Ignite Creation Date:
2025-12-25 @ 2:49 AM
Ignite Modification Date:
2026-03-03 @ 4:15 PM
Study NCT ID:
NCT00560833
Status:
COMPLETED
Last Update Posted:
2019-04-02
First Post:
2007-11-16
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Dose-Finding Safety and Efficacy Trial of Org50081 (Esmirtazapine) in the Treatment of Vasomotor Symptoms (46101/P06459/MK-8265-012)
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'removedCountries': ['United States']}, 'interventionBrowseModule': {'meshes': [{'id': 'D000078785', 'term': 'Mirtazapine'}], 'ancestors': [{'id': 'D003984', 'term': 'Dibenzazepines'}, {'id': 'D006575', 'term': 'Heterocyclic Compounds, 3-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'ClinicalTrialsDisclosure@merck.com', 'phone': '1-800-672-6372', 'title': 'Senior Vice President, Global Clinical Development', 'organization': 'Merck Sharp & Dohme Corp'}, 'certainAgreement': {'restrictionType': 'LTE60', 'piSponsorEmployee': False, 'restrictiveAgreement': True}}, 'adverseEventsModule': {'timeFrame': 'Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.', 'eventGroups': [{'id': 'EG000', 'title': 'Placebo', 'description': 'Participants receive placebo, encapsulated tablets, orally (PO), once daily (QD) for up to 12 weeks', 'otherNumAtRisk': 317, 'otherNumAffected': 128, 'seriousNumAtRisk': 317, 'seriousNumAffected': 2}, {'id': 'EG001', 'title': 'Esmirtazapine 2.25 mg', 'description': 'Participants receive esmirtazapine 2.25 mg, encapsulated tablets, PO, QD for up to 12 weeks', 'otherNumAtRisk': 154, 'otherNumAffected': 93, 'seriousNumAtRisk': 154, 'seriousNumAffected': 1}, {'id': 'EG002', 'title': 'Esmirtazapine 4.5 mg', 'description': 'Participants receive esmirtazapine 4.5 mg, encapsulated tablets, PO, QD for up to 12 weeks', 'otherNumAtRisk': 160, 'otherNumAffected': 99, 'seriousNumAtRisk': 160, 'seriousNumAffected': 3}, {'id': 'EG003', 'title': 'Esmirtazapine 9 mg', 'description': 'Participants receive esmirtazapine 9 mg, encapsulated tablets, PO, QD for up to 12 weeks', 'otherNumAtRisk': 155, 'otherNumAffected': 102, 'seriousNumAtRisk': 155, 'seriousNumAffected': 2}, {'id': 'EG004', 'title': 'Esmirtazapine 18mg', 'description': 'Participants receive esmirtazapine 18 mg, encapsulated tablets, PO, QD for up to 12 weeks', 'otherNumAtRisk': 155, 'otherNumAffected': 123, 'seriousNumAtRisk': 155, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'Abdominal distension', 'stats': [{'groupId': 'EG000', 'numAtRisk': 317, 'numEvents': 8, 'numAffected': 8}, {'groupId': 'EG001', 'numAtRisk': 154, 'numEvents': 5, 'numAffected': 5}, {'groupId': 'EG002', 'numAtRisk': 160, 'numEvents': 12, 'numAffected': 8}, {'groupId': 'EG003', 'numAtRisk': 155, 'numEvents': 4, 'numAffected': 3}, {'groupId': 'EG004', 'numAtRisk': 155, 'numEvents': 10, 'numAffected': 9}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 9.1'}, {'term': 'Dry mouth', 'stats': [{'groupId': 'EG000', 'numAtRisk': 317, 'numEvents': 6, 'numAffected': 6}, {'groupId': 'EG001', 'numAtRisk': 154, 'numEvents': 9, 'numAffected': 9}, {'groupId': 'EG002', 'numAtRisk': 160, 'numEvents': 7, 'numAffected': 7}, {'groupId': 'EG003', 'numAtRisk': 155, 'numEvents': 21, 'numAffected': 18}, {'groupId': 'EG004', 'numAtRisk': 155, 'numEvents': 23, 'numAffected': 22}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 9.1'}, {'term': 'Nausea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 317, 'numEvents': 19, 'numAffected': 17}, {'groupId': 'EG001', 'numAtRisk': 154, 'numEvents': 5, 'numAffected': 5}, {'groupId': 'EG002', 'numAtRisk': 160, 'numEvents': 5, 'numAffected': 5}, {'groupId': 'EG003', 'numAtRisk': 155, 'numEvents': 7, 'numAffected': 6}, {'groupId': 'EG004', 'numAtRisk': 155, 'numEvents': 5, 'numAffected': 5}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 9.1'}, {'term': 'Fatigue', 'stats': [{'groupId': 'EG000', 'numAtRisk': 317, 'numEvents': 12, 'numAffected': 11}, {'groupId': 'EG001', 'numAtRisk': 154, 'numEvents': 24, 'numAffected': 19}, {'groupId': 'EG002', 'numAtRisk': 160, 'numEvents': 20, 'numAffected': 19}, {'groupId': 'EG003', 'numAtRisk': 155, 'numEvents': 22, 'numAffected': 19}, {'groupId': 'EG004', 'numAtRisk': 155, 'numEvents': 23, 'numAffected': 20}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 9.1'}, {'term': 'Oedema peripheral', 'stats': [{'groupId': 'EG000', 'numAtRisk': 317, 'numEvents': 10, 'numAffected': 8}, {'groupId': 'EG001', 'numAtRisk': 154, 'numEvents': 14, 'numAffected': 9}, {'groupId': 'EG002', 'numAtRisk': 160, 'numEvents': 11, 'numAffected': 11}, {'groupId': 'EG003', 'numAtRisk': 155, 'numEvents': 10, 'numAffected': 7}, {'groupId': 'EG004', 'numAtRisk': 155, 'numEvents': 9, 'numAffected': 9}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 9.1'}, {'term': 'Nasopharyngitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 317, 'numEvents': 16, 'numAffected': 15}, {'groupId': 'EG001', 'numAtRisk': 154, 'numEvents': 10, 'numAffected': 10}, {'groupId': 'EG002', 'numAtRisk': 160, 'numEvents': 11, 'numAffected': 11}, {'groupId': 'EG003', 'numAtRisk': 155, 'numEvents': 12, 'numAffected': 11}, {'groupId': 'EG004', 'numAtRisk': 155, 'numEvents': 11, 'numAffected': 10}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 9.1'}, {'term': 'Weight increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 317, 'numEvents': 18, 'numAffected': 18}, {'groupId': 'EG001', 'numAtRisk': 154, 'numEvents': 25, 'numAffected': 25}, {'groupId': 'EG002', 'numAtRisk': 160, 'numEvents': 24, 'numAffected': 24}, {'groupId': 'EG003', 'numAtRisk': 155, 'numEvents': 33, 'numAffected': 32}, {'groupId': 'EG004', 'numAtRisk': 155, 'numEvents': 46, 'numAffected': 45}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 9.1'}, {'term': 'Increased appetite', 'stats': [{'groupId': 'EG000', 'numAtRisk': 317, 'numEvents': 14, 'numAffected': 13}, {'groupId': 'EG001', 'numAtRisk': 154, 'numEvents': 12, 'numAffected': 12}, {'groupId': 'EG002', 'numAtRisk': 160, 'numEvents': 21, 'numAffected': 21}, {'groupId': 'EG003', 'numAtRisk': 155, 'numEvents': 16, 'numAffected': 14}, {'groupId': 'EG004', 'numAtRisk': 155, 'numEvents': 29, 'numAffected': 