24 Mar 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

Haziza C, de La Bourdonnaye G, Donelli A, Skiada D, Poux V, Weitkunat R, Baker G, Picavet P, Ludicke F. Favorable Changes in Biomarkers of Potential Harm to Reduce the Adverse Health Effects of Smoking in Smokers Switching to the Menthol Tobacco Heating System 2.2 for 3 Months (Part 2). Nicotine Tob Res. 2020 Apr 17;22(4):549-559. doi: 10.1093/ntr/ntz084.
PubMed 31125079
Haziza C, de La Bourdonnaye G, Donelli A, Poux V, Skiada D, Weitkunat R, Baker G, Picavet P, Ludicke F. Reduction in Exposure to Selected Harmful and Potentially Harmful Constituents Approaching Those Observed Upon Smoking Abstinence in Smokers Switching to the Menthol Tobacco Heating System 2.2 for 3 Months (Part 1). Nicotine Tob Res. 2020 Apr 17;22(4):539-548. doi: 10.1093/ntr/ntz013.
PubMed 30722062

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?

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Study at a glance

From the registry record, last updated by the sponsor on 24 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Controlled, Open-label, 3-arm Parallel Group, Multi-center Study to Demonstrate Reductions in Exposure to Selected Smoke Constituents in Apparently Healthy Smokers Switching to the Tobacco Heating System 2.2 Menthol (THS 2.2 Menthol) or Observing Smoking Abstinence, Compared to Continuing to Use Menthol Conventional Cigarettes, for 5 Days in Confinement and Prolonged by 86 Days in an Ambulatory Setting
ClinicalTrials.gov ID: NCT01989156
Acronym / sponsor ID: ZRHM-REXA-08-US
Conditions: Smoking
Keywords: Smoking, Candidate modified risk tobacco product, Menthol conventional cigarettes, Reduced exposure, HPHCs, Ambulatory
Study type: Interventional
Recruitment status: Completed
Enrolment: 160 participants (actual)
Lead sponsor: Philip Morris Products S.A.Industry (pharma, biotech, devices)
Study start: Dec 2013
Primary completion: Oct 2014 (actual)
Study completion: May 2015 (actual)
First posted: 20 Nov 2013 (estimated)
Results: Posted 5 Apr 2017

Clinical summary

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

Detailed description

Study design

Primary purpose: Other
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
THS 2.2 Menthol (mTHS 2.2)	Experimental	Other: THS 2.2 Menthol (mTHS 2.2)Ad libitum use of THS 2.2 Menthol for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting
Menthol Conventional Cigarette (mCC)	Active comparator	Other: Menthol Conventional Cigarette (mCC)Ad libitum use of subject's own preferred brand of mCC for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting
Smoking abstinence (SA)	Sham comparator	Other: Smoking Abstinence (SA)Abstinence from smoking for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting

Who may qualify

Ages: 22 years and older
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

Smoking, apparently healthy subject as judged by the Investigator.
Subject smokes at least 10 commercially available mCCs per day (no brand restrictions) for the last 4 weeks, based on self-reporting.
Subject has smoked for at least the last 3 consecutive years.
Subject does not plan to quit smoking within the next 6 months.

Key exclusion criteria (4 listed)

As per Investigator judgment, the subject cannot participate in the study for any reason (e.g., medical, psychiatric, and/or social reason).
The subject has received medication within 14 days or within 5 half-lives of the medication (whichever is longer), which has an impact on CYP1A2 or CYP2A6 activity.
For women: Subject is pregnant or is breast feeding.
For women: Subject does not agree to use an acceptable method of effective contraception.

