Ignite Creation Date:
2025-12-24 @ 11:18 PM
Ignite Modification Date:
2026-01-16 @ 1:37 PM
Study NCT ID:
NCT01989156
Status:
COMPLETED
Last Update Posted:
2020-03-24
First Post:
2013-11-14
Is Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Reduced Exposure Study Using THS 2.2 Menthol With 5 Days in a Confinement Setting Followed by 86 Days in an Ambulatory Setting
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D012907', 'term': 'Smoking'}], 'ancestors': [{'id': 'D001519', 'term': 'Behavior'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'Christelle.Haziza@pmi.com', 'phone': '+41 (58) 242 2625', 'title': 'Christelle Haziza, PhD', 'organization': 'Philip Morris Products S.A.'}, 'certainAgreement': {'otherDetails': "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.\n\nThe Intellectual Property rights and research results from the present study belong to the Sponsor.", 'restrictionType': 'OTHER', 'piSponsorEmployee': False, 'restrictiveAgreement': True}, 'limitationsAndCaveats': {'description': '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.'}}, 'adverseEventsModule': {'timeFrame': '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)).', 'description': 'The adverse events and serious adverse events reported are for the post-randomization period.\n\nThe safety was assessed in the safety population, consisting of 165 subjects: 160 randomized subjects (80 in mTHS 2.2, 41 in mCC and 39 in SA) and 5 subjects exposed to mTHS 2.2 from the product trial on Day -2 but not randomized. After randomization, the Safety Population consisted of 160 subjects with one valid post-randomization safety assessment.', 'eventGroups': [{'id': 'EG000', 'title': 'THS 2.2 Menthol (mTHS 2.2)', 'description': 'Ad libitum use of THS 2.2 Menthol for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting', 'otherNumAtRisk': 80, 'otherNumAffected': 31, 'seriousNumAtRisk': 80, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Menthol Conventional Cigarette (mCC)', 'description': "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", 'otherNumAtRisk': 41, 'otherNumAffected': 12, 'seriousNumAtRisk': 41, 'seriousNumAffected': 0}, {'id': 'EG002', 'title': 'Smoking Abstinence (SA)', 'description': 'Abstinence from smoking for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting', 'otherNumAtRisk': 39, 'otherNumAffected': 16, 'seriousNumAtRisk': 39, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'Upper respiratory tract infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 80, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 41, 'numEvents': 4, 'numAffected': 4}, {'groupId': 'EG002', 'numAtRisk': 39, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.0'}, {'term': 'Muscle strain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 80, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 41, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 39, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.0'}, {'term': 'Blood triglycerides increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 80, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 41, 'numEvents': 3, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 39, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Investigations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.0'}, {'term': 'Haemoglobin decreased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 80, 'numEvents': 14, 'numAffected': 11}, {'groupId': 'EG001', 'numAtRisk': 41, 'numEvents': 5, 'numAffected': 4}, {'groupId': 'EG002', 'numAtRisk': 39, 'numEvents': 8, 'numAffected': 6}], 'organSystem': 'Investigations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.0'}, {'term': 'Lymphocyte count increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 80, 'numEvents': 7, 'numAffected': 6}, {'groupId': 'EG001', 'numAtRisk': 41, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 39, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Investigations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.0'}, {'term': 'Dizziness', 'stats': [{'groupId': 'EG000', 'numAtRisk': 80, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 41, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 39, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.0'}, {'term': 'Headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 80, 'numEvents': 4, 'numAffected': 4}, {'groupId': 'EG001', 'numAtRisk': 41, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 39, 'numEvents': 4, 'numAffected': 3}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.0'}, {'term': 'Neutrophil count decreased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 80, 'numEvents': 5, 'numAffected': 4}, {'groupId': 'EG001', 'numAtRisk': 41, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 39, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Investigations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.0'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Concentration of Monohydroxybutenylmercapturic Acid (MHBMA)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '65', 'groupId': 'OG000'}, {'value': '30', 'groupId': 'OG001'}, {'value': '21', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'THS 2.2 Menthol (mTHS 2.2)', 'description': 'Ad libitum use of THS 2.2 Menthol for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting'}, {'id': 'OG001', 'title': 'Menthol Conventional Cigarette (mCC)', 'description': "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"}, {'id': 'OG002', 'title': 'Smoking Abstinence (SA)', 'description': 'Abstinence from smoking for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting'}], 'classes': [{'categories': [{'measurements': [{'value': '110.96', 'groupId': 'OG000', 'lowerLimit': '93.49', 'upperLimit': '131.68'}, {'value': '882.25', 'groupId': 'OG001', 'lowerLimit': '687.25', 'upperLimit': '1132.57'}, {'value': '94.97', 'groupId': 'OG002', 'lowerLimit': '70.67', 'upperLimit': '127.61'}]}]}], 'analyses': [{'pValue': '<0.001', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Geometric LS Mean Ratio', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '12.58', 'ciLowerLimit': '9.27', 'ciUpperLimit': '17.05', 'pValueComment': 'The primary endpoints were tested using a multiple testing procedure to preserve the overall alpha level by simultaneously testing the endpoints using a closed procedure with each test performed at an alpha level of 2.5% one sided.', 'estimateComment': 'Geometric LS Mean Ratio mTHS 2.2:mCC', 'groupDescription': 'The hypothesis to be tested is that the geometric mean level on Day 5 of the biomarker of exposure for mTHS 2.2 is lower relative to mCC.\n\nAnalysis of the biomarkers of exposure (BoExp) was conducted on the natural log scale in order to test the following hypothesis (one sided test with 2.5% type I error probability):\n\n* Null hypothesis (H0): m1≥m2\n* Alternative hypothesis (H1): m1\\<m2 Where m1 and m2 are the geometric means of the BoExp levels on Day 5 for mTHS 2.2 and mCC respectively.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY', 'statisticalComment': 'ANCOVA model on MHBMA levels with product, sex, cigarette consumption, and baseline value as covariates.'}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': '5 days', 'description': '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.', 'unitOfMeasure': 'pg/mg creat', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': '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.'}, {'type': 'PRIMARY', 'title': 'Concentration of 3-hydroxypropylmercapturic Acid (3-HPMA)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '67', 'groupId': 'OG000'}, {'value': '30', 'groupId': 'OG001'}, {'value': '21', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'THS 2.2 Menthol (mTHS 2.2)', 'description': 'Ad libitum use of THS 2.2 Menthol for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting'}, {'id': 'OG001', 'title': 'Menthol Conventional Cigarette (mCC)', 'description': "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"}, {'id': 'OG002', 'title': 'Smoking Abstinence (SA)', 'description': 'Abstinence from smoking for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting'}], 'classes': [{'categories': [{'measurements': [{'value': '278.13', 'groupId': 'OG000', 'lowerLimit': '254.95', 'upperLimit': '303.43'}, {'value': '607.68', 'groupId': 'OG001', 'lowerLimit': '534.34', 'upperLimit': '691.09'}, {'value': '152.05', 'groupId': 'OG002', 'lowerLimit': '130.47', 'upperLimit': '177.19'}]}]}], 'analyses': [{'pValue': '<0.001', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Geometric LS Mean Ratio', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '45.77', 'ciLowerLimit': '39.22', 'ciUpperLimit': '53.41', 'pValueComment': 'The primary endpoints were tested using a multiple testing procedure to preserve the overall alpha level by simultaneously testing the endpoints using a closed procedure with each test performed at an alpha level of 2.5% one sided.', 'estimateComment': 'Geometric LS mean ratio mTHS 2.2:mCC', 'groupDescription': 'The hypothesis to be tested is that the geometric mean level on Day 5 of the biomarker of exposure for mTHS 2.2 is lower relative to mCC.\n\nAnalysis of the BoExp was conducted on the natural log scale in order to test the following hypothesis (one sided test with 2.5% type I error probability):\n\n* Null hypothesis (H0): m1≥m2\n* Alternative hypothesis (H1): m1\\<m2 Where m1 and m2 are the geometric means of the BoExp levels on Day 5 for mTHS 2.2 and mCC respectively.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY', 'statisticalComment': 'ANCOVA model on 3-HPMA levels with product, sex, cigarette consumption, and baseline value as covariates.'