Bacterial InfectionPhase 4NCT03369951
Minocycline Pharmacokinetics (ACUMIN)
A Phase 4 study testing Minocycline in people with Bacterial Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 15 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Bacterial Infection
- What is being tested?
- Minocycline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 15 sitesUnited States
- Study dates
- 28 Mar 2018to 20 Jul 2019
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
United States15 sites
Northwestern Memorial Hospital - ICU
Chicago, Illinois, 60611-2908
Northwestern Medicine - Department of Obstetrics and Gynecology - Division of Female Pelvic Medicine and Reconstructive Surgery
Chicago, Illinois, 60611
University of Cincinnati College of Medicine - Division of Infectious Diseases
Cincinnati, Ohio, 45267
Case Western Reserve University School of Medicine - Medicine - Infectious Diseases and HIV Medicine
Cleveland, Ohio, 44106-1716
Emory Decatur Hospital - Clinical Trials - Immunology/Infectious Disease
Decatur, Georgia, 30033
Henry Ford Health System - Henry Ford Hospital
Detroit, Michigan, 48202-2608
Duke University School of Medicine - Duke Clinical Research Institute - Duke Clinical Research Unit
Durham, North Carolina, 27701
Duke University Hospital - Duke Medicine Pavilion - MICU
Durham, North Carolina, 27710
East Carolina University - Infectious Diseases and Tropical/Travel Medicine Clinic
Greenville, North Carolina, 27834-9997
University of Kentucky - UK Albert B Chandler Hospital
Lexington, Kentucky, 40536
University of Louisville School of Medicine - Surgery
Louisville, Kentucky, 40202-1622
University of Pittsburgh - Medicine - Infectious Diseases
Pittsburgh, Pennsylvania, 15213-3403
Oregon Health and Science University - Division of Pulmonary and Critical Care Medicine
Portland, Oregon, 97239
William Beaumont Hospital - Royal Oak Campus - Infectious Disease
Royal Oak, Michigan, 48073-6700
Washington University School of Medicine in St. Louis - Infectious Diseases
St Louis, Missouri, 63110-1010
About this study
Official title: A Phase IV Open-Label Pharmacokinetic Study of Minocycline for Injection Following a Single Infusion in Critically-Ill Adults (ACUMIN)
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.
Read the 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.
- Conditions
- Bacterial Infection
- Being tested
- Minocycline
- Keywords
- ACUMIN, Infusion, Injection, Minocycline, Pharmacokinetic, PK
- Medical subject headings
- Bacterial Infections, cyclopia sequence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MinocyclineDrug
Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.
| Study group | Role | What they receive |
|---|---|---|
| Minocin® IV | Experimental | 200 mg minocycline hydrochloride IV infusion over approximately 60 minutes, n=50 Receives: Drug: Minocycline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, and 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.
Measured: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
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.
Measured: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
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).
Measured: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
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.
Measured: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
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.
Measured: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, and 24 hours post 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.
Measured: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, and 24 hours post dose
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.
Measured: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
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.
Measured: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
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).
Measured: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
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.
Measured: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
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.
Measured: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, and 24 hours post dose
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).
Measured: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
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%).
Measured: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
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).
Measured: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
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.
Measured: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
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).
Measured: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
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.
Measured: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
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.
Measured: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
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.
Measured: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
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.
Measured: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
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.
Measured: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2017
- Study start28 Mar 2018
- Primary completion20 Jul 2019
- Study completion20 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Bacterial InfectionStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03369951
- Sponsor's protocol ID
- 16-0011
- Other IDs
- 2UM1AI104681-08
- Status last verified
- 4 Dec 2017
- First submitted
- 7 Dec 2017
- Last updated
- 3 Dec 2020
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IV Open-Label Pharmacokinetic Study of Minocycline for Injection Following a Single Infusion in Critically-Ill Adults (ACUMIN)
- ClinicalTrials.gov ID
- NCT03369951
- Acronym / sponsor ID
- 16-0011
- Conditions
- Bacterial Infection
- Keywords
- ACUMIN, Infusion, Injection, Minocycline, Pharmacokinetic, PK
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 58 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 28 Mar 2018 (actual)
- Primary completion
- 20 Jul 2019 (actual)
- Study completion
- 20 Jul 2019 (actual)
- First posted
- 12 Dec 2017 (actual)
- Results
- Posted 27 Aug 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Minocin® IV | Experimental | Drug: Minocycline200 mg minocycline hydrochloride IV infusion over approximately 60 minutes, n=50 |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (10 listed)
- 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".
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MinocyclineMinocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms. | Drug | Minocin® IV |
Primary outcome
Calculated Exposure Measures for Area Under the Curve 0 to 24 Hours After a Dose (AUC0-24)
Time frame: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, and 24 hours post dose
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
Time frame: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
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
Time frame: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
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)
Time frame: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
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)
Time frame: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
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)
Time frame: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, and 24 hours post dose
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)
Time frame: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, and 24 hours post dose
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
Time frame: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
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
Time frame: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
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)
Time frame: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
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)
Time frame: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
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)
Time frame: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, and 24 hours post dose
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)
Time frame: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
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)
Time frame: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
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)
Time frame: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
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)
Time frame: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
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)
Time frame: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
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)
Time frame: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
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)
Time frame: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
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)
Time frame: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
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)
Time frame: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
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)
Time frame: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, 24, 36, and 48 post dose
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.
Results and safety
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Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Minocycline in people with Bacterial Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 15 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Calculated Exposure Measures for Area Under the Curve 0 to 24 Hours After a Dose (AUC0-24) (time frame: Pre-dose, immediately after infusion termination (~1 hour) and at 4, 12, and 24 hours post dose). The study lists 22 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Dec 2020.