Ignite Creation Date:
2025-12-24 @ 11:34 PM
Ignite Modification Date:
2026-02-23 @ 6:27 AM
Study NCT ID:
NCT02275156
Status:
COMPLETED
Last Update Posted:
2022-11-07
First Post:
2014-07-15
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Estimation Study to Assess the Effect of Severe Renal Impairment and End-stage Renal Disease Hemodialysis on the Pharmacokinetics of Evolocumab
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D006949', 'term': 'Hyperlipidemias'}, {'id': 'D051437', 'term': 'Renal Insufficiency'}, {'id': 'D007676', 'term': 'Kidney Failure, Chronic'}], 'ancestors': [{'id': 'D050171', 'term': 'Dyslipidemias'}, {'id': 'D052439', 'term': 'Lipid Metabolism Disorders'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}, {'id': 'D007674', 'term': 'Kidney Diseases'}, {'id': 'D014570', 'term': 'Urologic Diseases'}, {'id': 'D052776', 'term': 'Female Urogenital Diseases'}, {'id': 'D005261', 'term': 'Female Urogenital Diseases and Pregnancy Complications'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D052801', 'term': 'Male Urogenital Diseases'}, {'id': 'D051436', 'term': 'Renal Insufficiency, Chronic'}, {'id': 'D002908', 'term': 'Chronic Disease'}, {'id': 'D020969', 'term': 'Disease Attributes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C577155', 'term': 'evolocumab'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'phone': '866-572-6436', 'title': 'Study Director', 'organization': 'Amgen Inc.'}, 'certainAgreement': {'otherDetails': "The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. 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': 'From the first dose of study drug up until Day 57', 'description': 'Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.\n\nSummary of Adverse Events includes only those subjects who received at least one dose of investigational product.\n\nESRD = End stage renal disease requiring dialysis.', 'eventGroups': [{'id': 'EG000', 'title': 'Evolocumab 140 mg - Normal Renal Function', 'description': 'Participants with normal renal function (defined as an estimated glomerular filtration rate \\[eGFR\\] ≥ 90 mL/min/1.73 m²) received a single 140 mg dose of evolocumab subcutaneously on Day 1.', 'otherNumAtRisk': 6, 'otherNumAffected': 1, 'seriousNumAtRisk': 6, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Evolocumab 140 mg - Severe RI', 'description': 'Participants with severe renal impairment (defined as eGFR 15 to 29 mL/min/1.73 m²) received a single 140 mg dose of evolocumab subcutaneously on Day 1.', 'otherNumAtRisk': 6, 'otherNumAffected': 1, 'seriousNumAtRisk': 6, 'seriousNumAffected': 1}, {'id': 'EG002', 'title': 'Evolocumab 140 mg - ESRD Requiring Hemodialysis', 'description': 'Participants with end-stage renal disease (ESRD) requiring hemodialysis received a single 140 mg dose of evolocumab subcutaneously on Day 1.', 'otherNumAtRisk': 6, 'otherNumAffected': 2, 'seriousNumAtRisk': 6, 'seriousNumAffected': 0}, {'id': 'EG003', 'title': 'Evolocumab 140 mg - Total', 'description': 'Participants received a single 140 mg dose of evolocumab subcutaneously on Day 1.', 'otherNumAtRisk': 18, 'otherNumAffected': 4, 'seriousNumAtRisk': 18, 'seriousNumAffected': 1}], 'otherEvents': [{'term': 'Abdominal pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 6, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 6, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 17.1'}, {'term': 'Vomiting', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 6, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 6, 'numAffected': 1}, {'groupId': 'EG003', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 17.1'}, {'term': 'Tooth infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 6, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 6, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 17.1'}, {'term': 'Contusion', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 6, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 6, 'numAffected': 1}, {'groupId': 'EG003', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 17.1'}, {'term': 'Upper-airway cough syndrome', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 6, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 6, 'numAffected': 1}, {'groupId': 'EG003', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 17.1'}, {'term': 'Dermatitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 6, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 6, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 17.1'}], 'seriousEvents': [{'term': 'Hyperkalaemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 6, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 6, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 17.1'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Maximum Observed Serum Concentration (Cmax) of Evolocumab', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}, {'value': '6', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Normal Renal Function', 'description': 'Participants with normal renal function (defined as an estimated glomerular filtration rate \\[eGFR\\] ≥ 90 mL/min/1.73 m²) received a single 140 mg dose of evolocumab subcutaneously on Day 1.'}, {'id': 'OG001', 'title': 'Severe Renal Impairment', 'description': 'Participants with severe renal impairment (defined as eGFR 15 to 29 mL/min/1.73 m²) received a single 140 mg dose of evolocumab subcutaneously on Day 1.'}, {'id': 'OG002', 'title': 'End Stage Renal Disease', 'description': 'Participants with end-stage renal disease (ESRD) requiring hemodialysis received a single 140 mg dose of evolocumab subcutaneously on Day 1.'}], 'classes': [{'categories': [{'measurements': [{'value': '21.3', 'spread': '9.00', 'groupId': 'OG000'}, {'value': '15.1', 'spread': '8.86', 'groupId': 'OG001'}, {'value': '11.7', 'spread': '7.20', 'groupId': 'OG002'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Predose and 4 hours, 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 50 and 57 days postdose', 'description': 'Serum concentrations of evolocumab were measured by a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) of the assay was 800 ng/mL.', 'unitOfMeasure': 'μg/mL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Pharmacokinetic (PK) analysis set (all participants for whom at least 1 PK parameter could be adequately estimated)'}, {'type': 'PRIMARY', 'title': 'Area Under the Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC0-last) for Evolocumab', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}, {'value': '6', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Normal Renal Function', 'description': 'Participants with normal renal function (defined as an estimated glomerular filtration rate \\[eGFR\\] ≥ 90 mL/min/1.73 m²) received a single 140 mg dose of evolocumab subcutaneously on Day 1.'}, {'id': 'OG001', 'title': 'Severe Renal Impairment', 'description': 'Participants with severe renal impairment (defined as eGFR 15 to 29 mL/min/1.73 m²) received a single 140 mg dose of evolocumab subcutaneously on Day 1.'}, {'id': 'OG002', 'title': 'End Stage Renal Disease', 'description': 'Participants with end-stage renal disease (ESRD) requiring hemodialysis received a single 140 mg dose of evolocumab subcutaneously on Day 1.'}], 'classes': [{'categories': [{'measurements': [{'value': '185', 'spread': '92.5', 'groupId': 'OG000'}, {'value': '141', 'spread': '109', 'groupId': 'OG001'}, {'value': '102', 'spread': '80.1', 'groupId': 'OG002'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Predose and 4 hours, 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 50 and 57 days postdose', 'unitOfMeasure': 'day*μg/mL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'PK analysis set'}, {'type': 'SECONDARY', 'title': 'Number of Participants With Adverse Events', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}, {'value': '6', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Normal Renal Function', 'description': 'Participants with normal renal function (defined as an estimated glomerular filtration rate \\[eGFR\\] ≥ 90 mL/min/1.73 m²) received a single 140 mg dose of evolocumab subcutaneously on Day 1.'