}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': '5 days', 'description': '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.', 'unitOfMeasure': 'ng/mg creat', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': '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.'}, {'type': 'PRIMARY', 'title': 'Concentration of S-phenylmercapturic Acid (S-PMA)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '65', 'groupId': 'OG000'}, {'value': '30', 'groupId': 'OG001'}, {'value': '21', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'THS 2.2 Menthol (mTHS 2.2)', 'description': 'Ad libitum use of THS 2.2 Menthol for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting'}, {'id': 'OG001', 'title': 'Menthol Conventional Cigarette (mCC)', 'description': "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"}, {'id': 'OG002', 'title': 'Smoking Abstinence (SA)', 'description': 'Abstinence from smoking for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting'}], 'classes': [{'categories': [{'measurements': [{'value': '134.11', 'groupId': 'OG000', 'lowerLimit': '114.63', 'upperLimit': '156.90'}, {'value': '1065.91', 'groupId': 'OG001', 'lowerLimit': '848.45', 'upperLimit': '1339.09'}, {'value': '131.05', 'groupId': 'OG002', 'lowerLimit': '99.78', 'upperLimit': '172.13'}]}]}], 'analyses': [{'pValue': '<0.001', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Geometric LS Mean Ratio', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '12.58', 'ciLowerLimit': '9.54', 'ciUpperLimit': '16.58', 'pValueComment': 'The primary endpoints were tested using a multiple testing procedure to preserve the overall alpha level by simultaneously testing the endpoints using a closed procedure with each test performed at an alpha level of 2.5% one sided.', 'estimateComment': 'Geometric LS mean ratio mTHS 2.2:mCC', 'groupDescription': 'The hypothesis to be tested is that the geometric mean level on Day 5 of the biomarker of exposure for mTHS 2.2 is lower relative to mCC.\n\nAnalysis of the BoExp was conducted on the natural log scale in order to test the following hypothesis (one sided test with 2.5% type I error probability):\n\n* Null hypothesis (H0): m1≥m2\n* Alternative hypothesis (H1): m1\\<m2 Where m1 and m2 are the geometric means of the BoExp levels on Day 5 for mTHS 2.2 and mCC respectively.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY', 'statisticalComment': 'ANCOVA model on S-PMA levels with product, sex, cigarette consumption, and baseline value as covariates.'}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': '5 days', 'description': '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.', 'unitOfMeasure': 'pg/mg creat', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': '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.'}, {'type': 'PRIMARY', 'title': 'Levels of Total 4-(Methylnitrosamino)-1-(3- Pyridyl)-1-butanol (Total NNAL)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '43', 'groupId': 'OG000'}, {'value': '29', 'groupId': 'OG001'}, {'value': '9', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'THS 2.2 Menthol (mTHS 2.2)', 'description': 'Ad libitum use of THS 2.2 Menthol for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting'}, {'id': 'OG001', 'title': 'Menthol Conventional Cigarette (mCC)', 'description': "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"}, {'id': 'OG002', 'title': 'Smoking Abstinence (SA)', 'description': 'Abstinence from smoking for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting'}], 'classes': [{'categories': [{'measurements': [{'value': '41.05', 'groupId': 'OG000', 'lowerLimit': '31.28', 'upperLimit': '53.86'}, {'value': '155.45', 'groupId': 'OG001', 'lowerLimit': '112.46', 'upperLimit': '214.88'}, {'value': '54.03', 'groupId': 'OG002', 'lowerLimit': '30', 'upperLimit': '97.28'}]}]}], 'analyses': [{'pValue': '<0.001', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Geometric LS Mean Ratio', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '26.41', 'ciLowerLimit': '17.31', 'ciUpperLimit': '40.26', 'pValueComment': 'The primary endpoints were tested using a multiple testing procedure to preserve the overall alpha level by simultaneously testing the endpoints using a closed procedure with each test performed at an alpha level of 2.5% one sided.', 'estimateComment': 'Geometric LS mean ratio mTHS 2.2:mCC', 'groupDescription': 'The hypothesis to be tested is that the geometric mean level on Day 90 of the biomarker of exposure for mTHS 2.2 is lower relative to mCC.\n\nAnalysis of the BoExp was conducted on the natural log scale in order to test the following hypothesis (one sided test with 2.5% type I error probability):\n\n* Null hypothesis (H0): m1≥m2\n* Alternative hypothesis (H1): m1\\<m2 Where m1 and m2 are the geometric means of the BoExp levels on Day 90 for mTHS 2.2 and mCC respectively.