28}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 9.1'}, {'term': 'Arthralgia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 317, 'numEvents': 17, 'numAffected': 16}, {'groupId': 'EG001', 'numAtRisk': 154, 'numEvents': 5, 'numAffected': 5}, {'groupId': 'EG002', 'numAtRisk': 160, 'numEvents': 10, 'numAffected': 9}, {'groupId': 'EG003', 'numAtRisk': 155, 'numEvents': 16, 'numAffected': 14}, {'groupId': 'EG004', 'numAtRisk': 155, 'numEvents': 5, 'numAffected': 5}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 9.1'}, {'term': 'Dizziness', 'stats': [{'groupId': 'EG000', 'numAtRisk': 317, 'numEvents': 15, 'numAffected': 12}, {'groupId': 'EG001', 'numAtRisk': 154, 'numEvents': 10, 'numAffected': 6}, {'groupId': 'EG002', 'numAtRisk': 160, 'numEvents': 15, 'numAffected': 12}, {'groupId': 'EG003', 'numAtRisk': 155, 'numEvents': 7, 'numAffected': 6}, {'groupId': 'EG004', 'numAtRisk': 155, 'numEvents': 18, 'numAffected': 14}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 9.1'}, {'term': 'Headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 317, 'numEvents': 74, 'numAffected': 54}, {'groupId': 'EG001', 'numAtRisk': 154, 'numEvents': 11, 'numAffected': 11}, {'groupId': 'EG002', 'numAtRisk': 160, 'numEvents': 18, 'numAffected': 13}, {'groupId': 'EG003', 'numAtRisk': 155, 'numEvents': 16, 'numAffected': 14}, {'groupId': 'EG004', 'numAtRisk': 155, 'numEvents': 26, 'numAffected': 19}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 9.1'}, {'term': 'Lethargy', 'stats': [{'groupId': 'EG000', 'numAtRisk': 317, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 154, 'numEvents': 7, 'numAffected': 7}, {'groupId': 'EG002', 'numAtRisk': 160, 'numEvents': 17, 'numAffected': 14}, {'groupId': 'EG003', 'numAtRisk': 155, 'numEvents': 6, 'numAffected': 5}, {'groupId': 'EG004', 'numAtRisk': 155, 'numEvents': 4, 'numAffected': 4}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 9.1'}, {'term': 'Somnolence', 'stats': [{'groupId': 'EG000', 'numAtRisk': 317, 'numEvents': 20, 'numAffected': 19}, {'groupId': 'EG001', 'numAtRisk': 154, 'numEvents': 43, 'numAffected': 33}, {'groupId': 'EG002', 'numAtRisk': 160, 'numEvents': 49, 'numAffected': 37}, {'groupId': 'EG003', 'numAtRisk': 155, 'numEvents': 54, 'numAffected': 44}, {'groupId': 'EG004', 'numAtRisk': 155, 'numEvents': 63, 'numAffected': 50}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 9.1'}, {'term': 'Insomnia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 317, 'numEvents': 18, 'numAffected': 13}, {'groupId': 'EG001', 'numAtRisk': 154, 'numEvents': 6, 'numAffected': 6}, {'groupId': 'EG002', 'numAtRisk': 160, 'numEvents': 10, 'numAffected': 10}, {'groupId': 'EG003', 'numAtRisk': 155, 'numEvents': 6, 'numAffected': 6}, {'groupId': 'EG004', 'numAtRisk': 155, 'numEvents': 14, 'numAffected': 13}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 9.1'}], 'seriousEvents': [{'term': 'Appendicitis perforated', 'stats': [{'groupId': 'EG000', 'numAtRisk': 317, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 154, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 160, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 155, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 155, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 9.1'}, {'term': 'Large intestine perforation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 317, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 154, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 160, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG003', 'numAtRisk': 155, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 155, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 9.1'}, {'term': 'Oedema peripheral', 'stats': [{'groupId': 'EG000', 'numAtRisk': 317, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 154, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 160, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 155, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG004', 'numAtRisk': 155, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 9.1'}, {'term': 'Pyelonephritis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 317, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 154, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 160, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 155, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 155, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 9.1'}, {'term': 'Diabetic ketoacidosis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 317, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 154, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 160, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG003', 'numAtRisk': 155, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 155, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 9.1'}, {'term': 'Conversion disorder', 'stats': [{'groupId': 'EG000', 'numAtRisk': 317, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 154, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 160, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG003', 'numAtRisk': 155, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 155, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 9.1'}, {'term': 'Vaginal lesion', 'stats': [{'groupId': 'EG000', 'numAtRisk': 317, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 154, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 160, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 155, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG004', 'numAtRisk': 155, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Reproductive system and breast disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 9.1'}, {'term': 'Scar', 'stats': [{'groupId': 'EG000', 'numAtRisk': 317, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 154, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 160, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 155, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 155, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 9.1'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Change From Baseline in Average Daily Frequency