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 2.2 Menthol (mTHS 2.2)THS 2.2 Menthol ad libitum for 5 days in confinement prolonged by 86 days in an ambulatory setting	Other	THS 2.2 Menthol (mTHS 2.2)
Menthol Conventional Cigarette (mCC)Subject's own preferred brand of mCC ad libitum for 5 days in confinement prolonged by 86 days in an ambulatory setting	Other	Menthol Conventional Cigarette (mCC)
Smoking Abstinence (SA)SA for 5 days in confinement prolonged by 86 days in an ambulatory setting	Other	Smoking abstinence (SA)

Primary outcome

Concentration of Monohydroxybutenylmercapturic Acid (MHBMA)
Time frame: 5 days
Concentrations measured in urine, adjusted for creatinine, at Day 5 for the smokers of all arms (mTHS, mCC and SA). Geometric Least Squares means are provided as descriptive statistics.
Concentration of 3-hydroxypropylmercapturic Acid (3-HPMA)
Time frame: 5 days
Concentrations measured in urine, adjusted for creatinine, at Day 5 for the smokers of all arms (mTHS, mCC and SA). Geometric Least Squares means are provided as descriptive statistics.
Concentration of S-phenylmercapturic Acid (S-PMA)
Time frame: 5 days
Concentrations measured in urine, adjusted for creatinine, at Day 5 for the smokers of all arms (mTHS, mCC and SA). Geometric Least Squares means are provided as descriptive statistics.
Levels of Total 4-(Methylnitrosamino)-1-(3- Pyridyl)-1-butanol (Total NNAL)
Time frame: 90 days
Concentrations measured in urine, adjusted for creatinine, at Day 90 for the smokers of all arms (mTHS, mCC and SA). Geometric Least Squares means are provided as descriptive statistics.
Levels of Carboxyhemoglobin (COHb)
Time frame: 5 days
Carboxyhemoglobin (COHb) is assayed from whole blood. Expressed as % of saturation of hemoglobin. Blood measurements performed in the evening of Day 5, for the smokers of all arms (mTHS, mCC and SA). Geometric Least Squares means are provided as descriptive statistics.

Results and safety

Results posted to the registry on 5 Apr 2017, 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 Menthol (mTHS 2.2)	80	80
Menthol Conventional Cigarette (mCC)	41	40
Smoking Abstinence (SA)	39	34

Primary outcome: Concentration of Monohydroxybutenylmercapturic Acid (MHBMA)

Time frame: 5 days. Geometric mean (95% Confidence Interval). Unit: pg/mg creat

Measure	THS 2.2 Menthol (mTHS 2.2) n = 65	Menthol Conventional Cigarette (mCC) n = 30	Smoking Abstinence (SA) n = 21
Value	110.96 (93.49 to 131.68)	882.25 (687.25 to 1132.57)	94.97 (70.67 to 127.61)

THS 2.2 Menthol (mTHS 2.2) vs Menthol Conventional Cigarette (mCC): Geometric LS Mean Ratio: 12.58 (95% CI 9.27 to 17.05), p <0.001, ANCOVA

Population analysed: The analysis was performed on the Per Protocol set (PP) which included all randomized subjects who had no major protocol deviation impacting the evaluability during the confinement period.

Primary outcome: Concentration of 3-hydroxypropylmercapturic Acid (3-HPMA)

Time frame: 5 days. Geometric mean (95% Confidence Interval). Unit: ng/mg creat

Measure	THS 2.2 Menthol (mTHS 2.2) n = 67	Menthol Conventional Cigarette (mCC) n = 30	Smoking Abstinence (SA) n = 21
Value	278.13 (254.95 to 303.43)	607.68 (534.34 to 691.09)	152.05 (130.47 to 177.19)

THS 2.2 Menthol (mTHS 2.2) vs Menthol Conventional Cigarette (mCC): Geometric LS Mean Ratio: 45.77 (95% CI 39.22 to 53.41), p <0.001, ANCOVA

Primary outcome: Concentration of S-phenylmercapturic Acid (S-PMA)

Time frame: 5 days. Geometric mean (95% Confidence Interval). Unit: pg/mg creat

Measure	THS 2.2 Menthol (mTHS 2.2) n = 65	Menthol Conventional Cigarette (mCC) n = 30	Smoking Abstinence (SA) n = 21
Value	134.11 (114.63 to 156.90)	1065.91 (848.45 to 1339.09)	131.05 (99.78 to 172.13)

THS 2.2 Menthol (mTHS 2.2) vs Menthol Conventional Cigarette (mCC): Geometric LS Mean Ratio: 12.58 (95% CI 9.54 to 16.58), p <0.001, ANCOVA

Primary outcome: Levels of Total 4-(Methylnitrosamino)-1-(3- Pyridyl)-1-butanol (Total NNAL)

Time frame: 90 days. Geometric mean (95% Confidence Interval). Unit: pg/mg creat

Measure	THS 2.2 Menthol (mTHS 2.2) n = 43	Menthol Conventional Cigarette (mCC) n = 29	Smoking Abstinence (SA) n = 9
Value	41.05 (31.28 to 53.86)	155.45 (112.46 to 214.88)	54.03 (30 to 97.28)

THS 2.2 Menthol (mTHS 2.2) vs Menthol Conventional Cigarette (mCC): Geometric LS Mean Ratio: 26.41 (95% CI 17.31 to 40.26), p <0.001, ANCOVA

Adverse events

Time frame: From the informed consent form (ICF) signature until the end of the safety follow-up period, up to 150 days (including a screening period of up to 28 days, an 8-day confinement period followed by an 85-day ambulatory setting, and by a 28-day safety follow-up period (28 days after discharge of the subject or early discontinuation)).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
THS 2.2 Menthol (mTHS 2.2)	0 of 80 (0%)	31 of 80 (38.8%)	Not reported
Menthol Conventional Cigarette (mCC)	0 of 41 (0%)	12 of 41 (29.3%)	Not reported
Smoking Abstinence (SA)	0 of 39 (0%)	16 of 39 (41%)	Not reported

Limitations and caveats (from the sponsor): Analysis of Primary Outcomes required data from the PP set at Baseline, Day 5 (MHBMA, 3-HPMA, S-PMA, and COHb), and Day 90 (Total NNAL). Differences in the number of participants for each outcome is due to missing data at baseline or at Day5/90.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 31125079Haziza C, de La Bourdonnaye G, Donelli A, Skiada D, Poux V, Weitkunat R, Baker G, Picavet P, Ludicke F. Favorable Changes in Biomarkers of Potential Harm to Reduce the Adverse Health Effects of Smoking in Smokers Switching to the Menthol Tobacco Heating System 2.2 for 3 Months (Part 2). Nicotine Tob Res. 2020 Apr 17;22(4):549-559. doi: 10.1093/ntr/ntz084.
Derived from this study: PubMed 30722062Haziza C, de La Bourdonnaye G, Donelli A, Poux V, Skiada D, Weitkunat R, Baker G, Picavet P, Ludicke F. Reduction in Exposure to Selected Harmful and Potentially Harmful Constituents Approaching Those Observed Upon Smoking Abstinence in Smokers Switching to the Menthol Tobacco Heating System 2.2 for 3 Months (Part 1). Nicotine Tob Res. 2020 Apr 17;22(4):539-548. doi: 10.1093/ntr/ntz013.
Individual participant dataSharing planned: No

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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.

William Lewis, MD principal investigator

Covance Dallas

Frank Farmer, MD principal investigator

Covance Daytona Beach

Christelle Haziza, PhD study chair

Philip Morris Products S.A.

2 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 Menthol (mTHS 2.2), Menthol Conventional Cigarette (mCC) and Smoking Abstinence (SA) in people with Smoking, run by Philip Morris Products S.A. at 2 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 4 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 24 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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. Some participants in this study may receive a placebo. 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 5 Apr 2017). 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?

Concentration of Monohydroxybutenylmercapturic Acid (MHBMA) (time frame: 5 days). The study lists 5 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 NCT01989156, 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 24 Mar 2020.