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

Sponsor

Rempex (a wholly owned subsidiary of Melinta Therapeutics, Inc.) (Industry)

Overall Status

Recruiting

CT.gov ID

NCT02687906

Collaborator

Department of Health and Human Services (U.S. Fed)

Enrollment

Locations

Arm

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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 Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

N/A

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 :

Jul 1, 2016

Anticipated Primary Completion Date :

May 1, 2023

Anticipated Study Completion Date :

Jun 1, 2023

Arms and Interventions

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

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 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.

Drug: Vabomere

Vabomere (meropenem-vaborbactam) for IV injection

Other Names:

Combination meropenem and vaborbactam

carbapenem and beta-lactamase inhibitor

Outcome Measures

Primary Outcome Measures

Pharmacokinetics: AUC0-∞ [From pre-dose until 6 hours after the start of the infusion]
AUC from time zero to infinity
Pharmacokinetics: Cmax [From pre-dose until 6 hours after the start of the infusion]
maximum measured plasma concentration
Pharmacokinetics: time to maximum plasma concentration (Tmax) [From pre-dose until 6 hours after the start of the infusion]
time to Cmax
Pharmacokinetics: drug clearance (CL) [From pre-dose until 6 hours after the start of the infusion]
total body clearance
Pharmacokinetics: t1/2 [From pre-dose until 6 hours after the start of the infusion]
elimination half- life
Pharmacokinetics: Cmin [From pre-dose until 6 hours after the start of the infusion]
minimum plasma concentration
Pharmacokinetics: Vss [From pre-dose until 6 hours after the start of the infusion]
Volume of distribution
Safety and tolerability: AEs/SAEs [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 [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 [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 [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

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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; 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.

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

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 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 or investigational device within 30 days prior to enrollment;
Prior exposure to vaborbactam 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;
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;
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.)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arkansas Children's Hospital	Little Rock	Arkansas	United States	72202
2	Ronald Reagan UCLA Medical Center	Los Angeles	California	United States	90095
3	Children's Hospital of Orange County	Orange	California	United States	92868
4	Rady Children's Hospital San Diego	San Diego	California	United States	92123
5	Los Angeles Biomedical Research Institute	Torrance	California	United States	90502
6	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois	United States	60614
7	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198-2162
8	Rutgers Robert Wood Johnson Hospital	New Brunswick	New Jersey	United States	08901
9	Rainbow Babies and Childrens Hospital	Cleveland	Ohio	United States	44106
10	Toledo Children's Hospital	Toledo	Ohio	United States	43606