LYS228 PK, Clinical Response, Safety and Tolerability in Patients With Complicated Urinary Tract Infection (cUTI)

Study Overview
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Brief Summary
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The purpose of the study is to evaluate whether LYS228 can be developed for the treatment of complicated urinary tract infections

Official Title
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A Randomized, Controlled, Evaluator-blinded, Multi-center, Study to Evaluate LYS228 Pharmacokinetics, Clinical Response, Safety and Tolerability in Patients With Complicated Urinary Tract Infection

Conditions
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Complicated Urinary Tract Infections

Intervention / Treatment
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* Drug: LYS228
* Drug: Standard of care therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients 18 to 85 years of age with suspected and/or bacteriologically documented complicated UTI judges by the investigator to be serious (required patient to be hospitalized for treatment with intravenous antibiotics) Exclusion Criteria: Urine Gram stain that demonstrated that a Gram-positive organism was present, or if urine culture results were available, demonstrated Gram- positive organisms were present at ≥10E5 CFU/mL Urine culture result available at enrollment and demonstrating more than 2 different species of microorganisms regardless of the colony count Urine culture result available demonstrating fungal UTI with colony count >10E3 CFU/mL Patient had received prior antibiotics within 72 hours before the initiation of study therapy Patients with estimated glomerular filtration rate < 30mL/min calculated based in study qualified formula

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LYS228<br>IV infusion | Drug: LYS228<br>* LYS228 IV infusion<br>|
| Active Comparator: Standard of care<br>IV infusion of standard of care antibiotics for at least 5 days | Drug: Standard of care therapy<br>* IV infusion of standard of care antibiotics<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline of the Clinical Response at Day 7 | Clinical success at 7 days after randomization determined by signs and symptoms of infection and the need for additional antibiotics | Baseline, Day 7 | 
| Plasma Pharmacokinetics (PK) of LYS228: Area Under the Plasma Concentration-time Curve from time zero to the end of dosing interval tau (AUCtau) | Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5 | Day 5 | 
| Plasma Pharmacokinetics (PK) of LYS228: The observed maximum plasma concentration following drug administration (Cmax) | Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5 | Day 5 | 
| Plasma Pharmacokinetics (PK) of LYS228: The time to reach the maximum concentration after drug administration (Tmax) | Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5 | Day 5 | 
| Plasma Pharmacokinetics (PK) of LYS228: The systemic (or total body) clearance from plasma following intravenous administration (CL) | Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5 | Day 5 | 
| Plasma Pharmacokinetics (PK) of LYS228: The volume of distribution at steady state following intravenous administration (Vss) | Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5 | Day 5 | 
| Plasma Pharmacokinetics (PK) of LYS228: The terminal elimination half-life (T 1/2) | Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5 | Day 5 | 
| Plasma Pharmacokinetics (PK) of LYS228: The amount of time in which the unbound drug concentration exceeds the minimum inhibitory concentration of the organism (%fT>MIC) | Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5 | Day 5 | 
| Urine Pharmacokinetics (PK) of LYS228: The amount of drug eliminated in Urine from 0 hours up to 6 hours following intravenus administration (Ae0-6h) | Calculated based on LYS228 concentration in urine at different time points following drug administration on Day 5 | Day 5 | 
| Urine Pharmacokinetics (PK) of LYS228: Renal Clearance (CLr) | Calculated based on LYS228 concentration in urine at different time points following drug administration on Day 5 | Day 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline of the Microbiological Response at Day 7 | Microbiologic success at 7 days after randomization determined by microbial growth in urine culture | Baseline, Day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Urinary tract infection, LYS228, beta-lactam antibiotics, creatinine clearance, Enterobactericeae