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

NCT02687906 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: Rempex 5072016-000656-99
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 9

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

Conditions

Bacterial Infections

Outcome Measures

Primary Outcomes (11)

• Pharmacokinetics: AUC0-∞

  AUC from time zero to infinity

  From pre-dose until 6 hours after the start of the infusion

• Pharmacokinetics: Cmax

  maximum measured plasma concentration

  From pre-dose until 6 hours after the start of the infusion

• Pharmacokinetics: time to maximum plasma concentration (Tmax)

  time to Cmax

  From pre-dose until 6 hours after the start of the infusion

• Pharmacokinetics: drug clearance (CL)

  total body clearance

  From pre-dose until 6 hours after the start of the infusion

• Pharmacokinetics: t1/2

  elimination half- life

  From pre-dose until 6 hours after the start of the infusion

• Pharmacokinetics: Cmin

  minimum plasma concentration

  From pre-dose until 6 hours after the start of the infusion

• Pharmacokinetics: Vss

  Volume of distribution

  From pre-dose until 6 hours after the start of the infusion

• 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

• 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

• 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

• 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

Study Arms (1)

Single dose IV meropenem-vaborbactam

EXPERIMENTAL

Vabomere (meropenem-vaborbactam) for IV injection will be administered as a single dose diluted in normal saline infused IV over 3 hours * Cohort 1 (n=8): 12 to \< 18 years of age (40 mg/kg) * Cohort 2 (n=8): 6 to \< 12 years of age (40 mg/kg) * Cohort 2b (n=4): 6 to \< 12 years of age (60 mg/kg) * Cohort 3 (n=8): 2 to \< 6 years of age (60 mg/kg) * Cohort 4 (n=8): 3 months to \< 2 years of age (60 mg/kg) * Cohort 5 (n=24): Birth to \< 3 months of age (dose TBD) * Group A: Gestational Age (GA) \< 32 weeks, Postnatal Age (PNA) \< 2 weeks (n=6) * Group B: GA \< 32 weeks, PNA \> 2 weeks (n=6) * Group C: GA \> 32 weeks, PNA \< 2 weeks (n=6) * Group D: GA \> 32 weeks, PNA \> 2 weeks (n=6) * Cohort 6 (n=7): 2 to \< 12 years of age and ≤ 35 kg of weight (80 mg/kg)

Drug: Vabomere

Interventions

Vabomere DRUG

Vabomere (meropenem-vaborbactam) for IV injection

Also known as: Combination meropenem and vaborbactam, carbapenem and beta-lactamase inhibitor

Single dose IV meropenem-vaborbactam

Eligibility Criteria

• Age: Up to 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• A signed and dated written informed consent from the parent or legal representative and a subject assent (according to local IRB requirements);
• Male or female from birth to \< 18 years of age;
• 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;
• The subject will be observed in the hospital for at least 6 hours after the study drug is administered;
• 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;
• Sufficient intravascular access (peripheral or central) to receive study drug.

You may not qualify if:

• Signs of severe sepsis including:
• Shock or profound hypotension that is not responsive to fluid challenge;
• Hypothermia (core temperature \< 35.6 ºC or 96.1 ºF);
• Disseminated intravascular coagulation as evidenced by prothrombin time or partial thromboplastin time ≥ 2X the ULN or platelets \< 50% of the lower limit of normal;
• 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;
• 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;
• 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;
• 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);
• 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.
• Treatment within 30 days prior to enrollment with valproic acid;
• Treatment within 30 days prior to enrollment with probenecid;

Sponsors & Collaborators

• Rempex (a wholly owned subsidiary of Melinta Therapeutics, LLC): lead
• Department of Health and Human Services: collaborator

Study Sites (9)

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

Location

Ronald Reagan UCLA Medical Center

Los Angeles, California, 90095, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

Rady Children's Hospital San Diego

San Diego, California, 92123, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60614, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68114, United States

Location

Rutger's University

New Brunswick, New Jersey, 08901, United States

Location

Rainbow Babies and Childrens Hospital

Cleveland, Ohio, 44106, United States

Location

Toledo Children's Hospital

Toledo, Ohio, 43606, United States

Location

Related Publications (1)

• Bradley JS, Harvey H, Stout D, Momper J, Capparelli E, Avedissian SN, Barbato C, Mak RH, Jones TP, Jones D, Le J. Subtherapeutic Meropenem Antibiotic Exposure in Children With Septic Shock Assessed by Noncompartmental Pharmacokinetic Analysis in a Prospective Dataset. Pediatr Crit Care Med. 2025 Apr 1;26(4):e507-e515. doi: 10.1097/PCC.0000000000003698. Epub 2025 Feb 18.

  PMID: 39964222 DERIVED

MeSH Terms

Conditions

Bacterial Infections

Interventions

meropenem and vaborbactam; vaborbactam; Carbapenems; beta-Lactamase Inhibitors

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

beta-Lactams; Lactams; Amides; Organic Chemicals; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Anti-Bacterial Agents; Anti-Infective Agents; Therapeutic Uses

Study Officials

• Study Director

  Melinta Therapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2016
• First Posted: February 22, 2016
• Study Start: July 1, 2016
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: July 25, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)