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A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Meropenem-Vaborbactam in Children With Complicated Urinary Tract Infection, Including Acute Pyelonephritis

Phase 2
Recruiting
Conditions
Acute Pyelonephritis
Complicated Urinary Tract Infection
Interventions
Drug: Meropenem-Vaborbactam
Drug: Antibiotics
Registration Number
NCT06672978
Lead Sponsor
Rempex (a wholly owned subsidiary of Melinta Therapeutics, LLC)
Brief Summary

The primary objective of the study is to assess the safety and tolerability of meropenem-vaborbactam administered by intravenous (IV) infusion in children 3 months and above to less than 12 years with complicated urinary tract infections (cUTI), including acute pyelonephritis (AP)

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
66
Inclusion Criteria
  • Have a clinically suspected and/or bacteriologically documented cUTI or AP judged by the Investigator to require hospitalization for treatment with at least 3 days of IV antibiotics.

  • Evidence of pyuria, confirmed by either of the following:

    • A urine specimen that is positive for leukocyte esterase via urine dipstick or urinalysis, or
    • A urine specimen with either > 10 white blood cells (WBCs) per microliter from an unspun urine or > 5WBCs per high power field from a centrifuged specimen
  • Symptomatic or asymptomatic cUTI or AP as specified in the protocol.

    • Acute Pyelonephritis (qualifying symptoms specified in protocol)
  • Have a pretreatment "baseline" urine specimen obtained for culture by an acceptable method, including suprapubic aspiration (SPA), clean urethral catheterization, in dwelling urethral catheter, or mid-stream clean catch (urine specimens obtained from externally placed urine bags will not be allowed) within 48 hours before the start of the administration of the first dose of IV study drug therapy.

  • Must, based on the judgment of the Investigator, require hospitalization initially and 7 to14 days of antibacterial therapy for the treatment of the presumed cUTI.

Key

Exclusion Criteria
  • History of hypersensitivity or allergic reaction to beta-lactam antibiotics (for example [e.g.],cephalosporins, penicillins, carbapenems, monobactams).
  • Known Vabomere-resistant gram-negative organism from study-qualifying urine or blood culture, confirmed cUTI or AP only due to gram-positive organism from study-qualifying urine or blood culture, or known or suspected infection with organisms that are not adequately covered by Vabomere (e.g., viral, mycobacterial, fungal).
  • Receipt of a potentially effective antibacterial drug therapy for cUTI for a duration of more than 24 hours during the previous 72 hours prior to enrollment. Exceptions: participants with unequivocal clinical evidence of treatment failure (that is, worsening signs and symptoms); urine culture confirms resistance to the initial antibiotic; or the participant developed signs and symptoms of cUTI or AP while on antibiotics for another indication.
  • Participants undergoing dialysis or with estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m^2, as calculated using the updated bedside Schwartz formula.
  • Evidence of significant hepatic disease or dysfunction, including known acute viral or inactive chronic hepatitis or hepatic encephalopathy, or aspartate aminotransferase or alanine aminotransferase > 3 × upper limit normal (ULN), or total bilirubin > 1.5 × ULN.

Note: Other protocol-defined Inclusion/Exclusion criteria may apply.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Cohort 2: Age 2 to < 6 yearsMeropenem-VaborbactamParticipants will receive meropenem-vaborbactam IV infusion for a minimum of 3 days, for up to 14 days. Participants with clinical improvement have the option to switch to an oral antibiotic after Day 3.
Cohort 2: Age 2 to < 6 yearsAntibioticsParticipants will receive meropenem-vaborbactam IV infusion for a minimum of 3 days, for up to 14 days. Participants with clinical improvement have the option to switch to an oral antibiotic after Day 3.
Cohort 3: Age 3 months to < 2 yearsMeropenem-VaborbactamParticipants will receive meropenem-vaborbactam IV infusion for a minimum of 3 days, for up to 14 days. Participants with clinical improvement have the option to switch to an oral antibiotic after Day 3.
Cohort 1: Age 6 to < 12 yearsMeropenem-VaborbactamParticipants will receive meropenem-vaborbactam via an intravenous (IV) infusion for a minimum of 3 days, for up to 14 days. Participants with clinical improvement have the option to switch to an oral antibiotic after Day 3.
Cohort 1: Age 6 to < 12 yearsAntibioticsParticipants will receive meropenem-vaborbactam via an intravenous (IV) infusion for a minimum of 3 days, for up to 14 days. Participants with clinical improvement have the option to switch to an oral antibiotic after Day 3.
Cohort 3: Age 3 months to < 2 yearsAntibioticsParticipants will receive meropenem-vaborbactam IV infusion for a minimum of 3 days, for up to 14 days. Participants with clinical improvement have the option to switch to an oral antibiotic after Day 3.
Primary Outcome Measures
NameTimeMethod
Number of Participants With Adverse Events (AEs)Up to 28 days
Secondary Outcome Measures
NameTimeMethod
Area Under the Plasma Concentration Curve From Zero to infinity (AUC0-inf)Day 1 and Day 3: Up to 3 hours post-dose
Overall Response (OR)Up to 14 days

OR as assessed by the combined per-participant clinical cure and favorable microbiological response.

Time to Maximum Observed Plasma Concentration (Tmax)Day 1 and Day 3: Up to 3 hours post-dose
Maximum Observed Plasma Concentration (Cmax)Day 1 and Day 3: Up to 3 hours post-dose
Clinical CureUp to 14 days

Clinical cure is defined as the complete resolution or significant improvement of signs and symptoms of cUTI or AP present at baseline, no new symptoms, and participant is alive.

Favorable Microbiological Response (Microbiological Eradication)Up to 14 days

Favorable microbial response is defined as the reduction of baseline pathogen(s) (\< 10\^3 colony-forming units per milliliter \[CFU/mL\] and at least 1-log reduction from baseline) or negative urine culture, negative repeated blood culture if blood culture was positive for pathogen(s) growth at baseline, and participant is alive.

Trial Locations

Locations (3)

University Multiprofile Hospital for Active Treatment 'Kanev', Ruse, Department of Pediatrics

🇧🇬

Ruse, Bulgaria

Multiprofile Hospital for Active Treatment "Dr. Ivan Seliminski", Sliven

🇧🇬

Sliven, Bulgaria

Children's Hospital of Orange County

🇺🇸

Orange, California, United States

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