Ignite Creation Date:
2025-12-24 @ 11:44 PM
Ignite Modification Date:
2025-12-25 @ 9:36 PM
Study NCT ID:
NCT01375751
Status:
COMPLETED
Last Update Posted:
2022-11-15
First Post:
2011-06-16
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
Reduction of Low-Density Lipoprotein Cholesterol (LDL-C) With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder Study
Sponsor:
Organization:
Raw JSON
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The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.", 'restrictionType': 'OTHER', 'piSponsorEmployee': False, 'restrictiveAgreement': True}}, 'adverseEventsModule': {'timeFrame': '12 weeks', 'description': 'Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.', 'eventGroups': [{'id': 'EG000', 'title': 'Placebo', 'description': 'Participants received placebo subcutaneous injection once every 4 weeks for 12 weeks.', 'otherNumAtRisk': 56, 'otherNumAffected': 24, 'seriousNumAtRisk': 56, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Evolocumab 350 mg', 'description': 'Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.', 'otherNumAtRisk': 55, 'otherNumAffected': 22, 'seriousNumAtRisk': 55, 'seriousNumAffected': 0}, {'id': 'EG002', 'title': 'Evolocumab 420 mg', 'description': 'Participants received 420 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{'groupId': 'EG002', 'numAtRisk': 56, 'numAffected': 2}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 15.0'}, {'term': 'Influenza', 'stats': [{'groupId': 'EG000', 'numAtRisk': 56, 'numAffected': 6}, {'groupId': 'EG001', 'numAtRisk': 55, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 56, 'numAffected': 4}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 15.0'}, {'term': 'Nasopharyngitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 56, 'numAffected': 6}, {'groupId': 'EG001', 'numAtRisk': 55, 'numAffected': 7}, {'groupId': 'EG002', 'numAtRisk': 56, 'numAffected': 7}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 15.0'}, {'term': 'Sinusitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 56, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 55, 'numAffected': 3}, {'groupId': 'EG002', 'numAtRisk': 56, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 15.0'}, {'term': 'Upper respiratory tract infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 56, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 55, 'numAffected': 3}, {'groupId': 'EG002', 'numAtRisk': 56, 'numAffected': 2}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 15.0'}, {'term': 'Pain in extremity', 'stats': [{'groupId': 'EG000', 'numAtRisk': 56, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 55, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 56, 'numAffected': 0}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 15.0'}, {'term': 'Headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 56, 'numAffected': 5}, {'groupId': 'EG001', 'numAtRisk': 55, 'numAffected': 3}, {'groupId': 'EG002', 'numAtRisk': 56, 'numAffected': 3}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 15.0'}, {'term': 'Cough', 'stats': [{'groupId': 'EG000', 'numAtRisk': 56, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 55, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 56, 'numAffected': 0}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 15.0'}], 'seriousEvents': [{'term': 'Atrial fibrillation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 56, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 55, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 56, 'numAffected': 1}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 15.0'}, {'term': 'Appendicitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 56, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 55, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 56, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 15.0'}, {'term': 'Postoperative wound infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 56, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 55, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 56, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 15.0'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12', 'denoms': [{'units': 'Participants', 'counts': [{'value': '56', 'groupId': 'OG000'}, {'value': '55', 'groupId': 'OG001'}, {'value': '56', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Participants received placebo subcutaneous injection once every 4 weeks for 12 weeks.'