of Vasomotor Symptoms (Frequency Score A) at Week 4', 'denoms': [{'units': 'Participants', 'counts': [{'value': '294', 'groupId': 'OG000'}, {'value': '138', 'groupId': 'OG001'}, {'value': '139', 'groupId': 'OG002'}, {'value': '137', 'groupId': 'OG003'}, {'value': '138', 'groupId': 'OG004'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Participants receive placebo, encapsulated tablets, orally (PO), once daily (QD) for up to 12 weeks'}, {'id': 'OG001', 'title': 'Esmirtazapine 2.25 mg', 'description': 'Participants receive esmirtazapine 2.25 mg, encapsulated tablets, PO, QD for up to 12 weeks'}, {'id': 'OG002', 'title': 'Esmirtazapine 4.5 mg', 'description': 'Participants receive esmirtazapine 4.5 mg, encapsulated tablets, PO, QD for up to 12 weeks'}, {'id': 'OG003', 'title': 'Esmirtazapine 9 mg', 'description': 'Participants receive esmirtazapine 9 mg, encapsulated tablets, PO, QD for up to 12 weeks'}, {'id': 'OG004', 'title': 'Esmirtazapine 18mg', 'description': 'Participants receive esmirtazapine 18 mg, encapsulated tablets, PO, QD for up to 12 weeks'}], 'classes': [{'categories': [{'measurements': [{'value': '-3.9', 'spread': '4.2', 'groupId': 'OG000'}, {'value': '-5.6', 'spread': '3.8', 'groupId': 'OG001'}, {'value': '-6.0', 'spread': '3.6', 'groupId': 'OG002'}, {'value': '-6.0', 'spread': '4.0', 'groupId': 'OG003'}, {'value': '-6.0', 'spread': '4.4', 'groupId': 'OG004'}]}]}], 'analyses': [{'pValue': '<0.01', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-1.4', 'ciLowerLimit': '-2.3', 'ciUpperLimit': '-0.4', 'pValueComment': 'Dunnet-adjusted from ANCOVA with factors for treatment and (pooled) center and a covariate for baseline value.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER'}, {'pValue': '<0.01', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-2.2', 'ciLowerLimit': '-3.1', 'ciUpperLimit': '-1.2', 'pValueComment': 'Dunnet-adjusted from ANCOVA with factors for treatment and (pooled) center and a covariate for baseline value.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER'}, {'pValue': '<0.01', 'groupIds': ['OG000', 'OG003'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-1.9', 'ciLowerLimit': '-2.9', 'ciUpperLimit': '-1.0', 'pValueComment': 'Dunnet-adjusted from ANCOVA with factors for treatment and (pooled) center and a covariate for baseline value.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER'}, {'pValue': '<0.01', 'groupIds': ['OG000', 'OG004'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-1.9', 'ciLowerLimit': '-2.9', 'ciUpperLimit': '-1.0', 'pValueComment': 'Dunnet-adjusted from ANCOVA with factors for treatment and (pooled) center and a covariate for baseline value.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER'}], 'paramType': 'MEAN', 'timeFrame': 'Baseline and Week 4', 'description': 'Participants recorded the frequency of vasomotor symptoms (hot flushes) on an electronic diary card (LogPad®) on a daily basis during screening and treatment. Frequency score A was based on the number of moderate hot flushes + the number of severe hot flushes in one day. Baseline average was derived from, at most, 7 completely observed pre-treatment days. Weekly averages during treatment were calculated if at least 4 days with non-missing data were completely observed; if less than 4 days were completely observed, the averages of the previous week were carried forward (last observation carried forward, or LOCF). If the number of days observed in Week 1 were not sufficient, baseline values were carried forward.', 'unitOfMeasure': 'Number of events', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'The intent-to-treat (ITT) population, defined as all randomized particpants having at least one recorded pre-baseline value of the number of moderate and severe hot flushes.'}, {'type': 'SECONDARY', 'title': "Change From Baseline in Vasomotor Symptoms Score Per Women's Health Questionnaire (WHQ) at Week 12", 'denoms': [{'units': 'Participants', 'counts': [{'value': '282', 'groupId': 'OG000'}, {'value': '136', 'groupId': 'OG001'}, {'value': '135', 'groupId': 'OG002'}, {'value': '133', 'groupId': 'OG003'}, {'value': '136', 'groupId': 'OG004'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Participants receive placebo, encapsulated tablets, orally (PO), once daily (QD) for up to 12 weeks'}, {'id': 'OG001', 'title': 'Esmirtazapine 2.25 mg', 'description': 'Participants receive esmirtazapine 2.25 mg, encapsulated tablets, PO, QD for up to 12 weeks'}, {'id': 'OG002', 'title': 'Esmirtazapine 4.5 mg', 'description': 'Participants receive esmirtazapine 4.5 mg, encapsulated tablets, PO, QD for up to 12 weeks'}, {'id': 'OG003', 'title': 'Esmirtazapine 9 mg', 'description': 'Participants receive esmirtazapine 9 mg, encapsulated tablets, PO, QD for up to 12 weeks'}, {'id': 'OG004', 'title': 'Esmirtazapine 18mg', 'description': 'Participants receive esmirtazapine 18 mg, encapsulated tablets, PO, QD for up to 12 weeks'}], 'classes': [{'title': 'Baseline', 'categories': [{'measurements': [{'value': '0.984', 'spread': '0.088', 'groupId': 'OG000'}, {'value': '0.993', 'spread': '0.060', 'groupId': 'OG001'}, {'value': '0.985', 'spread': '0.085', 'groupId': 'OG002'}, {'value': '0.981', 'spread': '0.114', 'groupId': 'OG003'}, {'value': '0.985', 'spread': '0.085', 'groupId': 'OG004'}]}]}, {'title': 'Change from baseline', 'categories': [{'measurements': [{'value': '-0.151', 'spread': '0.329', 'groupId': 'OG000'}, {'value': '-0.235', 'spread': '0.355', 'groupId': 'OG001'}, {'value': '-0.256', 'spread': '0.355', 'groupId': 'OG002'}, {'value': '-0.256', 'spread': '0.372', 'groupId': 'OG003'}, {'value': '-0.246', 'spread': '0.385', 'groupId': 'OG004'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Baseline and Week 12', 'description': "The WHQ is a 36-item, user-friendly, and rapid way of assessing nine domains of physical and emotional health for mid-aged women. Participants self-administered the WHQ questionnaire; scoring is based on a 4-point scale as follows: 'Yes definitely=1', 'Yes sometimes=2', 'No not much=3' and 'No not at all=4'. Each score is transformed to a value '1' for scores '1' and '2' and to a value '0' for scores '3' and '4'. Vasomotor symptoms encompass Items 19 and 27 of the 36 total items. The transformed sums of items 19+27 are divided by 2 to get the score; therefore, the domain ranges from 0 to 1, where lower values are better.", 'unitOfMeasure': 'Score on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'All participants receiving study drug with diary compliance adequate for this measure.'