Minocycline Pharmacokinetics (ACUMIN)

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.

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.

Inclusion Criteria:

1. Male or female > / = 18 years of age.
2. Subject is in the ICU, or is being admitted to the ICU.
3. 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.
4. 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.
5. 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.
6. The subject, or legally authorized representative (LAR), is able and willing to provide signed informed consent.

Exclusion Criteria:

1. History of significant hypersensitivity or allergic reaction to tetracycline antibiotics.

2. Receipt of oral or intravenous tetracycline class drugs within 7 days of enrollment (e.g., minocycline, tetracycline, tigecycline, doxycycline).

3. Use of isotretinoin within 2 weeks of enrollment into the study.

4. 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".

5. Pregnant or breastfeeding women.

6. Patient is being treated for intracranial hypertension.

7. 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.

8. 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.