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

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

Sponsors

Lead sponsor: Rempex (a wholly owned subsidiary of Melinta Therapeutics, Inc.)

Collaborator: Department of Health and Human Services

Source Melinta Therapeutics, Inc.
Brief 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

Detailed 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 serious bacterial infections

Overall Status Recruiting
Start Date July 2016
Completion Date September 2021
Primary Completion Date August 2021
Phase Phase 1
Study Type Interventional
Primary Outcome
Measure Time Frame
Pharmacokinetics: AUC0-∞ From pre-dose until 6 hours after the start of the infusion
Pharmacokinetics: AUC0-∞ From pre-dose until 6 hours after the start of the infusion
Pharmacokinetics: AUC0-∞ From pre-dose until 6 hours after the start of the infusion
Pharmacokinetics: Cmax From pre-dose until 6 hours after the start of the infusion
Pharmacokinetics: Cmax From pre-dose until 6 hours after the start of the infusion
Pharmacokinetics: Cmax From pre-dose until 6 hours after the start of the infusion
Pharmacokinetics: time to maximum plasma concentration (Tmax) From pre-dose until 6 hours after the start of the infusion
Pharmacokinetics: time to maximum plasma concentration (Tmax) From pre-dose until 6 hours after the start of the infusion
Pharmacokinetics: time to maximum plasma concentration (Tmax) From pre-dose until 6 hours after the start of the infusion
Pharmacokinetics: drug clearance (CL) From pre-dose until 6 hours after the start of the infusion
Pharmacokinetics: drug clearance (CL) From pre-dose until 6 hours after the start of the infusion
Pharmacokinetics: drug clearance (CL) From pre-dose until 6 hours after the start of the infusion
Pharmacokinetics: t1/2 From pre-dose until 6 hours after the start of the infusion
Pharmacokinetics: t1/2 From pre-dose until 6 hours after the start of the infusion
Pharmacokinetics: t1/2 From pre-dose until 6 hours after the start of the infusion
Pharmacokinetics: Cmin From pre-dose until 6 hours after the start of the infusion
Pharmacokinetics: Cmin From pre-dose until 6 hours after the start of the infusion
Pharmacokinetics: Cmin From pre-dose until 6 hours after the start of the infusion
Pharmacokinetics: Vss From pre-dose until 6 hours after the start of the infusion
Pharmacokinetics: Vss From pre-dose until 6 hours after the start of the infusion
Pharmacokinetics: Vss From pre-dose until 6 hours after the start of the infusion
Safety and tolerability: AEs/SAEs From assent / consent until day 7 safety follow up call
Safety and tolerability: AEs/SAEs From assent / consent until day 7 safety follow up call
Safety and tolerability: AEs/SAEs From assent / consent until day 7 safety follow up call
Safety and tolerability: clinical safety laboratory results From assent / consent until day 7 safety follow up call
Safety and tolerability: clinical safety laboratory results From assent / consent until day 7 safety follow up call
Safety and tolerability: clinical safety laboratory results From assent / consent until day 7 safety follow up call
Safety and tolerability: vital signs From assent / consent until day 7 safety follow up call
Safety and tolerability: vital signs From assent / consent until day 7 safety follow up call
Safety and tolerability: vital signs From assent / consent until day 7 safety follow up call
Safety and tolerability: ECGs From assent / consent until day 7 safety follow up call
Safety and tolerability: ECGs From assent / consent until day 7 safety follow up call
Safety and tolerability: ECGs From assent / consent until day 7 safety follow up call
Enrollment 60
Condition
Intervention

Intervention type: Drug

Intervention name: Vabomere

Description: Vabomere (meropenem-vaborbactam) for IV injection

Arm group label: Single dose IV meropenem-vaborbactam

Eligibility

Criteria:

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 β-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 using the Cockcroft-Gault formula;

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. 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. 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.)

Gender: All

Minimum age: N/A

Maximum age: 17 Years

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Karen Fusaro Study Director Sponsor GmbH
Overall Contact

Last name: Karen Fusaro

Email: [email protected]

Location
facility status contact investigator
Arkansas Children's Hospital Recruiting Robin Gibson, RN 501-364-1542 [email protected] Jose R. Romero, MD Principal Investigator
Ronald Reagan UCLA Medical Center Recruiting Elizabeth Lang [email protected] Jaime Deville, MD Principal Investigator
Children's Hospital of Orange County Recruiting Claudia Enriquez 714-509-4064 [email protected] Antonio Arrieta, MD Principal Investigator
Rady Children's Hospital San Diego Recruiting Mike Farrell, RN 858-966-8381 [email protected] John Bradley, MD Principal Investigator
Los Angeles Biomedical Research Institute Withdrawn
Ann & Robert H. Lurie Children's Hospital of Chicago Recruiting Laura Fearn [email protected] William Muller, M.D. Principal Investigator
University of Nebraska Medical Center Recruiting Kristin Malone 402-559-2977 [email protected] Kari Simonsen, MD Principal Investigator
Rutgers Robert Wood Johnson Hospital Recruiting Lisa Cerrachio [email protected] Sunanda Gaur, MD Principal Investigator
Rainbow Babies and Childrens Hospital Completed
Toledo Children's Hospital Completed
Location Countries

United States

Verification Date

January 2020

Responsible Party

Responsible party type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Arm group label: Single dose IV meropenem-vaborbactam

Arm group type: Experimental

Description: Vabomere (meropenem-vaborbactam) for IV injection will be administered as a single dose diluted in normal saline infused IV over 3 hours The starting dose for Cohort 1 (ages 12 to <18 years) was 40 mg/kg meropenem and 40 mg/kg vaborbactam, or 2 g meropenem 2 g vaborbactam for subjects ≥50kg in weight. Following completion of Cohorts 1 and 2 an independent DSMB assessed the PK, safety and tolerability data and determined that the new starting dose for Cohort 3 (ages 2 to < 6 years) would be 60 mg/kg or 2 g meropenem 2 g vaborbactam for subjects >33 kg in weight.

Acronym TANGOKIDS
Patient Data No
Study Design Info

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov