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

Phase 2

Terminated

• Conditions: Intra-abdominal Infections
• Interventions: Drug: Standard of care therapy; Drug: LYS228

• Registration Number: NCT03354754
• Lead Sponsor: Novartis Pharmaceuticals

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-11-22
• Study First Submitted QC: 2017-11-22
• Study First Posted: 2017-11-28
• Study Start: 2018-05-15
• Primary Completion: 2018-09-24
• Study Completion: 2018-09-24
• Results First Submitted: 2019-09-18
• Results First Submitted QC: 2019-09-18
• Results First Posted: 2019-10-08
• Status Verified: 2021-10
• Last Update Submitted: 2021-10-07
• Last Update Posted: 2021-10-11

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 3

Inclusion Criteria

• Male and female patients 18 to 85 years of age with visual confirmation (presence of pus within the abdominal cavity) of an intra-abdominal infection associated with peritonitis including at least one inclusionary diagnosis during surgical intervention.

Exclusion Criteria

• 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.

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard of care	Standard of care therapy	IV infusion of standard of care antibiotics for at least 5 days
LYS228	LYS228	IV infusion every 6 hours for at least 5 days

Primary Outcome Measures

Name	Time	Method
Plasma Pharmacokinetics (PK) of LYS228: The Terminal Elimination Half-life (T1/2)	Day 5	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)	Day 5	Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5
Clinical Success at Day 28	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.
Plasma Pharmacokinetics (PK) of LYS228: The Observed Maximum Plasma Concentration Following Drug Administration (Cmax)	Day 5	Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5
Plasma Pharmacokinetics (PK) of LYS228: Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau)	Day 5	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)	Day 5	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)	Day 5	Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5

Secondary Outcome Measures

Name	Time	Method
Microbiological Response at Day 28	Day 28	Microbiologic success at 28 days after randomization determined by microbial growth in culture from the intra-abdominal focus of infection when available or presumed eradication based on clinical success
Number of Patients With Adverse Events	Daily	Number of patients with at least one Adverse Event

Trial Locations

Locations (1)

Novartis Investigative Site; 🇺🇸 Somers Point, New Jersey, United States