Clinical trial NCT03377426: LYS228 PK, Clinical Response, Safety and Tolerability in Patients With Complicated Urinary Tract Infection (cUTI)
Official title: A Randomized, Controlled, Evaluator-blinded, Multi-center, Study to Evaluate LYS228 Pharmacokinetics, Clinical Response, Safety and Tolerability in Patients With Complicated Urinary Tract Infection
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Complicated Urinary Tract Infections
Keywords: Urinary tract infection, LYS228, beta-lactam antibiotics, creatinine clearance, Enterobactericeae
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2017-12-19
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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


Eligibility criteria: 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

Primary outcomes:
measure: Change from Baseline of the Clinical Response at Day 7
timeFrame: Baseline, Day 7
measure: Plasma Pharmacokinetics (PK) of LYS228: Area Under the Plasma Concentration-time Curve from time zero to the end of dosing interval tau (AUCtau)
timeFrame: Day 5
measure: Plasma Pharmacokinetics (PK) of LYS228: The observed maximum plasma concentration following drug administration (Cmax)
timeFrame: Day 5
measure: Plasma Pharmacokinetics (PK) of LYS228: The time to reach the maximum concentration after drug administration (Tmax)
timeFrame: Day 5
measure: Plasma Pharmacokinetics (PK) of LYS228: The systemic (or total body) clearance from plasma following intravenous administration (CL)
timeFrame: Day 5
measure: Plasma Pharmacokinetics (PK) of LYS228: The volume of distribution at steady state following intravenous administration (Vss)
timeFrame: Day 5
measure: Plasma Pharmacokinetics (PK) of LYS228: The terminal elimination half-life (T 1/2)
timeFrame: Day 5
measure: 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)
timeFrame: Day 5
measure: Urine Pharmacokinetics (PK) of LYS228: The amount of drug eliminated in Urine from 0 hours up to 6 hours following intravenus administration (Ae0-6h)
timeFrame: Day 5
measure: Urine Pharmacokinetics (PK) of LYS228: Renal Clearance (CLr)
timeFrame: Day 5
Secondary outcomes:
measure: Change from Baseline of the Microbiological Response at Day 7
timeFrame: Baseline, Day 7
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Novartis Investigative Site
state: Michigan
city: Newark
country: United States
facility: Novartis Investigative Site
state: New Jersey
city: Seattle
country: United States
facility: Novartis Investigative Site
state: Washington
city: Odense
country: Denmark
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
Study officials:
References:
citation: Dean CR, Barkan DT, Bermingham A, Blais J, Casey F, Casarez A, Colvin R, Fuller J, Jones AK, Li C, Lopez S, Metzger LE 4th, Mostafavi M, Prathapam R, Rasper D, Reck F, Ruzin A, Shaul J, Shen X, Simmons RL, Skewes-Cox P, Takeoka KT, Tamrakar P, Uehara T, Wei JR. Mode of Action of the Monobactam LYS228 and Mechanisms Decreasing In Vitro Susceptibility in Escherichia coli and Klebsiella pneumoniae. Antimicrob Agents Chemother. 2018 Sep 24;62(10):e01200-18. doi: 10.1128/AAC.01200-18. Print 2018 Oct.