}, {'id': 'OG001', 'title': 'Evolocumab 350 mg', 'description': 'Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.'}, {'id': 'OG002', 'title': 'Evolocumab 420 mg', 'description': 'Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.'}], 'classes': [{'categories': [{'measurements': [{'value': '1.12', 'spread': '2.88', 'groupId': 'OG000'}, {'value': '-42.70', 'spread': '2.93', 'groupId': 'OG001'}, {'value': '-55.24', 'spread': '2.88', 'groupId': 'OG002'}]}]}], 'analyses': [{'pValue': '<0.001', 'groupIds': ['OG000', 'OG001'], 'paramType': 'LS Mean Treatment Difference', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-43.82', 'ciLowerLimit': '-51.56', 'ciUpperLimit': '-36.09', 'pValueComment': 'Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '3.92', 'estimateComment': 'Placebo is the reference.', 'groupDescription': 'The null hypothesis was that there was no mean difference in the percent change from baseline at Week 12 in LDL-C between evolocumab and placebo.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY', 'statisticalComment': 'ANCOVA model includes treatment group and LDL-C level and baseline ezetimibe use as covariates.'}, {'pValue': '<0.001', 'groupIds': ['OG000', 'OG002'], 'paramType': 'LS Mean Treatment Difference', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-56.36', 'ciLowerLimit': '-64.06', 'ciUpperLimit': '-48.67', 'pValueComment': 'Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '3.90', 'estimateComment': 'Placebo is the reference', 'groupDescription': 'The null hypothesis was that there was no mean difference in the percent change from baseline at Week 12 in LDL-C between evolocumab and placebo.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY', 'statisticalComment': 'ANCOVA model includes treatment group and LDL-C level and baseline ezetimibe use as covariates.'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline and Week 12', 'description': 'LDL-C was measured using ultracentrifugation.', 'unitOfMeasure': 'percent change', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Full analysis set; Missing ultracentrifugation (UC) LDL-C data at Week 12 were imputed using last observation carried forward (LOCF) and calculated LDL-C.'}, {'type': 'SECONDARY', 'title': 'Absolute Change From Baseline in LDL-C at Week 12', 'denoms': [{'units': 'Participants', 'counts': [{'value': '56', 'groupId': 'OG000'}, {'value': '55', 'groupId': 'OG001'}, {'value': '56', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Participants received placebo subcutaneous injection once every 4 weeks for 12 weeks.'}, {'id': 'OG001', 'title': 'Evolocumab 350 mg', 'description': 'Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.'}, {'id': 'OG002', 'title': 'Evolocumab 420 mg', 'description': 'Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.'}], 'classes': [{'categories': [{'measurements': [{'value': '4.2', 'spread': '5.2', 'groupId': 'OG000'}, {'value': '-61.3', 'spread': '5.4', 'groupId': 'OG001'}, {'value': '-80.5', 'spread': '5.2', 'groupId': 'OG002'}]}]}], 'analyses': [{'pValue': '<0.001', 'groupIds': ['OG000', 'OG001'], 'paramType': 'LS Mean Treatment Difference', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-65.5', 'ciLowerLimit': '-79.6', 'ciUpperLimit': '-51.4', 'pValueComment': 'Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '7.1', 'estimateComment': 'Placebo is the reference', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY', 'statisticalComment': 'ANCOVA model includes treatment group and LDL-C level and baseline ezetimibe use as covariates.'}, {'pValue': '<0.001', 'groupIds': ['OG000', 'OG002'], 'paramType': 'LS Mean Treatment Difference', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-84.7', 'ciLowerLimit': '-98.8', 'ciUpperLimit': '-70.7', 'pValueComment': 'Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '7.1', 'estimateComment': 'Placebo is the reference', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY', 'statisticalComment': 'ANCOVA model includes treatment group and LDL-C level and baseline ezetimibe use as covariates.'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline and Week 12', 'description': 'LDL-C was measured using ultracentrifugation.', 'unitOfMeasure': 'mg/dL', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Full analysis set; LOCF imputation was used.'