Ignite Creation Date:
2025-12-24 @ 9:47 PM
Ignite Modification Date:
2026-01-02 @ 5:40 PM
Study NCT ID:
NCT01959932
Status:
COMPLETED
Last Update Posted:
2020-03-12
First Post:
2013-10-08
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Reduced Exposure Study in Smokers Using THS 2.2 With 5 Days in a Confinement 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 belongs to the Sponsor.", 'restrictionType': 'OTHER', 'piSponsorEmployee': False, 'restrictiveAgreement': True}}, 'adverseEventsModule': {'timeFrame': 'From the informed consent form (ICF) signature until the end of the safety follow-up period (7 days after discharge of the subject).', 'description': 'The safety was assessed in the safety population, consisting of 169 subjects: 160 randomized subjects (80 in THS 2.2, 41 in CC and 39 in SA) and 9 subjects exposed to THS 2.2 from the product trial on Day -2 but not randomized.', 'eventGroups': [{'id': 'EG000', 'title': 'Tobacco Heating System (THS 2.2)', 'description': 'Ad libitum use of THS 2.2 for 5 days in confinement', 'otherNumAtRisk': 80, 'otherNumAffected': 44, 'seriousNumAtRisk': 80, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Smoking Abstinence (SA)', 'description': 'Abstinence from smoking for 5 days in confinement', 'otherNumAtRisk': 39, 'otherNumAffected': 22, 'seriousNumAtRisk': 39, 'seriousNumAffected': 0}, {'id': 'EG002', 'title': 'Conventional Cigarette (CC)', 'description': "Ad libitum use of subject's own preferred brand of CC for 5 days in confinement", 'otherNumAtRisk': 41, 'otherNumAffected': 26, 'seriousNumAtRisk': 41, 'seriousNumAffected': 0}, {'id': 'EG003', 'title': 'Enrolled But Not Randomized', 'description': 'Subjects who tried the THS 2.2 at Admission (Day -2) but were not randomized in 1 of the 3 arms as they were back-up subjects', 'otherNumAtRisk': 9, 'otherNumAffected': 9, 'seriousNumAtRisk': 9, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'Headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 80, 'numEvents': 30, 'numAffected': 24}, {'groupId': 'EG001', 'numAtRisk': 39, 'numEvents': 15, 'numAffected': 13}, {'groupId': 'EG002', 'numAtRisk': 41, 'numEvents': 19, 'numAffected': 16}, {'groupId': 'EG003', 'numAtRisk': 9, 'numEvents': 3, 'numAffected': 3}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (16.0)'}, {'term': 'Syncope', 'stats': [{'groupId': 'EG000', 'numAtRisk': 80, 'numEvents': 6, 'numAffected': 6}, {'groupId': 'EG001', 'numAtRisk': 39, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 41, 'numEvents': 4, 'numAffected': 4}, {'groupId': 'EG003', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (16.0)'}, {'term': 'Spirometry abnormal', 'stats': [{'groupId': 'EG000', 'numAtRisk': 80, 'numEvents': 4, 'numAffected': 4}, {'groupId': 'EG001', 'numAtRisk': 39, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 41, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG003', 'numAtRisk': 9, 'numEvents': 3, 'numAffected': 3}], 'organSystem': 'Investigations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (16.0)'}, {'term': 'Lymphocyte count increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 80, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 39, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 41, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 9, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Investigations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (16.0)'}, {'term': 'Constipation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 80, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 39, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 41, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG003', 'numAtRisk': 9, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (16.0)'}, {'term': 'Toothache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 80, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 39, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 41, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG003', 'numAtRisk': 9, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (16.0)'}, {'term': 'Abdominal distension', 'stats': [{'groupId': 'EG000', 'numAtRisk': 80, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 39, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 41, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (16.0)'}, {'term': 'Oropharyngeal pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 