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| ID | Type | Description | Link |
|---|---|---|---|
| ZRHM-REXA-07-JP | Other Identifier | Philip Morris Products S.A. |
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The main goal of the study is to evaluate if the ad libitum use of the THS 2.2 Menthol (mTHS 2.2) for 5 days in confinement and after 85 days of product use in an ambulatory setting, by Japanese adult healthy smokers results in a reduction in the levels of biomarkers of exposure for selected harmful and potentially harmful smoke 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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| THS 2.2 Menthol (mTHS 2.2) | Experimental | Ad libitum use of THS 2.2 Menthol for 5 Days in a Confinement Setting and 85 Days in an Ambulatory Setting |
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| Smoking abstinence (SA) | Active Comparator | Abstinence from smoking for 5 Days in a Confinement Setting and 85 Days in an Ambulatory Setting |
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| 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 85 Days in an Ambulatory Setting |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| THS 2.2 Menthol (mTHS 2.2) | Other | THS 2.2 Menthol ad libitum for 5 days in confinement prolonged by 85 days in an ambulatory setting |
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| Measure | Description | Time Frame |
|---|---|---|
| Concentration of Monohydroxybutenyl Mercapturic Acid (MHBMA) | Concentrations measured at Day 5 in urine, adjusted for creatinine. Geometric Least Squares (LS) means are provided as descriptive statistics. | 5 days |
| Concentration of 3-hydroxypropylmercapturic Acid (3-HPMA) | Concentrations measured at Day 5 in urine, adjusted for creatinine. Geometric Least Squares (LS) means are provided as descriptive statistics. | 5 days |
| Concentration of S-phenylmercapturic Acid (S-PMA) | Concentrations measured at Day 5 in urine, adjusted for creatinine. Geometric Least Squares (LS) means are provided as descriptive statistics. | 5 days |
| Levels of Carboxyhemoglobin (COHb) | % COHb blood measurements performed in the evening of Day 5, expressed as % of saturation of hemoglobin. Geometric Least Squares means are provided as descriptive statistics. | 5 days |
| Concentration of Total 4-(Methylnitrosamino)-1-(3- Pyridyl)-1-butanol) (Total NNAL) | Concentrations measured at Day 90 in urine, adjusted for creatinine. Geometric Least Squares (LS) means are provided as descriptive statistics. | 90 days |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Masahiro Endo, MD | Osaki Hospital Tokyo Heart Center | Principal Investigator |
| Christelle Haziza, PhD | Philip Morris Products S.A. | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Osaki Hospital Tokyo Heart Center, 5-4-12, Kitashinagawa, Shinagawa-ku | Tokyo | Japan |
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Enrolled and randomized population = 160 subjects
Number of subjects enrolled but NOT randomized (who tried the mTHS 2.2 at Day -2) = 0
Study initiated (first subject screened): 01 August 2013
At admission (Day -2), all the subjects performed a product trial of the THS 2.2 Menthol. During the baseline period, they continued smoking their single preferred brand of mCC. Then, on Day 0, they were randomized to one of the 3 study arms (mTHS 2.2, mCC or SA) in a 2:1:1 ratio.
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| ID | Title | Description |
|---|---|---|
| FG000 | THS 2.2 Menthol (mTHS 2.2) | Ad libitum use of THS 2.2 Menthol for 5 days in a confinement setting and 85 days in an ambulatory setting |
| FG001 | Menthol Conventional Cigarette (mCC) |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Confinement Period (Population at Day 5) |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 7, 2014 | Mar 9, 2020 |
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| Smoking Abstinence (SA) | Other | SA for 5 days in confinement prolonged by 85 days in an ambulatory setting |
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| Menthol Conventional Cigarette (mCC) | Other | Subject's own preferred brand of mCC ad libitum for 5 days in confinement prolonged by 85 days in an ambulatory setting |
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Ad libitum use of subject's own preferred brand of mCC for 5 days in a confinement setting and 85 days in an ambulatory setting
| FG002 | Smoking Abstinence (SA) | Abstinence from smoking for 5 days in a confinement setting and 85 days in an ambulatory setting |
| COMPLETED |
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| NOT COMPLETED |
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| End of Study (Population at Day 90) |
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Study population = all randomized subjects who had at least one post randomization product use experience and at least one valid biomarker of exposure measurement.