}, {'type': 'SECONDARY', 'title': 'Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (HDL-C) at Week 12', 'denoms': [{'units': 'Participants', 'counts': [{'value': '56', 'groupId': 'OG000'}, {'value': '55', 'groupId': 'OG001'}, {'value': '56', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Participants received placebo subcutaneous injection once every 4 weeks for 12 weeks.'}, {'id': 'OG001', 'title': 'Evolocumab 350 mg', 'description': 'Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.'}, {'id': 'OG002', 'title': 'Evolocumab 420 mg', 'description': 'Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.'}], 'classes': [{'categories': [{'measurements': [{'value': '2.48', 'spread': '2.80', 'groupId': 'OG000'}, {'value': '-39.31', 'spread': '2.86', 'groupId': 'OG001'}, {'value': '-50.98', 'spread': '2.80', 'groupId': 'OG002'}]}]}], 'analyses': [{'pValue': '<0.001', 'groupIds': ['OG000', 'OG001'], 'paramType': 'LS Mean Treatment Difference', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-41.79', 'ciLowerLimit': '-49.32', 'ciUpperLimit': '-34.26', 'pValueComment': 'Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '3.81', 'estimateComment': 'Placebo is the reference', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY', 'statisticalComment': 'ANCOVA model includes treatment group and LDL-C level and baseline ezetimibe use as covariates.'}, {'pValue': '<0.001', 'groupIds': ['OG000', 'OG002'], 'paramType': 'LS Mean Treatment Difference', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-53.46', 'ciLowerLimit': '-60.95', 'ciUpperLimit': '-45.97', 'pValueComment': 'Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '3.79', 'estimateComment': 'Placebo is the reference', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY', 'statisticalComment': 'ANCOVA model includes treatment group and LDL-C level and baseline ezetimibe use as covariates.'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline and Week 12', 'unitOfMeasure': 'percent change', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Full analysis set; LOCF imputation was used.'}, {'type': 'SECONDARY', 'title': 'Percent Change From Baseline in Apolipoprotein B at Week 12', 'denoms': [{'units': 'Participants', 'counts': [{'value': '56', 'groupId': 'OG000'}, {'value': '55', 'groupId': 'OG001'}, {'value': '56', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Participants received placebo subcutaneous injection once every 4 weeks for 12 weeks.'}, {'id': 'OG001', 'title': 'Evolocumab 350 mg', 'description': 'Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.'}, {'id': 'OG002', 'title': 'Evolocumab 420 mg', 'description': 'Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.'}], 'classes': [{'categories': [{'measurements': [{'value': '2.86', 'spread': '2.61', 'groupId': 'OG000'}, {'value': '-31.89', 'spread': '2.66', 'groupId': 'OG001'}, {'value': '-43.34', 'spread': '2.61', 'groupId': 'OG002'}]}]}], 'analyses': [{'pValue': '<0.001', 'groupIds': ['OG000', 'OG001'], 'paramType': 'LS Mean Treatment Difference', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-34.75', 'ciLowerLimit': '-41.77', 'ciUpperLimit': '-27.74', 'pValueComment': 'Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '3.55', 'estimateComment': 'Placebo is the reference', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY', 'statisticalComment': 'ANCOVA model includes treatment group and LDL-C level and baseline ezetimibe use as covariates.'}, {'pValue': '<0.001', 'groupIds': ['OG000', 'OG002'], 'paramType': 'LS Mean Treatment Difference', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-46.20', 'ciLowerLimit': '-53.18', 'ciUpperLimit': '-39.23', 'pValueComment': 'Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '3.53', 'estimateComment': 'Placebo is the reference', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY', 'statisticalComment': 'ANCOVA model includes treatment group and LDL-C level and baseline ezetimibe use as covariates.'