}, {'id': 'OG001', 'title': 'Severe Renal Impairment', 'description': 'Participants with severe renal impairment (defined as eGFR 15 to 29 mL/min/1.73 m²) received a single 140 mg dose of evolocumab subcutaneously on Day 1.'}, {'id': 'OG002', 'title': 'End Stage Renal Disease', 'description': 'Participants with end-stage renal disease (ESRD) requiring hemodialysis received a single 140 mg dose of evolocumab subcutaneously on Day 1.'}], 'classes': [{'title': 'Any adverse event', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}, {'value': '2', 'groupId': 'OG002'}]}]}, {'title': 'Grade ≥ 2', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}, {'value': '0', 'groupId': 'OG002'}]}]}, {'title': 'Grade ≥ 3', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}, {'value': '0', 'groupId': 'OG002'}]}]}, {'title': 'Grade ≥ 4', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}, {'value': '0', 'groupId': 'OG002'}]}]}, {'title': 'Serious adverse events', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}, {'value': '0', 'groupId': 'OG002'}]}]}, {'title': 'Leading to discontinuation of study drug', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}, {'value': '0', 'groupId': 'OG002'}]}]}, {'title': 'Leading to discontinuation from study', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}, {'value': '0', 'groupId': 'OG002'}]}]}, {'title': 'Fatal adverse events', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}, {'value': '0', 'groupId': 'OG002'}]}]}, {'title': 'Treatment-related adverse events', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}, {'value': '0', 'groupId': 'OG002'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'From the first dose of study drug up until Day 57', 'description': 'The severity of each adverse event was graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4. A serious adverse event is defined as an adverse event that meets at least 1 of the following serious criteria:\n\n* fatal;\n* life threatening (places the participant at immediate risk of death);\n* requires in patient hospitalization or prolongation of existing hospitalization;\n* results in persistent or significant disability/incapacity;\n* congenital anomaly/birth defect;\n* other medically important serious event.\n\nThe investigator assessed whether each adverse event was possibly related to the study drug.', 'unitOfMeasure': 'participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Safety analysis set (all participants who received at least 1 dose of study drug)'}, {'type': 'SECONDARY', 'title': 'Number of Participants With Clinically Relevant Vital Sign or Clinical Laboratory Changes', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}, {'value': '6', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Normal Renal Function', 'description': 'Participants with normal renal function (defined as an estimated glomerular filtration rate \\[eGFR\\] ≥ 90 mL/min/1.73 m²) received a single 140 mg dose of evolocumab subcutaneously on Day 1.'}, {'id': 'OG001', 'title': 'Severe Renal Impairment', 'description': 'Participants with severe renal impairment (defined as eGFR 15 to 29 mL/min/1.73 m²) received a single 140 mg dose of evolocumab subcutaneously on Day 1.'}, {'id': 'OG002', 'title': 'End Stage Renal Disease', 'description': 'Participants with end-stage renal disease (ESRD) requiring hemodialysis received a single 140 mg dose of evolocumab subcutaneously on Day 1.'