Ignite Creation Date:
2025-12-24 @ 7:38 PM
Ignite Modification Date:
2025-12-26 @ 11:49 PM
Study NCT ID:
NCT01446003
Status:
COMPLETED
Last Update Posted:
2019-02-05
First Post:
2011-09-30
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
A Study of the Effect of MK-8457 on Blood Pressure in Hypertensive Participants (MK-8457-004-AM1)
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D006973', 'term': 'Hypertension'}], 'ancestors': [{'id': 'D014652', 'term': 'Vascular Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}]}}, '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': {'otherDetails': 'The Sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission.', 'restrictionType': 'OTHER', 'piSponsorEmployee': False, 'restrictiveAgreement': True}}, 'adverseEventsModule': {'timeFrame': 'Up to 70 days', 'description': 'The safety population consisted of all participants who received at least one dose of the investigational drug.', 'eventGroups': [{'id': 'EG000', 'title': 'MK-8457 100 mg BID', 'description': 'Participants received MK-8457 100 mg BID for 10 days', 'otherNumAtRisk': 31, 'otherNumAffected': 8, 'seriousNumAtRisk': 31, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Placebo', 'description': 'Participants received Placebo for MK-8457 for 10 days', 'otherNumAtRisk': 29, 'otherNumAffected': 9, 'seriousNumAtRisk': 29, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'Lymphadenopathy', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 29, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA v 15.0'}, {'term': 'Tinnitus', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 29, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Ear and labyrinth disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA v 15.0'}, {'term': 'Bloating', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 29, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA v 15.0'}, {'term': 'Diarrhoea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 29, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA v 15.0'}, {'term': 'Nausea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 29, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA v 15.0'}, {'term': 'Energy decreased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 29, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA v 15.0'}, {'term': 'Flu-like symptoms', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 29, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA v 15.0'}, {'term': 'Swelling of fingers', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 29, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA v 15.0'}, {'term': 'Venipuncture site pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 29, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA v 15.0'}, {'term': 'Viral upper respiratory tract infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 29, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA v 15.0'}, {'term': 'White blood cell count abnormal', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 29, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA v 15.0'}, {'term': 'Knee pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 29, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA v 15.0'}, {'term': 'Headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 29, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA v 15.0'}, {'term': 'Lightheadedness', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 29, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA v 15.0'}, {'term': 'Cough', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 29, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA v 15.0'}, {'term': 'Nasal congestion', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 29, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA v 15.0'}, {'term': 'Rhinorrhoea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 29, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA v 15.0'}, {'term': 'Dry skin', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 29, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA v 15.0'}, {'term': 'Deep vein thrombosis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 31, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 29, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Vascular disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA v 15.0'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Change From Baseline to Day 10 in 24-hour Mean Ambulatory Systolic Blood Pressure (SBP)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '29', 'groupId': 'OG000'}, {'value': '28', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'MK-8457 100 mg BID', 'description': 'Participants received MK-8457 100 mg BID for 10 days followed by Placebo for 10 days. Each treatment was separated by a 10-day washout.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Participants received Placebo for 10 days followed by MK-8457 100 mg BID for 10 days. Each treatment was separated by a 10-day washout.'}], 'classes': [{'categories': [{'measurements': [{'value': '-0.47', 'groupId': 'OG000', 'lowerLimit': '-2.60', 'upperLimit': '1.66'}, {'value': '-2.49', 'groupId': 'OG001', 'lowerLimit': '-4.66', 'upperLimit': '-0.31'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '2.02', 'ciLowerLimit': '-0.52', 'ciUpperLimit': '4.56', 'groupDescription': 'If the upper limit of the 90% confidence interval lies below the bound 5 mmHg, the hypothesis that change from baseline in ambulatory 24-hour mean SBP in participants with mild to moderate hypertension following 10 days of multiple dosing of MK-8457 is similar to placebo will be supported.', 'statisticalMethod': 'Linear mixed effect models', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'statisticalComment': 'The model contained period and treatment as fixed effect, Day -1 baseline as a fixed continuous covariate, and participant as random effect.'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline and Day 10', 'description': 'SBP was measured using ambulatory blood pressure monitoring (ABPM) on Day -1 and Day 10 of each treatment period. The 24-hour least squares (LS) mean ambulatory SBP change from baseline was then determined for Day 10, the last day of multiple dose treatment. Baseline is defined as the average 24-hour SBP for each participant on Day -1. Increased values represent an increase in hypertensive severity.', 'unitOfMeasure': 'mmHg', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'The per-protocol population consisting of participants who comply with the protocol sufficiently to ensure that data were likely to exhibit the effects of treatment according to the underlying scientific model used for analysis (change in 24-hour mean ambulatory SBP).'}, {'type': 'SECONDARY', 'title': 'Change From Baseline to Day 10 in 24-hour Mean Ambulatory Diastolic Blood Pressure (DBP)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '29', 'groupId': 'OG000'}, {'value': '28', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'MK-8457 100 mg BID', 'description': 'Participants received MK-8457 100 mg BID for 10 days followed by Placebo for 10 days. Each treatment was separated by a 10-day washout.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Participants received Placebo for 10 days followed by MK-8457 100 mg BID for 10 days. Each treatment was separated by a 10-day washout.'}], 'classes': [{'categories': [{'measurements': [{'value': '0.22', 'groupId': 'OG000', 'lowerLimit': '-1.33', 'upperLimit': '1.78'}, {'value': '-1.35', 'groupId': 'OG001', 'lowerLimit': '-2.93', 'upperLimit': '0.23'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Median Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '1.57', 'ciLowerLimit': '0.19', 'ciUpperLimit': '2.96', 'statisticalMethod': 'Linear mixed effects model', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'statisticalComment': 'The model contained period and treatment as fixed effect, Day -1 baseline as a fixed continuous covariate, and participant as random effect.'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline and Day 10', 'description': 'DBP was measured using ambulatory blood pressure monitoring (ABPM) on Day -1 and Day 10 of each treatment period. The 24-hour LS mean ambulatory DBP change from baseline was then determined for Day 10, the last day of multiple dose treatment. Baseline is defined as the average 24-hour DBP for each participant on Day -1. Increased values represent an increase in hypertensive severity.', 'unitOfMeasure': 'mmHg', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'The per-protocol population consisting of participants who comply with the protocol sufficiently to ensure that data were likely to exhibit the effects of treatment according to the underlying scientific model used for analysis (change in 24-hour mean ambulatory DBP).'}, {'type': 'SECONDARY', 'title': 'Change From Baseline to Day 10 in Maximum Moving Average (maxMAΔ) Blood Pressure Measured Over 4 Hours', 'denoms': [{'units': 'Participants', 'counts': [{'value': '29', 'groupId': 'OG000'}, {'value': '28', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'MK-8457 100 mg BID', 'description': 'Participants received MK-8457 100 mg BID for 10 days followed by Placebo for 10 days. Each treatment was separated by a 10-day washout.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Participants received Placebo for 10 days followed by MK-8457 100 mg BID for 10 days. Each treatment was separated by a 10-day washout.'}], 'classes': [{'title': 'SBP - AM (n=29,28)', 'categories': [{'measurements': [{'value': '17.80', 'spread': '13.36', 'groupId': 'OG000', 'lowerLimit': '12.36', 'upperLimit': '23.23'}, {'value': '9.90', 'spread': '10.05', 'groupId': 'OG001', 'lowerLimit': '4.37', 'upperLimit': '15.43'}]}]}, {'title': 'SBP - PM (n=29,27)', 'categories': [{'measurements': [{'value': '12.68', 'spread': '12.28', 'groupId': 'OG000', 'lowerLimit': '8.63', 'upperLimit': '16.72'}, {'value': '13.61', 'spread': '11.31', 'groupId': 'OG001', 'lowerLimit': '9.40', 'upperLimit': '17.83'}]}]}, {'title': 'DBP - AM (n=29,28)', 'categories': [{'measurements': [{'value': '16.90', 'spread': '8.17', 'groupId': 'OG000', 'lowerLimit': '13.14', 'upperLimit': '20.66'}, {'value': '11.64', 'spread': '8.26', 'groupId': 'OG001', 'lowerLimit': '7.80', 'upperLimit': '15.48'}]}]}, {'title': 'DBP - PM (n=29,27)', 'categories': [{'measurements': [{'value': '10.89', 'spread': '11.52', 'groupId': 'OG000', 'lowerLimit': '8.02', 'upperLimit': '13.76'}, {'value': '12.58', 'spread': '10.89', 'groupId': 'OG001', 'lowerLimit': '9.60', 'upperLimit': '15.56'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '7.90', 'ciLowerLimit': '2.44', 'ciUpperLimit': '13.35', 'groupDescription': 'Treatment comparison of maxMAΔ in SBP from baseline to Day 10 after AM dosing', 'statisticalMethod': 'Linear mixed effects model', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'statisticalComment': 'The model contained period and treatment as fixed effect, Day -1 baseline as a fixed continuous covariate, and participant as random effect.'}, {'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '-0.94', 'ciLowerLimit': '-5.68', 'ciUpperLimit': '3.81', 'groupDescription': 'Treatment comparison of maxMAΔ in SBP from baseline to Day 10 after PM dosing', 'statisticalMethod': 'Linear mixed effects model', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'statisticalComment': 'The model contained period and treatment as fixed effect, Day -1 baseline as a fixed continuous covariate, and participant as random effect.'}, {'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '5.26', 'ciLowerLimit': '0.81', 'ciUpperLimit': '9.71', 'groupDescription': 'Treatment comparison of maxMAΔ in DBP from baseline to Day 10 after AM dosing', 'statisticalMethod': 'Linear mixed effects model', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'statisticalComment': 'The model contained period and treatment as fixed effect, Day -1 baseline as a fixed continuous covariate, and participant as random effect.'}, {'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '-1.69', 'ciLowerLimit': '-4.55', 'ciUpperLimit': '1.17', 'groupDescription': 'Treatment comparison of maxMAΔ in DBP from baseline to Day 10 after PM dosing', 'statisticalMethod': 'Linear mixed effects model', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'statisticalComment': 'The model contained period and treatment as fixed effect, Day -1 baseline as a fixed continuous covariate, and participant as random effect.'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Up to 4 hours postdose on Days 1 and 10', 'description': 'The effect of drug on resting blood pressure was estimated using maxMAΔ. The maxMAΔ in blood pressure was calculated as the maximum moving average change from baseline to Day 10 of 3 consecutive 15-minute blood pressure measurements across the first 4 hours after the morning (AM) and evening (PM) doses. In this method, the LS means of three consecutive time points over the 4 hour period were determined and the maximum LS mean was used for the endpoint. Blood pressure was determined using continuous monitoring at rest. Increased values represent an increase in hypertensive severity.', 'unitOfMeasure': 'mmHg', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'The per-protocol population consisting of participants who comply with the protocol sufficiently to ensure that data were likely to exhibit the effects of treatment according to the underlying scientific model used for analysis (maxMAΔ in blood pressure).'}, {'type': 'SECONDARY', 'title': 'Area Under the Plasma Concentration-time Curve From Time 0 to 12 Hours (AUC0-12hr) of MK-8457', 'denoms': [{'units': 'Participants', 'counts': [{'value': '31', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'MK-8457 100 mg BID', 'description': 'Participants received MK-8457 100 mg BID for 10 days followed by Placebo for 10 days. Each treatment was separated by a 10-day washout.'