WithdrawnNCT03377426Updated Oct 26, 2018

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

A Phase 2 interventional study of LYS228 and Standard of care therapy in Complicated Urinary Tract Infections, sponsored by Novartis Pharmaceuticals. Withdrawn at 5 sites in 3 countries. Open to participants aged 18 Years to 85 Years. Per ClinicalTrials.gov, last updated 2018-10-26.

Sponsored by Novartis Pharmaceuticals · Phase 2, Interventional, and Basic science

Why this study was withdrawn

The trial was terminated due to an out-licensing agreement after the new sponsor did not wish to continue the trial

Phase: Phase 2
Study type: Interventional
Enrollment: 0
Allocation: Randomized
Ages: 18 Years to 85 Years
Sex: All

Study summary

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

Conditions studied

Complicated Urinary Tract Infections

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Keywords

Urinary tract infection, LYS228, beta-lactam antibiotics, creatinine clearance, Enterobactericeae

Who can participate

Ages eligible: 18 Years to 85 Years
Sexes eligible: All
Accepts healthy volunteers: No

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

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 design

Phase: Phase 2
Primary purpose: Basic science
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Single (Outcomes assessor)
Enrollment: 0 participants (actual)

Study arms

Experimental
LYS228
IV infusion
Drug: LYS228
Active comparator
Standard of care
IV infusion of standard of care antibiotics for at least 5 days
Drug: Standard of care therapy

Interventions

DrugLYS228
LYS228 IV infusion
DrugStandard of care therapy
IV infusion of standard of care antibiotics

What researchers measure

Primary outcomes

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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Day 5

Secondary outcomes

Change from Baseline of the Microbiological Response at Day 7
Microbiologic success at 7 days after randomization determined by microbial growth in urine culture
Time frame: Baseline, Day 7

Study locations

5 sites

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

References and documents

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. PubMed 30061293 ↗

Individual participant data

Plan to share: Undecided — 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

Registry details

Key details

Study ID: NCT03377426
Lead sponsor: Novartis Pharmaceuticals
Responsible party: Sponsor
First posted: Dec 19, 2017
Start date: Oct 19, 2018 (estimated)
Primary completion: Oct 28, 2019 (estimated)
Completion: Oct 28, 2019 (estimated)
Last update: Oct 26, 2018

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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