}], 'classes': [{'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}, {'value': '0', 'groupId': 'OG002'}]}]}], 'paramType': 'NUMBER', 'timeFrame': '57 days', 'description': "The investigator reviewed vital signs and laboratory test results and determined whether an abnormal value in an individual participant represented a clinically significant change from the participant's baseline values.", 'unitOfMeasure': 'participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Safety analysis set'}, {'type': 'SECONDARY', 'title': 'Number of Participants With Anti-evolocumab Antibodies', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}, {'value': '6', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Normal Renal Function', 'description': 'Participants with normal renal function (defined as an estimated glomerular filtration rate \\[eGFR\\] ≥ 90 mL/min/1.73 m²) received a single 140 mg dose of evolocumab subcutaneously on Day 1.'}, {'id': 'OG001', 'title': 'Severe Renal Impairment', 'description': 'Participants with severe renal impairment (defined as eGFR 15 to 29 mL/min/1.73 m²) received a single 140 mg dose of evolocumab subcutaneously on Day 1.'}, {'id': 'OG002', 'title': 'End Stage Renal Disease', 'description': 'Participants with end-stage renal disease (ESRD) requiring hemodialysis received a single 140 mg dose of evolocumab subcutaneously on Day 1.'}], 'classes': [{'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}, {'value': '0', 'groupId': 'OG002'}]}]}], 'paramType': 'NUMBER', 'timeFrame': '57 days', 'description': 'Blood samples were tested using an electrochemiluminescence-based bridging immunoassay to detect antibodies capable of binding to evolocumab.', 'unitOfMeasure': 'participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Safety analysis set'}, {'type': 'SECONDARY', 'title': 'Area Under the Effect Curve From Baseline to Day 57 (AUECday1-57) for Low-density Lipoprotein Cholesterol (LDL-C)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}, {'value': '6', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Normal Renal Function', 'description': 'Participants with normal renal function (defined as an estimated glomerular filtration rate \\[eGFR\\] ≥ 90 mL/min/1.73 m²) received a single 140 mg dose of evolocumab subcutaneously on Day 1.'}, {'id': 'OG001', 'title': 'Severe Renal Impairment', 'description': 'Participants with severe renal impairment (defined as eGFR 15 to 29 mL/min/1.73 m²) received a single 140 mg dose of evolocumab subcutaneously on Day 1.'}, {'id': 'OG002', 'title': 'End Stage Renal Disease', 'description': 'Participants with end-stage renal disease (ESRD) requiring hemodialysis received a single 140 mg dose of evolocumab subcutaneously on Day 1.'}], 'classes': [{'categories': [{'measurements': [{'value': '4438.6', 'groupId': 'OG000', 'lowerLimit': '3873.3', 'upperLimit': '5086.5'}, {'value': '4087.5', 'groupId': 'OG001', 'lowerLimit': '3555.5', 'upperLimit': '4699.1'}, {'value': '4620.2', 'groupId': 'OG002', 'lowerLimit': '4050.8', 'upperLimit': '5269.6'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': '4 hours, 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 50 and 57 days postdose', 'description': 'The derived log-transformed AUECday1-57 for direct LDL-C was analyzed using a mixed-effect analysis of variance model. Log-transformed baseline LDL-C was the covariate.', 'unitOfMeasure': 'mg/dL*day', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Safety analysis set'}, {'type': 'SECONDARY', 'title': 'Mean Percent Change From Baseline in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}, {'value': '6', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Normal Renal Function', 'description': 'Participants with normal renal function (defined as an estimated glomerular filtration rate \\[eGFR\\] ≥ 90 mL/min/1.73 m²) received a single 140 mg dose of evolocumab subcutaneously on Day 1.'