Back to resultsMinocycline Pharmacokinetics (ACUMIN)
Primary Purpose
Bacterial Infection
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Minocycline
Sponsored by
About this trial
This is an interventional treatment trial for Bacterial Infection focused on measuring ACUMIN, Infusion, Injection, Minocycline, Pharmacokinetic, PK
Eligibility Criteria
Inclusion Criteria:
- Male or female > / = 18 years of age.
- Subject is in the ICU, or is being admitted to the ICU.
- 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.
- 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.
- 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.
- The subject, or legally authorized representative (LAR), is able and willing to provide signed informed consent.
Exclusion Criteria:
- History of significant hypersensitivity or allergic reaction to tetracycline antibiotics.
- Receipt of oral or intravenous tetracycline class drugs within 7 days of enrollment (e.g., minocycline, tetracycline, tigecycline, doxycycline).
- Use of isotretinoin within 2 weeks of enrollment into the study.
Major surgery* within 48 hours prior to enrollment.
*Major surgery is defined as "the opening of either a body cavity or the mesenchymal barrier, using general anesthesia".
- Pregnant or breastfeeding women.
- Patient is being treated for intracranial hypertension.
Any condition that, in the judgment of the investigator, precludes participation because it could affect subject safety.*
*Subjects on, or who may be considered for Renal Replacement Therapy (RRT) during the study period are not excluded from participating in the study.
- 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.
Sites / Locations
- Emory Decatur Hospital - Clinical Trials - Immunology/Infectious Disease
- Northwestern Memorial Hospital - ICU
- Northwestern Medicine - Department of Obstetrics and Gynecology - Division of Female Pelvic Medicine and Reconstructive Surgery
- University of Kentucky - UK Albert B Chandler Hospital
- University of Louisville School of Medicine - Surgery
- Henry Ford Health System - Henry Ford Hospital
- William Beaumont Hospital - Royal Oak Campus - Infectious Disease
- Washington University School of Medicine in St. Louis - Infectious Diseases
- Duke University School of Medicine - Duke Clinical Research Institute - Duke Clinical Research Unit
- Duke University Hospital - Duke Medicine Pavilion - MICU
- East Carolina University - Infectious Diseases and Tropical/Travel Medicine Clinic
- University of Cincinnati College of Medicine - Division of Infectious Diseases
- Case Western Reserve University School of Medicine - Medicine - Infectious Diseases and HIV Medicine
- Oregon Health and Science University - Division of Pulmonary and Critical Care Medicine
- University of Pittsburgh - Medicine - Infectious Diseases
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Minocin® IV
Arm Description
200 mg minocycline hydrochloride IV infusion over approximately 60 minutes, n=50
Outcomes
Primary Outcome Measures
Calculated Exposure Measures for Area Under the Curve 0 to 24 Hours After a Dose (AUC0-24)
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.
Calculated Exposure Measures for Area Under the Curve From 0 to Infinity (AUC0-inf) Using Free-drug Concentrations
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.
Calculated Exposure Measures for Area Under the Curve From 0 to Infinity (AUC0-inf) Using Total-drug Concentrations
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.
Calculated Exposure Measures for Area Under the Curve to the Last Quantifiable Sample (AUC0-last)
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).
Calculated Exposure Measures for Maximum Plasma Concentration (Cmax)
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.
Calculated Exposure Measures for Plasma Concentration at 24 Hours After Dose (C24)
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.
Individual Post-hoc PK Parameter Estimates for Area Under the Curve 0 to 24 Hours After a Dose (AUC0-24)
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.
Individual Post-hoc PK Parameter Estimates for Area Under the Curve From 0 to Infinity (AUC0-inf) Using Free-drug Concentrations
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.
Individual Post-hoc PK Parameter Estimates for Area Under the Curve From 0 to Infinity (AUC0-inf) Using Total-drug Concentrations
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.
Individual Post-hoc PK Parameter Estimates for Area Under the Curve to the Last Quantifiable Sample (AUC0-last)
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).
Individual Post-hoc PK Parameter Estimates for Maximum Plasma Concentration (Cmax)
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.
