Ignite Creation Date:
2025-12-24 @ 11:54 PM
Ignite Modification Date:
2026-02-25 @ 8:15 PM
Study NCT ID:
NCT03369951
Status:
COMPLETED
Last Update Posted:
2020-12-03
First Post:
2017-12-07
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Minocycline Pharmacokinetics (ACUMIN)
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'submissionTracking': {'firstMcpInfo': {'postDateStruct': {'date': '2020-08-05', 'type': 'ACTUAL'}}}}, 'conditionBrowseModule': {'meshes': [{'id': 'D001424', 'term': 'Bacterial Infections'}, {'id': 'C562573', 'term': 'cyclopia sequence'}], 'ancestors': [{'id': 'D001423', 'term': 'Bacterial Infections and Mycoses'}, {'id': 'D007239', 'term': 'Infections'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D008911', 'term': 'Minocycline'}], 'ancestors': [{'id': 'D013754', 'term': 'Tetracyclines'}, {'id': 'D009279', 'term': 'Naphthacenes'}, {'id': 'D011084', 'term': 'Polycyclic Aromatic Hydrocarbons'}, {'id': 'D006841', 'term': 'Hydrocarbons, Aromatic'}, {'id': 'D006844', 'term': 'Hydrocarbons, Cyclic'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D011083', 'term': 'Polycyclic Compounds'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'r-wunderink@northwestern.edu', 'phone': '312-695-1878', 'title': 'Richard G. Wunderink, MD', 'organization': 'Northwestern University of Feinberg School of Medicine'}, 'certainAgreement': {'restrictionType': 'LTE60', 'piSponsorEmployee': False, 'restrictiveAgreement': True}}, 'adverseEventsModule': {'timeFrame': 'Serious Adverse Events (SAEs) were recorded and reported from the start of the Minocin IV infusion until 24 hours from the start of infusion.', 'description': 'As this is an approved product at an approved dose, and the study is being performed in subjects in the ICU who were anticipated to have multiple events due to their underlying disease, only SAEs were captured in this protocol.', 'eventGroups': [{'id': 'EG000', 'title': 'Minocin® IV', 'description': '200 mg minocycline hydrochloride IV infusion over approximately 60 minutes\n\nMinocycline: Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.', 'otherNumAtRisk': 0, 'deathsNumAtRisk': 57, 'otherNumAffected': 0, 'seriousNumAtRisk': 57, 'deathsNumAffected': 1, 'seriousNumAffected': 1}], 'seriousEvents': [{'term': 'Cardio-Respiratory Arrest', 'stats': [{'groupId': 'EG000', 'numAtRisk': 57, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (22.0)'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Calculated Exposure Measures for Area Under the Curve 0 to 24 Hours After a Dose (AUC0-24)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '55', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Minocin® IV', 'description': '200 mg minocycline hydrochloride IV infusion over approximately 60 minutes\n\nMinocycline: Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.'}], 'classes': [{'categories': [{'measurements': [{'value': '24.3', 'spread': '7.88', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, and 24 hours post dose', 'description': 'Total AUC0-24 is defined as area under the plasma minocycline concentration-time curve from 0 to 24 hours after a dose (milligrams x hours per liter (mg•hr/L)). Patient dosing histories along with the individual post-hoc PK parameters were used to generate total concentration-time profiles. The AUC0-24 was calculated using numerical integration using the data from 0 to 24 hours post-dose.', 'unitOfMeasure': 'mg·hr/L', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'PK population which is defined as participants who (1) received the full infusion of study drug, (2) had at least one PK specimen was processed per the Manual of Procedures, and (3) had at least one such sample provided a quantifiable minocycline concentration available for analysis.'}, {'type': 'PRIMARY', 'title': 'Calculated Exposure Measures for Area Under the Curve From 0 to Infinity (AUC0-inf) Using Free-drug Concentrations', 'denoms': [{'units': 'Participants', 'counts': [{'value': '55', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Minocin® IV', 'description': '200 mg minocycline hydrochloride IV infusion over approximately 60 minutes\n\nMinocycline: Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.'}], 'classes': [{'categories': [{'measurements': [{'value': '14.1', 'spread': '6.68', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose', 'description': 'Free-drug (unbound) AUC0-inf is defined as area under the plasma minocycline concentration-time curve from 0 to infinity after a dose (mg•hr/L). Patient dosing histories along with the individual post-hoc PK parameters were used to generate unbound concentration-time profiles. The AUC0-inf was calculated as Dose/CL.', 'unitOfMeasure': 'mg·hr/L', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'PK population which is defined as participants who (1) received the full infusion of study drug, (2) had at least one PK specimen was processed per the Manual of Procedures, and (3) had at least one such sample provided a quantifiable minocycline concentration available for analysis.'}, {'type': 'PRIMARY', 'title': 'Calculated Exposure Measures for Area Under the Curve From 0 to Infinity (AUC0-inf) Using Total-drug Concentrations', 'denoms': [{'units': 'Participants', 'counts': [{'value': '55', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Minocin® IV', 'description': '200 mg minocycline hydrochloride IV infusion over approximately 60 minutes\n\nMinocycline: Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.'}], 'classes': [{'categories': [{'measurements': [{'value': '46.6', 'spread': '19.7', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose', 'description': 'Total AUC0-inf is defined as area under the plasma minocycline concentration-time curve from 0 to infinity after a dose (mg•hr/L). Patient dosing histories along with the individual post-hoc PK parameters were used to generate total concentration-time profiles. The AUC0-inf was calculated as Dose/CL.', 'unitOfMeasure': 'mg·hr/L', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'PK population which is defined as participants who (1) received the full infusion of study drug, (2) had at least one PK specimen was processed per the Manual of Procedures, and (3) had at least one such sample provided a quantifiable minocycline concentration available for analysis.'}, {'type': 'PRIMARY', 'title': 'Calculated Exposure Measures for Area Under the Curve to the Last Quantifiable Sample (AUC0-last)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '51', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Minocin® IV', 'description': '200 mg minocycline hydrochloride IV infusion over approximately 60 minutes\n\nMinocycline: Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.'}], 'classes': [{'categories': [{'measurements': [{'value': '10.5', 'spread': '3.91', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose', 'description': 'AUC0-last is defined as the area under the plasma minocycline concentration-time curve from 0 to the time of the last quantifiable sample after a dose (mg•hr/L). This was not calculated for the primary outcome measure using the individual post-hoc PK parameters, however was calculated as part of the Non-compartmental analysis using the linear trapezoidal rule (linear up, log down calculation method).', 'unitOfMeasure': 'mg·h/L', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'PK population which is defined as participants who (1) received the full infusion of study drug, (2) had at least one PK specimen was processed per the Manual of Procedures, and (3) had at least one such sample provided a quantifiable minocycline concentration available for analysis.'}, {'type': 'PRIMARY', 'title': 'Calculated Exposure Measures for Maximum Plasma Concentration (Cmax)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '55', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Minocin® IV', 'description': '200 mg minocycline hydrochloride IV infusion over approximately 60 minutes\n\nMinocycline: Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.'}], 'classes': [{'categories': [{'measurements': [{'value': '2.58', 'spread': '1.33', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose', 'description': 'Total-drug Cmax is defined as the maximum plasma total minocycline concentration (mg/L) Patient dosing histories along with the individual post-hoc PK parameters were used to generate total concentration-time profiles. Total Cmax was calculated for each simulated patient as the maximum simulated concentration.', 'unitOfMeasure': 'mg/L', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'PK population which is defined as participants who (1) received the full infusion of study drug, (2) had at least one PK specimen was processed per the Manual of Procedures, and (3) had at least one such sample provided a quantifiable minocycline concentration available for analysis.'}, {'type': 'PRIMARY', 'title': 'Calculated Exposure Measures for Plasma Concentration at 24 Hours After Dose (C24)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '55', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Minocin® IV', 'description': '200 mg minocycline hydrochloride IV infusion over approximately 60 minutes\n\nMinocycline: Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.'}], 'classes': [{'categories': [{'measurements': [{'value': '0.603', 'spread': '0.225', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, and 24 hours post dose', 'description': 'Total-drug C24 is defined as total plasma minocycline concentration at 24 hours after a dose (mg/L). Patient dosing histories along with the individual post-hoc PK parameters were used to generate total concentration-time profiles. The total C24 were calculated for each simulated patient as the simulated concentration at 24 hours after dose.', 'unitOfMeasure': 'mg/L', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'PK population which is defined as participants who (1) received the full infusion of study drug, (2) had at least one PK specimen was processed per the Manual of Procedures, and (3) had at least one such sample provided a quantifiable minocycline concentration available for analysis.'}, {'type': 'PRIMARY', 'title': 'Individual Post-hoc PK Parameter Estimates for Area Under the Curve 0 to 24 Hours After a Dose (AUC0-24)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Minocin® IV', 'description': '200 mg minocycline hydrochloride IV infusion over approximately 60 minutes\n\nMinocycline: Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.'}], 'timeFrame': 'Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, and 24 hours post dose', 'description': 'Total AUC0-24 is defined as area under the plasma minocycline concentration-time curve from 0 to 24 hours after a dose (mg•hr/L). Patient dosing histories along with the individual post-hoc PK parameters were used to generate total concentration-time profiles. The AUC0-24 was calculated for each individual using numerical integration using the data from 0 to 24 hours post-dose. Summary statistics were calculated using the individual post-hoc parameters and reported as calculated exposure measures.', 'reportingStatus': 'POSTED', 'populationDescription': 'Individual post-hoc PK parameter estimate for AUC0-24 was calculated for each patient, summarized by mean and standard deviation, and reported as outcome measure 1 calculated exposure measures for area under the curve 0 to 24 hours after a dose (AUC0-24).'}, {'type': 'PRIMARY', 'title': 'Individual Post-hoc PK Parameter Estimates for Area Under the Curve From 0 to Infinity (AUC0-inf) Using Free-drug Concentrations', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Minocin® IV', 'description': '200 mg minocycline hydrochloride IV infusion over approximately 60 minutes\n\nMinocycline: Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.'}], 'timeFrame': 'Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose', 'description': 'Free-drug (unbound) AUC0-inf is defined as area under the plasma minocycline concentration-time curve from 0 to infinity after a dose (mg•hr/L). Patient dosing histories along with the individual post-hoc PK parameters were used to generate unbound concentration-time profiles. The AUC0-inf was calculated for each individual as Dose/CL. Summary statistics were calculated using the individual post-hoc parameters and reported as calculated exposure measures.', 'reportingStatus': 'POSTED', 'populationDescription': 'Individual post-hoc PK parameter estimate for free-drug AUC0-inf was calculated for each patient, summarized by mean and standard deviation, and reported as outcome measure 2 Calculated exposure measures for area under the curve from 0 to infinity (AUC0-inf) using free-drug concentrations.'}, {'type': 'PRIMARY', 'title': 'Individual Post-hoc PK Parameter Estimates for Area Under the Curve From 0 to Infinity (AUC0-inf) Using Total-drug Concentrations', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Minocin® IV', 'description': '200 mg minocycline hydrochloride IV infusion over approximately 60 minutes\n\nMinocycline: Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.'}], 'timeFrame': 'Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose', 'description': 'Total AUC0-inf is defined as area under the plasma minocycline concentration-time curve from 0 to infinity after a dose (mg•hr/L). Patient dosing histories along with the individual post-hoc PK parameters were used to generate total concentration-time profiles. The AUC0-inf was calculated for each individual as Dose/CL. Summary statistics were calculated using the individual post-hoc parameters and reported as calculated exposure measures.', 'reportingStatus': 'POSTED', 'populationDescription': 'Individual post-hoc PK parameter estimate for total AUC0-inf was calculated for each patient, summarized by mean and standard deviation, and reported as outcome measure 3 calculated exposure measures for area under the curve from 0 to infinity (AUC0-inf) using total-drug concentrations.'}, {'type': 'PRIMARY', 'title': 'Individual Post-hoc PK Parameter Estimates for Area Under the Curve to the Last Quantifiable Sample (AUC0-last)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Minocin® IV', 'description': '200 mg minocycline hydrochloride IV infusion over approximately 60 minutes\n\nMinocycline: Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.'