Trial Outcomes & Findings for Minocycline Pharmacokinetics (ACUMIN) (NCT NCT03369951)
NCT ID: NCT03369951
Last Updated: 2020-12-03
Results Overview
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.
COMPLETED
PHASE4
58 participants
Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, and 24 hours post dose
2020-12-03
Participant Flow
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.
Participant milestones
| Measure |
Minocin® IV
200 mg minocycline hydrochloride IV infusion over approximately 60 minutes
Minocycline: Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.
|
|---|---|
|
Overall Study
STARTED
|
58
|
|
Overall Study
Received Study Drug
|
57
|
|
Overall Study
COMPLETED
|
52
|
|
Overall Study
NOT COMPLETED
|
6
|
Reasons for withdrawal
| Measure |
Minocin® IV
200 mg minocycline hydrochloride IV infusion over approximately 60 minutes
Minocycline: Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
3
|
|
Overall Study
Death
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
|
Overall Study
Protocol Violation
|
1
|
Baseline Characteristics
Minocycline Pharmacokinetics (ACUMIN)
Baseline characteristics by cohort
| Measure |
Minocin® IV
n=57 Participants
200 mg minocycline hydrochloride IV infusion over approximately 60 minutes
Minocycline: Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
29 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
28 Participants
n=5 Participants
|
|
Age, Continuous
|
61.6 years
STANDARD_DEVIATION 15.2 • n=5 Participants
|
|
Sex: Female, Male
Female
|
25 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
32 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
56 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
21 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
35 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
57 participants
n=5 Participants
|
|
Body Mass Index (BMI)
|
31.1 kg/m^2
STANDARD_DEVIATION 10.46 • n=5 Participants
|
PRIMARY outcome
Timeframe: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, and 24 hours post dosePopulation: 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.
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.
Outcome measures
| Measure |
Minocin® IV
n=55 Participants
200 mg minocycline hydrochloride IV infusion over approximately 60 minutes
Minocycline: Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.
|
|---|---|
|
Calculated Exposure Measures for Area Under the Curve 0 to 24 Hours After a Dose (AUC0-24)
|
24.3 mg·hr/L
Standard Deviation 7.88
|
PRIMARY outcome
Timeframe: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dosePopulation: 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.
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.
Outcome measures
| Measure |
Minocin® IV
n=55 Participants
200 mg minocycline hydrochloride IV infusion over approximately 60 minutes
Minocycline: Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.
|
|---|---|
|
Calculated Exposure Measures for Area Under the Curve From 0 to Infinity (AUC0-inf) Using Free-drug Concentrations
|
14.1 mg·hr/L
Standard Deviation 6.68
|
PRIMARY outcome
Timeframe: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dosePopulation: 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.
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.
Outcome measures
| Measure |
Minocin® IV
n=55 Participants
200 mg minocycline hydrochloride IV infusion over approximately 60 minutes
Minocycline: Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.
|
|---|---|
|
Calculated Exposure Measures for Area Under the Curve From 0 to Infinity (AUC0-inf) Using Total-drug Concentrations
|
46.6 mg·hr/L
Standard Deviation 19.7
|
PRIMARY outcome
Timeframe: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dosePopulation: 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.
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).
Outcome measures
| Measure |
Minocin® IV
n=51 Participants
200 mg minocycline hydrochloride IV infusion over approximately 60 minutes
Minocycline: Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.
|
|---|---|
|
Calculated Exposure Measures for Area Under the Curve to the Last Quantifiable Sample (AUC0-last)
|
10.5 mg·h/L
Standard Deviation 3.91
|
PRIMARY outcome
Timeframe: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dosePopulation: 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.
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.
Outcome measures
| Measure |
Minocin® IV
n=55 Participants
200 mg minocycline hydrochloride IV infusion over approximately 60 minutes
Minocycline: Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.
|
|---|---|
|
Calculated Exposure Measures for Maximum Plasma Concentration (Cmax)
|
2.58 mg/L
Standard Deviation 1.33
|
PRIMARY outcome
Timeframe: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, and 24 hours post dosePopulation: 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.
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.
Outcome measures
| Measure |
Minocin® IV
n=55 Participants
200 mg minocycline hydrochloride IV infusion over approximately 60 minutes
Minocycline: Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.
|
|---|---|
|
Calculated Exposure Measures for Plasma Concentration at 24 Hours After Dose (C24)
|
0.603 mg/L
Standard Deviation 0.225
|
PRIMARY outcome
Timeframe: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, and 24 hours post dosePopulation: 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).