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline and Week 12', 'unitOfMeasure': 'percent change', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Full analysis set; LOCF imputation was used'}, {'type': 'SECONDARY', 'title': 'Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12', 'denoms': [{'units': 'Participants', 'counts': [{'value': '56', 'groupId': 'OG000'}, {'value': '55', 'groupId': 'OG001'}, {'value': '56', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Participants received placebo subcutaneous injection once every 4 weeks for 12 weeks.'}, {'id': 'OG001', 'title': 'Evolocumab 350 mg', 'description': 'Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.'}, {'id': 'OG002', 'title': 'Evolocumab 420 mg', 'description': 'Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.'}], 'classes': [{'categories': [{'measurements': [{'value': '2.98', 'spread': '2.73', 'groupId': 'OG000'}, {'value': '-33.69', 'spread': '2.79', 'groupId': 'OG001'}, {'value': '-42.03', 'spread': '2.73', 'groupId': 'OG002'}]}]}], 'analyses': [{'pValue': '<0.001', 'groupIds': ['OG000', 'OG001'], 'paramType': 'LS Mean Treatment Difference', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-36.66', 'ciLowerLimit': '-44.01', 'ciUpperLimit': '-29.32', 'pValueComment': 'Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '3.72', 'estimateComment': 'Placbo is the reference', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY', 'statisticalComment': 'ANCOVA model includes treatment group and LDL-C level and baseline ezetimibe use as covariates.'}, {'pValue': '<0.001', 'groupIds': ['OG000', 'OG002'], 'paramType': 'LS Mean Treatment Difference', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-45.01', 'ciLowerLimit': '-52.32', 'ciUpperLimit': '-37.70', 'pValueComment': 'Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '3.70', 'estimateComment': 'Placebo is the reference', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY', 'statisticalComment': 'ANCOVA model includes treatment group and LDL-C level and baseline ezetimibe use as covariates.'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline and Week 12', 'unitOfMeasure': 'percent change', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Full analysis set; LOCF imputaton was used.'}, {'type': 'SECONDARY', 'title': 'Percent Change From Baseline in Apolipoprotein B /Apolipoprotein A-1 Ratio at Week 12', 'denoms': [{'units': 'Participants', 'counts': [{'value': '56', 'groupId': 'OG000'}, {'value': '55', 'groupId': 'OG001'}, {'value': '56', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Participants received placebo subcutaneous injection once every 4 weeks for 12 weeks.'}, {'id': 'OG001', 'title': 'Evolocumab 350 mg', 'description': 'Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.'}, {'id': 'OG002', 'title': 'Evolocumab 420 mg', 'description': 'Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.'}], 'classes': [{'categories': [{'measurements': [{'value': '-4.10', 'spread': '2.53', 'groupId': 'OG000'}, {'value': '-38.02', 'spread': '2.58', 'groupId': 'OG001'}, {'value': '-48.74', 'spread': '2.53', 'groupId': 'OG002'}]}]}], 'analyses': [{'pValue': '<0.001', 'groupIds': ['OG000', 'OG001'], 'paramType': 'LS Mean Treatment Difference', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-33.92', 'ciLowerLimit': '-40.72', 'ciUpperLimit': '-27.11', 'pValueComment': 'Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '3.45', 'estimateComment': 'Placebo is the reference', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY', 'statisticalComment': 'ANCOVA model includes treatment group and LDL-C level and baseline ezetimibe use as covariates.'}, {'pValue': '<0.001', 'groupIds': ['OG000', 'OG002'], 'paramType': 'LS Mean Treatment Difference', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-44.64', 'ciLowerLimit': '-51.41', 'ciUpperLimit': '-37.86', 'pValueComment': 'Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '3.43', 'estimateComment': 'Placebo is the reference', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY', 'statisticalComment': 'ANCOVA model includes treatment group and LDL-C level and baseline ezetimibe use as covariates.'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline and Week 12', 'unitOfMeasure': 'percent change', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Full analysis set; LOCF imputation was used.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Placebo', 'description': 'Participants received placebo subcutaneous injection once every 4 weeks for 12 weeks.'