}], 'timeFrame': 'Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose', 'description': 'AUC0-last is defined as the area under the plasma minocycline concentration-time curve from 0 to the time of the last quantifiable sample after a dose (mg•hr/L). This was not calculated of the primary outcome measure for the population PK model, however was calculated as part of the Non-compartmental analysis using the linear trapezoidal rule (linear up, log down calculation method).', 'reportingStatus': 'POSTED', 'populationDescription': 'Individual AUC0-last were calculated as part of the Non-compartmental analysis using the linear trapezoidal rule, summarized by mean and standard deviation, and reported as outcome measure 4 calculated exposure measures for area under the curve to the last quantifiable sample (AUC0-last).'}, {'type': 'PRIMARY', 'title': 'Individual Post-hoc PK Parameter Estimates for Maximum Plasma Concentration (Cmax)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Minocin® IV', 'description': '200 mg minocycline hydrochloride IV infusion over approximately 60 minutes\n\nMinocycline: Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.'}], 'timeFrame': 'Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose', 'description': 'Total-drug Cmax is defined as the maximum plasma total minocycline concentration (mg/L). Patient dosing histories along with the individual post-hoc PK parameters were used to generate total concentration-time profiles. The Individual post-hoc PK parameter estimate for total Cmax was calculated for each simulated patient as the maximum simulated concentration. Summary statistics were calculated using the individual post-hoc parameters and reported as calculated exposure measures.', 'reportingStatus': 'POSTED', 'populationDescription': 'Individual post-hoc PK parameter estimate for total-drug Cmax was calculated for each patient, summarized by mean and standard deviation, and reported as outcome measure 5 calculated exposure measures for maximum plasma concentration (Cmax).'}, {'type': 'PRIMARY', 'title': 'Individual Post-hoc PK Parameter Estimates for Plasma Concentration at 24 Hours After Dose (C24)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Minocin® IV', 'description': '200 mg minocycline hydrochloride IV infusion over approximately 60 minutes\n\nMinocycline: Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.'}], 'timeFrame': 'Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, and 24 hours post dose', 'description': 'Total-drug C24 is defined as total Plasma minocycline concentration at 24 hours after a dose (mg/L). Patient dosing histories along with the individual post-hoc PK parameters were used to generate total concentration-time profiles. The Individual post-hoc PK parameter estimates for the total C24 were calculated for each simulated patient as the simulated concentration at 24 hours after dose. Summary statistics were calculated using the individual post-hoc parameters and reported as calculated exposure measures.', 'reportingStatus': 'POSTED', 'populationDescription': 'Individual post-hoc PK parameter estimate for total-drug C24 was calculated for each patient, summarized by mean and standard deviation, and reported as outcome measure 6 calculated exposure measures for plasma concentration at 24 hours after dose (C24).'}, {'type': 'PRIMARY', 'title': 'Magnitude of the Inter-individual Variability for Central Volume of Distribution (Vc)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '55', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Minocin® IV', 'description': '200 mg minocycline hydrochloride IV infusion over approximately 60 minutes\n\nMinocycline: Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.'}], 'classes': [{'categories': [{'measurements': [{'value': '49.9', 'groupId': 'OG000'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose', 'description': 'Vc was estimated from the structural two-compartment population PK model with constant fraction unbound (fub) which was used to characterize the total and unbound minocycline concentration-time data from ICU patients. The model was developed on using nonlinear mixed effects modeling on PK time points collected up to 48 hours after a single-dose on Day 1. Magnitude of the inter-individual variability is expressed as percent coefficient of variation (%CV).', 'unitOfMeasure': '%CV', 'reportingStatus': 'POSTED', 'populationDescription': 'PK population which is defined as participants who (1) received the full infusion of study drug, (2) had at least one PK specimen was processed per the Manual of Procedures, and (3) had at least one such sample provided a quantifiable minocycline concentration available for analysis.'}, {'type': 'PRIMARY', 'title': 'Magnitude of the Inter-individual Variability for Distribution Clearance (CLd)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '55', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Minocin® IV', 'description': '200 mg minocycline hydrochloride IV infusion over approximately 60 minutes\n\nMinocycline: Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.'}], 'classes': [{'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose', 'description': 'CLd was estimated from the structural two-compartment population PK model with constant fraction unbound (fub) which was used to characterize the total and unbound minocycline concentration-time data from ICU patients. The model was developed on using nonlinear mixed effects modeling on PK time points collected up to 48 hours after a single-dose on Day 1. The standard error of the mean as fixed. Magnitude of the inter-individual variability is expressed as percent coefficient of variation (CV%).', 'unitOfMeasure': '%CV', 'reportingStatus': 'POSTED', 'populationDescription': 'PK population which is defined as participants who (1) received the full infusion of study drug, (2) had at least one PK specimen was processed per the Manual of Procedures, and (3) had at least one such sample provided a quantifiable minocycline concentration available for analysis.'}, {'type': 'PRIMARY', 'title': 'Magnitude of the Inter-individual Variability for Free-drug Clearance (CL)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Minocin® IV', 'description': '200 mg minocycline hydrochloride IV infusion over approximately 60 minutes\n\nMinocycline: Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.'}], 'timeFrame': 'Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose', 'description': 'Unbound minocycline concentration is determined as the product of total minocycline concentrations and fub. Total minocycline concentrations and fub were estimated from the structural two-compartment population PK model with constant fraction unbound (fub) which was used to characterize the total and unbound minocycline concentration-time data from ICU patients. Magnitude of the inter-individual variability is expressed as percent coefficient of variation (%CV).', 'reportingStatus': 'POSTED', 'populationDescription': 'The model was fit with total drug clearance and then fraction unbound so the magnitude of the inter-individual variability was estimated for those parameters rather than free-drug.'