}, {'type': 'PRIMARY', 'title': 'Change From Baseline in Average Daily Frequency of Vasomotor Symptoms (Frequency Score A) at Week 12', 'denoms': [{'units': 'Participants', 'counts': [{'value': '294', 'groupId': 'OG000'}, {'value': '138', 'groupId': 'OG001'}, {'value': '139', 'groupId': 'OG002'}, {'value': '137', 'groupId': 'OG003'}, {'value': '138', 'groupId': 'OG004'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Participants receive placebo, encapsulated tablets, orally (PO), once daily (QD) for up to 12 weeks'}, {'id': 'OG001', 'title': 'Esmirtazapine 2.25 mg', 'description': 'Participants receive esmirtazapine 2.25 mg, encapsulated tablets, PO, QD for up to 12 weeks'}, {'id': 'OG002', 'title': 'Esmirtazapine 4.5 mg', 'description': 'Participants receive esmirtazapine 4.5 mg, encapsulated tablets, PO, QD for up to 12 weeks'}, {'id': 'OG003', 'title': 'Esmirtazapine 9 mg', 'description': 'Participants receive esmirtazapine 9 mg, encapsulated tablets, PO, QD for up to 12 weeks'}, {'id': 'OG004', 'title': 'Esmirtazapine 18mg', 'description': 'Participants receive esmirtazapine 18 mg, encapsulated tablets, PO, QD for up to 12 weeks'}], 'classes': [{'categories': [{'measurements': [{'value': '-4.9', 'spread': '4.8', 'groupId': 'OG000'}, {'value': '-6.2', 'spread': '5.1', 'groupId': 'OG001'}, {'value': '-6.7', 'spread': '3.9', 'groupId': 'OG002'}, {'value': '-6.9', 'spread': '4.4', 'groupId': 'OG003'}, {'value': '-6.5', 'spread': '4.4', 'groupId': 'OG004'}]}]}], 'analyses': [{'pValue': '0.06', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-1.0', 'ciLowerLimit': '-2.0', 'ciUpperLimit': '0.0', 'pValueComment': 'Dunnet-adjusted from ANCOVA with factors for treatment and (pooled) center and a covariate for baseline value.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER'}, {'pValue': '<0.01', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-2.0', 'ciLowerLimit': '-3.0', 'ciUpperLimit': '-0.9', 'pValueComment': 'Dunnet-adjusted from ANCOVA with factors for treatment and (pooled) center and a covariate for baseline value.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER'}, {'pValue': '<0.01', 'groupIds': ['OG000', 'OG003'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-1.9', 'ciLowerLimit': '-2.9', 'ciUpperLimit': '-0.9', 'pValueComment': 'Dunnet-adjusted from ANCOVA with factors for treatment and (pooled) center and a covariate for baseline value.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER'}, {'pValue': '<0.01', 'groupIds': ['OG000', 'OG004'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-1.5', 'ciLowerLimit': '-2.6', 'ciUpperLimit': '-0.5', 'pValueComment': 'Dunnet-adjusted from ANCOVA with factors for treatment and (pooled) center and a covariate for baseline value.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER'}], 'paramType': 'MEAN', 'timeFrame': 'Baseline and Week 12', 'description': 'Participants recorded the frequency of vasomotor symptoms (hot flushes) on a LogPad on a daily basis during screening and treatment. Frequency score A was based on the number of moderate hot flushes + the number of severe hot flushes in one day. Baseline average was derived from, at most, 7 completely observed pre-treatment days. Weekly averages during treatment were calculated if at least 4 days with non-missing data were completely observed; if less than 4 days were completely observed, the averages of the previous week were carried forward (last observation carried forward, or LOCF). If the number of days observed in Week 1 were not sufficient, baseline values were carried forward.', 'unitOfMeasure': 'number of events', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'The ITT population, defined as all randomized particpants having at least one recorded pre-baseline value of the number of moderate and severe hot flushes.'}, {'type': 'PRIMARY', 'title': 'Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) at Week 4', 'denoms': [{'units': 'Participants', 'counts': [{'value': '294', 'groupId': 'OG000'}, {'value': '138', 'groupId': 'OG001'}, {'value': '139', 'groupId': 'OG002'}, {'value': '137', 'groupId': 'OG003'}, {'value': '138', 'groupId': 'OG004'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Participants receive placebo, encapsulated tablets, orally (PO), once daily (QD) for up to 12 weeks'}, {'id': 'OG001', 'title': 'Esmirtazapine 2.25 mg', 'description': 'Participants receive esmirtazapine 2.25 mg, encapsulated tablets, PO, QD for up to 12 weeks'}, {'id': 'OG002', 'title': 'Esmirtazapine 4.5 mg', 'description': 'Participants receive esmirtazapine 4.5 mg, encapsulated tablets, PO, QD for up to 12 weeks'}, {'id': 'OG003', 'title': 'Esmirtazapine 9 mg', 'description': 'Participants receive esmirtazapine 9 mg, encapsulated tablets, PO, QD for up to 12 weeks'}, {'id': 'OG004', 'title': 'Esmirtazapine 18mg', 'description': 'Participants receive esmirtazapine 18 mg, encapsulated tablets, PO, QD for up to 12 weeks'}], 'classes': [{'categories': [{'measurements': [{'value': '-0.09', 'spread': '0.23', 'groupId': 'OG000'}, {'value': '-0.11', 'spread': '0.22', 'groupId': 'OG001'}, {'value': '-0.15', 'spread': '0.25', 'groupId': 'OG002'}, {'value': '-0.16', 'spread': '0.24', 'groupId': 'OG003'}, {'value': '-0.15', 'spread': '0.24', 'groupId': 'OG004'}]}]}], 'analyses': [{'pValue': '0.62', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.03', 'ciLowerLimit': '-0.09', 'ciUpperLimit': '0.03', 'pValueComment': 'Dunnet-adjusted from ANCOVA with factors for treatment and (pooled) center and a covariate for baseline value.