Back to resultsLYS228 PK, Clinical Response, Safety and Tolerability in Patients With Complicated Urinary Tract Infection (cUTI)
Primary Purpose
Complicated Urinary Tract Infections
Status
Withdrawn
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
LYS228
Standard of care therapy
Sponsored by
About this trial
This is an interventional basic science trial for Complicated Urinary Tract Infections focused on measuring Urinary tract infection, LYS228, beta-lactam antibiotics, creatinine clearance, Enterobactericeae
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
Sites / Locations
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
LYS228
Standard of care
Arm Description
IV infusion
IV infusion of standard of care antibiotics for at least 5 days
Outcomes
Primary Outcome Measures
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
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
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
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
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
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
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
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
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
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
Secondary Outcome Measures
Change from Baseline of the Microbiological Response at Day 7
Microbiologic success at 7 days after randomization determined by microbial growth in urine culture
Full Information
NCT ID
NCT03377426
First Posted
December 14, 2017
Last Updated
October 24, 2018
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT03377426
Brief Title
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
2. Study Status
Record Verification Date
October 2018
Overall Recruitment Status
Withdrawn
Why Stopped
The trial was terminated due to an out-licensing agreement after the new sponsor did not wish to continue the trial
Study Start Date
October 19, 2018 (Anticipated)
Primary Completion Date
October 28, 2019 (Anticipated)
Study Completion Date
October 28, 2019 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of the study is to evaluate whether LYS228 can be developed for the treatment of complicated urinary tract infections
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Complicated Urinary Tract Infections
Keywords
Urinary tract infection, LYS228, beta-lactam antibiotics, creatinine clearance, Enterobactericeae
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Masking Description
A blinded evaluator will perform the safety and efficacy assessments
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
LYS228
Arm Type
Experimental
Arm Description
IV infusion
Arm Title
Standard of care
Arm Type
Active Comparator
Arm Description
IV infusion of standard of care antibiotics for at least 5 days
Intervention Type
Drug
Intervention Name(s)
LYS228
Intervention Description
LYS228 IV infusion
Intervention Type
Drug
Intervention Name(s)
Standard of care therapy
Intervention Description
IV infusion of standard of care antibiotics
Primary Outcome Measure Information:
Title
Change from Baseline of the Clinical Response at Day 7
Description
Clinical success at 7 days after randomization determined by signs and symptoms of infection and the need for additional antibiotics
Time Frame
Baseline, Day 7
Title
Plasma Pharmacokinetics (PK) of LYS228: Area Under the Plasma Concentration-time Curve from time zero to the end of dosing interval tau (AUCtau)
Description
Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5
Time Frame
Day 5
Title
Plasma Pharmacokinetics (PK) of LYS228: The observed maximum plasma concentration following drug administration (Cmax)
Description
Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5
Time Frame
Day 5
Title
Plasma Pharmacokinetics (PK) of LYS228: The time to reach the maximum concentration after drug administration (Tmax)
Description
Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5
Time Frame
Day 5
Title
Plasma Pharmacokinetics (PK) of LYS228: The systemic (or total body) clearance from plasma following intravenous administration (CL)
Description
Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5
Time Frame
Day 5
Title
Plasma Pharmacokinetics (PK) of LYS228: The volume of distribution at steady state following intravenous administration (Vss)
Description
Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5
Time Frame
Day 5
Title
Plasma Pharmacokinetics (PK) of LYS228: The terminal elimination half-life (T 1/2)
Description
Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5
Time Frame
Day 5
Title
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)
Description
Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5
Time Frame
Day 5
Title
Urine Pharmacokinetics (PK) of LYS228: The amount of drug eliminated in Urine from 0 hours up to 6 hours following intravenus administration (Ae0-6h)
Description
Calculated based on LYS228 concentration in urine at different time points following drug administration on Day 5
Time Frame
Day 5
Title
Urine Pharmacokinetics (PK) of LYS228: Renal Clearance (CLr)
Description
Calculated based on LYS228 concentration in urine at different time points following drug administration on Day 5
Time Frame
Day 5
Secondary Outcome Measure Information:
Title
Change from Baseline of the Microbiological Response at Day 7
Description
Microbiologic success at 7 days after randomization determined by microbial growth in urine culture
Time Frame
Baseline, Day 7
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
Novartis Investigative Site
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Novartis Investigative Site
City
Newark
State/Province
New Jersey
ZIP/Postal Code
07102
Country
United States
Facility Name
Novartis Investigative Site
City
Seattle
State/Province
Washington
ZIP/Postal Code
98195
Country
United States
Facility Name
Novartis Investigative Site
City
Odense
ZIP/Postal Code
5000
Country
Denmark
Facility Name
Novartis Investigative Site
City
Athens
ZIP/Postal Code
115 27
Country
Greece
12. IPD Sharing Statement
Plan to Share IPD
Undecided
IPD Sharing 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
Citations:
PubMed Identifier
30061293
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.
Results Reference
derived
Learn more about this trial
LYS228 PK, Clinical Response, Safety and Tolerability in Patients With Complicated Urinary Tract Infection (cUTI)
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