}, {'id': 'OG001', 'title': 'Severe Renal Impairment', 'description': 'Participants with severe renal impairment (defined as eGFR 15 to 29 mL/min/1.73 m²) received a single 140 mg dose of evolocumab subcutaneously on Day 1.'}, {'id': 'OG002', 'title': 'End Stage Renal Disease', 'description': 'Participants with end-stage renal disease (ESRD) requiring hemodialysis received a single 140 mg dose of evolocumab subcutaneously on Day 1.'}], 'classes': [{'title': 'Day 1, Hour 4', 'categories': [{'measurements': [{'value': '-91.69', 'groupId': 'OG000', 'lowerLimit': '-94.66', 'upperLimit': '-87.09'}, {'value': '-79.20', 'groupId': 'OG001', 'lowerLimit': '-86.63', 'upperLimit': '-67.64'}, {'value': '-72.95', 'groupId': 'OG002', 'lowerLimit': '-82.59', 'upperLimit': '-57.97'}]}]}, {'title': 'Day 2', 'categories': [{'measurements': [{'value': '-96.67', 'groupId': 'OG000', 'lowerLimit': '-97.86', 'upperLimit': '-94.83'}, {'value': '-95.87', 'groupId': 'OG001', 'lowerLimit': '-97.34', 'upperLimit': '-93.57'}, {'value': '-94.41', 'groupId': 'OG002', 'lowerLimit': '-96.40', 'upperLimit': '-91.31'}]}]}, {'title': 'Day 3', 'categories': [{'measurements': [{'value': '-96.67', 'groupId': 'OG000', 'lowerLimit': '-97.86', 'upperLimit': '-94.83'}, {'value': '-96.33', 'groupId': 'OG001', 'lowerLimit': '-97.64', 'upperLimit': '-94.29'}, {'value': '-95.58', 'groupId': 'OG002', 'lowerLimit': '-97.16', 'upperLimit': '-93.14'}]}]}, {'title': 'Day 4', 'categories': [{'measurements': [{'value': '-96.67', 'groupId': 'OG000', 'lowerLimit': '-97.86', 'upperLimit': '-94.83'}, {'value': '-96.33', 'groupId': 'OG001', 'lowerLimit': '-97.64', 'upperLimit': '-94.29'}, {'value': '-96.53', 'groupId': 'OG002', 'lowerLimit': '-97.77', 'upperLimit': '-94.61'}]}]}, {'title': 'Day 6', 'categories': [{'measurements': [{'value': '-96.67', 'groupId': 'OG000', 'lowerLimit': '-97.86', 'upperLimit': '-94.83'}, {'value': '-96.33', 'groupId': 'OG001', 'lowerLimit': '-97.64', 'upperLimit': '-94.29'}, {'value': '-95.39', 'groupId': 'OG002', 'lowerLimit': '-97.03', 'upperLimit': '-92.83'}]}]}, {'title': 'Day 8', 'categories': [{'measurements': [{'value': '-96.67', 'groupId': 'OG000', 'lowerLimit': '-97.86', 'upperLimit': '-94.83'}, {'value': '-96.33', 'groupId': 'OG001', 'lowerLimit': '-97.64', 'upperLimit': '-94.29'}, {'value': '-95.01', 'groupId': 'OG002', 'lowerLimit': '-96.79', 'upperLimit': '-92.25'}]}]}, {'title': 'Day 11', 'categories': [{'measurements': [{'value': '-96.67', 'groupId': 'OG000', 'lowerLimit': '-97.86', 'upperLimit': '-94.83'}, {'value': '-95.96', 'groupId': 'OG001', 'lowerLimit': '-97.40', 'upperLimit': '-93.71'}, {'value': '-94.69', 'groupId': 'OG002', 'lowerLimit': '-96.58', 'upperLimit': '-91.75'}]}]}, {'title': 'Day 15', 'categories': [{'measurements': [{'value': '-90.42', 'groupId': 'OG000', 'lowerLimit': '-93.84', 'upperLimit': '-85.12'}, {'value': '-86.41', 'groupId': 'OG001', 'lowerLimit': '-91.26', 'upperLimit': '-78.86'}, {'value': '-82.97', 'groupId': 'OG002', 'lowerLimit': '-89.04', 'upperLimit': '-73.53'}]}]}, {'title': 'Day 22', 'categories': [{'measurements': [{'value': '-65.84', 'groupId': 'OG000', 'lowerLimit': '-78.02', 'upperLimit': '-46.40'}, {'value': '-57.92', 'groupId': 'OG001', 'lowerLimit': '-72.95', 'upperLimit': '-34.54'}, {'value': '-60.33', 'groupId': 'OG002', 'lowerLimit': '-74.47', 'upperLimit': '-38.36'}]}]}, {'title': 'Day 29', 'categories': [{'measurements': [{'value': '-49.12', 'groupId': 'OG000', 'lowerLimit': '-67.26', 'upperLimit': '-20.93'}, {'value': '-53.66', 'groupId': 'OG001', 'lowerLimit': '-70.21', 'upperLimit': '-27.91'}, {'value': '-51.88', 'groupId': 'OG002', 'lowerLimit': '-69.03', 'upperLimit': '-25.23'}]}]}, {'title': 'Day 43', 'categories': [{'measurements': [{'value': '-24.93', 'groupId': 'OG000', 'lowerLimit': '-51.70', 'upperLimit': '16.67'}, {'value': '-36.30', 'groupId': 'OG001', 'lowerLimit': '-59.05', 'upperLimit': '-0.92'}, {'value': '-42.44', 