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER'}, {'pValue': '0.02', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.06', 'ciLowerLimit': '-0.12', 'ciUpperLimit': '-0.01', 'pValueComment': 'Dunnet-adjusted from ANCOVA with factors for treatment and (pooled) center and a covariate for baseline value.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER'}, {'pValue': '0.01', 'groupIds': ['OG000', 'OG003'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.07', 'ciLowerLimit': '-0.13', 'ciUpperLimit': '-0.01', 'pValueComment': 'Dunnet-adjusted from ANCOVA with factors for treatment and (pooled) center and a covariate for baseline value.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER'}, {'pValue': '0.02', 'groupIds': ['OG000', 'OG004'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.06', 'ciLowerLimit': '-0.12', 'ciUpperLimit': '-0.01', 'pValueComment': 'Dunnet-adjusted from ANCOVA with factors for treatment and (pooled) center and a covariate for baseline value.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER'}], 'paramType': 'MEAN', 'timeFrame': 'Baseline and Week 4', 'description': "Participants recorded the severity of hot flushes on a LogPad on a daily basis during screening and treatment. The severity of hot flushes was defined as: mild (sensation of heat without sweating); moderate (sensation of heat with sweating, able to continue activity); and severe (sensation of heat with sweating, causing cessation of activity). Severity score A was calculated as the number of moderate hot flushes x 2 + the number of severe hot flushes x 3, divided by the total number of moderate and severe hot flushes. If no hot flushes were experienced, this was to be recorded as 'no sensation of heat'. Baseline values were based on, at most, 7 completely observed pre-treatment days. If less than 4 days were completely observed during treatment, the averages of the previous week were carried forward (last observation carried forward, or LOCF). If the number of days observed in Week 1 were not sufficient, baseline values were carried forward.", 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'The ITT population, defined as all randomized particpants having at least one recorded pre-baseline value of the number of moderate and severe hot flushes.'}, {'type': 'PRIMARY', 'title': 'Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) at Week 12', 'denoms': [{'units': 'Participants', 'counts': [{'value': '294', 'groupId': 'OG000'}, {'value': '138', 'groupId': 'OG001'}, {'value': '139', 'groupId': 'OG002'}, {'value': '137', 'groupId': 'OG003'}, {'value': '138', 'groupId': 'OG004'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Participants receive placebo, encapsulated tablets, orally (PO), once daily (QD) for up to 12 weeks'}, {'id': 'OG001', 'title': 'Esmirtazapine 2.25 mg', 'description': 'Participants receive esmirtazapine 2.25 mg, encapsulated tablets, PO, QD for up to 12 weeks'}, {'id': 'OG002', 'title': 'Esmirtazapine 4.5 mg', 'description': 'Participants receive esmirtazapine 4.5 mg, encapsulated tablets, PO, QD for up to 12 weeks'}, {'id': 'OG003', 'title': 'Esmirtazapine 9 mg', 'description': 'Participants receive esmirtazapine 9 mg, encapsulated tablets, PO, QD for up to 12 weeks'}, {'id': 'OG004', 'title': 'Esmirtazapine 18mg', 'description': 'Participants receive esmirtazapine 18 mg, encapsulated tablets, PO, QD for up to 12 weeks'}], 'classes': [{'categories': [{'measurements': [{'value': '-0.12', 'spread': '0.28', 'groupId': 'OG000'}, {'value': '-0.10', 'spread': '0.27', 'groupId': 'OG001'}, {'value': '-0.15', 'spread': '0.29', 'groupId': 'OG002'}, {'value': '-0.18', 'spread': '0.26', 'groupId': 'OG003'}, {'value': '-0.17', 'spread': '0.26', 'groupId': 'OG004'}]}]}], 'analyses': [{'pValue': '1.0', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.01', 'ciLowerLimit': '-0.06', 'ciUpperLimit': '0.07', 'pValueComment': 'Dunnet-adjusted from ANCOVA with factors for treatment and (pooled) center and a covariate for baseline value.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER'}, {'pValue': '0.72', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.03', 'ciLowerLimit': '-0.09', 'ciUpperLimit': '0.04', 'pValueComment': 'Dunnet-adjusted from ANCOVA with factors for treatment and (pooled) center and a covariate for baseline value.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER'}, {'pValue': '0.13', 'groupIds': ['OG000', 'OG003'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.06', 'ciLowerLimit': '-0.12', 'ciUpperLimit': '0.01', 'pValueComment': 'Dunnet-adjusted from ANCOVA with factors for treatment and (pooled) center and a covariate for baseline value.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER'}, {'pValue': '0.15', 'groupIds': ['OG000', 'OG004'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.05', 'ciLowerLimit': '-0.12', 'ciUpperLimit': '0.01', 'pValueComment': 'Dunnet-adjusted from ANCOVA with factors for treatment and (pooled) center and a covariate for baseline value.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER'}], 'paramType': 'MEAN', 'timeFrame': 'Baseline and Week 12', 'description': "Participants recorded the severity of hot flushes on a LogPad on a daily basis during screening and treatment. The severity of hot flushes was defined as: mild (sensation of heat without sweating); moderate (sensation of heat with sweating, able to continue activity); and severe (sensation of heat with sweating, causing cessation of activity). Severity score A was calculated as the number of moderate hot flushes x 2 + the number of severe hot flushes x 3, divided by the total number of moderate and severe hot flushes. If no hot flushes were experienced, this was to be recorded as 'no sensation of heat'. Baseline values were based on, at most, 7 completely observed pre-treatment days. If less than 4 days were completely observed during treatment, the averages of the previous week were carried forward (last observation carried forward, or LOCF). If the number of days observed in Week 1 were not sufficient, baseline values were carried forward.", 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'The ITT population, defined as all randomized particpants having at least one recorded pre-baseline value of the number of moderate and severe hot flushes.