This phase 2 study is to assess the safety and efficacy of APX-115 active doses in Contrast Induced Acute Kidney Disease compared to placebo following multiple oral dosing in patients with undergoing percutaneous coronary intervention. It is anticipated that approximately 230 patients will be randomized into the study in a 1:1 ratio to 400 mg APX-115 (Isuzinaxib hydrochloride) or placebo arm.
Patients with chronic kidney disease undergoing percutaneous coronary intervention deserve careful consideration of various clinical options to minimize the risk of contrast-induced acute kidney injury and to optimize clinical outcomes. Contrast-induced acute kidney injury (CI-AKI) is a leading cause of a hospital-acquired renal failure and has been reported to affect both the mortality and morbidity of patients receiving contrast media. Contrast-induced acute kidney injury is the third leading cause of hospital-acquired acute kidney injury and has been recognized as a serious complication of percutaneous coronary intervention (PCI), which may be associated with increased morbidity and mortality. APX-115 is a potent small molecule inhibitor of NADPH-oxidase (NOX) isozymes developed by AptaBio Therapeutics, Inc. In-vivo study results suggest that multiple NOX isoforms may contribute to renal injury in CI-AKI model, and pan-NOX inhibition may be a new therapeutic approach for prevention of CI-AKI.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
218
Treatment allocation in 1:1 ratio to Isuzinaxib or Placebo
Treatment allocation in 1:1 ratio to Isuzinaxib or Placebo
Baylor Scott & White Research Institute
Dallas, Texas, United States
Kangwon National University Hospital
Chuncheon, South Korea
Keimyung University Dongsan Hospital
Daegu, South Korea
Safety endpoints: adverse event
Number of adverse events
Time frame: Day -2 to day 84
Safety endpoints: vital sign
Number of subjects with abnormal Vital Signs
Time frame: Day 0 to day 84
Safety endpoints: physical exam
Abnormal physical examination
Time frame: Day 0 to day 84
Safety endpoints: ECG
Abnormal Electrocardiogram (ECG)
Time frame: Day 0 to day 84
Safety endpoints: labs
Number of abnormal results of Hematology, Biochemistry and Urinalysis
Time frame: Day 0 to day 84
Incidence rate of Acute kidney injury
definition of CI-AKI: Serum Creatinine absolute variation ≥ 0.5mg/dL or Serum creatinine relative variation increasing 25% from baseline up to 72 hours after CAG with the exposure of contrast medium and PCI
Time frame: from baseline up to 72 hours after PCI procedure
Long term kidney function: Serum creatinine
Serum creatinine level
Time frame: week 4 and week 12
Long term kidney function: eGFR
eGFR level
Time frame: week 4 and week 12
Kidney function parameters: creatinine, BUN
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Chungnam National University Hospital
Daejeon, South Korea
Inje University Ilsan Paik Hospital
Goyang, South Korea
Chonnam National University Hospital
Gwangju, South Korea
Seoul National University Bundang Hospital
Seongnam-si, South Korea
Kangbuk Samsung Hospital
Seoul, South Korea
Korea University Anam Hospital
Seoul, South Korea
Samsung Medical Center
Seoul, South Korea
...and 4 more locations
Serum creatinine and BUN level
Time frame: over 12-week period
Kidney function parameters: eGFR
eGFR using CKD-EPI
Time frame: over 12-week period
pharmacokinetics parameters: the area under the plasma concentration-time curve (AUC0-last, AUCtau)
to be assessed from plasma and urine samples (subset of subjects only)
Time frame: Day -2~2
pharmacokinetics parameters: peak concentration (Cmax, Tmax)
to be assessed from plasma and urine samples (subset of subjects only)
Time frame: Day -2~2
pharmacokinetics parameters: steady state peak plasma concentration (Css,max)
to be assessed from plasma and urine samples (subset of subjects only)
Time frame: Day -2~2
pharmacokinetics parameters: steady state trough plasma concentration (Css,min)
to be assessed from plasma and urine samples (subset of subjects only)
Time frame: Day -2~2
pharmacokinetics parameters: steady state after 5 consecutive days of drug administration
to be assessed from plasma and urine samples (subset of subjects only)
Time frame: Day -2~2
pharmacokinetics parameters: apparent total clearance (CL/F)
to be assessed from plasma and urine samples (subset of subjects only)
Time frame: Day -2~2
pharmacokinetics parameters: renal clearance (CLR)
to be assessed from plasma and urine samples (subset of subjects only)
Time frame: Day -2~2
pharmacokinetics parameters: apparent nonrenal clearance (CLNR/F)
to be assessed from plasma and urine samples (subset of subjects only)
Time frame: Day -2~2
pharmacokinetics parameters: apparent volume of distribution (V/F)
to be assessed from plasma and urine samples (subset of subjects only)
Time frame: Day -2~2
pharmacokinetics parameters: terminal half-life (t1/2)
to be assessed from plasma and urine samples (subset of subjects only)
Time frame: Day -2~2
pharmacokinetics parameters: fraction/cumulated fraction of excreted in urine
to be assessed from plasma and urine samples (subset of subjects only)
Time frame: Day -2~2
Adverse event in patients with eGFR < 45 mL/min/1.73m2
Number of adverse events
Time frame: Day -2 to day 84
Vital signs in patients with eGFR < 45 mL/min/1.73m2
number of subjects with abnormal vital signs
Time frame: Day 0 to day 84
Number of subjects with eGFR < 45 mL/min/1.73m2 with clinically significant findings on physical examination
The number of subjects within the specified subgroup who exhibit clinically significant abnormal findings based on investigator's physical examination will be assessed over time.
Time frame: Day 0 to day 84
Number of subjects with eGFR < 45 mL/min/1.73m2 with normal or abnormal electrocardiogram (ECG) results
The number of subjects within the specified subgroup who exhibit normal or abnormal ECG findings will be assessed over time.
Time frame: Day 0 to day 84
Labs in patients with eGFR < 45 mL/min/1.73m2
Number of abnormal results of hematology, biochemistry and urinalysis
Time frame: Day 0 to day 84