Phase 4 N=58 Treatment

Minocycline Pharmacokinetics (ACUMIN)

Bacterial Infection

Bottom Line

View on ClinicalTrials.gov: NCT03369951 ↗

Enrolled (actual)

Serious AEs

1.8%

Results posted

Aug 2020

Primary outcome: Primary: Calculated Exposure Measures for Area Under the Curve 0 to 24 Hours After a Dose (AUC0-24) — 24.3 mg·hr/L

Study Design & Population

Study type: Interventional
Phase: Phase 4
Interventions: Minocycline (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Primary completion: Jul 2019

Outcome Measures

Outcome	Result	p-value
PRIMARY Calculated Exposure Measures for Area Under the Curve 0 to 24 Hours After a Dose (AUC0-24)	24.3	—
PRIMARY Calculated Exposure Measures for Area Under the Curve From 0 to Infinity (AUC0-inf) Using Free-drug Concentrations	14.1	—
PRIMARY Calculated Exposure Measures for Area Under the Curve From 0 to Infinity (AUC0-inf) Using Total-drug Concentrations	46.6	—
PRIMARY Calculated Exposure Measures for Area Under the Curve to the Last Quantifiable Sample (AUC0-last)	10.5	—
PRIMARY Calculated Exposure Measures for Maximum Plasma Concentration (Cmax)	2.58	—
PRIMARY Calculated Exposure Measures for Plasma Concentration at 24 Hours After Dose (C24)	0.603	—
PRIMARY Individual Post-hoc PK Parameter Estimates for Area Under the Curve 0 to 24 Hours After a Dose (AUC0-24)	—	—
PRIMARY Individual Post-hoc PK Parameter Estimates for Area Under the Curve From 0 to Infinity (AUC0-inf) Using Free-drug Concentrations	—	—
PRIMARY Individual Post-hoc PK Parameter Estimates for Area Under the Curve From 0 to Infinity (AUC0-inf) Using Total-drug Concentrations	—	—
PRIMARY Individual Post-hoc PK Parameter Estimates for Area Under the Curve to the Last Quantifiable Sample (AUC0-last)	—	—
PRIMARY Individual Post-hoc PK Parameter Estimates for Maximum Plasma Concentration (Cmax)	—	—
PRIMARY Individual Post-hoc PK Parameter Estimates for Plasma Concentration at 24 Hours After Dose (C24)	—	—
PRIMARY Magnitude of the Inter-individual Variability for Central Volume of Distribution (Vc)	49.9	—
PRIMARY Magnitude of the Inter-individual Variability for Distribution Clearance (CLd)	—	—
PRIMARY Magnitude of the Inter-individual Variability for Free-drug Clearance (CL)	—	—
PRIMARY Magnitude of the Inter-individual Variability for Peripheral Volume of Distribution (Vp)	34.2	—
PRIMARY Magnitude of the Inter-individual Variability for Total-drug Clearance (CL)	45.6	—
PRIMARY Population Mean PK Parameter Estimates for Central Volume of Distribution (Vc)	74.5	—
PRIMARY Population Mean PK Parameter Estimates for Distribution Clearance (CLd)	16.0	—
PRIMARY Population Mean PK Parameter Estimates for Free-drug Clearance (CL)	1.32	—
PRIMARY Population Mean PK Parameter Estimates for Peripheral Volume of Distribution (Vp)	58.9	—
PRIMARY Population Mean PK Parameter Estimates for Total-drug Clearance (CL)	4.7	—

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.

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.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03369951). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.