Acute Pyelonephritis, Complicated Urinary Tract Infection
Conditions
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).
Interventions
Administered as specified in the treatment arm
DRUGAntibiotics
Administered as prescribed by the study physician in accordance with local guidelines and regulations.
Sponsors
Biomedical Advanced Research and Development Authority
Rempex (a wholly owned subsidiary of Melinta Therapeutics, LLC)
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Months to 11 Years
Healthy volunteers
No
Inclusion criteria
Key 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 \> 5 WBCs 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/minute/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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With Adverse Events (AEs) | Up to 28 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) | Day 1 and Day 3: Up to 3 hours post-dose | — |
| Time to Maximum Observed Plasma Concentration (Tmax) | Day 1 and Day 3: Up to 3 hours post-dose | — |
| Clinical Cure | Up 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. |
| Overall Response (OR) | Up to 14 days | OR as assessed by the combined per-participant clinical cure and favorable microbiological response. |
| 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. |
| Area Under the Plasma Concentration Curve from Zero to Infinity (AUC0-inf) | Day 1 and Day 3: Up to 3 hours post-dose | — |
Countries
Bulgaria, Croatia, Georgia, Greece, Poland, United States
Contacts
Primary ContactMedical Information Study Director Melinta Therapeutics, LLC
Outcome results
None listed