Individual Post-hoc PK Parameter Estimates for Plasma Concentration at 24 Hours After Dose (C24)
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.
Magnitude of the Inter-individual Variability for Central Volume of Distribution (Vc)
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).
Magnitude of the Inter-individual Variability for Distribution Clearance (CLd)
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%).
Magnitude of the Inter-individual Variability for Free-drug Clearance (CL)
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).
Magnitude of the Inter-individual Variability for Peripheral Volume of Distribution (Vp)
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.
Magnitude of the Inter-individual Variability for Total-drug Clearance (CL)
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).
Population Mean PK Parameter Estimates for Central Volume of Distribution (Vc)
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.
Population Mean PK Parameter Estimates for Distribution Clearance (CLd)
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.
Population Mean PK Parameter Estimates for Free-drug Clearance (CL)
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.
Population Mean PK Parameter Estimates for Peripheral Volume of Distribution (Vp)
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.
Population Mean PK Parameter Estimates for Total-drug Clearance (CL)
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.
Secondary Outcome Measures
Full Information
NCT ID
NCT03369951
First Posted
December 7, 2017
Last Updated
November 10, 2020
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
1. Study Identification
Unique Protocol Identification Number
NCT03369951
Brief Title
Minocycline Pharmacokinetics (ACUMIN)
Official Title
A Phase IV Open-Label Pharmacokinetic Study of Minocycline for Injection Following a Single Infusion in Critically-Ill Adults (ACUMIN)
Study Type
Interventional
2. Study Status
Record Verification Date
December 4, 2017
Overall Recruitment Status
Completed
Study Start Date
March 28, 2018 (Actual)
Primary Completion Date
July 20, 2019 (Actual)
Study Completion Date
July 20, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
5. Study Description
Brief Summary
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.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bacterial Infection
Keywords
ACUMIN, Infusion, Injection, Minocycline, Pharmacokinetic, PK
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
58 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Minocin® IV
Arm Type
Experimental
Arm Description
200 mg minocycline hydrochloride IV infusion over approximately 60 minutes, n=50
Intervention Type
Drug
Intervention Name(s)
Minocycline
Intervention Description
Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.
Primary Outcome Measure Information:
Title
Calculated Exposure Measures for Area Under the Curve 0 to 24 Hours After a Dose (AUC0-24)
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.
Time Frame
Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, and 24 hours post dose
Title
Calculated Exposure Measures for Area Under the Curve From 0 to Infinity (AUC0-inf) Using Free-drug Concentrations
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.
Time Frame
Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
Title
Calculated Exposure Measures for Area Under the Curve From 0 to Infinity (AUC0-inf) Using Total-drug Concentrations
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.
Time Frame
Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
Title
Calculated Exposure Measures for Area Under the Curve to the Last Quantifiable Sample (AUC0-last)
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).
Time Frame
Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
Title
Calculated Exposure Measures for Maximum Plasma Concentration (Cmax)
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.
Time Frame
Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
Title
Calculated Exposure Measures for Plasma Concentration at 24 Hours After Dose (C24)
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.
Time Frame
Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, and 24 hours post dose
Title
Individual Post-hoc PK Parameter Estimates for Area Under the Curve 0 to 24 Hours After a Dose (AUC0-24)
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.
Time Frame
Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, and 24 hours post dose
Title
Individual Post-hoc PK Parameter Estimates for Area Under the Curve From 0 to Infinity (AUC0-inf) Using Free-drug Concentrations
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.
Time Frame
Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
Title
Individual Post-hoc PK Parameter Estimates for Area Under the Curve From 0 to Infinity (AUC0-inf) Using Total-drug Concentrations
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.
Time Frame
Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
Title
Individual Post-hoc PK Parameter Estimates for Area Under the Curve to the Last Quantifiable Sample (AUC0-last)
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).
Time Frame
Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
Title
Individual Post-hoc PK Parameter Estimates for Maximum Plasma Concentration (Cmax)
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.
Time Frame
Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
Title
Individual Post-hoc PK Parameter Estimates for Plasma Concentration at 24 Hours After Dose (C24)
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.