}, {'type': 'PRIMARY', 'title': 'Magnitude of the Inter-individual Variability for Peripheral Volume of Distribution (Vp)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '55', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Minocin® IV', 'description': '200 mg minocycline hydrochloride IV infusion over approximately 60 minutes\n\nMinocycline: Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.'}], 'classes': [{'categories': [{'measurements': [{'value': '34.2', 'groupId': 'OG000'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose', 'description': 'Vp was estimated from the structural two-compartment population PK model with constant fraction unbound (fub), which was used to characterize the total and unbound minocycline concentration-time data from ICU patients. The model was developed on using nonlinear mixed effects modeling on PK time points collected up to 48 hours after a single-dose on Day 1.', 'unitOfMeasure': '%CV', 'reportingStatus': 'POSTED', 'populationDescription': 'PK population which is defined as participants who (1) received the full infusion of study drug, (2) had at least one PK specimen was processed per the Manual of Procedures, and (3) had at least one such sample provided a quantifiable minocycline concentration available for analysis.'}, {'type': 'PRIMARY', 'title': 'Magnitude of the Inter-individual Variability for Total-drug Clearance (CL)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '55', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Minocin® IV', 'description': '200 mg minocycline hydrochloride IV infusion over approximately 60 minutes\n\nMinocycline: Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.'}], 'classes': [{'categories': [{'measurements': [{'value': '45.6', 'groupId': 'OG000'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose', 'description': 'CL was estimated from the structural two-compartment population PK model with constant fraction unbound (fub) which was used to characterize the total and unbound minocycline concentration-time data from ICU patients. The model was developed on using nonlinear mixed effects modeling on PK time points collected up to 48 hours after a single-dose on Day 1. Magnitude of the inter-individual variability is expressed as percent coefficient of variation (%CV).', 'unitOfMeasure': '%CV', 'reportingStatus': 'POSTED', 'populationDescription': 'PK population which is defined as participants who (1) received the full infusion of study drug, (2) had at least one PK specimen was processed per the Manual of Procedures, and (3) had at least one such sample provided a quantifiable minocycline concentration available for analysis.'}, {'type': 'PRIMARY', 'title': 'Population Mean PK Parameter Estimates for Central Volume of Distribution (Vc)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '55', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Minocin® IV', 'description': '200 mg minocycline hydrochloride IV infusion over approximately 60 minutes\n\nMinocycline: Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.'}], 'classes': [{'categories': [{'measurements': [{'value': '74.5', 'spread': '6.60', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose', 'description': 'Vc was estimated from the structural two-compartment population PK model with constant fraction unbound (fub) which was used to characterize the total and unbound minocycline concentration-time data from ICU patients. The model was developed on using nonlinear mixed effects modeling on PK time points collected up to 48 hours after a single-dose on Day 1.', 'unitOfMeasure': 'L', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'PK population which is defined as participants who (1) received the full infusion of study drug, (2) had at least one PK specimen was processed per the Manual of Procedures, and (3) had at least one such sample provided a quantifiable minocycline concentration available for analysis.'}, {'type': 'PRIMARY', 'title': 'Population Mean PK Parameter Estimates for Distribution Clearance (CLd)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '55', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Minocin® IV', 'description': '200 mg minocycline hydrochloride IV infusion over approximately 60 minutes\n\nMinocycline: Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.'}], 'classes': [{'categories': [{'measurements': [{'value': '16.0', 'spread': '8.66', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose', 'description': 'CLd was estimated from the structural two-compartment population PK model with constant fraction unbound (fub), which was used to characterize the total and unbound minocycline concentration-time data from ICU patients. The model was developed on using nonlinear mixed effects modeling on PK time points collected up to 48 hours after a single-dose on Day 1.', 'unitOfMeasure': 'L/hr', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'PK population which is defined as participants who (1) received the full infusion of study drug, (2) had at least one PK specimen was processed per the Manual of Procedures, and (3) had at least one such sample provided a quantifiable minocycline concentration available for analysis.'}, {'type': 'PRIMARY', 'title': 'Population Mean PK Parameter Estimates for Free-drug Clearance (CL)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '55', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Minocin® IV', 'description': '200 mg minocycline hydrochloride IV infusion over approximately 60 minutes\n\nMinocycline: Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.'}], 'classes': [{'categories': [{'measurements': [{'value': '1.32', 'spread': '0', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose', 'description': 'Unbound minocycline concentration is determined as the product of total minocycline concentrations and fub. Total minocycline concentrations and fub were estimated from the structural two-compartment population PK model with constant fraction unbound (fub) which was used to characterize the total and unbound minocycline concentration-time data from ICU patients.', 'unitOfMeasure': 'L/hr', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'PK population which is defined as participants who (1) received the full infusion of study drug, (2) had at least one PK specimen was processed per the Manual of Procedures, and (3) had at least one such sample provided a quantifiable minocycline concentration available for analysis.'}, {'type': 'PRIMARY', 'title': 'Population Mean PK Parameter Estimates for Peripheral Volume of Distribution (Vp)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '55', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Minocin® IV', 'description': '200 mg minocycline hydrochloride IV infusion over approximately 60 minutes\n\nMinocycline: Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.'}], 'classes': [{'categories': [{'measurements': [{'value': '58.9', 'spread': '5.89', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose', 'description': 'Vp was estimated from the structural two-compartment population PK model with constant fraction unbound (fub), which was used to characterize the total and unbound minocycline concentration-time data from ICU patients. The model was developed on using nonlinear mixed effects modeling on PK time points collected up to 48 hours after a single-dose on Day 1.', 'unitOfMeasure': 'L', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'PK population which is defined as participants who (1) received the full infusion of study drug, (2) had at least one PK specimen was processed per the Manual of Procedures, and (3) had at least one such sample provided a quantifiable minocycline concentration available for analysis.'