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY', 'statisticalComment': 'ANCOVA model on Total NNAL levels with product, sex, cigarette consumption, and baseline value as covariates'}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': '90 days', 'description': '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.', 'unitOfMeasure': 'pg/mg creat', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': '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.'}, {'type': 'PRIMARY', 'title': 'Levels of Carboxyhemoglobin (COHb)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '74', 'groupId': 'OG000'}, {'value': '34', 'groupId': 'OG001'}, {'value': '23', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'THS 2.2 Menthol (mTHS 2.2)', 'description': 'Ad libitum use of THS 2.2 Menthol for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting'}, {'id': 'OG001', 'title': 'Menthol Conventional Cigarette (mCC)', 'description': "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"}, {'id': 'OG002', 'title': 'Smoking Abstinence (SA)', 'description': 'Abstinence from smoking for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting'}], 'classes': [{'categories': [{'measurements': [{'value': '2.33', 'groupId': 'OG000', 'lowerLimit': '2.19', 'upperLimit': '2.48'}, {'value': '6.11', 'groupId': 'OG001', 'lowerLimit': '5.58', 'upperLimit': '6.68'}, {'value': '2.39', 'groupId': 'OG002', 'lowerLimit': '2.14', 'upperLimit': '2.67'}]}]}], 'analyses': [{'pValue': '<0.001', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Geometric LS Mean Ratio', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '38.14', 'ciLowerLimit': '34.24', 'ciUpperLimit': '42.47', 'pValueComment': 'The primary endpoints were tested using a multiple testing procedure to preserve the overall alpha level by simultaneously testing the endpoints using a closed procedure with each test performed at an alpha level of 2.5% one sided.', 'estimateComment': 'Geometric LS mean ratio mTHS 2.2:mCC', 'groupDescription': 'The hypothesis to be tested is that the geometric mean level on Day 90 of the biomarker of exposure for mTHS 2.2 is lower relative to mCC.\n\nAnalysis of the BoExp was conducted on the natural log scale in order to test the following hypothesis (one sided test with 2.5% type I error probability):\n\n* Null hypothesis (H0): m1≥m2\n* Alternative hypothesis (H1): m1\\<m2 Where m1 and m2 are the geometric means of the BoExp levels on Day 90 for mTHS 2.2 and mCC respectively.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY', 'statisticalComment': 'ANCOVA model on COHb levels with product, sex, cigarette consumption, and baseline value as covariates.'}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': '5 days', 'description': '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.', 'unitOfMeasure': '% of saturation of hemoglobin', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': '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.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'THS 2.2 Menthol (mTHS 2.2)', 'description': 'Ad libitum use of THS 2.2 Menthol for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting'}, {'id': 'FG001', 'title': 'Menthol Conventional Cigarette (mCC)', 'description': "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"}, {'id': 'FG002', 'title': 'Smoking Abstinence (SA)', 'description': 'Abstinence from smoking for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting'}], 'periods': [{'title': 'Confinement Period (Population at Day 5)', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '80'}, {'groupId': 'FG001', 'numSubjects': '41'}, {'groupId': 'FG002', 'numSubjects': '39'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '80'}, {'groupId': 'FG001', 'numSubjects': '40'}, {'groupId': 'FG002', 'numSubjects': '34'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '1'}, {'groupId': 'FG002', 'numSubjects': '5'}]}], 'dropWithdraws': [{'type': 'Withdrawal by Subject', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '1'}, {'groupId': 'FG002', 'numSubjects': '3'}]}, {'type': 'Patient Anxiety', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '1'}]}, {'type': 'Adverse Event', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '1'}]}]}, {'title': 'End of Study (Population at Day 90)', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '80'}, {'groupId': 'FG001', 'numSubjects': '40'}, {'groupId': 'FG002', 'numSubjects': '34'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '73'}, {'groupId': 'FG001', 'numSubjects': '35'}, {'groupId': 'FG002', 'numSubjects': '31'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '7'}, {'groupId': 'FG001', 'numSubjects': '5'}, {'groupId': 'FG002', 'numSubjects': '3'}]}], 'dropWithdraws': [{'type': 'Withdrawal by Subject', 'reasons': [{'groupId': 'FG000', 