80, 'numEvents': 7, 'numAffected': 7}, {'groupId': 'EG001', 'numAtRisk': 39, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 41, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG003', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (16.0)'}, {'term': 'Cough', 'stats': [{'groupId': 'EG000', 'numAtRisk': 80, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 39, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 41, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 9, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (16.0)'}, {'term': 'Polyuria', 'stats': [{'groupId': 'EG000', 'numAtRisk': 80, 'numEvents': 8, 'numAffected': 6}, {'groupId': 'EG001', 'numAtRisk': 39, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 41, 'numEvents': 6, 'numAffected': 4}, {'groupId': 'EG003', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Renal and urinary disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (16.0)'}, {'term': 'Hypertriglyceridaemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 80, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 39, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 41, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG003', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (16.0)'}, {'term': 'Hyperglycaemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 80, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 39, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 41, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 9, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (16.0)'}, {'term': 'Hyperkalaemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 80, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 39, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 41, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 9, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (16.0)'}, {'term': 'Back pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 80, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 39, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG002', 'numAtRisk': 41, 'numEvents': 3, 'numAffected': 2}, {'groupId': 'EG003', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (16.0)'}, {'term': 'Hypertension', 'stats': [{'groupId': 'EG000', 'numAtRisk': 80, 'numEvents': 2, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 39, 'numEvents': 5, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 41, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG003', 'numAtRisk': 9, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Vascular disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (16.0)'}, {'term': 'Influenza like illness', 'stats': [{'groupId': 'EG000', 'numAtRisk': 80, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 39, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG002', 'numAtRisk': 41, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG003', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (16.0)'}, {'term': 'Vertigo', 'stats': [{'groupId': 'EG000', 'numAtRisk': 80, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 39, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 41, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Ear and labyrinth disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (16.0)'}, {'term': 'Ventricular extrasystoles', 'stats': [{'groupId': 'EG000', 'numAtRisk': 80, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 39, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 41, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 9, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (16.0)'}, {'term': 'Leukocytosis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 80, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 39, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 41, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 9, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (16.0)'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Concentration of Monohydroxybutenyl Mercapturic Acid (MHBMA)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '79', 'groupId': 'OG000'}, {'value': '41', 'groupId': 'OG001'}, {'value': '39', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Tobacco Heating System (THS 2.2)', 'description': 'Ad libitum use of THS 2.2 for 5 days in confinement'}, {'id': 'OG001', 'title': 'Conventional Cigarette (CC)', 'description': "Ad