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Dose-finding, Pharmacokinetics, and Safety of VABOMERE in Pediatric Subjects With 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 : January 11, 2023
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.) )

Tracking Information
First Submitted Date  ICMJE February 17, 2016
First Posted Date  ICMJE February 22, 2016
Last Update Posted Date January 11, 2023
Actual Study Start Date  ICMJE July 2016
Estimated Primary Completion Date May 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 17, 2016)
  • Pharmacokinetics: AUC0-∞ [ Time Frame: From pre-dose until 6 hours after the start of the infusion ]
    AUC from time zero to infinity
  • Pharmacokinetics: Cmax [ Time Frame: From pre-dose until 6 hours after the start of the infusion ]
    maximum measured plasma concentration
  • Pharmacokinetics: time to maximum plasma concentration (Tmax) [ Time Frame: From pre-dose until 6 hours after the start of the infusion ]
    time to Cmax
  • Pharmacokinetics: drug clearance (CL) [ Time Frame: From pre-dose until 6 hours after the start of the infusion ]
    total body clearance
  • Pharmacokinetics: t1/2 [ Time Frame: From pre-dose until 6 hours after the start of the infusion ]
    elimination half- life
  • Pharmacokinetics: Cmin [ Time Frame: From pre-dose until 6 hours after the start of the infusion ]
    minimum plasma concentration
  • Pharmacokinetics: Vss [ Time Frame: From pre-dose until 6 hours after the start of the infusion ]
    Volume of distribution
  • 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
  • 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
  • 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
  • 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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dose-finding, Pharmacokinetics, and Safety of VABOMERE in Pediatric Subjects With Bacterial Infections
Official Title  ICMJE 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
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
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Bacterial Infections
Intervention  ICMJE Drug: Vabomere
Vabomere (meropenem-vaborbactam) for IV injection
Other Names:
  • Combination meropenem and vaborbactam
  • carbapenem and beta-lactamase inhibitor
Study Arms  ICMJE 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

  • 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)
Intervention: Drug: Vabomere
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 10, 2023)		 67
Original Estimated Enrollment  ICMJE
 (submitted: February 17, 2016)		 56
Estimated Study Completion Date  ICMJE December 2023
Estimated Primary Completion Date May 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Richard J Lazauskas, DC 1-844-633-6568 rlazauskas@melinta.com
Contact: William Waverczak, MS 1-844-633-6568 wwaverczak@melinta.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02687906
Other Study ID Numbers  ICMJE Rempex 507
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Melinta Therapeutics, Inc. ( Rempex (a wholly owned subsidiary of Melinta Therapeutics, Inc.) )
Original Responsible Party Rempex Pharmaceuticals (a wholly owned subsidiary of The Medicines Company)
Current Study Sponsor  ICMJE Rempex (a wholly owned subsidiary of Melinta Therapeutics, Inc.)
Original Study Sponsor  ICMJE Rempex Pharmaceuticals (a wholly owned subsidiary of The Medicines Company)
Collaborators  ICMJE Department of Health and Human Services
Investigators  ICMJE
Study Director: Study Director Melinta Therapeutics, Inc.
PRS Account Melinta Therapeutics, Inc.
Verification Date January 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP