Phase 4
Completed N=58
Minocycline Pharmacokinetics (ACUMIN)
Source: ClinicalTrials.gov NCT03369951 ↗Enrolled (actual)
58
Serious AEs
1.8%
Results posted
Aug 2020
Primary outcomePrimary: Calculated Exposure Measures for Area Under the Curve 0 to 24 Hours After a Dose (AUC0-24) — 24.3 mg·hr/L
◆ Published Evidence
No publication linked
No peer-reviewed publication reporting this trial's results has been linked yet. This can indicate results are unpublished — a known publication-bias signal. We re-check periodically.
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.
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 | — |
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.
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. Informational only — not medical advice.