}], 'classes': [{'title': 'Day 1 (n=31)', 'categories': [{'measurements': [{'value': '29600', 'spread': '36', 'groupId': 'OG000'}]}]}, {'title': 'Day 10 (n=30)', 'categories': [{'measurements': [{'value': '56200', 'spread': '44', 'groupId': 'OG000'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'pre-AM dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post AM dose on Days 1 and 10', 'description': 'AUC0-12hr is an estimate of total plasma exposure to study drug over the dosing interval (12hr). Plasma concentrations of MK-8457 were determined on Day 1 (after initial dosing) and Day 10 (after multiple dosing). The placebo group is not included; this endpoint evaluated only the MK-8457 group.', 'unitOfMeasure': 'nM*hr', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'The per-protocol population consisting of participants who comply with the protocol sufficiently to ensure that data were likely to exhibit the effects of treatment according to the underlying scientific model used for analysis (AUC0-12hr).'}, {'type': 'SECONDARY', 'title': 'Maximum Concentration (Cmax) of MK-8457', 'denoms': [{'units': 'Participants', 'counts': [{'value': '31', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'MK-8457 100 mg BID', 'description': 'Participants received MK-8457 100 mg BID for 10 days followed by Placebo for 10 days. Each treatment was separated by a 10-day washout.'}], 'classes': [{'title': 'Day 1 (n=31)', 'categories': [{'measurements': [{'value': '5680', 'spread': '31', 'groupId': 'OG000'}]}]}, {'title': 'Day 10 (n=30)', 'categories': [{'measurements': [{'value': '8630', 'spread': '38', 'groupId': 'OG000'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'pre-AM dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post AM dose on Days 1 and 10; 24 hrs post-AM dose on Day 10', 'description': 'Maximum plasma concentrations of MK-8521 were determined for the AM dose on Day 1 and Day 10. The placebo group was not included; this endpoint evaluated only the MK-8457 group.', 'unitOfMeasure': 'nM', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'The per-protocol population consisting of participants who comply with the protocol sufficiently to ensure that data were likely to exhibit the effects of treatment according to the underlying scientific model used for analysis (Cmax).'}, {'type': 'SECONDARY', 'title': 'Time to Maximum Concentration (Tmax) of MK-8457', 'denoms': [{'units': 'Participants', 'counts': [{'value': '31', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'MK-8457 100 mg BID', 'description': 'Participants received MK-8457 100 mg BID for 10 days followed by Placebo for 10 days. Each treatment was separated by a 10-day washout.'}], 'classes': [{'title': 'Day 1 (n=31)', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000', 'lowerLimit': '0.75', 'upperLimit': '2.0'}]}]}, {'title': 'Day 10 (n=30)', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000', 'lowerLimit': '0.5', 'upperLimit': '3.0'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'pre-AM dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post AM dose on Days 1 and 10; 24 hrs post-AM dose on Day 10', 'description': 'Tmax was determined for the AM dose on Day 1 and Day 10. The placebo group was not included; this endpoint evaluated only the MK-8457 group.', 'unitOfMeasure': 'hr', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'The per-protocol population consisting of participants who comply with the protocol sufficiently to ensure that data were likely to exhibit the effects of treatment according to the underlying scientific model used for analysis (Tmax).'}, {'type': 'SECONDARY', 'title': 'Trough Plasma Concentration (Ctrough) of MK-8457', 'denoms': [{'units': 'Participants', 'counts': [{'value': '31', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'MK-8457 100 mg BID', 'description': 'Participants received MK-8457 100 mg BID for 10 days followed by Placebo for 10 days. Each treatment was separated by a 10-day washout.'}], 'classes': [{'title': 'Day 1 (n=31)', 'categories': [{'measurements': [{'value': '999', 'spread': '56', 'groupId': 'OG000'}]}]}, {'title': 'Day 10 (n=30)', 'categories': [{'measurements': [{'value': '2540', 'spread': '56', 'groupId': 'OG000'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'pre-AM dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post AM dose on Days 1 and 10; pre-AM dose on Day 5 or 6', 'description': 'The lowest plasma concentration reached by the drug prior to the next administration was determined for Day 1 (after initial dosing) and Day 10 (after multiple dosing). The placebo group was not included; this endpoint evaluated only the MK-8457 group.', 'unitOfMeasure': 'nM', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'The per-protocol population consisting of participants who comply with the protocol sufficiently to ensure that data were likely to exhibit the effects of treatment according to the underlying scientific model used for analysis (Ctrough).'}, {'type': 'PRIMARY', 'title': 'Number of Participants Who Experienced at Least One Adverse Event (AE)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '31', 'groupId': 'OG000'}, {'value': '29', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'MK-8457 100 mg BID', 'description': 'Participants received MK-8457 100 mg BID for 10 days followed by Placebo for 10 days. Each treatment was separated by a 10-day washout.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Participants received Placebo for 10 days followed by MK-8457 100 mg BID for 10 days. Each treatment was separated by a 10-day washout.'}], 'classes': [{'categories': [{'measurements': [{'value': '8', 'groupId': 'OG000', 'lowerLimit': '-2.60', 'upperLimit': '1.66'}, {'value': '9', 'groupId': 'OG001', 'lowerLimit': '-4.66', 'upperLimit': '-0.31'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Up to 70 days', 'description': 'An AE is defined as any unfavorable and unintended medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.', 'unitOfMeasure': 'Participant', 'reportingStatus': 'POSTED', 'populationDescription': 'The safety population consisted of all participants who received at least one dose of the investigational drug.'}, {'type': 'PRIMARY', 'title': 'Number of Participants Who Discontinued the Study Medication Due to an AE', 'denoms': [{'units': 'Participants', 'counts': [{'value': '31', 'groupId': 'OG000'}, {'value': '29', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'MK-8457 100 mg BID', 'description': 'Participants received MK-8457 100 mg BID for 10 days followed by Placebo for 10 days. Each treatment was separated by a 10-day washout.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Participants received Placebo for 10 days followed by MK-8457 100 mg BID for 10 days. Each treatment was separated by a 10-day washout.'}], 'classes': [{'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000', 'lowerLimit': '-2.60', 'upperLimit': '1.66'}, {'value': '0', 'groupId': 'OG001', 'lowerLimit': '-4.66', 'upperLimit': '-0.31'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Up to 70 days', 'description': 'An AE is defined as any unfavorable and unintended medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.', 'unitOfMeasure': 'Participant', 'reportingStatus': 'POSTED', 'populationDescription': 'The safety population consisted of all participants who received at least one dose of the investigational drug.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'MK-8457-Placebo Sequence', 'description': 'Participants received MK-8457 100 mg twice daily (BID) for 10 days followed by Placebo for 10 days. Each treatment was separated by a 10-day washout.'}, {'id': 'FG001', 'title': 'Placebo-MK-8457 Sequence', 'description': 'Participants received Placebo for 10 days followed by MK-8457 100 mg BID for 10 days. Each treatment was separated by a 10-day washout.'}], 'periods': [{'title': 'Period 1', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '16'}, {'groupId': 'FG001', 'numSubjects': '15'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '14'}, {'groupId': 'FG001', 'numSubjects': '15'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '2'}, {'groupId': 'FG001', 'numSubjects': '0'}]}], 'dropWithdraws': [{'type': 'Protocol Violation', 'reasons': [{'groupId': 'FG000', 'numSubjects': '2'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}, {'title': 'Period 2', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '14'}, {'groupId': 'FG001', 'numSubjects': '15'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '13'}, {'groupId': 'FG001', 'numSubjects': '15'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}], 'dropWithdraws': [{'type': 'Adverse Event', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '31', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'All Participants'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '52.3', 'spread': '5.9', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'Years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Age, Customized', 'classes': [{'title': 'Between 18 and 65 years', 'categories': [{'measurements': [{'value': '30', 'groupId': 'BG000'}]}]}, {'title': '>=65 years', 'categories': [{'measurements': [{'value': '1', 'groupId': 'BG000'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'Participants'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '9', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '22', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}], 'populationDescription': 'All participants that received treatment with either MK-8457 or Placebo in the study.'}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'CROSSOVER'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 31}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2011-10-25', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2019-01', 'completionDateStruct': {'date': '2012-03-03', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2019-01-18', 'studyFirstSubmitDate': '2011-09-30', 'resultsFirstSubmitDate': '2017-03-20', 'studyFirstSubmitQcDate': '2011-10-03', 'lastUpdatePostDateStruct': {'date': '2019-02-05', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2017-03-20', 'studyFirstPostDateStruct': {'date': '2011-10-04', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2017-05-02', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2012-02-18', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Change From Baseline to Day 10 in 24-hour Mean Ambulatory Systolic Blood Pressure (SBP)', 'timeFrame': 'Baseline and Day 10', 'description': 'SBP was measured using ambulatory blood pressure monitoring (ABPM) on Day -1 and Day 10 of each treatment period. The 24-hour least squares (LS) mean ambulatory SBP change from baseline was then determined for Day 10, the last day of multiple dose treatment. Baseline is defined as the average 24-hour SBP for each participant on Day -1. Increased values represent an increase in hypertensive severity.'}, {'measure': 'Number of Participants Who Experienced at Least One Adverse Event (AE)', 'timeFrame': 'Up to 70 days', 'description': 'An AE is defined as any unfavorable and unintended medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.'}, {'measure': 'Number of Participants Who Discontinued the Study Medication Due to an AE', 'timeFrame': 'Up to 70 days', 'description': 'An AE is defined as any unfavorable and unintended medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.'}], 'secondaryOutcomes': [{'measure': 'Change From Baseline to Day 10 in 24-hour Mean Ambulatory Diastolic Blood Pressure (DBP)', 'timeFrame': 'Baseline and Day 10', 'description': 'DBP was measured using ambulatory blood pressure monitoring (ABPM) on Day -1 and Day 10 of each treatment period. The 24-hour LS mean ambulatory DBP change from baseline was then determined for Day 10, the last day of multiple dose treatment. Baseline is defined as the average 24-hour DBP for each participant on Day -1. Increased values represent an increase in hypertensive severity.'}, {'measure': 'Change From Baseline to Day 10 in Maximum Moving Average (maxMAΔ) Blood Pressure Measured Over 4 Hours', 'timeFrame': 'Up to 4 hours postdose on Days 1 and 10', 'description': 'The effect of drug on resting blood pressure was estimated using maxMAΔ. The maxMAΔ in blood pressure was calculated as the maximum moving average change from baseline to Day 10 of 3 consecutive 15-minute blood pressure measurements across the first 4 hours after the morning (AM) and evening (PM) doses. In this method, the LS means of three consecutive time points over the 4 hour period were determined and the maximum LS mean was used for the endpoint. Blood pressure was determined using continuous monitoring at rest. Increased values represent an increase in hypertensive severity.'}, {'measure': 'Area Under the Plasma Concentration-time Curve From Time 0 to 12 Hours (AUC0-12hr) of MK-8457', 'timeFrame': 'pre-AM dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post AM dose on Days 1 and 10', 'description': 'AUC0-12hr is an estimate of total plasma exposure to study drug over the dosing interval (12hr). Plasma concentrations of MK-8457 were determined on Day 1 (after initial dosing) and Day 10 (after multiple dosing). The placebo group is not included; this endpoint evaluated only the MK-8457 group.'}, {'measure': 'Maximum Concentration (Cmax) of MK-8457', 'timeFrame': 'pre-AM dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post AM dose on Days 1 and 10; 24 hrs post-AM dose on Day 10', 'description': 'Maximum plasma concentrations of MK-8521 were determined for the AM dose on Day 1 and Day 10. The placebo group was not included; this endpoint evaluated only the MK-8457 group.'}, {'measure': 'Time to Maximum Concentration (Tmax) of MK-8457', 'timeFrame': 'pre-AM dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post AM dose on Days 1 and 10; 24 hrs post-AM dose on Day 10', 'description': 'Tmax was determined for the AM dose on Day 1 and Day 10. The placebo group was not included; this endpoint evaluated only the MK-8457 group.'