libitum use of subject's own preferred brand of CC for 5 days in confinement"}, {'id': 'OG002', 'title': 'Smoking Abstinence (SA)', 'description': 'Abstinence from smoking for 5 days in confinement'}], 'classes': [{'categories': [{'measurements': [{'value': '194.05', 'groupId': 'OG000', 'lowerLimit': '173.23', 'upperLimit': '217.38'}, {'value': '2314.37', 'groupId': 'OG001', 'lowerLimit': '1975.39', 'upperLimit': '2711.52'}, {'value': '168.01', 'groupId': 'OG002', 'lowerLimit': '142.88', 'upperLimit': '197.55'}]}]}], 'analyses': [{'pValue': '<0.001', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Geometric LS Mean Ratio', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '8.38', 'ciLowerLimit': '6.89', 'ciUpperLimit': '10.20', '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': 'LS mean ratio THS 2.2:CC', 'groupDescription': 'The hypothesis to be tested is that the geometric mean level on Day 5 of the biomarker of exposure for THS 2.2 is lower relative to CC.\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 THS 2.2 and CC 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': 'LEAST_SQUARES_MEAN', 'timeFrame': '5 days', 'description': 'Concentrations measured at Day 5 in urine, adjusted for creatinine.\n\nGeometric Least Squares (LS) means are provided as descriptive statistics.', 'unitOfMeasure': 'pg/mg creat', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'The analysis was performed on the full analysis set (FAS) population.\n\nThe FAS consisted of all the randomized subjects who had at least 1 post randomization product use experience (if randomized to THS 2.2 or CC) and had at least 1 valid biomarker of exposure (BoExp) measurement (THS 2.2, CC, SA arms).'}, {'type': 'PRIMARY', 'title': 'Concentration of 3-hydroxypropylmercapturic Acid (3-HPMA)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '79', 'groupId': 'OG000'}, {'value': '41', 'groupId': 'OG001'}, {'value': '39', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Tobacco Heating System (THS 2.2)', 'description': 'Ad libitum use of THS 2.2 for 5 days in confinement'}, {'id': 'OG001', 'title': 'Conventional Cigarette (CC)', 'description': "Ad libitum use of subject's own preferred brand of CC for 5 days in confinement"}, {'id': 'OG002', 'title': 'Smoking Abstinence (SA)', 'description': 'Abstinence from smoking for 5 days in confinement'}], 'classes': [{'categories': [{'measurements': [{'value': '398.87', 'groupId': 'OG000', 'lowerLimit': '376.74', 'upperLimit': '422.30'}, {'value': '958.03', 'groupId': 'OG001', 'lowerLimit': '884.99', 'upperLimit': '1037.09'}, {'value': '242.56', 'groupId': 'OG002', 'lowerLimit': '223.64', 'upperLimit': '263.09'}]}]}], 'analyses': [{'pValue': '<0.001', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Geometric LS mean ratio', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '41.63', 'ciLowerLimit': '37.75', 'ciUpperLimit': '45.91', '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': 'LS mean ratio THS 2.2:CC', 'groupDescription': 'The hypothesis to be tested is that the geometric mean level on Day 5 of the biomarker of exposure for THS 2.2 is lower relative to CC.\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 THS 2.2 and CC 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': 'LEAST_SQUARES_MEAN', 'timeFrame': '5 days', 'description': 'Concentrations measured at Day 5 in urine, adjusted for creatinine.\n\nGeometric 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 full analysis set (FAS) population.\n\nThe FAS consisted of all the randomized subjects who had at least 1 post randomization product use experience (if randomized to THS 2.2 or CC) and had at least 1 valid BoExp measurement (THS 2.2, CC, SA arms).'}, {'type': 'PRIMARY', 'title': 'Concentration of S-phenylmercapturic Acid (S-PMA)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '79', 'groupId': 'OG000'}, {'value': '41', 'groupId': 'OG001'}, {'value': '39', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Tobacco Heating System (THS 2.2)', 'description': 'Ad libitum use of THS 2.2 for 5 days in confinement'}, {'id': 'OG001', 'title': 'Conventional Cigarette (CC)', 'description': "Ad libitum use of subject's own preferred brand of CC for 5 days in confinement"}, {'id': 'OG002', 'title': 'Smoking Abstinence (SA)', 'description': 'Abstinence from smoking for 5 days in confinement'}], 