Time Frame
Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, and 24 hours post dose
Title
Magnitude of the Inter-individual Variability for Central Volume of Distribution (Vc)
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).
Time Frame
Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
Title
Magnitude of the Inter-individual Variability for Distribution Clearance (CLd)
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%).
Time Frame
Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
Title
Magnitude of the Inter-individual Variability for Free-drug Clearance (CL)
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).
Time Frame
Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
Title
Magnitude of the Inter-individual Variability for Peripheral Volume of Distribution (Vp)
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.
Time Frame
Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
Title
Magnitude of the Inter-individual Variability for Total-drug Clearance (CL)
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).
Time Frame
Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
Title
Population Mean PK Parameter Estimates for Central Volume of Distribution (Vc)
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.
Time Frame
Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
Title
Population Mean PK Parameter Estimates for Distribution Clearance (CLd)
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.
Time Frame
Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
Title
Population Mean PK Parameter Estimates for Free-drug Clearance (CL)
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.
Time Frame
Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
Title
Population Mean PK Parameter Estimates for Peripheral Volume of Distribution (Vp)
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.
Time Frame
Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
Title
Population Mean PK Parameter Estimates for Total-drug Clearance (CL)
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.
Time Frame
Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female > / = 18 years of age.
Subject is in the ICU, or is being admitted to the ICU.
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.
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.
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.
The subject, or legally authorized representative (LAR), is able and willing to provide signed informed consent.
Exclusion Criteria:
History of significant hypersensitivity or allergic reaction to tetracycline antibiotics.
Receipt of oral or intravenous tetracycline class drugs within 7 days of enrollment (e.g., minocycline, tetracycline, tigecycline, doxycycline).
Use of isotretinoin within 2 weeks of enrollment into the study.
Major surgery* within 48 hours prior to enrollment.
*Major surgery is defined as "the opening of either a body cavity or the mesenchymal barrier, using general anesthesia".
Pregnant or breastfeeding women.
Patient is being treated for intracranial hypertension.
Any condition that, in the judgment of the investigator, precludes participation because it could affect subject safety.*
*Subjects on, or who may be considered for Renal Replacement Therapy (RRT) during the study period are not excluded from participating in the study.
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.
Facility Information:
Facility Name
Emory Decatur Hospital - Clinical Trials - Immunology/Infectious Disease
City
Decatur
State/Province
Georgia
ZIP/Postal Code
30033
Country
United States
Facility Name
Northwestern Memorial Hospital - ICU
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611-2908
Country
United States
Facility Name
Northwestern Medicine - Department of Obstetrics and Gynecology - Division of Female Pelvic Medicine and Reconstructive Surgery
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
University of Kentucky - UK Albert B Chandler Hospital
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536
Country
United States
Facility Name
University of Louisville School of Medicine - Surgery
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202-1622
Country
United States
Facility Name
Henry Ford Health System - Henry Ford Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202-2608
Country
United States
Facility Name
William Beaumont Hospital - Royal Oak Campus - Infectious Disease
City
Royal Oak
State/Province
Michigan
ZIP/Postal Code
48073-6700
Country
United States
Facility Name
Washington University School of Medicine in St. Louis - Infectious Diseases
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110-1010
Country
United States
Facility Name
Duke University School of Medicine - Duke Clinical Research Institute - Duke Clinical Research Unit
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27701
Country
United States
Facility Name
Duke University Hospital - Duke Medicine Pavilion - MICU
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
East Carolina University - Infectious Diseases and Tropical/Travel Medicine Clinic
City
Greenville
State/Province
North Carolina
ZIP/Postal Code
27834-9997
Country
United States
Facility Name
University of Cincinnati College of Medicine - Division of Infectious Diseases
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
Case Western Reserve University School of Medicine - Medicine - Infectious Diseases and HIV Medicine
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106-1716
Country
United States
Facility Name
Oregon Health and Science University - Division of Pulmonary and Critical Care Medicine
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
University of Pittsburgh - Medicine - Infectious Diseases
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213-3403
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Minocycline Pharmacokinetics (ACUMIN)
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