ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 3 of 7 for:    carbavance

Dose-finding, Pharmacokinetics, Safety, and Tolerability of VABOMERE (Meropenem-Vaborbactam) in Pediatric Subjects With Serious Bacterial Infections (TANGOKIDS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02687906
Recruitment Status : Recruiting
First Posted : February 22, 2016
Last Update Posted : May 2, 2018
Sponsor:
Collaborator:
Department of Health and Human Services
Information provided by (Responsible Party):
Melinta Therapeutics, Inc. ( Rempex (a wholly owned subsidiary of 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

Condition or disease Intervention/treatment Phase
Bacterial Infections Drug: Vabomere Phase 1

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


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : July 2016
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : September 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Meropenem

Arm Intervention/treatment
Experimental: Single dose IV meropenem-vaborbactam

Vabomere (meropenem-vaborbactam) for IV injection will be administered as a single dose diluted in normal saline infused IV over 3 hours

Starting dose for Cohort 1 (ages 12-18 years) is 40mg/kg meropenem and 40mg/kg vaborbactam, or 2g meropenem 2g vaborbactam for subjects ≥50kg in weight. Following completion of each cohort an independent DSMB will assess the PK, safety and tolerability data to determine the subsequent cohort's dose

Drug: Vabomere
Vabomere (meropenem-vaborbactam) for IV injection
Other Names:
  • Combination meropenem and vaborbactam
  • carbapenem and beta-lactamase inhibitor




Primary Outcome Measures :
  1. Pharmacokinetics: AUC0-∞ [ Time Frame: From pre-dose until 6 hours after the start of the infusion ]
    AUC from time zero to infinity

  2. Pharmacokinetics: Cmax [ Time Frame: From pre-dose until 6 hours after the start of the infusion ]
    maximum measured plasma concentration

  3. Pharmacokinetics: time to maximum plasma concentration (Tmax) [ Time Frame: From pre-dose until 6 hours after the start of the infusion ]
    time to Cmax

  4. Pharmacokinetics: drug clearance (CL) [ Time Frame: From pre-dose until 6 hours after the start of the infusion ]
    total body clearance

  5. Pharmacokinetics: t1/2 [ Time Frame: From pre-dose until 6 hours after the start of the infusion ]
    elimination half- life

  6. Pharmacokinetics: Cmin [ Time Frame: From pre-dose until 6 hours after the start of the infusion ]
    minimum plasma concentration

  7. Pharmacokinetics: Vss [ Time Frame: From pre-dose until 6 hours after the start of the infusion ]
    Volume of distribution

  8. Safety and tolerability: AEs/SAEs [ Time Frame: From assent / consent until day 7 safety follow up call ]
    a composite measure of the number and types of AEs/SAEs encountered and relationship to time of dosing

  9. Safety and tolerability: clinical safety laboratory results [ Time Frame: From assent / consent until day 7 safety follow up call ]
    A composite measure of multiple laboratory results assessing the clinical significance of any changes from baseline

  10. Safety and tolerability: vital signs [ Time Frame: From assent / consent until day 7 safety follow up call ]
    A composite of multiple vital sign measurements, assessing the clinical significance of any changes from baseline

  11. Safety and tolerability: ECGs [ Time Frame: From assent / consent until day 7 safety follow up call ]
    A composite of multiple ECG measurements, assessing the clinical significance of any changes from baseline



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   up to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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;
  • In the investigator's opinion, the subject will require hospitalization for at least 24 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.

Exclusion Criteria:

  • Presence of any of the following conditions:

    1. Endocarditis
    2. Meningitis
    3. Necrotizing fasciitis
    4. Gas gangrene
  • 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 (DIC) as evidenced by prothrombin time or partial thromboplastin time ≥ 2X the upper limit of normal (ULN) or platelets < 50% of the lower limit of normal;
  • Surgery up to 48 hours prior to enrollment or for procedures that are using a scope (i.e., laparoscope, etc.) up to 24 hours prior to enrollment;
  • 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;
  • Pregnant or breastfeeding female adolescent subjects or has a positive serum β-human chorionic gonadotropin (hCG) pregnancy test at screening and at pre-dose Day 1;
  • Males who are unwilling to practice abstinence or use an acceptable method of birth control during the entire study period (i.e. condom with spermicide);
  • Renal function at screening as estimated by creatinine clearance < 50 mL/min using the Cockcroft-Gault formula;
  • Treatment within 30 days prior to enrollment with valproic acid;
  • Treatment within 30 days prior to enrollment with probenecid;
  • Evidence of significant hepatic disease or dysfunction, including known acute viral hepatitis or hepatic encephalopathy;
  • Neutropenia with absolute neutrophil count (ANC) < 500 cells/mm3.
  • Aspartate aminotransferase or alanine aminotransferase ≥ 3X ULN or total bilirubin ≥ 1.5X ULN;
  • Receipt of any investigational medication within 30 days prior to enrollment;
  • Previous exposure to vaborbactam (previously RPX7009) or Vabomere;
  • Use of meropenem within 48 hours of administration of study drug or 12 hours after study drug administration.
  • Known significant hypersensitivity to any beta-lactam antibiotic;
  • Unable or unwilling in the judgment of the Investigator, to comply with the protocol;
  • 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.
  • Receipt of a blood or blood component (e.g., red blood cells, fresh frozen plasma, platelets) transfusion during the 24-hour period prior to enrolment or anticipated need up to 24 hours after study drug administration;
  • 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.)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02687906


Contacts
Contact: Karen Fusaro kfusaro@melinta.com
Contact: Stephanie Durso sdurso@melinta.com

Locations
United States, Arkansas
Arkansas Children's Hospital Recruiting
Little Rock, Arkansas, United States, 72202
Contact: Robin Gibson, RN    501-364-1542    GibsonRobinA@uams.edu   
Principal Investigator: Jose R. Romero, MD         
United States, California
Children's Hospital of Orange County Recruiting
Orange, California, United States, 92868
Contact: Claudia Enriquez    714-509-4064    cenriquez@choc.org   
Principal Investigator: Antonio Arrieta, MD         
Rady Children's Hospital San Diego Recruiting
San Diego, California, United States, 92123
Contact: Mike Farrell, RN    858-966-8381    mfarrell@rchsd.org   
Contact: Sara Hingtgen, RN    858-966-8381    shingtgen@rchsd.org   
Principal Investigator: John Bradley, MD         
Los Angeles Biomedical Research Institute Withdrawn
Torrance, California, United States, 90502
United States, Nebraska
University of Nebraska Medical Center Recruiting
Omaha, Nebraska, United States, 68198-2162
Contact: Kristin Malone    402-559-2977    Kristin.malone@unmc.edu   
Principal Investigator: Kari Simonsen, MD         
United States, Ohio
Rainbow Babies and Childrens Hospital Completed
Cleveland, Ohio, United States, 44106
Toledo Children's Hospital Completed
Toledo, Ohio, United States, 43606
Sponsors and Collaborators
Rempex (a wholly owned subsidiary of Melinta Therapeutics, Inc.)
Department of Health and Human Services
Investigators
Study Director: Karen Fusaro Sponsor GmbH

Responsible Party: Rempex (a wholly owned subsidiary of Melinta Therapeutics, Inc.)
ClinicalTrials.gov Identifier: NCT02687906     History of Changes
Other Study ID Numbers: Rempex 507
First Posted: February 22, 2016    Key Record Dates
Last Update Posted: May 2, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Infection
Communicable Diseases
Bacterial Infections
Meropenem
Thienamycins
beta-Lactamase Inhibitors
Anti-Bacterial Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action