Dose-finding, Pharmacokinetics, and Safety of VABOMERE in Pediatric Subjects With Bacterial Infections

Bacterial Infections Clinical Trial

— TANGOKIDS  

Official title:

An Open Label, Dose-finding, Pharmacokinetics, Safety, and Tolerability Study of a Single Dose Infusion of VABOMERE (Meropenem-Vaborbactam) in Pediatric Subjects From Birth to Less Than 18 Years of Age With Serious Bacterial Infections

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02687906
• Other study ID #: Rempex 507
• Secondary ID: 2016-000656-99
• Status: Recruiting
• Phase: Phase 1
• Start date: July 2016
• Est. completion date: June 2025

Study information

• Verified date: March 2024
• Source: Melinta Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A single dose infusion of Vabomere (meropenem-vaborbactam) is being tested for dose-finding, pharmacokinetics, safety, and tolerability in pediatric subjects from birth to less than 18 years of age with serious bacterial infections

Description:

In the current era of increased resistance to extended spectrum cephalosporins, carbapenem antimicrobial agents are frequently the antibiotics of "last defense" for the most resistant pathogens in serious infections, including those found in complicated Urinary Tract Infections (cUTI). The recent dissemination of serine carbapenemases (e.g. KPC) in Enterobacteriaceae in many hospitals worldwide now poses a considerable threat to the carbapenems and other members of the beta-lactam class of antimicrobial agents.

Rempex developed meropenem-vaborbactam administered as a fixed combination by IV infusion, to treat serious Gram-negative infections, such as cUTIs, including those infections caused by bacteria resistant to currently available carbapenems.

This study is an open label, dose-finding, pharmacokinetics, safety, and tolerability study of a single dose infusion of meropenem-vaborbactam in pediatric subjects from birth to less than 18 years of age with suspected or confirmed bacterial infection receiving antibiotic therapy or subjects receiving peri-operative prophylactic use of antibiotics.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 67
• Est. completion date: June 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 17 Years

Eligibility

Inclusion Criteria:

1. A signed and dated written informed consent from the parent or legal representative and a subject assent (according to local IRB requirements);

2. Male or female from birth to < 18 years of age;

3. Are hospitalized, in stable condition, and receiving systemic antibiotics for a known or suspected bacterial infection; or subjects receiving peri-operative prophylactic use of antibiotics;

4. The subject will be observed in the hospital for at least 6 hours after the study drug is administered;

5. If female and has reached menarche, or has reached Tanner Stage 3 breast development (even if not having reached menarche), the subject is practicing appropriate birth control or is sexually abstinent;

6. Sufficient intravascular access (peripheral or central) to receive study drug.

Subjects will be excluded from the study if any of the following exclusion criteria apply prior to randomization:

1. Signs of severe sepsis including:

1. Shock or profound hypotension that is not responsive to fluid challenge;

2. Hypothermia (core temperature < 35.6 ºC or 96.1 ºF);

3. Disseminated intravascular coagulation as evidenced by prothrombin time or partial thromboplastin time = 2X the ULN or platelets < 50% of the lower limit of normal;

2. Any surgical or medical condition which, in the opinion of the investigator, would put the subject at increased risk or is likely to interfere with study procedures or PK of the study drug;

3. Females who are of childbearing potential and unwilling to practice abstinence or use at least two methods of contraception (oral contraceptives, barrier methods, approved contraceptive implant) during the entire study period;

4. Female adolescent subjects who are pregnant or breastfeeding or have a positive serum ß-hCG pregnancy test at screening and at pre-dose Day 1;

5. Males who are unwilling to practice abstinence or use an acceptable method of broth control during the entire study period (i.e. condom with spermicide);

6. Renal function at screening as estimated by creatinine clearance < 50 mL/min /1.73 m^2 as calculated using the updated Schwartz bedside formula: eGFR = k x (height in cm) ÷ serum creatinine

• k = 0.33 in pre-term infants.