'numSubjects': '2'}, {'groupId': 'FG001', 'numSubjects': '2'}, {'groupId': 'FG002', 'numSubjects': '2'}]}, {'type': 'Lost to Follow-up', 'reasons': [{'groupId': 'FG000', 'numSubjects': '3'}, {'groupId': 'FG001', 'numSubjects': '2'}, {'groupId': 'FG002', 'numSubjects': '0'}]}, {'type': 'Physician Decision', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '1'}]}, {'type': 'Moved out of state', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '0'}]}, {'type': 'Employment Conflict', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '1'}, {'groupId': 'FG002', 'numSubjects': '0'}]}]}], 'recruitmentDetails': 'Study initiated (first subject screened): 17 December 2013\n\nAt admission (Day -2), all the subjects performed a product trial of THS 2.2 Menthol. During the baseline period, they continued to smoke 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.', 'preAssignmentDetails': 'Enrolled and randomized population = 160 subjects\n\n* 80 subjects in mTHS 2.2\n* 41 subjects in mCC\n* 39 subjects in SA\n\nNumber of subjects exposed to the product test = 165\n\n* Number of subjects enrolled but NOT randomized = 4\n* Number of subjects failed screening = 1'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '80', 'groupId': 'BG000'}, {'value': '41', 'groupId': 'BG001'}, {'value': '39', 'groupId': 'BG002'}, {'value': '160', 'groupId': 'BG003'}]}], 'groups': [{'id': 'BG000', 'title': 'THS 2.2 Menthol (mTHS 2.2)', 'description': 'Ad libitum use of THS 2.2 Menthol for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting'}, {'id': 'BG001', 'title': 'Menthol Conventional Cigarette (mCC)', 'description': "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"}, {'id': 'BG002', 'title': 'Smoking Abstinence (SA)', 'description': 'Abstinence from smoking for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting'}, {'id': 'BG003', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '39.2', 'spread': '11.72', 'groupId': 'BG000'}, {'value': '33.7', 'spread': '10.17', 'groupId': 'BG001'}, {'value': '38.8', 'spread': '11.42', 'groupId': 'BG002'}, {'value': '37.7', 'spread': '11.45', 'groupId': 'BG003'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '32', 'groupId': 'BG000'}, {'value': '17', 'groupId': 'BG001'}, {'value': '15', 'groupId': 'BG002'}, {'value': '64', 'groupId': 'BG003'}]}, {'title': 'Male', 'measurements': [{'value': '48', 'groupId': 'BG000'}, {'value': '24', 'groupId': 'BG001'}, {'value': '24', 'groupId': 'BG002'}, {'value': '96', 'groupId': 'BG003'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Daily mCC consumption at screening', 'classes': [{'title': '10 to 19 cig/day', 'categories': [{'measurements': [{'value': '43', 'groupId': 'BG000'}, {'value': '21', 'groupId': 'BG001'}, {'value': '18', 'groupId': 'BG002'}, {'value': '82', 'groupId': 'BG003'}]}]}, {'title': '> 19 cig/day', 'categories': [{'measurements': [{'value': '36', 'groupId': 'BG000'}, {'value': '20', 'groupId': 'BG001'}, {'value': '21', 'groupId': 'BG002'}, {'value': '77', 'groupId': 'BG003'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}], 'populationDescription': 'Study population = all randomized subjects who had at least one post randomization product use experience and at least one valid biomarker of exposure measurement.\n\n160 randomized subjects: 80 in mTHS 2.2, 41 in mCC and 39 in SA arms'}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2014-04-14', 'size': 3875845, 'label': 'Study Protocol', 'hasIcf': False, 'hasSap': False, 'filename': 'Prot_000.pdf', 'typeAbbrev': 'Prot', 'uploadDate': '2020-03-09T12:03', 'hasProtocol': True}, {'date': '2015-05-29', 'size': 2699024, 'label': 'Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'SAP_001.pdf', 'typeAbbrev': 'SAP', 'uploadDate': '2020-03-09T12:07', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'OTHER', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 160}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2013-12'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2020-03', 'completionDateStruct': {'date': '2015-05', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2020-03-11', 'studyFirstSubmitDate': '2013-11-14', 'resultsFirstSubmitDate': '2016-12-21', 'studyFirstSubmitQcDate': '2013-11-19', 'lastUpdatePostDateStruct': {'date': '2020-03-24', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2017-02-17', 'studyFirstPostDateStruct': {'date': '2013-11-20', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2017-04-05', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2014-10', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Concentration of Monohydroxybutenylmercapturic Acid (MHBMA)', 'timeFrame': '5 days', 'description': '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.'}, {'measure': 'Concentration of 3-hydroxypropylmercapturic Acid (3-HPMA)', 'timeFrame': '5 days', 'description': '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.'