}, {'id': 'FG001', 'title': 'Evolocumab 350 mg', 'description': 'Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.'}, {'id': 'FG002', 'title': 'Evolocumab 420 mg', 'description': 'Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '56'}, {'groupId': 'FG001', 'numSubjects': '56'}, {'groupId': 'FG002', 'numSubjects': '56'}]}, {'type': 'Received Treatment', 'achievements': [{'groupId': 'FG000', 'numSubjects': '56'}, {'groupId': 'FG001', 'numSubjects': '55'}, {'groupId': 'FG002', 'numSubjects': '56'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '56'}, {'groupId': 'FG001', 'numSubjects': '55'}, {'groupId': 'FG002', 'numSubjects': '56'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '1'}, {'groupId': 'FG002', 'numSubjects': '0'}]}], 'dropWithdraws': [{'type': 'Other', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '1'}, {'groupId': 'FG002', 'numSubjects': '0'}]}]}], 'recruitmentDetails': 'Men and women 18 to to 75 years of age, with a diagnosis of heterozygous familial hypercholesterolemia, fasting low-density lipoprotein cholesterol (LDL-C) of ≥ 100 mg/dL, and fasting triglycerides ≤ 400 mg/dL were eligible for this study.\n\nThe first patient was enrolled on 02 August 2011 and the last patient was enrolled on 20 February 2012.', 'preAssignmentDetails': 'Randomization was stratified on the basis of screening LDL-C level (\\< 130 mg/dL \\[3.4 mmol/L\\] or ≥ 130 mg/dL) and ezetimibe use at baseline (yes or no).'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '56', 'groupId': 'BG000'}, {'value': '55', 'groupId': 'BG001'}, {'value': '56', 'groupId': 'BG002'}, {'value': '167', 'groupId': 'BG003'}]}], 'groups': [{'id': 'BG000', 'title': 'Placebo', 'description': 'Participants received placebo subcutaneous injection once every 4 weeks for 12 weeks.'}, {'id': 'BG001', 'title': 'Evolocumab 350 mg', 'description': 'Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.'}, {'id': 'BG002', 'title': 'Evolocumab 420 mg', 'description': 'Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.'}, {'id': 'BG003', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '49.3', 'spread': '11.3', 'groupId': 'BG000'}, {'value': '47.6', 'spread': '13.6', 'groupId': 'BG001'}, {'value': '51.8', 'spread': '13.0', 'groupId': 'BG002'}, {'value': '49.6', 'spread': '12.7', 'groupId': 'BG003'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '32', 'groupId': 'BG000'}, {'value': '25', 'groupId': 'BG001'}, {'value': '21', 'groupId': 'BG002'}, {'value': '78', 'groupId': 'BG003'}]}, {'title': 'Male', 'measurements': [{'value': '24', 'groupId': 'BG000'}, {'value': '30', 'groupId': 'BG001'}, {'value': '35', 'groupId': 'BG002'}, {'value': '89', 'groupId': 'BG003'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race/Ethnicity, Customized', 'classes': [{'title': 'Hispanic or Latino', 'categories': [{'measurements': [{'value': '2', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '2', 'groupId': 'BG003'}]}]}, {'title': 'Not Hispanic or Latino', 'categories': [{'measurements': [{'value': '54', 'groupId': 'BG000'}, {'value': '55', 'groupId': 'BG001'}, {'value': '56', 'groupId': 'BG002'}, {'value': '165', 'groupId': 'BG003'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}, {'title': 'Race/Ethnicity, Customized', 'classes': [{'title': 'Asian', 'categories': [{'measurements': [{'value': '3', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '3', 'groupId': 'BG002'}, {'value': '7', 'groupId': 'BG003'}]}]}, {'title': 'Black or African American', 'categories': [{'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}, {'value': '4', 'groupId': 'BG003'}]}]}, {'title': 'White', 'categories': [{'measurements': [{'value': '48', 'groupId': 'BG000'}, {'value': '48', 'groupId': 'BG001'}, {'value': '52', 'groupId': 'BG002'}, {'value': '148', 'groupId': 'BG003'}]}]}, {'title': 'Other', 'categories': [{'measurements': [{'value': '4', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '7', 'groupId': 'BG003'}]}]}, {'title': 'Mixed Race', 'categories': [{'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '1', 'groupId': 'BG003'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}, {'title': 'Stratification Factor: LDL-C Level', 'classes': [{'title': '< 130 mg/dL', 'categories': [{'measurements': [{'value': '19', 'groupId': 'BG000'}, {'value': '17', 'groupId': 'BG001'}, {'value': '19', 'groupId': 'BG002'}, {'value': '55', 'groupId': 