}, {'type': 'PRIMARY', 'title': 'Population Mean PK Parameter Estimates for Total-drug Clearance (CL)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '55', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Minocin® IV', 'description': '200 mg minocycline hydrochloride IV infusion over approximately 60 minutes\n\nMinocycline: Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.'}], 'classes': [{'categories': [{'measurements': [{'value': '4.7', 'spread': '6.24', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose', 'description': 'Total-drug clearance (CL) was estimated from the structural two-compartment population PK model with constant fraction unbound (fub), which was used to characterize the total and unbound minocycline concentration-time data from ICU patients. The model was developed on using nonlinear mixed effects modeling on PK time points collected up to 48 hours after a single-dose on Day 1.', 'unitOfMeasure': 'L/hr', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'PK population which is defined as participants who (1) received the full infusion of study drug, (2) had at least one PK specimen was processed per the Manual of Procedures, and (3) had at least one such sample provided a quantifiable minocycline concentration available for analysis.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Minocin® IV', 'description': '200 mg minocycline hydrochloride IV infusion over approximately 60 minutes\n\nMinocycline: Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '58'}]}, {'type': 'Received Study Drug', 'achievements': [{'groupId': 'FG000', 'numSubjects': '57'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '52'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '6'}]}], 'dropWithdraws': [{'type': 'Withdrawal by Subject', 'reasons': [{'groupId': 'FG000', 'numSubjects': '3'}]}, {'type': 'Death', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}]}, {'type': 'Lost to Follow-up', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}]}, {'type': 'Protocol Violation', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}]}]}], 'recruitmentDetails': 'Participants were recruited from those presenting at the ICU critically-ill with illness known or suspected to be caused by infection with Gram-negative bacteria. Enrollment occurred between 28MAR2018 and 18JUL2019.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '57', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Minocin® IV', 'description': '200 mg minocycline hydrochloride IV infusion over approximately 60 minutes\n\nMinocycline: Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'categories': [{'title': '<=18 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '29', 'groupId': 'BG000'}]}, {'title': '>=65 years', 'measurements': [{'value': '28', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '61.6', 'spread': '15.2', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '25', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '32', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Ethnicity (NIH/OMB)', 'classes': [{'categories': [{'title': 'Hispanic or Latino', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}, {'title': 'Not Hispanic or Latino', 'measurements': [{'value': '56', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Asian', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Black or African American', 'measurements': [{'value': '21', 'groupId': 'BG000'}]}, {'title': 'White', 'measurements': [{'value': '35', 'groupId': 'BG000'}]}, {'title': 'More than one race', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '57', 'groupId': 'BG000'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}, {'title': 'Body Mass Index (BMI)', 'classes': [{'categories': [{'measurements': [{'value': '31.1', 'spread': '10.46', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'kg/m^2', 'dispersionType': 'STANDARD_DEVIATION'}], 'populationDescription': 'All subjects enrolled and receiving study product are included in the baseline analysis population description.'}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2018-11-19', 'size': 475567, 'label': 'Study Protocol', 'hasIcf': False, 'hasSap': False, 'filename': 'Prot_000.pdf', 'typeAbbrev': 'Prot', 'uploadDate': '2020-07-16T12:52', 'hasProtocol': True}, {'date': '2019-07-11', 'size': 1454227, 'label': 'Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'SAP_001.pdf', 'typeAbbrev': 'SAP', 'uploadDate': '2020-07-16T12:53', 'hasProtocol': False}, {'date': '2019-06-03', 'size': 188938, 'label': 'Informed Consent Form', 'hasIcf': True, 'hasSap': False, 'filename': 'ICF_002.pdf', 'typeAbbrev': 'ICF', 'uploadDate': '2020-10-21T12:22', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 58}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2018-03-28', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2017-12-04', 'completionDateStruct': {'date': '2019-07-20', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2020-11-10', 'studyFirstSubmitDate': '2017-12-07', 'resultsFirstSubmitDate': '2020-07-16', 'studyFirstSubmitQcDate': '2017-12-07', 'lastUpdatePostDateStruct': {'date': '2020-12-03', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2020-08-13', 'studyFirstPostDateStruct': {'date': '2017-12-12', 'type': 'ACTUAL'}, 'resultsFirstPostDateStruct': {'date': '2020-08-27', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2019-07-20', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Calculated Exposure Measures for Area Under the Curve 0 to 24 Hours After a Dose (AUC0-24)', 'timeFrame': 'Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, and 24 hours post dose', 'description': 'Total AUC0-24 is defined as area under the plasma minocycline concentration-time curve from 0 to 24 hours after a dose (milligrams x hours per liter (mg•hr/L)). Patient dosing histories along with the individual post-hoc PK parameters were used to generate total concentration-time profiles. The AUC0-24 was calculated using numerical integration using the data from 0 to 24 hours post-dose.'}, {'measure': 'Calculated Exposure Measures for Area Under the Curve From 0 to Infinity (AUC0-inf) Using Free-drug Concentrations', 'timeFrame': 'Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose', 'description': 'Free-drug (unbound) AUC0-inf is defined as area under the plasma minocycline concentration-time curve from 0 to infinity after a dose (mg•hr/L). Patient dosing histories along with the individual post-hoc PK parameters were used to generate unbound concentration-time profiles. The AUC0-inf was calculated as Dose/CL.'}, {'measure': 'Calculated Exposure Measures for Area Under the Curve From 0 to Infinity (AUC0-inf) Using Total-drug Concentrations', 'timeFrame': 'Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose', 'description': 'Total AUC0-inf is defined as area under the plasma minocycline concentration-time curve from 0 to infinity after a dose (mg•hr/L). Patient dosing histories along with the individual post-hoc PK parameters were used to generate total concentration-time profiles. The AUC0-inf was calculated as Dose/CL.'