}, {'measure': 'Trough Plasma Concentration (Ctrough) of MK-8457', 'timeFrame': 'pre-AM dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post AM dose on Days 1 and 10; pre-AM dose on Day 5 or 6', 'description': 'The lowest plasma concentration reached by the drug prior to the next administration was determined for Day 1 (after initial dosing) and Day 10 (after multiple dosing). The placebo group was not included; this endpoint evaluated only the MK-8457 group.'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Hypertension']}, 'descriptionModule': {'briefSummary': 'This study will evaluate the effect of treatment with multiple doses of MK-8457 on systolic blood pressure in participants with mild to moderate hypertension in addition to safety and tolerability. The study hypothesis is that MK-8457 does not increase systolic blood pressure to a clinically significant extent, as measured by 24-hour mean ambulatory systolic blood pressure change from baseline after 10 days of dosing.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '65 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* If female, must be of non-childbearing potential\n* If male with female partner(s) of child-bearing potential must agree to use a medically acceptable method of contraception during the study and for 90 days after the last dose of study drug\n* Body mass index (BMI) ≤35 kg/m\\^2\n* Mild-to-moderate hypertension requiring treatment with one or more antihypertensive agents\n* Receiving stable treatment for hypertension for at least 8 weeks prior to the start of dosing and continuing therapy for duration of study\n* No clinically significant arrhythmias or clinically significant abnormality on electrocardiogram\n* Nonsmoker and/or has not used nicotine or nicotine-containing products for at least approximately 6 months\n\nExclusion Criteria:\n\n* Any illness that might confound the results of the study or poses an additional risk\n* History of stroke, chronic seizures, or major neurological disorder\n* Clinically significant endocrine, gastrointestinal, hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases\n* Clinically significant cardiovascular disease or has active angina\n* History of malignant neoplastic disease\n* Taking 325 mg aspirin daily\n* Taking 3 or more medications for the treatment of hypertension\n* Unable to refrain from or anticipates the use of any non-steroidal anti-inflammatory drugs (NSAIDs)\n* Consumes excessive amounts of alcohol and/or coffee, tea, cola, or other caffeinated beverages\n* Has had major surgery, donated or lost 1 unit of blood or participated in another investigational study within 4 weeks\n* Significant multiple and/or severe allergies\n* Regular user of any illicit drugs or has a history of drug (including alcohol) abuse within approximately 2 years'}, 'identificationModule': {'nctId': 'NCT01446003', 'briefTitle': 'A Study of the Effect of MK-8457 on Blood Pressure in Hypertensive Participants (MK-8457-004-AM1)', 'organization': {'class': 'INDUSTRY', 'fullName': 'Merck Sharp & Dohme LLC'}, 'officialTitle': 'A Multiple-Dose Clinical Trial to Study the Effect of MK-8457 on Ambulatory Blood Pressure in Hypertensive Patients', 'orgStudyIdInfo': {'id': '8457-004'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'MK-8457-Placebo Sequence', 'description': 'Participants received MK-8457 100 mg twice daily (BID) for 10 days followed by Placebo for 10 days. Each treatment was separated by a 10-day washout.', 'interventionNames': ['Drug: MK-8457', 'Drug: Placebo for MK-8457']}, {'type': 'EXPERIMENTAL', 'label': 'Placebo-MK-8457 Sequence', 'description': 'Participants received Placebo for 10 days followed by MK-8457 100 mg BID for 10 days. Each treatment was separated by a 10-day washout.', 'interventionNames': ['Drug: MK-8457', 'Drug: Placebo for MK-8457']}], 'interventions': [{'name': 'MK-8457', 'type': 'DRUG', 'description': '10 x 10-mg capsule BID for 10 days', 'armGroupLabels': ['MK-8457-Placebo Sequence', 'Placebo-MK-8457 Sequence']}, {'name': 'Placebo for MK-8457', 'type': 'DRUG', 'description': '10 x 10-mg capsule BID for 10 days', 'armGroupLabels': ['MK-8457-Placebo Sequence', 'Placebo-MK-8457 Sequence']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Miramar', 'state': 'Florida', 'country': 'United States', 'facility': 'Call for Information', 'geoPoint': {'lat': 25.98731, 'lon': -80.23227}}, {'city': 'Tacoma', 'state': 'Washington', 'country': 'United States', 'facility': 'Call for Information', 'geoPoint': {'lat': 47.25288, 'lon': -122.44429}}], 'overallOfficials': [{'name': 'Medical Director', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Merck Sharp & Dohme LLC'}]}, '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'}}}}