Clinical trial NCT03354754: LYS228 PK, Clinical Response, Safety and Tolerability in Patients With Complicated Intra-abdominal Infection (cIAI)
Official title: A Randomized, Controlled, Evaluator-blinded, Multi-center Study to Evaluate LYS228 Pharmacokinetics, Clinical Response, Safety, and Tolerability in Patients With Complicated Intra-abdominal Infection
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Intra-abdominal Infections
Keywords: Intra-abdominal infection
LYS228
beta-lactam antibiotics
creatinine clearance
enterobacteriaceae
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2017-11-28
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Clinical Success at Day 28
timeFrame: Day 28
measure: Plasma Pharmacokinetics (PK) of LYS228: Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau)
timeFrame: Day 5
measure: Plasma Pharmacokinetics (PK) of LYS228: The Observed Maximum Plasma Concentration Following Drug Administration (Cmax)
timeFrame: Day 5
measure: Plasma Pharmacokinetics (PK) of LYS228: The Time to Reach the Maximum Concentration After Drug Administration (Tmax)
timeFrame: Day 5
measure: Plasma Pharmacokinetics (PK) of LYS228: The Systemic (or Total Body) Clearance From Plasma Following Intravenous Administration (CL)
timeFrame: Day 5
measure: Plasma Pharmacokinetics (PK) of LYS228: The Volume of Distribution at Steady State Following Intravenous Administration (Vss)
timeFrame: Day 5
measure: Plasma Pharmacokinetics (PK) of LYS228: The Terminal Elimination Half-life (T1/2)
timeFrame: Day 5
Secondary outcomes:
measure: Number of Patients With Adverse Events
timeFrame: Daily
measure: Microbiological Response at Day 28
timeFrame: Day 28
Other outcomes:
Locations:
city: Somers Point
country: United States
facility: Novartis Investigative Site
state: New Jersey
Study officials:
References:
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.