Minocycline Pharmacokinetics (ACUMIN)

NCT ID: NCT03369951

Last Updated: 2020-12-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-28
• Study Completion Date: 2019-07-20

Brief 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.

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

Keywords

ACUMIN; Infusion; Injection; Minocycline; Pharmacokinetic; PK

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Minocin® IV

200 mg minocycline hydrochloride IV infusion over approximately 60 minutes, n=50

Group Type: EXPERIMENTAL

Minocycline

Intervention Type: DRUG

Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.

Interventions

Minocycline

Minocycline is a semisynthetic derivative of tetracycline and is indicated for the treatment of infections due to susceptible isolates of designated microorganisms.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Emory Decatur Hospital - Clinical Trials - Immunology/Infectious Disease

Decatur, Georgia, United States

Northwestern Memorial Hospital - ICU

Chicago, Illinois, United States

Northwestern Medicine - Department of Obstetrics and Gynecology - Division of Female Pelvic Medicine and Reconstructive Surgery

Chicago, Illinois, United States

University of Kentucky - UK Albert B Chandler Hospital

Lexington, Kentucky, United States

University of Louisville School of Medicine - Surgery

Louisville, Kentucky, United States

Henry Ford Health System - Henry Ford Hospital

Detroit, Michigan, United States

William Beaumont Hospital - Royal Oak Campus - Infectious Disease

Royal Oak, Michigan, United States

Washington University School of Medicine in St. Louis - Infectious Diseases

St Louis, Missouri, United States

Duke University School of Medicine - Duke Clinical Research Institute - Duke Clinical Research Unit

Durham, North Carolina, United States

Duke University Hospital - Duke Medicine Pavilion - MICU

Durham, North Carolina, United States

East Carolina University - Infectious Diseases and Tropical/Travel Medicine Clinic

Greenville, North Carolina, United States

University of Cincinnati College of Medicine - Division of Infectious Diseases

Cincinnati, Ohio, United States

Case Western Reserve University School of Medicine - Medicine - Infectious Diseases and HIV Medicine

Cleveland, Ohio, United States

Oregon Health and Science University - Division of Pulmonary and Critical Care Medicine

Portland, Oregon, United States

University of Pittsburgh - Medicine - Infectious Diseases

Pittsburgh, Pennsylvania, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

2UM1AI104681-08

Identifier Type: NIH

Identifier Source: secondary_id

View Link

16-0011

Identifier Type: -

Identifier Source: org_study_id