LYS228 PK, Clinical Response, Safety and Tolerability in Patients With Complicated Intra-abdominal Infection (cIAI)

NCT03354754 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: CLYS228X2202
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study was to evaluate whether LYS228 can be developed for the treatment of complicated intra-abdominal infections. It was planned that LYS228 exposure across patients with varying renal function would be evaluated during the study to confirm that LYS228 concentrations are predicted to be adequate to treat the patient population. It was planned that the PK exposure of the initial 8 patients would be analyzed. PK analysis was not conducted as per protocol the first analysis required 8 patients.

Conditions

Intra-abdominal Infections

Keywords

Intra-abdominal infection; LYS228; beta-lactam antibiotics; creatinine clearance; enterobacteriaceae

Outcome Measures

Primary Outcomes (7)

• Clinical Success at Day 28

  Clinical success is defined as resolution, or substantial improvement (i.e. reduction of severity of all baseline signs and symptoms and worsening of none) of all or most baseline signs and symptoms of cIAI infection without the need for additional antibiotic therapy other than any oral antibiotics given to complete treatment at home following discontinuation of Study Drug and no drainage or surgical reintervention required 96 hours after the start of Study Drug.

  Day 28

• Plasma Pharmacokinetics (PK) of LYS228: Area Under the Plasma Concentration-time Curve From Time Zero to the End of the 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 (T1/2)

  Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5

  Day 5

Secondary Outcomes (2)

• Number of Patients With Adverse Events

  Daily

• Microbiological Response at Day 28

  Day 28

Study Arms (2)

LYS228

EXPERIMENTAL

IV infusion every 6 hours for at least 5 days

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 every 6 hours

LYS228

Standard of care therapy DRUG

IV infusion of standard of care antibiotics

Standard of care

Eligibility Criteria

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

You may not qualify if:

• Any of the excluded diagnoses: abdominal wall abscess, small bowel obstruction, traumatic bowel perforation undergoing surgery within 12 hours, perforation of gastroduodenal ulcer with surgery within 24 hours, an intra-abdominal process that is not likely caused by infection.
• Pre-operative treatment of any duration with non-study Drug systemic antibiotic therapy for peritonitis or abscess is not allowed unless certain criteria are met.
• Concomitant bacterial infection at time of enrollment requiring non-Study Drug antibiotics and that may interfere with the evaluation of clinical response to the study antibiotic.
• Known non-abdominal source of infection, including endocarditis, osteomyelitis, abscess, meningitis, or pneumonia diagnosed within 7 days prior to enrollment.
• Patient has an Acute Physiology and Chronic Health Evaluation II (APACHE II) score \> 30 or is considered, in the judgement of the investigator, unlikely to survive 4 weeks (e.g. rapidly progressive terminal illness, including septic shock).
• Patients that meet sepsis criteria as defined by the quick sequential sepsis-related organ failure assessment (qSOFA).
• Women of child-bearing potential unless they are using highly effective methods of contraception during dosing and for 7 days after stopping study treatment.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (1)

Novartis Investigative Site

Somers Point, New Jersey, 08230, United States

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

Related Links

• A Plain Language Trial Summary is available on novartisclinicaltrials.com

MeSH Terms

Conditions

Intraabdominal Infections

Condition Hierarchy (Ancestors)

Infections

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: November 22, 2017
• First Posted: November 28, 2017
• Study Start: May 15, 2018
• Primary Completion: September 24, 2018
• Study Completion: September 24, 2018
• Last Updated: October 11, 2021
• Results First Posted: October 8, 2019

Record last verified: 2021-10

Locations

US (1)