• k = 0.45 in term infants to 1 year of age.

• k = 0.55 in children and adolescent girls.

• k = 0.70 in adolescent boys.

7. Treatment within 30 days prior to enrollment with valproic acid;

8. Treatment within 30 days prior to enrollment with probenecid;

9. Evidence of significant hepatic disease or dysfunction, including known acute viral hepatitis or hepatic encephalopathy;

10. Neutropenia with absolute neutrophil count (ANC) < 500 cells/mm3;

11. Aspartate aminotransferase or alanine aminotransferase = 3X ULN or total bilirubin = 1.5X ULN;

12. Receipt of any investigational medication or investigational device within 30 days prior to enrollment;

13. Prior exposure to vaborbactam or Vabomere;

14. Use of meropenem within 48 hours of administration of study drug or 12 hours after study drug administration;

15. Known significant hypersensitivity to any beta-lactam antibiotic;

16. Unable or unwilling in the judgment of the Investigator, to comply with the protocol;

17. Subject is a child of an employee of the Investigator or study center with direct involvement in the proposed study or other studies under the direction of that Investigator or study center, as well as a family member of the employee or the Investigator;

18. Body Mass Index (BMI) outside the range (below the 5th percentile or above the 95th percentile) for height, age and weight except for children < 2 years of age.)

Related Conditions & MeSH terms

• Bacterial Infections
• Communicable Diseases
• Infections

Intervention

Drug:
• Vabomere
Vabomere (meropenem-vaborbactam) for IV injection

Locations

Country	Name	City	State
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Rainbow Babies and Childrens Hospital	Cleveland	Ohio
United States	Arkansas Children's Hospital	Little Rock	Arkansas
United States	Ronald Reagan UCLA Medical Center	Los Angeles	California
United States	Rutger's University	New Brunswick	New Jersey
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Children's Hospital of Orange County	Orange	California
United States	Rady Children's Hospital San Diego	San Diego	California
United States	Toledo Children's Hospital	Toledo	Ohio
United States	Los Angeles Biomedical Research Institute	Torrance	California

Sponsors (2)

Lead Sponsor	Collaborator
Rempex (a wholly owned subsidiary of Melinta Therapeutics, LLC)	Department of Health and Human Services

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetics: AUC0-8	AUC from time zero to infinity	From pre-dose until 6 hours after the start of the infusion
Primary	Pharmacokinetics: Cmax	maximum measured plasma concentration	From pre-dose until 6 hours after the start of the infusion
Primary	Pharmacokinetics: time to maximum plasma concentration (Tmax)	time to Cmax	From pre-dose until 6 hours after the start of the infusion
Primary	Pharmacokinetics: drug clearance (CL)	total body clearance	From pre-dose until 6 hours after the start of the infusion
Primary	Pharmacokinetics: t1/2	elimination half- life	From pre-dose until 6 hours after the start of the infusion
Primary	Pharmacokinetics: Cmin	minimum plasma concentration	From pre-dose until 6 hours after the start of the infusion
Primary	Pharmacokinetics: Vss	Volume of distribution	From pre-dose until 6 hours after the start of the infusion
Primary	Safety and tolerability: AEs/SAEs	a composite measure of the number and types of AEs/SAEs encountered and relationship to time of dosing	From assent / consent until day 7 safety follow up call
Primary	Safety and tolerability: clinical safety laboratory results	A composite measure of multiple laboratory results assessing the clinical significance of any changes from baseline	From assent / consent until day 7 safety follow up call
Primary	Safety and tolerability: vital signs	A composite of multiple vital sign measurements, assessing the clinical significance of any changes from baseline	From assent / consent until day 7 safety follow up call
Primary	Safety and tolerability: ECGs	A composite of multiple ECG measurements, assessing the clinical significance of any changes from baseline	From assent / consent until day 7 safety follow up call