'BG003'}]}]}, {'title': '≥ 130 mg/dL', 'categories': [{'measurements': [{'value': '37', 'groupId': 'BG000'}, {'value': '38', 'groupId': 'BG001'}, {'value': '37', 'groupId': 'BG002'}, {'value': '112', 'groupId': 'BG003'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}, {'title': 'Stratification Factor: Baseline Use Of Ezetimibe', 'classes': [{'title': 'No', 'categories': [{'measurements': [{'value': '20', 'groupId': 'BG000'}, {'value': '19', 'groupId': 'BG001'}, {'value': '20', 'groupId': 'BG002'}, {'value': '59', 'groupId': 'BG003'}]}]}, {'title': 'Yes', 'categories': [{'measurements': [{'value': '36', 'groupId': 'BG000'}, {'value': '36', 'groupId': 'BG001'}, {'value': '36', 'groupId': 'BG002'}, {'value': '108', 'groupId': 'BG003'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}, {'title': 'LDL-C Concentration', 'classes': [{'categories': [{'measurements': [{'value': '160.8', 'spread': '44.0', 'groupId': 'BG000'}, {'value': '156.8', 'spread': '46.1', 'groupId': 'BG001'}, {'value': '149.5', 'spread': '36.3', 'groupId': 'BG002'}, {'value': '155.7', 'spread': '42.3', 'groupId': 'BG003'}]}]}], 'paramType': 'MEAN', 'description': 'LDL-C was measured using ultacentrifugation', 'unitOfMeasure': 'mg/dL', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Non-High-Density Lipoprotein Cholesterol (non-HDL-C) Concentration', 'classes': [{'categories': [{'measurements': [{'value': '182.7', 'spread': '52.6', 'groupId': 'BG000'}, {'value': '178.0', 'spread': '51.7', 'groupId': 'BG001'}, {'value': '171.0', 'spread': '43.6', 'groupId': 'BG002'}, {'value': '177.2', 'spread': '49.4', 'groupId': 'BG003'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'mg/dL', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Apolipoprotein B Concentration', 'classes': [{'categories': [{'measurements': [{'value': '125.2', 'spread': '30.3', 'groupId': 'BG000'}, {'value': '120.9', 'spread': '29.3', 'groupId': 'BG001'}, {'value': '119.3', 'spread': '27.6', 'groupId': 'BG002'}, {'value': '121.8', 'spread': '29.0', 'groupId': 'BG003'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'mg/dL', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Total Cholesterol/HDL-C Ratio', 'classes': [{'categories': [{'measurements': [{'value': '4.895', 'spread': '1.790', 'groupId': 'BG000'}, {'value': '5.119', 'spread': '1.923', 'groupId': 'BG001'}, {'value': '4.857', 'spread': '1.688', 'groupId': 'BG002'}, {'value': '4.956', 'spread': '1.795', 'groupId': 'BG003'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'ratio', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Apolipoprotein B/Apolipoprotein A1 Ratio', 'classes': [{'categories': [{'measurements': [{'value': '0.899', 'spread': '0.277', 'groupId': 'BG000'}, {'value': '0.901', 'spread': '0.286', 'groupId': 'BG001'}, {'value': '0.867', 'spread': '0.264', 'groupId': 'BG002'}, {'value': '0.899', 'spread': '0.274', 'groupId': 'BG003'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'ratio', 'dispersionType': 'STANDARD_DEVIATION'}], 'populationDescription': 'Full analysis set (all randomized participants who received at least 1 dose of investigational product).'}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 168}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2011-08-02', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2022-11', 'dispFirstSubmitDate': '2013-04-02', 'completionDateStruct': {'date': '2012-05-16', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2022-11-10', 'studyFirstSubmitDate': '2011-06-16', 'dispFirstSubmitQcDate': '2013-04-02', 'resultsFirstSubmitDate': '2015-08-28', 'studyFirstSubmitQcDate': '2011-06-16', 'dispFirstPostDateStruct': {'date': '2013-04-09', 'type': 'ESTIMATED'}, 'lastUpdatePostDateStruct': {'date': '2022-11-15', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2015-08-28', 'studyFirstPostDateStruct': {'date': '2011-06-17', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2015-09-29', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2012-05-16', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12', 'timeFrame': 'Baseline and Week 12', 'description': 'LDL-C was measured using ultracentrifugation.'}], 'secondaryOutcomes': [{'measure': 'Absolute Change From Baseline in LDL-C at Week 12', 'timeFrame': 'Baseline and Week 12', 'description': 'LDL-C was measured using ultracentrifugation.'