'groupId': 'OG002', 'lowerLimit': '-62.95', 'upperLimit': '-10.56'}]}]}, {'title': 'Day 50', 'categories': [{'measurements': [{'value': '-2.88', 'groupId': 'OG000', 'lowerLimit': '-37.51', 'upperLimit': '50.95'}, {'value': '-26.57', 'groupId': 'OG001', 'lowerLimit': '-52.79', 'upperLimit': '14.22'}, {'value': '-37.04', 'groupId': 'OG002', 'lowerLimit': '-59.48', 'upperLimit': '-2.17'}]}]}, {'title': 'Day 57', 'categories': [{'measurements': [{'value': '-1.46', 'groupId': 'OG000', 'lowerLimit': '-36.60', 'upperLimit': '53.14'}, {'value': '-14.49', 'groupId': 'OG001', 'lowerLimit': '-45.03', 'upperLimit': '33.02'}, {'value': '-37.74', 'groupId': 'OG002', 'lowerLimit': '-59.93', 'upperLimit': '-3.25'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Baseline and 4 hours, 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 50 and 57 days postdose', 'description': 'Serum PCSK9 concentrations were determined using a qualified ELISA. The LLOQ of the assay was 15 ng/mL.\n\nLog-transformed baseline PCSK9 was included in the model as a covariate and participant as a random effect.', 'unitOfMeasure': 'percent change', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Safety analysis set'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Normal Renal Function', 'description': 'Participants with normal renal function (defined as an estimated glomerular filtration rate \\[eGFR\\] ≥ 90 mL/min/1.73 m²) received a single 140 mg dose of evolocumab subcutaneously on Day 1.'}, {'id': 'FG001', 'title': 'Severe Renal Impairment', 'description': 'Participants with severe renal impairment (defined as eGFR 15 to 29 mL/min/1.73 m²) received a single 140 mg dose of evolocumab subcutaneously on Day 1.'}, {'id': 'FG002', 'title': 'End Stage Renal Disease', 'description': 'Participants with end-stage renal disease (ESRD) requiring hemodialysis received a single 140 mg dose of evolocumab subcutaneously on Day 1.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '6'}, {'groupId': 'FG001', 'numSubjects': '6'}, {'groupId': 'FG002', 'numSubjects': '6'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '6'}, {'groupId': 'FG001', 'numSubjects': '6'}, {'groupId': 'FG002', 'numSubjects': '6'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '0'}]}]}], 'recruitmentDetails': 'Eighteen participants were enrolled at 1 center in the United States. The first participant enrolled on 19 August 2014 and the last participant enrolled on 28 October 2014.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'BG000'}, {'value': '6', 'groupId': 'BG001'}, {'value': '6', 'groupId': 'BG002'}, {'value': '18', 'groupId': 'BG003'}]}], 'groups': [{'id': 'BG000', 'title': 'Normal Renal Function', 'description': 'Participants with normal renal function (defined as an estimated glomerular filtration rate \\[eGFR\\] ≥ 90 mL/min/1.73 m²) received a single 140 mg dose of evolocumab subcutaneously on Day 1.'}, {'id': 'BG001', 'title': 'Severe Renal Impairment', 'description': 'Participants with severe renal impairment (defined as eGFR 15 to 29 mL/min/1.73 m²) received a single 140 mg dose of evolocumab subcutaneously on Day 1.'}, {'id': 'BG002', 'title': 'End Stage Renal Disease', 'description': 'Participants with end-stage renal disease (ESRD) requiring hemodialysis received a single 140 mg dose of evolocumab subcutaneously on Day 1.'