'classes': [{'categories': [{'measurements': [{'value': '164.51', 'groupId': 'OG000', 'lowerLimit': '151.82', 'upperLimit': '178.25'}, {'value': '2748.16', 'groupId': 'OG001', 'lowerLimit': '2457.56', 'upperLimit': '3073.13'}, {'value': '153.66', 'groupId': 'OG002', 'lowerLimit': '137.03', 'upperLimit': '172.31'}]}]}], 'analyses': [{'pValue': '<0.001', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Geometric LS Mean Ratio', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '5.99', 'ciLowerLimit': '5.21', 'ciUpperLimit': '6.87', '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': 'LS mean ratio THS 2.2:CC', 'groupDescription': 'The hypothesis to be tested is that the geometric mean level on Day 5 of the biomarker of exposure for THS 2.2 is lower relative to CC.\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 THS 2.2 and CC 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': 'LEAST_SQUARES_MEAN', 'timeFrame': '5 days', 'description': 'Concentrations measured at Day 5 in urine, adjusted for creatinine.\n\nGeometric 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 full analysis set (FAS) population.\n\nThe FAS consisted of all the randomized subjects who had at least 1 post randomization product use experience (if randomized to THS 2.2 or CC) and had at least 1 valid BoExp measurement (THS 2.2, CC, SA arms).'}, {'type': 'PRIMARY', 'title': 'Levels of Carboxyhemoglobin (COHb)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '79', 'groupId': 'OG000'}, {'value': '41', 'groupId': 'OG001'}, {'value': '39', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Tobacco Heating System (THS 2.2)', 'description': 'Ad libitum use of THS 2.2 for 5 days in confinement'}, {'id': 'OG001', 'title': 'Conventional Cigarette (CC)', 'description': "Ad libitum use of subject's own preferred brand of CC for 5 days in confinement"}, {'id': 'OG002', 'title': 'Smoking Abstinence (SA)', 'description': 'Abstinence from smoking for 5 days in confinement'}], 'classes': [{'categories': [{'measurements': [{'value': '1.06', 'groupId': 'OG000', 'lowerLimit': '1.02', 'upperLimit': '1.11'}, {'value': '4.53', 'groupId': 'OG001', 'lowerLimit': '4.29', 'upperLimit': '4.77'}, {'value': '0.98', 'groupId': 'OG002', 'lowerLimit': '0.93', 'upperLimit': '1.04'}]}]}], 'analyses': [{'pValue': '<0.001', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Geometric LS Mean Ratio', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '23.45', 'ciLowerLimit': '22.00', 'ciUpperLimit': '24.99', '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': 'LS mean ratio THS 2.2:CC', 'groupDescription': 'The hypothesis to be tested is that the geometric mean level on Day 5 of the biomarker of exposure for THS 2.2 is lower relative to CC.\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 THS 2.2 and CC 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': 'LEAST_SQUARES_MEAN', 'timeFrame': '5 days', 'description': '% COHb blood measurements performed in the evening of Day 5, expressed as % of saturation of hemoglobin.\n\nGeometric 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 full analysis set (FAS) population.\n\nThe FAS consisted of all the randomized subjects who had at least 1 post randomization product use experience (if randomized to THS 2.2 or CC) and had at least 1 valid BoExp measurement (THS 2.2, CC, SA arms).'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Tobacco Heating System (THS 2.2)', 'description': 'Ad libitum use of THS 2.2 for 5 days in confinement'}, {'id': 'FG001', 'title': 'Conventional Cigarette (CC)', 'description': "Ad libitum use of subject's own preferred brand of CC for 5 days in confinement"}, {'id': 'FG002', 'title': 'Smoking Abstinence (SA)', 'description': 'Abstinence from smoking for 5 days in confinement'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '80'}, {'groupId': 'FG001', 'numSubjects': '41'}, {'groupId': 'FG002', 'numSubjects': '39'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '79'}, {'groupId': 'FG001', 'numSubjects': '41'}, {'groupId': 'FG002', 'numSubjects': '39'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '0'}]}], 'dropWithdraws': [{'type': 'Withdrawal by Subject', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '0'}]}]}], 'recruitmentDetails': 'Study initiated (first subject screened): 29 June 2013\n\nAt admission (Day -2), all the subjects performed a product trial of the THS 2.2. During the baseline period, they continued smoking their single preferred brand of CC. Then, on Day 0, subjects were randomized to one of the 3 study arms (THS 2.2, CC or SA) in a 2:1:1 ratio.', 'preAssignmentDetails': 'Enrolled and randomized population = 160 subjects\n\n* 80 subjects in THS 2.2\n* 41 subjects in CC\n* 39 subjects in SA\n\nNumber of subjects enrolled but NOT randomized (who tried the THS 2.2 at Day -2) = 9'}, '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': 'Tobacco Heating System (THS 2.2)', 'description': 'Ad libitum use of THS 2.2 for 5 days in confinement'}, {'id': 'BG001', 'title': 'Conventional Cigarette (CC)', 'description': "Ad libitum use of subject's own preferred brand of CC for 5 days in confinement"}, {'id': 'BG002', 'title': 'Smoking Abstinence (SA)', 'description': 'Abstinence from smoking for 5 days in confinement'}, {'id': 'BG003', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Customized', 'classes': [{'title': 'Between 21 and 65 years', 'categories': [{'measurements': [{'value': '35.4', 'spread': '9.40', 'groupId': 'BG000'}, {'value': '32.6', 'spread': '10.06', 'groupId': 'BG001'}, {'value': '33.6', 'spread': '11.51', 'groupId': 'BG002'}, {'value': '34.3', 'spread': '10.12', 'groupId': 'BG003'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '41', 'groupId': 'BG000'}, {'value': '20', 'groupId': 'BG001'}, {'value': '19', 'groupId': 'BG002'}, {'value': '80', 'groupId': 'BG003'}]}, {'title': 'Male', 'measurements': [{'value': '39', 'groupId': 'BG000'}, {'value': '21', 'groupId': 'BG001'}, {'value': '20', 'groupId': 'BG002'}, {'value': '80', 'groupId': 'BG003'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Daily CC consumption at Screening', 'classes': [{'title': '10 to 19 cig/day', 'categories': [{'measurements': [{'value': '41', 'groupId': 'BG000'}, {'value': '21', 'groupId': 'BG001'}, {'value': '19', 'groupId': 'BG002'}, {'value': '81', 'groupId': 'BG003'}]}]}, {'title': '> 19 cig/day', 'categories': [{'measurements': [{'value': '39', 'groupId': 'BG000'}, {'value': '20', 'groupId': 'BG001'}, {'value': '20', 'groupId': 'BG002'}, {'value': '79', 'groupId': 'BG003'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}], 'populationDescription': 'The study population consisted of all the randomized subjects who had at least 1 post randomization product use experience (THS 2.2 or CC arms), and 1 valid biomarker of exposure (BoExp) measurement.\n\n160 randomized subjects: 80 in THS 2.2, 41 in CC and 39 in SA\n\n159 completers: 1 subject (THS 2.2 arm) voluntarily withdrew on Day 3'}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2013-04-25', 'size': 2966137, 'label': 'Study Protocol', 'hasIcf': False, 'hasSap': False, 'filename': 'Prot_000.pdf', 'typeAbbrev': 'Prot', 'uploadDate': '2020-03-02T10:30', 'hasProtocol': True}, {'date': '2014-05-27', 'size': 10478489, 'label': 'Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'SAP_001.pdf', 'typeAbbrev': 'SAP', 'uploadDate': '2020-03-02T10:41', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'OTHER', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 169}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2013-06'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2020-03', 'completionDateStruct': {'date': '2014-06', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2020-03-03', 'studyFirstSubmitDate': '2013-10-08', 'resultsFirstSubmitDate': '2016-01-26', 'studyFirstSubmitQcDate': '2013-10-09', 'lastUpdatePostDateStruct': {'date': '2020-03-12', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2016-08-19', 'studyFirstPostDateStruct': {'date': '2013-10-10', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2016-10-13', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2013-09', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Concentration of Monohydroxybutenyl Mercapturic Acid (MHBMA)', 'timeFrame': '5 days', 'description': 'Concentrations measured at Day 5 in urine, adjusted for creatinine.\n\nGeometric Least Squares (LS) means are provided as descriptive statistics.'}, {'measure': 'Concentration of 3-hydroxypropylmercapturic Acid (3-HPMA)', 'timeFrame': '5 days', 'description': 'Concentrations measured at Day 5 in urine, adjusted for creatinine.\n\nGeometric Least Squares means are provided as descriptive statistics.'}, {'measure': 'Concentration of S-phenylmercapturic Acid (S-PMA)', 'timeFrame': '5 days', 'description': 'Concentrations measured at Day 5 in urine, adjusted for creatinine.