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Placebo', 'description': 'Participants receive placebo, encapsulated tablets, orally (PO), once daily (QD) for up to 12 weeks'}, {'id': 'FG001', 'title': 'Esmirtazapine 2.25 mg', 'description': 'Participants receive esmirtazapine 2.25 mg, encapsulated tablets, PO, QD for up to 12 weeks'}, {'id': 'FG002', 'title': 'Esmirtazapine 4.5 mg', 'description': 'Participants receive esmirtazapine 4.5 mg, encapsulated tablets, PO, QD for up to 12 weeks'}, {'id': 'FG003', 'title': 'Esmirtazapine 9 mg', 'description': 'Participants receive esmirtazapine 9 mg, encapsulated tablets, PO, QD for up to 12 weeks'}, {'id': 'FG004', 'title': 'Esmirtazapine 18mg', 'description': 'Participants receive esmirtazapine 18 mg, encapsulated tablets, PO, QD for up to 12 weeks'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '317'}, {'groupId': 'FG001', 'numSubjects': '155'}, {'groupId': 'FG002', 'numSubjects': '160'}, {'groupId': 'FG003', 'numSubjects': '155'}, {'groupId': 'FG004', 'numSubjects': '156'}]}, {'type': 'Treated', 'achievements': [{'comment': 'One participant was not randomized but was treated with placebo', 'groupId': 'FG000', 'numSubjects': '317'}, {'comment': 'One participant was randomized but not treated', 'groupId': 'FG001', 'numSubjects': '154'}, {'groupId': 'FG002', 'numSubjects': '160'}, {'groupId': 'FG003', 'numSubjects': '155'}, {'comment': 'One participant was randomized but not treated', 'groupId': 'FG004', 'numSubjects': '155'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '273'}, {'groupId': 'FG001', 'numSubjects': '129'}, {'groupId': 'FG002', 'numSubjects': '121'}, {'groupId': 'FG003', 'numSubjects': '124'}, {'groupId': 'FG004', 'numSubjects': '114'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '44'}, {'groupId': 'FG001', 'numSubjects': '26'}, {'groupId': 'FG002', 'numSubjects': '39'}, {'groupId': 'FG003', 'numSubjects': '31'}, {'groupId': 'FG004', 'numSubjects': '42'}]}], 'dropWithdraws': [{'type': 'Adverse Event', 'reasons': [{'groupId': 'FG000', 'numSubjects': '16'}, {'groupId': 'FG001', 'numSubjects': '10'}, {'groupId': 'FG002', 'numSubjects': '25'}, {'groupId': 'FG003', 'numSubjects': '23'}, {'groupId': 'FG004', 'numSubjects': '35'}]}, {'type': 'Lost to Follow-up', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '1'}, {'groupId': 'FG003', 'numSubjects': '0'}, {'groupId': 'FG004', 'numSubjects': '0'}]}, {'type': 'Lack of Efficacy', 'reasons': [{'groupId': 'FG000', 'numSubjects': '22'}, {'groupId': 'FG001', 'numSubjects': '9'}, {'groupId': 'FG002', 'numSubjects': '6'}, {'groupId': 'FG003', 'numSubjects': '4'}, {'groupId': 'FG004', 'numSubjects': '4'}]}, {'type': 'Participant uncooperative', 'reasons': [{'groupId': 'FG000', 'numSubjects': '5'}, {'groupId': 'FG001', 'numSubjects': '5'}, {'groupId': 'FG002', 'numSubjects': '4'}, {'groupId': 'FG003', 'numSubjects': '4'}, {'groupId': 'FG004', 'numSubjects': '2'}]}, {'type': 'Other', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '1'}, {'groupId': 'FG002', 'numSubjects': '3'}, {'groupId': 'FG003', 'numSubjects': '0'}, {'groupId': 'FG004', 'numSubjects': '0'}]}, {'type': 'Never received drug', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '1'}, {'groupId': 'FG002', 'numSubjects': '0'}, {'groupId': 'FG003', 'numSubjects': '0'}, {'groupId': 'FG004', 'numSubjects': '1'}]}]}], 'preAssignmentDetails': '942 participants were randomly assigned to treatment in this study, however, one screened participant was given placebo treatment without a randomization assignment. This participant is included in the study placebo population.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '317', 'groupId': 'BG000'}, {'value': '154', 'groupId': 'BG001'}, {'value': '160', 'groupId': 'BG002'}, {'value': '155', 'groupId': 'BG003'}, {'value': '155', 'groupId': 'BG004'}, {'value': '941', 'groupId': 'BG005'}]}], 'groups': [{'id': 'BG000', 'title': 'Placebo', 'description': 'Participants receive placebo, encapsulated tablets, orally (PO), once daily (QD) for up to 12 weeks'}, {'id': 'BG001', 'title': 'Esmirtazapine 2.25 mg', 'description': 'Participants receive esmirtazapine 2.25 mg, encapsulated tablets, PO, QD for up to 12 weeks'}, {'id': 'BG002', 'title': 'Esmirtazapine 4.5 mg', 'description': 'Participants receive esmirtazapine 4.5 mg, encapsulated tablets, PO, QD for up to 12 weeks'}, {'id': 'BG003', 'title': 'Esmirtazapine 9 mg', 'description': 'Participants receive esmirtazapine 9 mg, encapsulated tablets, PO, QD for up to 12 weeks'}, {'id': 'BG004', 'title': 'Esmertazapine 18 mg', 'description': 'Participants receive esmertazapine 18 mg, encapsulated tablet, PO, QD for up to 12 weeks'}, {'id': 'BG005', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '54.0', 'spread': '4.4', 'groupId': 'BG000'}, {'value': '53.4', 'spread': '4.4', 'groupId': 'BG001'}, {'value': '54.1', 'spread': '4.2', 'groupId': 'BG002'}, {'value': '54.9', 'spread': '4.8', 'groupId': 'BG003'}, {'value': '54.1', 'spread': '4.5', 'groupId': 'BG004'}, {'value': '54.1', 'spread': '4.4', 'groupId': 'BG005'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'Years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '317', 'groupId': 'BG000'}, {'value': '154', 'groupId': 'BG001'}, {'value': '160', 'groupId': 'BG002'}, {'value': '155', 'groupId': 'BG003'}, {'value': '155', 'groupId': 'BG004'}, {'value': '941', 'groupId': 'BG005'}]}, {'title': 'Male', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '0', 'groupId': 'BG003'}, {'value': '0', 'groupId': 'BG004'}, {'value': '0', 'groupId': 'BG005'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}], 'populationDescription': 'All participants who received any study drug (placebo or esmertazapine), whether or not randomized.'