}, {'id': 'BG003', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '51.2', 'spread': '9.9', 'groupId': 'BG000'}, {'value': '63.3', 'spread': '7.8', 'groupId': 'BG001'}, {'value': '57.0', 'spread': '8.1', 'groupId': 'BG002'}, {'value': '57.2', 'spread': '9.6', 'groupId': 'BG003'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '2', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '3', 'groupId': 'BG002'}, {'value': '7', 'groupId': 'BG003'}]}, {'title': 'Male', 'measurements': [{'value': '4', 'groupId': 'BG000'}, {'value': '4', 'groupId': 'BG001'}, {'value': '3', 'groupId': 'BG002'}, {'value': '11', 'groupId': 'BG003'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race/Ethnicity, Customized', 'classes': [{'title': 'Black (or African American)', 'categories': [{'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '4', 'groupId': 'BG002'}, {'value': '6', 'groupId': 'BG003'}]}]}, {'title': 'White', 'categories': [{'measurements': [{'value': '5', 'groupId': 'BG000'}, {'value': '5', 'groupId': 'BG001'}, {'value': '2', 'groupId': 'BG002'}, {'value': '12', 'groupId': 'BG003'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 18}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2014-08-19', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2022-11', 'completionDateStruct': {'date': '2014-12-19', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2022-11-03', 'studyFirstSubmitDate': '2014-07-15', 'resultsFirstSubmitDate': '2015-12-08', 'studyFirstSubmitQcDate': '2014-10-23', 'lastUpdatePostDateStruct': {'date': '2022-11-07', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2016-01-14', 'studyFirstPostDateStruct': {'date': '2014-10-27', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2016-01-29', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2014-12-19', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Maximum Observed Serum Concentration (Cmax) of Evolocumab', 'timeFrame': 'Predose and 4 hours, 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 50 and 57 days postdose', 'description': 'Serum concentrations of evolocumab were measured by a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) of the assay was 800 ng/mL.'}, {'measure': 'Area Under the Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC0-last) for Evolocumab', 'timeFrame': 'Predose and 4 hours, 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 50 and 57 days postdose'}], 'secondaryOutcomes': [{'measure': 'Number of Participants With Adverse Events', 'timeFrame': 'From the first dose of study drug up until Day 57', 'description': 'The severity of each adverse event was graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4. A serious adverse event is defined as an adverse event that meets at least 1 of the following serious criteria:\n\n* fatal;\n* life threatening (places the participant at immediate risk of death);\n* requires in patient hospitalization or prolongation of existing hospitalization;\n* results in persistent or significant disability/incapacity;\n* congenital anomaly/birth defect;\n* other medically important serious event.\n\nThe investigator assessed whether each adverse event was possibly related to the study drug.'}, {'measure': 'Number of Participants With Clinically Relevant Vital Sign or Clinical Laboratory Changes', 'timeFrame': '57 days', 'description': "The investigator reviewed vital signs and laboratory test results and determined whether an abnormal value in an individual participant represented a clinically significant change from the participant's baseline values."}, {'measure': 'Number of Participants With Anti-evolocumab Antibodies', 'timeFrame': '57 days', 'description': 'Blood samples were tested using an electrochemiluminescence-based bridging immunoassay to detect antibodies capable of binding to evolocumab.'}, {'measure': 'Area Under the Effect Curve From Baseline to Day 57 (AUECday1-57) for Low-density Lipoprotein Cholesterol (LDL-C)', 'timeFrame': '4 hours, 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 50 and 57 days postdose', 'description': 'The derived log-transformed AUECday1-57 for direct LDL-C was analyzed using a mixed-effect analysis of variance model. Log-transformed baseline LDL-C was the covariate.'}, {'measure': 'Mean Percent Change From Baseline in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9)', 'timeFrame': 'Baseline and 4 hours, 2, 3, 4, 6, 8, 11, 15, 22, 29, 43, 50 and 57 days postdose', 'description': 'Serum PCSK9 concentrations were determined using a qualified ELISA. The LLOQ of the assay was 15 ng/mL.