}, {'measure': 'Concentration of S-phenylmercapturic Acid (S-PMA)', 'timeFrame': '5 days', 'description': '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.'}, {'measure': 'Levels of Total 4-(Methylnitrosamino)-1-(3- Pyridyl)-1-butanol (Total NNAL)', 'timeFrame': '90 days', 'description': '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.'}, {'measure': 'Levels of Carboxyhemoglobin (COHb)', 'timeFrame': '5 days', 'description': '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.'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Smoking', 'Candidate modified risk tobacco product', 'Menthol conventional cigarettes', 'Reduced exposure', 'HPHCs', 'Ambulatory'], 'conditions': ['Smoking']}, 'referencesModule': {'references': [{'pmid': '31125079', 'type': 'DERIVED', 'citation': '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.'}, {'pmid': '30722062', 'type': 'DERIVED', 'citation': '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.'}]}, 'descriptionModule': {'briefSummary': '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 harmful constituents (HPHCs).', 'detailedDescription': '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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '22 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Smoking, apparently healthy subject as judged by the Investigator.\n* Subject smokes at least 10 commercially available mCCs per day (no brand restrictions) for the last 4 weeks, based on self-reporting.\n* Subject has smoked for at least the last 3 consecutive years.\n* Subject does not plan to quit smoking within the next 6 months.\n\nExclusion Criteria:\n\n* As per Investigator judgment, the subject cannot participate in the study for any reason (e.g., medical, psychiatric, and/or social reason).\n* 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.\n* For women: Subject is pregnant or is breast feeding.\n* For women: Subject does not agree to use an acceptable method of effective contraception.'}, 'identificationModule': {'nctId': 'NCT01989156', 'briefTitle': 'Reduced Exposure Study Using THS 2.2 Menthol With 5 Days in a Confinement Setting Followed by 86 Days in an Ambulatory Setting', 'organization': {'class': 'INDUSTRY', 'fullName': 'Philip Morris Products S.A.'}, 'officialTitle': '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', 'orgStudyIdInfo': {'id': 'ZRHM-REXA-08-US'}, 'secondaryIdInfos': [{'id': 'ZRHM-REXA-08-US', 'type': 'OTHER', 'domain': 'Philip Morris Products S.A.'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'THS 2.2 Menthol (mTHS 2.2)', 'description': 'Ad libitum use of THS 2.2 Menthol for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting', 'interventionNames': ['Other: THS 2.2 Menthol (mTHS 2.2)']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Menthol Conventional Cigarette (mCC)', 'description': "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", 'interventionNames': ['Other: Menthol Conventional Cigarette (mCC)']}, {'type': 'SHAM_COMPARATOR', 'label': 'Smoking abstinence (SA)', 'description': 'Abstinence from smoking for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting', 'interventionNames': ['Other: Smoking Abstinence (SA)']}], 'interventions': [{'name': 'THS 2.2 Menthol (mTHS 2.2)', 'type': 'OTHER', 'description': 'THS 2.2 Menthol ad libitum for 5 days in confinement prolonged by 86 days in an ambulatory setting', 'armGroupLabels': ['THS 2.2 Menthol (mTHS 2.2)']}, {'name': 'Menthol Conventional Cigarette (mCC)', 'type': 'OTHER', 'description': "Subject's own preferred brand of mCC ad libitum for 5 days in confinement prolonged by 86 days in an ambulatory setting", 'armGroupLabels': ['Menthol Conventional Cigarette (mCC)']}, {'name': 'Smoking Abstinence (SA)', 'type': 'OTHER', 'description': 'SA for 5 days in confinement prolonged by 86 days in an ambulatory setting', 'armGroupLabels': ['Smoking abstinence (SA)']}]}, 'contactsLocationsModule': {'locations': [{'zip': '32117', 'city': 'Daytona Beach', 'state': 'Florida', 'country': 'United States', 'facility': 'Covance Daytona Beach, 1900 Mason Ave., Suite 140', 'geoPoint': {'lat': 29.21081, 'lon': -81.02283}}, {'zip': '75247', 'city': 'Dallas', 'state': 'Texas', 'country': 'United States', 'facility': 'Covance Dallas, 1341 W. Mockingbird Ln., Ste 400E', 'geoPoint': {'lat': 32.78306, 'lon': -96.80667}}], 'overallOfficials': [{'name': 'William Lewis, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Covance Dallas'}, {'name': 'Frank Farmer, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Covance Daytona Beach'}, {'name': 'Christelle Haziza, PhD', 'role': 'STUDY_CHAIR', 'affiliation': 'Philip Morris Products S.A.'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Philip Morris Products S.A.', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}