}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'DOUBLE', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 943}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2004-10-15', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2019-03', 'completionDateStruct': {'date': '2006-01-15', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2019-03-25', 'studyFirstSubmitDate': '2007-11-16', 'resultsFirstSubmitDate': '2014-05-28', 'studyFirstSubmitQcDate': '2007-11-16', 'lastUpdatePostDateStruct': {'date': '2019-04-02', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2014-05-28', 'studyFirstPostDateStruct': {'date': '2007-11-20', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2014-06-30', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2006-01-15', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Change From Baseline in Average Daily Frequency of Vasomotor Symptoms (Frequency Score A) at Week 4', 'timeFrame': 'Baseline and Week 4', 'description': 'Participants recorded the frequency of vasomotor symptoms (hot flushes) on an electronic diary card (LogPad®) on a daily basis during screening and treatment. Frequency score A was based on the number of moderate hot flushes + the number of severe hot flushes in one day. Baseline average was derived from, at most, 7 completely observed pre-treatment days. Weekly averages during treatment were calculated if at least 4 days with non-missing data were completely observed; if less than 4 days were completely observed, the averages of the previous week were carried forward (last observation carried forward, or LOCF). If the number of days observed in Week 1 were not sufficient, baseline values were carried forward.'}, {'measure': 'Change From Baseline in Average Daily Frequency of Vasomotor Symptoms (Frequency Score A) at Week 12', 'timeFrame': 'Baseline and Week 12', 'description': 'Participants recorded the frequency of vasomotor symptoms (hot flushes) on a LogPad on a daily basis during screening and treatment. Frequency score A was based on the number of moderate hot flushes + the number of severe hot flushes in one day. Baseline average was derived from, at most, 7 completely observed pre-treatment days. Weekly averages during treatment were calculated if at least 4 days with non-missing data were completely observed; if less than 4 days were completely observed, the averages of the previous week were carried forward (last observation carried forward, or LOCF). If the number of days observed in Week 1 were not sufficient, baseline values were carried forward.'}, {'measure': 'Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) at Week 4', 'timeFrame': 'Baseline and Week 4', 'description': "Participants recorded the severity of hot flushes on a LogPad on a daily basis during screening and treatment. The severity of hot flushes was defined as: mild (sensation of heat without sweating); moderate (sensation of heat with sweating, able to continue activity); and severe (sensation of heat with sweating, causing cessation of activity). Severity score A was calculated as the number of moderate hot flushes x 2 + the number of severe hot flushes x 3, divided by the total number of moderate and severe hot flushes. If no hot flushes were experienced, this was to be recorded as 'no sensation of heat'. Baseline values were based on, at most, 7 completely observed pre-treatment days. If less than 4 days were completely observed during treatment, the averages of the previous week were carried forward (last observation carried forward, or LOCF). If the number of days observed in Week 1 were not sufficient, baseline values were carried forward."}, {'measure': 'Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) at Week 12', 'timeFrame': 'Baseline and Week 12', 'description': "Participants recorded the severity of hot flushes on a LogPad on a daily basis during screening and treatment. The severity of hot flushes was defined as: mild (sensation of heat without sweating); moderate (sensation of heat with sweating, able to continue activity); and severe (sensation of heat with sweating, causing cessation of activity). Severity score A was calculated as the number of moderate hot flushes x 2 + the number of severe hot flushes x 3, divided by the total number of moderate and severe hot flushes. If no hot flushes were experienced, this was to be recorded as 'no sensation of heat'. Baseline values were based on, at most, 7 completely observed pre-treatment days. If less than 4 days were completely observed during treatment, the averages of the previous week were carried forward (last observation carried forward, or LOCF). If the number of days observed in Week 1 were not sufficient, baseline values were carried forward."}], 'secondaryOutcomes': [{'measure': "Change From Baseline in Vasomotor Symptoms Score Per Women's Health Questionnaire (WHQ) at Week 12", 'timeFrame': 'Baseline and Week 12', 'description': "The WHQ is a 36-item, user-friendly, and rapid way of assessing nine domains of physical and emotional health for mid-aged women. Participants self-administered the WHQ questionnaire; scoring is based on a 4-point scale as follows: 'Yes definitely=1', 'Yes sometimes=2', 'No not much=3' and 'No not at all=4'. Each score is transformed to a value '1' for scores '1' and '2' and to a value '0' for scores '3' and '4'. Vasomotor symptoms encompass Items 19 and 27 of the 36 total items. The transformed sums of items 19+27 are divided by 2 to get the score; therefore, the domain ranges from 0 to 1, where lower values are better."}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'conditions': ['Menopause', 'Vasomotor Symptoms']}, 'referencesModule': {'availIpds': [{'url': 'http://www.merck.com/clinical-trials/study.html?id=P06459&kw=P06459&tab=access', 'type': 'CSR Synopsis'}], 'references': [{'pmid': '30712391', 'type': 'RESULT', 'citation': 'Birkhaeuser M, Bitzer J, Braat S, Ramos Y. Esmirtazapine treatment of postmenopausal vasomotor symptoms: two randomized controlled trials. Climacteric. 2019 Jun;22(3):312-322. doi: 10.1080/13697137.2018.1561664. Epub 2019 Feb 4.'