\n\nLog-transformed baseline PCSK9 was included in the model as a covariate and participant as a random effect.'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['Subjects with normal renal function or severe renal impairment (RI) or end stage renal disease (ESRD) receiving hemodialysis'], 'conditions': ['Hyperlipidemia', 'Mixed Dyslipidemia']}, 'referencesModule': {'references': [{'pmid': '29353350', 'type': 'BACKGROUND', 'citation': 'Kasichayanula S, Grover A, Emery MG, Gibbs MA, Somaratne R, Wasserman SM, Gibbs JP. Clinical Pharmacokinetics and Pharmacodynamics of Evolocumab, a PCSK9 Inhibitor. Clin Pharmacokinet. 2018 Jul;57(7):769-779. doi: 10.1007/s40262-017-0620-7.'}, {'pmid': '30676701', 'type': 'BACKGROUND', 'citation': 'Lee E, Gibbs JP, Emery MG, Block G, Wasserman SM, Hamilton L, Kasichayanula S, Hanafin P, Somaratne R, Egbuna O. Influence of Renal Function on Evolocumab Exposure, Pharmacodynamics, and Safety. Clin Pharmacol Drug Dev. 2019 Apr;8(3):281-289. doi: 10.1002/cpdd.650. Epub 2019 Jan 24.'}], 'seeAlsoLinks': [{'url': 'http://www.amgentrials.com', 'label': 'AmgenTrials clinical trials website'}]}, 'descriptionModule': {'briefSummary': 'The primary objective of this study was to evaluate the pharmacokinetics of evolocumab after a single 140 mg subcutaneous (SC) dose in aduts with normal renal function or severe renal impairment or end-stage renal disease (ESRD) receiving hemodialysis.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '70 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Body mass index (BMI) of ≥ 18 and ≤ 35 kg/m² at screening.\n* Subjects will have low-density lipoprotein cholesterol (LDL-C) of 70-190 mg/dL (inclusive) and on statin therapy.\n* Other inclusion criteria may apply.\n\nExclusion Criteria:\n\n* Subject with current or prior history of statin intolerance\n* Subject has previously received Evolocumab (AMG 145) or any other investigational therapy directed against PCSK9\n* Known substance abuse (eg, alcohol, licit or illicit drugs) within 12 months of day -1\n* Testing positive for alcohol and/or drugs-of-abuse at screening, day -1, or day 1 (alcohol only)\n* History of hypersensitivity or allergic reaction to mammalian-derived drug preparations\n* Known sensitivity to any of the active substances or their excipients to be administered during dosing, eg, carboxymethylcellulose\n* Other exclusion criteria may apply.'}, 'identificationModule': {'nctId': 'NCT02275156', 'briefTitle': 'Estimation Study to Assess the Effect of Severe Renal Impairment and End-stage Renal Disease Hemodialysis on the Pharmacokinetics of Evolocumab', 'organization': {'class': 'INDUSTRY', 'fullName': 'Amgen'}, 'officialTitle': 'Phase 1, Open-label, Single-dose Study of Evolocumab (AMG 145) Administered Subcutaneously to Subjects With Normal Renal Function or Severe Renal Impairment or End Stage Renal Disease Receiving Hemodialysis', 'orgStudyIdInfo': {'id': '20140213'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Evolocumab', 'description': 'Participants received a single 140 mg dose of evolocumab subcutaneously on Day 1.', 'interventionNames': ['Biological: Evolocumab']}], 'interventions': [{'name': 'Evolocumab', 'type': 'BIOLOGICAL', 'otherNames': ['AMG 145', 'Repatha'], 'description': 'Administered by subcutaneous injection', 'armGroupLabels': ['Evolocumab']}]}, 'contactsLocationsModule': {'locations': [{'zip': '80230', 'city': 'Denver', 'state': 'Colorado', 'country': 'United States', 'facility': 'Research Site', 'geoPoint': {'lat': 39.73915, 'lon': -104.9847}}], 'overallOfficials': [{'name': 'MD', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Amgen'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Amgen', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}