}, {'measure': 'Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (HDL-C) at Week 12', 'timeFrame': 'Baseline and Week 12'}, {'measure': 'Percent Change From Baseline in Apolipoprotein B at Week 12', 'timeFrame': 'Baseline and Week 12'}, {'measure': 'Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12', 'timeFrame': 'Baseline and Week 12'}, {'measure': 'Percent Change From Baseline in Apolipoprotein B /Apolipoprotein A-1 Ratio at Week 12', 'timeFrame': 'Baseline and Week 12'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['Heterozygous Familial Hypercholesterolemia', 'Proprotein convertase subtilisin/kexin type 9 (PCSK9)'], 'conditions': ['Hypercholesterolemia, Familial']}, 'referencesModule': {'references': [{'pmid': '23129602', 'type': 'BACKGROUND', 'citation': 'Raal F, Scott R, Somaratne R, Bridges I, Li G, Wasserman SM, Stein EA. Low-density lipoprotein cholesterol-lowering effects of AMG 145, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease in patients with heterozygous familial hypercholesterolemia: the Reduction of LDL-C with PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder (RUTHERFORD) randomized trial. Circulation. 2012 Nov 13;126(20):2408-17. doi: 10.1161/CIRCULATIONAHA.112.144055. Epub 2012 Nov 5.'}], 'seeAlsoLinks': [{'url': 'http://www.amgentrials.com', 'label': 'AmgenTrials clinical trials website'}]}, 'descriptionModule': {'briefSummary': 'The primary objective of this study was to evaluate the effect of 12 weeks of subcutaneous evolocumab (AMG 145), compared with placebo, on percent change from baseline in LDL-C in adults with heterozygous familial hypercholesterolemia (HeFH).'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '75 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Male or female ≥ 18 to ≤ 75 years of age\n* Diagnosis of heterozygous familial hypercholesterolemia by having met the diagnostic criteria outlined by the Simon Broome Register Group (Scientific Steering Committee 1991)\n* On an approved statin, with or without ezetimibe, with stable dose(s) for at least 4 weeks\n* Fasting Low-Density Lipoprotein Cholesterol (LDL-C) ≥ 100 mg/dL\n* Fasting triglycerides ≤ 400 mg/dL\n\nExclusion Criteria:\n\n* Homozygous familial hypercholesterolemia\n* Low-Density Lipoprotein (LDL) or plasma apheresis within 12 months prior to randomization\n* New York Heart Association (NYHA) III or IV heart failure, or known left ventricular ejection fraction \\< 30%\n* Uncontrolled cardiac arrhythmia\n* Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or stroke within 3 months prior to randomization\n* Type 1 diabetes; newly diagnosed or poorly controlled type 2 diabetes (HbA1c \\> 8.5%)\n* Uncontrolled hypertension'}, 'identificationModule': {'nctId': 'NCT01375751', 'acronym': 'RUTHERFORD', 'briefTitle': 'Reduction of Low-Density Lipoprotein Cholesterol (LDL-C) With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder Study', 'organization': {'class': 'INDUSTRY', 'fullName': 'Amgen'}, 'officialTitle': 'A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate Tolerability and Efficacy of AMG 145 on LDL-C in Subject With Heterozygous Familial Hypercholesterolemia', 'orgStudyIdInfo': {'id': '20090158'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo', 'description': 'Participants received placebo subcutaneous injection once every 4 weeks for 12 weeks.', 'interventionNames': ['Biological: Placebo']}, {'type': 'EXPERIMENTAL', 'label': 'Evolocumab 350 mg', 'description': 'Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.', 'interventionNames': ['Biological: Evolocumab']}, {'type': 'EXPERIMENTAL', 'label': 'Evolocumab 420 mg', 'description': 'Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.', 'interventionNames': ['Biological: Evolocumab']}], 'interventions': [{'name': 'Evolocumab', 'type': 'BIOLOGICAL', 'otherNames': ['AMG 145', 'Repatha'], 'description': 'Administered by subcutaneous injection', 'armGroupLabels': ['Evolocumab 350 mg', 'Evolocumab 420 mg']}, {'name': 'Placebo', 'type': 'BIOLOGICAL', 'description': 'd by subcutaneous injection', 'armGroupLabels': ['Placebo']}]}, 'contactsLocationsModule': {'overallOfficials': [{'name': 'MD', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Amgen'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Amgen', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}