}, {'measure': 'Calculated Exposure Measures for Area Under the Curve to the Last Quantifiable Sample (AUC0-last)', 'timeFrame': 'Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose', 'description': 'AUC0-last is defined as the area under the plasma minocycline concentration-time curve from 0 to the time of the last quantifiable sample after a dose (mg•hr/L). This was not calculated for the primary outcome measure using the individual post-hoc PK parameters, however was calculated as part of the Non-compartmental analysis using the linear trapezoidal rule (linear up, log down calculation method).'}, {'measure': 'Calculated Exposure Measures for Maximum Plasma Concentration (Cmax)', 'timeFrame': 'Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose', 'description': 'Total-drug Cmax is defined as the maximum plasma total minocycline concentration (mg/L) Patient dosing histories along with the individual post-hoc PK parameters were used to generate total concentration-time profiles. Total Cmax was calculated for each simulated patient as the maximum simulated concentration.'}, {'measure': 'Calculated Exposure Measures for Plasma Concentration at 24 Hours After Dose (C24)', 'timeFrame': 'Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, and 24 hours post dose', 'description': 'Total-drug C24 is defined as total plasma minocycline concentration at 24 hours after a dose (mg/L). Patient dosing histories along with the individual post-hoc PK parameters were used to generate total concentration-time profiles. The total C24 were calculated for each simulated patient as the simulated concentration at 24 hours after dose.'}, {'measure': 'Individual Post-hoc PK Parameter Estimates for Area Under the Curve 0 to 24 Hours After a Dose (AUC0-24)', 'timeFrame': 'Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, and 24 hours post dose', 'description': 'Total AUC0-24 is defined as area under the plasma minocycline concentration-time curve from 0 to 24 hours after a dose (mg•hr/L). Patient dosing histories along with the individual post-hoc PK parameters were used to generate total concentration-time profiles. The AUC0-24 was calculated for each individual using numerical integration using the data from 0 to 24 hours post-dose. Summary statistics were calculated using the individual post-hoc parameters and reported as calculated exposure measures.'}, {'measure': 'Individual Post-hoc PK Parameter Estimates for Area Under the Curve From 0 to Infinity (AUC0-inf) Using Free-drug Concentrations', 'timeFrame': 'Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose', 'description': 'Free-drug (unbound) AUC0-inf is defined as area under the plasma minocycline concentration-time curve from 0 to infinity after a dose (mg•hr/L). Patient dosing histories along with the individual post-hoc PK parameters were used to generate unbound concentration-time profiles. The AUC0-inf was calculated for each individual as Dose/CL. Summary statistics were calculated using the individual post-hoc parameters and reported as calculated exposure measures.'}, {'measure': 'Individual Post-hoc PK Parameter Estimates for Area Under the Curve From 0 to Infinity (AUC0-inf) Using Total-drug Concentrations', 'timeFrame': 'Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose', 'description': 'Total AUC0-inf is defined as area under the plasma minocycline concentration-time curve from 0 to infinity after a dose (mg•hr/L). Patient dosing histories along with the individual post-hoc PK parameters were used to generate total concentration-time profiles. The AUC0-inf was calculated for each individual as Dose/CL. Summary statistics were calculated using the individual post-hoc parameters and reported as calculated exposure measures.'}, {'measure': 'Individual Post-hoc PK Parameter Estimates for Area Under the Curve to the Last Quantifiable Sample (AUC0-last)', 'timeFrame': 'Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose', 'description': 'AUC0-last is defined as the area under the plasma minocycline concentration-time curve from 0 to the time of the last quantifiable sample after a dose (mg•hr/L). This was not calculated of the primary outcome measure for the population PK model, however was calculated as part of the Non-compartmental analysis using the linear trapezoidal rule (linear up, log down calculation method).'}, {'measure': 'Individual Post-hoc PK Parameter Estimates for Maximum Plasma Concentration (Cmax)', 'timeFrame': 'Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose', 'description': 'Total-drug Cmax is defined as the maximum plasma total minocycline concentration (mg/L). Patient dosing histories along with the individual post-hoc PK parameters were used to generate total concentration-time profiles. The Individual post-hoc PK parameter estimate for total Cmax was calculated for each simulated patient as the maximum simulated concentration. Summary statistics were calculated using the individual post-hoc parameters and reported as calculated exposure measures.'}, {'measure': 'Individual Post-hoc PK Parameter Estimates for Plasma Concentration at 24 Hours After Dose (C24)', 'timeFrame': 'Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, and 24 hours post dose', 'description': 'Total-drug C24 is defined as total Plasma minocycline concentration at 24 hours after a dose (mg/L). Patient dosing histories along with the individual post-hoc PK parameters were used to generate total concentration-time profiles. The Individual post-hoc PK parameter estimates for the total C24 were calculated for each simulated patient as the simulated concentration at 24 hours after dose. Summary statistics were calculated using the individual post-hoc parameters and reported as calculated exposure measures.'}, {'measure': 'Magnitude of the Inter-individual Variability for Central Volume of Distribution (Vc)', 'timeFrame': 'Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose', 'description': 'Vc was estimated from the structural two-compartment population PK model with constant fraction unbound (fub) which was used to characterize the total and unbound minocycline concentration-time data from ICU patients. The model was developed on using nonlinear mixed effects modeling on PK time points collected up to 48 hours after a single-dose on Day 1. Magnitude of the inter-individual variability is expressed as percent coefficient of variation (%CV).'}, {'measure': 'Magnitude of the Inter-individual Variability for Distribution Clearance (CLd)', 'timeFrame': 'Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose', 'description': 'CLd was estimated from the structural two-compartment population PK model with constant fraction unbound (fub) which was used to characterize the total and unbound minocycline concentration-time data from ICU patients. The model was developed on using nonlinear mixed effects modeling on PK time points collected up to 48 hours after a single-dose on Day 1. The standard error of the mean as fixed. Magnitude of the inter-individual variability is expressed as percent coefficient of variation (CV%).'