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.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dosePopulation: 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.
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.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dosePopulation: 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.
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.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dosePopulation: 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).
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).
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dosePopulation: 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).
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.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, and 24 hours post dosePopulation: 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).
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.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dosePopulation: 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.
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).
Outcome measures
| Measure |
Minocin® IV
n=55 Participants
200 mg minocycline hydrochloride IV infusion over approximately 60 minutes
Minocycline: Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.
|
|---|---|
|
Magnitude of the Inter-individual Variability for Central Volume of Distribution (Vc)
|
49.9 %CV
|
PRIMARY outcome
Timeframe: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dosePopulation: 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.
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%).
Outcome measures
| Measure |
Minocin® IV
n=55 Participants
200 mg minocycline hydrochloride IV infusion over approximately 60 minutes
Minocycline: Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.
|
|---|---|
|
Magnitude of the Inter-individual Variability for Distribution Clearance (CLd)
|
0 %CV
|
PRIMARY outcome
Timeframe: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dosePopulation: 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.
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).
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dosePopulation: 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.
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.
Outcome measures
| Measure |
Minocin® IV
n=55 Participants
200 mg minocycline hydrochloride IV infusion over approximately 60 minutes
Minocycline: Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.
|
|---|---|
|
Magnitude of the Inter-individual Variability for Peripheral Volume of Distribution (Vp)
|
34.2 %CV
|
PRIMARY outcome
Timeframe: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dosePopulation: 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.
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).
Outcome measures
| Measure |
Minocin® IV
n=55 Participants
200 mg minocycline hydrochloride IV infusion over approximately 60 minutes
Minocycline: Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.
|
|---|---|
|
Magnitude of the Inter-individual Variability for Total-drug Clearance (CL)
|
45.6 %CV
|
PRIMARY outcome
Timeframe: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dosePopulation: 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.
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.
Outcome measures
| Measure |
Minocin® IV
n=55 Participants
200 mg minocycline hydrochloride IV infusion over approximately 60 minutes
Minocycline: Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.
|
|---|---|
|
Population Mean PK Parameter Estimates for Central Volume of Distribution (Vc)
|
74.5 L
Standard Error 6.60
|
PRIMARY outcome
Timeframe: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dosePopulation: 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.
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.
Outcome measures
| Measure |
Minocin® IV
n=55 Participants
200 mg minocycline hydrochloride IV infusion over approximately 60 minutes
Minocycline: Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.
|
|---|---|
|
Population Mean PK Parameter Estimates for Distribution Clearance (CLd)
|
16.0 L/hr
Standard Error 8.66
|
PRIMARY outcome
Timeframe: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dosePopulation: 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.
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.
Outcome measures
| Measure |
Minocin® IV
n=55 Participants
200 mg minocycline hydrochloride IV infusion over approximately 60 minutes
Minocycline: Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.
|
|---|---|
|
Population Mean PK Parameter Estimates for Free-drug Clearance (CL)
|
1.32 L/hr
Standard Error 0
|
PRIMARY outcome
Timeframe: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dosePopulation: 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.
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.
Outcome measures
| Measure |
Minocin® IV
n=55 Participants
200 mg minocycline hydrochloride IV infusion over approximately 60 minutes
Minocycline: Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.
|
|---|---|
|
Population Mean PK Parameter Estimates for Peripheral Volume of Distribution (Vp)
|
58.9 L
Standard Error 5.89
|
PRIMARY outcome
Timeframe: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dosePopulation: 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.
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.
Outcome measures
| Measure |
Minocin® IV
n=55 Participants
200 mg minocycline hydrochloride IV infusion over approximately 60 minutes
Minocycline: Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.
|
|---|---|
|
Population Mean PK Parameter Estimates for Total-drug Clearance (CL)
|
4.7 L/hr
Standard Error 6.24
|
Adverse Events
Minocin® IV
Serious adverse events
| Measure |
Minocin® IV
n=57 participants at risk
200 mg minocycline hydrochloride IV infusion over approximately 60 minutes
Minocycline: Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.
|
|---|---|
|
Cardiac disorders
Cardio-Respiratory Arrest
|
1.8%
1/57 • Number of events 1 • Serious Adverse Events (SAEs) were recorded and reported from the start of the Minocin IV infusion until 24 hours from the start of infusion.
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.
|
Other adverse events
Adverse event data not reported
Additional Information
Richard G. Wunderink, MD
Northwestern University of Feinberg School of Medicine
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60