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

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

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

Study Overview

• Status: Withdrawn
• Conditions: Complicated Urinary Tract Infections
• Intervention / Treatment: Drug: LYS228; Drug: Standard of care therapy

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Odense, Denmark, 5000
    • Novartis Investigative Site
• Greece
  • Athens, Greece, 115 27
    • Novartis Investigative Site
• United States
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Novartis Investigative Site
  • New Jersey
    • Newark, New Jersey, United States, 07102
      • Novartis Investigative Site
  • Washington
    • Seattle, Washington, United States, 98195
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LYS228; IV infusion	Drug: LYS228; LYS228 IV infusion
Active Comparator: Standard of care; IV infusion of standard of care antibiotics for at least 5 days	Drug: Standard of care therapy; IV infusion of standard of care antibiotics

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Anticipated): October 19, 2018
• Primary Completion (Anticipated): October 28, 2019
• Study Completion (Anticipated): October 28, 2019

Study Registration Dates

• First Submitted: December 14, 2017
• First Submitted That Met QC Criteria: December 14, 2017
• First Posted (Actual): December 19, 2017

Study Record Updates

• Last Update Posted (Actual): October 26, 2018
• Last Update Submitted That Met QC Criteria: October 24, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Urinary tract infection, LYS228, beta-lactam antibiotics, creatinine clearance, Enterobactericeae
• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Infections; Communicable Diseases; Urinary Tract Infections
• Other Study ID Numbers: CLYS228X2201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No