\n\nGeometric Least Squares means are provided as descriptive statistics.'}, {'measure': 'Levels of Carboxyhemoglobin (COHb)', 'timeFrame': '5 days', 'description': '% COHb blood measurements performed in the evening of Day 5, expressed as % of saturation of hemoglobin.\n\nGeometric Least Squares means are provided as descriptive statistics.'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['Smoking', 'Candidate Modified Risk Tobacco Product', 'Conventional cigarettes', 'Reduced exposure', 'Confinement'], 'conditions': ['Smoking']}, 'descriptionModule': {'briefSummary': 'The overall goal of the study is to evaluate if the ad libitum use of the Tobacco Heating System 2.2 (THS 2.2) for 5 days by adult healthy smokers results in a reduction in the levels of biomarkers of exposure (BoExp) for selected harmful and potentially harmful constituents (HPHCs) compared to smoking conventional cigarettes (CC) and smoking abstinence (SA).'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '65 Years', 'minimumAge': '21 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Subject is Caucasian.\n* Current healthy smoker as judged by the Principal Investigator.\n* Subject has smoked at least 10 commercially available non-menthol CCs per day (no brand restrictions) for the last 4 weeks.\n* Subject has smoked for at least the last 3 consecutive years.\n* Subject does not plan to quit smoking in the next 3 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* Subject has received medication within 14 days or within 5 half-lives of the medication (whichever is longer), which has an impact on cytochrome P450 1A2 (CYP1A2) or cytochrome P450 2A6 (CYP2A6) activity.\n* Female subject is pregnant or breast feeding.\n* Female subject does not agree to use an acceptable method of effective contraception.'}, 'identificationModule': {'nctId': 'NCT01959932', 'briefTitle': 'Reduced Exposure Study in Smokers Using THS 2.2 With 5 Days in a Confinement Setting.', 'organization': {'class': 'INDUSTRY', 'fullName': 'Philip Morris Products S.A.'}, 'officialTitle': 'A Randomized, Controlled, Open-label, 3-arm Parallel Group, Single-center Study to Demonstrate Reductions in Exposure to Selected Smoke Constituents in Smoking, Healthy Subjects Switching to the Tobacco Heating System 2.2 (THS 2.2) or Smoking Abstinence, Compared to Continuing to Use Conventional Cigarettes, for 5 Days in Confinement.', 'orgStudyIdInfo': {'id': 'ZRHR-REXC-03-EU'}, 'secondaryIdInfos': [{'id': 'ZRHR-REXC-03-EU', 'type': 'OTHER', 'domain': 'Philip Morris Products S.A.'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Tobacco Heating System (THS 2.2)', 'description': 'Ad libitum use of THS 2.2 for 5 days in confinement', 'interventionNames': ['Other: Tobacco Heating System (THS 2.2)']}, {'type': 'SHAM_COMPARATOR', 'label': 'Smoking abstinence (SA)', 'description': 'Abstinence from smoking for 5 days in confinement', 'interventionNames': ['Other: Smoking abstinence (SA)']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Conventional cigarette (CC)', 'description': "Ad libitum use of subject's own preferred brand of CC for 5 days in confinement", 'interventionNames': ['Other: Conventional cigarette (CC)']}], 'interventions': [{'name': 'Tobacco Heating System (THS 2.2)', 'type': 'OTHER', 'description': 'THS 2.2 ad libitum for 5 days in confinement', 'armGroupLabels': ['Tobacco Heating System (THS 2.2)']}, {'name': 'Smoking abstinence (SA)', 'type': 'OTHER', 'description': 'SA for 5 days in confinement', 'armGroupLabels': ['Smoking abstinence (SA)']}, {'name': 'Conventional cigarette (CC)', 'type': 'OTHER', 'description': "Subject's own preferred brand of CC ad libitum for 5 days in confinement", 'armGroupLabels': ['Conventional cigarette (CC)']}]}, 'contactsLocationsModule': {'locations': [{'zip': '05-830', 'city': 'Kajetany', 'country': 'Poland', 'facility': 'BioVirtus Research Site Sp. z o.o.', 'geoPoint': {'lat': 52.0927, 'lon': 20.8141}}], 'overallOfficials': [{'name': 'Christelle Haziza, PhD', 'role': 'STUDY_CHAIR', 'affiliation': 'Philip Morris Products S.A.'}, {'name': 'Katarzyna Jarus-Dziedzic, MD PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'BioVirtus Research Site'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Philip Morris Products S.A.', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}