}, {'measure': 'Magnitude of the Inter-individual Variability for Free-drug Clearance (CL)', 'timeFrame': 'Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose', 'description': 'Unbound minocycline concentration is determined as the product of total minocycline concentrations and fub. Total minocycline concentrations and fub were estimated from the structural two-compartment population PK model with constant fraction unbound (fub) which was used to characterize the total and unbound minocycline concentration-time data from ICU patients. Magnitude of the inter-individual variability is expressed as percent coefficient of variation (%CV).'}, {'measure': 'Magnitude of the Inter-individual Variability for Peripheral Volume of Distribution (Vp)', 'timeFrame': 'Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose', 'description': 'Vp was estimated from the structural two-compartment population PK model with constant fraction unbound (fub), which was used to characterize the total and unbound minocycline concentration-time data from ICU patients. The model was developed on using nonlinear mixed effects modeling on PK time points collected up to 48 hours after a single-dose on Day 1.'}, {'measure': 'Magnitude of the Inter-individual Variability for Total-drug Clearance (CL)', 'timeFrame': 'Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose', 'description': 'CL was estimated from the structural two-compartment population PK model with constant fraction unbound (fub) which was used to characterize the total and unbound minocycline concentration-time data from ICU patients. The model was developed on using nonlinear mixed effects modeling on PK time points collected up to 48 hours after a single-dose on Day 1. Magnitude of the inter-individual variability is expressed as percent coefficient of variation (%CV).'}, {'measure': 'Population Mean PK Parameter Estimates for Central Volume of Distribution (Vc)', 'timeFrame': 'Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose', 'description': 'Vc was estimated from the structural two-compartment population PK model with constant fraction unbound (fub) which was used to characterize the total and unbound minocycline concentration-time data from ICU patients. The model was developed on using nonlinear mixed effects modeling on PK time points collected up to 48 hours after a single-dose on Day 1.'}, {'measure': 'Population Mean PK Parameter Estimates for Distribution Clearance (CLd)', 'timeFrame': 'Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose', 'description': 'CLd was estimated from the structural two-compartment population PK model with constant fraction unbound (fub), which was used to characterize the total and unbound minocycline concentration-time data from ICU patients. The model was developed on using nonlinear mixed effects modeling on PK time points collected up to 48 hours after a single-dose on Day 1.'}, {'measure': 'Population Mean PK Parameter Estimates for Free-drug Clearance (CL)', 'timeFrame': 'Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose', 'description': 'Unbound minocycline concentration is determined as the product of total minocycline concentrations and fub. Total minocycline concentrations and fub were estimated from the structural two-compartment population PK model with constant fraction unbound (fub) which was used to characterize the total and unbound minocycline concentration-time data from ICU patients.'}, {'measure': 'Population Mean PK Parameter Estimates for Peripheral Volume of Distribution (Vp)', 'timeFrame': 'Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose', 'description': 'Vp was estimated from the structural two-compartment population PK model with constant fraction unbound (fub), which was used to characterize the total and unbound minocycline concentration-time data from ICU patients. The model was developed on using nonlinear mixed effects modeling on PK time points collected up to 48 hours after a single-dose on Day 1.'}, {'measure': 'Population Mean PK Parameter Estimates for Total-drug Clearance (CL)', 'timeFrame': 'Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose', 'description': 'Total-drug clearance (CL) was estimated from the structural two-compartment population PK model with constant fraction unbound (fub), which was used to characterize the total and unbound minocycline concentration-time data from ICU patients. The model was developed on using nonlinear mixed effects modeling on PK time points collected up to 48 hours after a single-dose on Day 1.'}]}, 'oversightModule': {'isUsExport': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['ACUMIN', 'Infusion', 'Injection', 'Minocycline', 'Pharmacokinetic', 'PK'], 'conditions': ['Bacterial Infection']}, 'descriptionModule': {'briefSummary': 'This is a Phase IV, multi-center open-label pharmacokinetic trial studying the pharmacokinetics and pharmacodynamics of a single dose of Minocin IV. Up to 67 subjects will be enrolled to obtain 50 evaluable, ICU patients who are already receiving antimicrobial therapy for a known or suspected Gram-negative infection. The entire study duration will be approximately 16 months and each subject participation duration will be approximately 2 days. The study will be conducted at approximately 13 clinical sites. Each subject will receive a single 200 mg dose of Minocin IV infused over approximately 60 minutes. Each subject will have 7 PK samples collected (1 pre-dose, 6 post-dose) at designated time points over a \\~48 hour period following the start of the Minocin IV infusion. The primary objectives are: 1) To characterize minocycline PK at the population level in critically-ill adults, with illness known or suspected to be caused by infection with Gram-negative bacteria and 2) To assess patient-level and clinical covariates associated with minocycline pharmacokinetic properties in critically-ill adults, with illness known or suspected to be caused by infection with Gram-negative bacteria.', 'detailedDescription': 'This is a Phase IV, multi-center open-label pharmacokinetic trial studying the pharmacokinetics and pharmacodynamics of a single dose of Minocin IV. Up to 67 subjects will be enrolled to obtain 50 evaluable, ICU patients who are already receiving antimicrobial therapy for a known or suspected Gram-negative infection. The entire study duration will be approximately 16 months and each subject participation duration will be approximately 2 days. The study will be conducted at approximately 13 clinical sites. Each subject will receive a single 200 mg dose of Minocin IV infused over approximately 60 minutes. Each subject will have 7 PK samples collected (1 pre-dose, 6 post-dose) at designated time points over a \\~48 hour period following the start of the Minocin IV infusion. The primary objectives are: 1) To characterize minocycline PK at the population level in critically-ill adults, with illness known or suspected to be caused by infection with Gram-negative bacteria and 2) To assess patient-level and clinical covariates associated with minocycline pharmacokinetic properties in critically-ill adults, with illness known or suspected to be caused by infection with Gram-negative bacteria. Up to 67 subjects will be enrolled in order to obtain 50 PK evaluable subjects in the study. To be considered PK evaluable, a subject must receive the full infusion of study drug, and is required to have at least 3 PK samples collected in the first 12 hours post dose and at least 1 PK sample collected 24-48 hours post dose. Subjects who are dosed with minocycline but do not meet this PK sampling requirement will still be included in the population PK analysis, but an additional subject will be enrolled as a replacement to meet the goal of having 50 PK evaluable subjects with intensive PK sampling.