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

NCT03377426 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: CLYS228X2201
• Study Type: interventional
• Target: N/A
• Locations: 3 countries
• Sites: 5

Brief Summary

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

Conditions

Complicated Urinary Tract Infections

Keywords

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

Outcome Measures

Primary Outcomes (10)

• 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 Outcomes (1)

• Change from Baseline of the Microbiological Response at Day 7

  Baseline, Day 7

Study Arms (2)

LYS228

EXPERIMENTAL

IV infusion

Drug: LYS228

Standard of care

ACTIVE COMPARATOR

IV infusion of standard of care antibiotics for at least 5 days

Drug: Standard of care therapy

Interventions

LYS228 DRUG

LYS228 IV infusion

LYS228

Standard of care therapy DRUG

IV infusion of standard of care antibiotics

Standard of care

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (5)

Novartis Investigative Site

Detroit, Michigan, 48202, United States

Location

Novartis Investigative Site

Newark, New Jersey, 07102, United States

Location

Novartis Investigative Site

Seattle, Washington, 98195, United States

Location

Novartis Investigative Site

Odense, 5000, Denmark

Location

Novartis Investigative Site

Athens, 115 27, Greece

Location

Related Publications (1)

• 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.

  PMID: 30061293 DERIVED

MeSH Terms

Conditions

Urinary Tract Infections

Condition Hierarchy (Ancestors)

Infections; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: A blinded evaluator will perform the safety and efficacy assessments
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2017
• First Posted: December 19, 2017
• Study Start: October 19, 2018
• Primary Completion: October 28, 2019
• Study Completion: October 28, 2019
• Last Updated: October 26, 2018

Record last verified: 2018-10

Locations

GR (1); DK (1); US (3)