160 randomized subjects: 78 in mTHS 2.2, 42 in mCC and 40 in SA arms
155 completed, subjects who withdrew: 2 in mTHS 2.2, 1 in mCC and 2 in SA arms
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| ID | Title | Description |
|---|---|---|
| BG000 | THS 2.2 Menthol (mTHS 2.2) | Ad libitum use of THS 2.2 Menthol for 5 days in a confinement setting and 85 days in an ambulatory setting |
| BG001 | Menthol Conventional Cigarette (mCC) | Ad libitum use of subject's own preferred brand of mCC for 5 days in a confinement setting and 85 days in an ambulatory setting |
| BG002 | Smoking Abstinence (SA) | Abstinence from smoking for 5 days in a confinement setting and 85 days in an ambulatory setting |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Daily mCC consumption at Screening | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Concentration of Monohydroxybutenyl Mercapturic Acid (MHBMA) | Concentrations measured at Day 5 in urine, adjusted for creatinine. Geometric Least Squares (LS) means are provided as descriptive statistics. | 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. | Posted | Least Squares Mean | 95% Confidence Interval | pg/mg creat | 5 days |
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| Primary | Concentration of 3-hydroxypropylmercapturic Acid (3-HPMA) | Concentrations measured at Day 5 in urine, adjusted for creatinine. Geometric Least Squares (LS) means are provided as descriptive statistics. | 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. | Posted | Least Squares Mean | 95% Confidence Interval | ng/mg creat | 5 days |
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| Primary | Concentration of S-phenylmercapturic Acid (S-PMA) | Concentrations measured at Day 5 in urine, adjusted for creatinine. Geometric Least Squares (LS) means are provided as descriptive statistics. | 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. | Posted | Least Squares Mean | 95% Confidence Interval | pg/mg creat | 5 days |
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| Primary | Levels of Carboxyhemoglobin (COHb) | % COHb blood measurements performed in the evening of Day 5, expressed as % of saturation of hemoglobin. Geometric Least Squares means are provided as descriptive statistics. | 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. | Posted | Least Squares Mean | 95% Confidence Interval | % of saturation of hemoglobin | 5 days |
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| Primary | Concentration of Total 4-(Methylnitrosamino)-1-(3- Pyridyl)-1-butanol) (Total NNAL) | Concentrations measured at Day 90 in urine, adjusted for creatinine. Geometric Least Squares (LS) means are provided as descriptive statistics. | 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 period Day 60 to Day 90. | Posted | Least Squares Mean | 95% Confidence Interval | pg/mg creat | 90 days |
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From the informed consent form signature until the end of the safety follow-up period, up to 150 days (including a screening period of up to 28 days, a 9-day confinement period followed by a 85-day ambulatory setting, and by a 28-day safety follow-up period (28 days after discharge of the subject or early discontinuation)).
The safety was assessed in the safety population, consisting of 160 subjects: 160 randomized subjects (78 in mTHS 2.2, 42 in mCC and 40 in SA) and no subject exposed to mTHS 2.2 from the product trial on Day -2 but not randomized.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | THS 2.2 Menthol (mTHS 2.2) | Ad libitum use of THS 2.2 Menthol for 5 days in a confinement setting and 85 days in an ambulatory setting | 0 | 78 | 16 | 78 | ||
| EG001 | Menthol Conventional Cigarette (mCC) | Ad libitum use of subject's own preferred brand of mCC for 5 days in a confinement setting and 85 days in an ambulatory setting | 0 | 42 | 4 | 42 | ||
| EG002 | Smoking Abstinence (SA) | Abstinence from smoking for 5 days in a confinement setting and 85 days in an ambulatory setting | 0 | 40 | 4 | 40 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Haemoglobin decreased | Investigations | MedDRA 16.0 | Non-systematic Assessment |
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| Neutrophil count decreased | Investigations | MedDRA 16.0 | Non-systematic Assessment |
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We confirm we have the contractual provisions in place which specifies that in no event will the study site be allowed to disclose to any third party (or publicly release) any information obtained through the study without the CRO's prior written consent which in turn cannot provide such consent without Sponsor's approval unless such publication is made to satisfy regulatory requirements.
The Intellectual Property rights and research results from the present study belongs to the Sponsor.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Christelle HAZIZA, PhD | Philip Morris Products S.A. | +41 (58) 242 2625 | Christelle.Haziza@pmi.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 7, 2014 | Mar 9, 2020 | SAP_001.pdf |
| ID | Term |
|---|---|
| D012907 | Smoking |
| ID | Term |
|---|---|
| D001519 | Behavior |
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| Male |
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| > 19 cig/day |
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Geometric LS mean ratio mTHS 2.2:mCC |
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