}]}, 'descriptionModule': {'briefSummary': 'The most direct treatment of vasomotor symptions (hot flushes) may be by means of 5-HT2A receptor antagonist. Mirtazapine is a potent blocker of 5-HT2A receptors and was found to be effective in reducing the number and intensity of hot flushes in preliminary trials. Also several Selective Serotonin Reuptake Inhibitors (SSRIs) and other similar compounds have been investigated to manage hot flushes, confirming the role of the serotonergic system. In the present trial, the efficacy and safety of four different doses of esmirtazapine compared to placebo was investigated in women with moderate to severe vasomotor symptoms associated with the menopause. The primary study hypothesis was that esmirtazapine would show superior efficacy to placebo.'}, 'eligibilityModule': {'sex': 'FEMALE', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '65 Years', 'minimumAge': '40 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* postmenopausal women, defined as:\n* 12 months of spontaneous amenorrhea;\n* OR 6 months of spontaneous amenorrhea with serum Follicle Stimulating Hormone\n\n(FSH) levels \\>40 mIU/mL;\n\n* OR 6 weeks post surgical bilateral oophorectomy with or without hysterectomy.\n* In case the menopausal status of a subject was unclear because of a hysterectomy, the serum FSH level had to be \\>40 mIU/mL. If the date of the last menstruation was not clear because of perimenopausal hormone use, then the subject had to have a serum FSH level \\>40 mIU/mL after completion of a washout period (see exclusion criteria below); be \\>= 40 and \\<= 65 years of age;\n* have a body mass index (BMI) \\>= 18 and \\<= 32 kg/m\\^2;\n* minimum of 7 moderate to severe hot flushes per day or 50 per week, as quantified from daily diary recordings during at least 7 days preceding randomization to trial medication;\n* able to handle the electronic diary device after training and having at least 80% compliance on complete daily diary entries during the period prior to randomization;\n* give voluntary written Informed Consent (IC) after the scope and nature of the investigation had been explained, before screening evaluations.\n\nExclusion Criteria:\n\n* history or presence of any malignancy, except non-melanoma skin cancers\n* any clinically unstable or uncontrolled renal, hepatic, endocrine,\n\nrespiratory, hematological, neurological, cardiovascular, or cerebrovascular disease that would put the subject at safety risk or mask measure of efficacy\n\n* history of seizures or epilepsy; history or presence of clinically significant depression or other psychiatric disorder which, in the opinion of the investigator, might compromise or confound the participant's participation in the trial; abnormal clinically relevant vaginal bleeding\n* any clinically relevant (opinion of investigator) abnormal finding during physical, gynecological and breast examination at screening; abnormal, clinically significant results of mammography. Mammography had to have been performed within the last 9 months prior to screening, otherwise it had to be done before inclusion into the trial. For non-US sites, if local laws or guidelines did not allow or advise such frequent mammograms, the documented local laws or guidelines were to be followed; abnormal cervical smear test results (corresponding to Pap III and higher, including Low-Grade Squamous Intraepithelial Lesion (LSIL), High-Grade Squamous Intraepithelial Lesion (HSIL), Cervical Intraepithelial Neoplasia (CIN) 1 and higher). A cervical smear had to have been performed within the last 9 months prior to screening, otherwise it had to be done before inclusion into the trial; hematological or biochemical values at screening outside the reference ranges considered clinically relevant in the opinion of the investigator\n* high blood pressure (BP) (sitting systolic BP \\>170 mmHg and/or diastolic BP \\>100 mmHg)\n* use of any drug product containing estrogens, progestins, androgens, or tibolone prior to screening (and up to and including randomization) within specified time frames"}, 'identificationModule': {'nctId': 'NCT00560833', 'briefTitle': 'Dose-Finding Safety and Efficacy Trial of Org50081 (Esmirtazapine) in the Treatment of Vasomotor Symptoms (46101/P06459/MK-8265-012)', 'organization': {'class': 'INDUSTRY', 'fullName': 'Merck Sharp & Dohme LLC'}, 'officialTitle': 'A Multicenter, Randomized, Parallel-Group, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Four Different Doses of Org 50081 in the Treatment of Moderate to Severe Vasomotor Symptoms Associated With the Menopause', 'orgStudyIdInfo': {'id': 'P06459'}, 'secondaryIdInfos': [{'id': '46101', 'type': 'OTHER', 'domain': 'Organon Study Number'}, {'id': 'MK-8265-012', 'type': 'OTHER', 'domain': 'Merck Study Number'}, {'id': '2004-000469-36', 'type': 'EUDRACT_NUMBER'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo', 'description': 'Participants receive placebo, encapsulated tablets, orally (PO), once daily (QD) for up to 12 weeks', 'interventionNames': ['Drug: Placebo']}, {'type': 'EXPERIMENTAL', 'label': 'Esmirtazapine 2.25 mg', 'description': 'Participants receive esmirtazapine 2.25 mg, encapsulated tablets, PO, QD for up to 12 weeks', 'interventionNames': ['Drug: esmirtazapine']}, {'type': 'EXPERIMENTAL', 'label': 'Esmirtazapine 4.5 mg', 'description': 'Participants receive esmirtazapine 4.5 mg, encapsulated tablets, PO, QD for up to 12 weeks', 'interventionNames': ['Drug: esmirtazapine']}, {'type': 'EXPERIMENTAL', 'label': 'Esmirtazapine 9 mg', 'description': 'Participants receive esmirtazapine 9 mg, encapsulated tablets, PO, QD for up to 12 weeks', 'interventionNames': ['Drug: esmirtazapine']}, {'type': 'EXPERIMENTAL', 'label': 'Esmirtazapine 18 mg', 'description': 'Participants receive esmirtazapine 18 mg, encapsulated tablets, PO, QD for up to 12 weeks', 'interventionNames': ['Drug: esmirtazapine']}], 'interventions': [{'name': 'esmirtazapine', 'type': 'DRUG', 'otherNames': ['Esmirtazapine maleate', 'SCH 900265', 'Org 50081'], 'armGroupLabels': ['Esmirtazapine 18 mg', 'Esmirtazapine 2.25 mg', 'Esmirtazapine 4.5 mg', 'Esmirtazapine 9 mg']}, {'name': 'Placebo', 'type': 'DRUG', 'armGroupLabels': ['Placebo']}]}, 'ipdSharingStatementModule': {'url': 'http://engagezone.msd.com/ds_documentation.php', 'ipdSharing': 'YES', 'description': 'http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Merck Sharp & Dohme LLC', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}