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '99 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Male or female \\> / = 18 years of age.\n2. Subject is in the ICU, or is being admitted to the ICU.\n3. Known or suspected Gram-negative infection for which the subject is receiving systemic antibiotics, and which was the reason for admission to the ICU, or reason for persistent need for ICU care.\n4. Expectation, in the judgment of the investigator, that the subject will remain admitted in the hospital for at least 48 hours following enrollment and that all study procedures will be completed.\n5. Expectation that intravenous access will be sufficient for drug infusion and either intravenous or arterial access will be sufficient to allow for all protocol required blood sampling to occur.\n6. The subject, or legally authorized representative (LAR), is able and willing to provide signed informed consent.\n\nExclusion Criteria:\n\n1. History of significant hypersensitivity or allergic reaction to tetracycline antibiotics.\n2. Receipt of oral or intravenous tetracycline class drugs within 7 days of enrollment (e.g., minocycline, tetracycline, tigecycline, doxycycline).\n3. Use of isotretinoin within 2 weeks of enrollment into the study.\n4. Major surgery\\* within 48 hours prior to enrollment.\n\n \\*Major surgery is defined as "the opening of either a body cavity or the mesenchymal barrier, using general anesthesia".\n5. Pregnant or breastfeeding women.\n6. Patient is being treated for intracranial hypertension.\n7. Any condition that, in the judgment of the investigator, precludes participation because it could affect subject safety.\\*\n\n \\*Subjects on, or who may be considered for Renal Replacement Therapy (RRT) during the study period are not excluded from participating in the study.\n8. Receipt of an investigational study product within 7 days prior to enrollment. Investigator discretion should be used when longer acting agents have been used in the previous 30 days.'}, 'identificationModule': {'nctId': 'NCT03369951', 'briefTitle': 'Minocycline Pharmacokinetics (ACUMIN)', 'organization': {'class': 'NIH', 'fullName': 'National Institute of Allergy and Infectious Diseases (NIAID)'}, 'officialTitle': 'A Phase IV Open-Label Pharmacokinetic Study of Minocycline for Injection Following a Single Infusion in Critically-Ill Adults (ACUMIN)', 'orgStudyIdInfo': {'id': '16-0011'}, 'secondaryIdInfos': [{'id': '2UM1AI104681-08', 'link': 'https://reporter.nih.gov/quickSearch/2UM1AI104681-08', 'type': 'NIH'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Minocin® IV', 'description': '200 mg minocycline hydrochloride IV infusion over approximately 60 minutes, n=50', 'interventionNames': ['Drug: Minocycline']}], 'interventions': [{'name': 'Minocycline', 'type': 'DRUG', 'description': 'Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.', 'armGroupLabels': ['Minocin® IV']}]}, 'contactsLocationsModule': {'locations': [{'zip': '30033', 'city': 'Decatur', 'state': 'Georgia', 'country': 'United States', 'facility': 'Emory Decatur Hospital - Clinical Trials - Immunology/Infectious Disease', 'geoPoint': {'lat': 33.77483, 'lon': -84.29631}}, {'zip': '60611-2908', 'city': 'Chicago', 'state': 'Illinois', 'country': 'United States', 'facility': 'Northwestern Memorial Hospital - ICU', 'geoPoint': {'lat': 41.85003, 'lon': -87.65005}}, {'zip': '60611', 'city': 'Chicago', 'state': 'Illinois', 'country': 'United States', 'facility': 'Northwestern Medicine - Department of Obstetrics and Gynecology - Division of Female Pelvic Medicine and Reconstructive Surgery', 'geoPoint': {'lat': 41.85003, 'lon': -87.65005}}, {'zip': '40536', 'city': 'Lexington', 'state': 'Kentucky', 'country': 'United States', 'facility': 'University of Kentucky - UK Albert B Chandler Hospital', 'geoPoint': {'lat': 37.98869, 'lon': -84.47772}}, {'zip': '40202-1622', 'city': 'Louisville', 'state': 'Kentucky', 'country': 'United States', 'facility': 'University of Louisville School of Medicine - Surgery', 'geoPoint': {'lat': 38.25424, 'lon': -85.75941}}, {'zip': '48202-2608', 'city': 'Detroit', 'state': 'Michigan', 'country': 'United States', 'facility': 'Henry Ford Health System - Henry Ford Hospital', 'geoPoint': {'lat': 42.33143, 'lon': -83.04575}}, {'zip': '48073-6700', 'city': 'Royal Oak', 'state': 'Michigan', 'country': 'United States', 'facility': 'William Beaumont Hospital - Royal Oak Campus - Infectious Disease', 'geoPoint': {'lat': 42.48948, 'lon': -83.14465}}, {'zip': '63110-1010', 'city': 'St Louis', 'state': 'Missouri', 'country': 'United States', 'facility': 'Washington University School of Medicine in St. Louis - Infectious Diseases', 'geoPoint': {'lat': 38.62727, 'lon': -90.19789}}, {'zip': '27701', 'city': 'Durham', 'state': 'North Carolina', 'country': 'United States', 'facility': 'Duke University School of Medicine - Duke Clinical Research Institute - Duke Clinical Research Unit', 'geoPoint': {'lat': 35.99403, 'lon': -78.89862}}, {'zip': '27710', 'city': 'Durham', 'state': 'North Carolina', 'country': 'United States', 'facility': 'Duke University Hospital - Duke Medicine Pavilion - MICU', 'geoPoint': {'lat': 35.99403, 'lon': -78.89862}}, {'zip': '27834-9997', 'city': 'Greenville', 'state': 'North Carolina', 'country': 'United States', 'facility': 'East Carolina University - Infectious Diseases and Tropical/Travel Medicine Clinic', 'geoPoint': {'lat': 35.61266, 'lon': -77.36635}}, {'zip': '45267', 'city': 'Cincinnati', 'state': 'Ohio', 'country': 'United States', 'facility': 'University of Cincinnati College of Medicine - Division of Infectious Diseases', 'geoPoint': {'lat': 39.12711, 'lon': -84.51439}}, {'zip': '44106-1716', 'city': 'Cleveland', 'state': 'Ohio', 'country': 'United States', 'facility': 'Case Western Reserve University School of Medicine - Medicine - Infectious Diseases and HIV Medicine', 'geoPoint': {'lat': 41.4995, 'lon': -81.69541}}, {'zip': '97239', 'city': 'Portland', 'state': 'Oregon', 'country': 'United States', 'facility': 'Oregon Health and Science University - Division of Pulmonary and Critical Care Medicine', 'geoPoint': {'lat': 45.52345, 'lon': -122.67621}}, {'zip': '15213-3403', 'city': 'Pittsburgh', 'state': 'Pennsylvania', 'country': 'United States', 'facility': 'University of Pittsburgh - Medicine - Infectious Diseases', 'geoPoint': {'lat': 40.44062, 'lon': -79.99589}}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'National Institute of Allergy and Infectious Diseases (NIAID)', 'class': 'NIH'}, 'responsibleParty': {'type': 'SPONSOR'}}}}