A Study of AST-120 for Evaluating Prevention of Progression In Chronic Kidney Disease (EPPIC-1)

Study Overview
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Brief Summary
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1) To evaluate the effectiveness of AST-120 (spherical carbon adsorbent) added to standard-of-care therapy in moderate to severe Chronic Kidney Disease (CKD), on time to first occurrence of any event of the triple composite outcome of initiation of dialysis, kidney transplant or doubling of serum creatinine (sCr) when compared with placebo; 2) To evaluate the safety and tolerability of long-term AST-120 therapy in patients with CKD; 3) To evaluate the effects of AST-120 versus placebo, on other measures of renal function.

Official Title
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A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of AST-120 for Prevention of Chronic Kidney Disease Progression in Patients With Moderate to Severe Chronic Kidney Disease

Conditions
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Chronic Kidney Disease

Intervention / Treatment
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* Drug: Placebo
* Drug: AST-120


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or older Moderate to severe CKD, not anticipated to require dialysis or renal transplant within the next 6 months Patient survival expected to be no less than one year Serum creatinine in men >= 2.0 mg/dL (>= 177 µmol/L) and <= 5.0 mg/dL (<= 442 µmol/L), and in women >= 1.5 mg/dL (>= 133 µmol/L) and <= 5.0 mg/dL (<= 442 µmol/L) at Screening Urinary total protein to urinary total creatinine ratio must be >= 0.5 on a spot void at Screening Blood pressure <= 160/90 mmHg at both Screening and Baseline. In addition, blood pressure, if measured, must have been stable in hypertensive patients over the 3 months prior to Screening, with no more than 1 blood pressure reading > 160/90 mmHg In patients being treated for hypertension, they should be on a stable anti-hypertensive regimen Exclusion Criteria: Obstructive or reversible cause of kidney disease Nephrotic syndrome defined as a ratio of urinary total protein to urinary creatinine of > 6.0 as measured on a spot void Adult polycystic kidney disease History of previous kidney transplant History of recent (within the past 6 months) accelerated or malignant hypertension Uncontrolled arrhythmia or severe cardiac disease within the past 6 months History of malabsorption, inflammatory bowel disease, hiatal hernia, active peptic ulcer, or severe GI dysmotility, not attributable to the use of a phosphate binder Received any investigational agent or participated in a clinical study within the previous 3 months Presence of any significant medical condition that might create an undue risk with study participation, or significantly confound the collection of safety and efficacy data in this study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* 9g /day (3 times a day)<br>|
| Experimental: AST-120<br> | Drug: AST-120<br>* 9g /day (3 times a day)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of Dialysis Initiation, Kidney Transplantation, and Serum Creatinine Doubling. Number of Participants Meeting the Criteria Are Reported. |  | Beyond Week 48, a 12-week visit cycle continued until the end of the study or until individual patients reached an endpoint | 
| Number of Participants With Treatment-emergent Adverse Events and Treatment-emergent Serious Adverse Events |  | Approximately 42 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Developed a Component of a Quadruple Composite Endpoint (Initiation of Dialysis, Kidney Transplant, Doubling of sCr, or Death) |  | Approximately 42 months | 
| Vitamin A Levels |  | Baseline, Week 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, Early Term/Discontinuation (Mean: 428.615 Days), Final Visit (Mean: 947.354 Days) | 
| Vitamin B12 Levels |  | Baseline, Week 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, Early Term/Discontinuation (Mean: 428.114 Days), Final Visit (Mean: 947.239 Days) | 
| 25-Hydroxyvitamin D Levels |  | Baseline, Week 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, Early Term/Discontinuation (Mean: 427.270 Days), Final Visit (Mean: 946.762 Days) | 
| Vitamin E Levels |  | Baseline, Week 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, Early Term/Discontinuation (Mean: 428.056 Days), Final Visit (Mean: 946.525 Days) | 
| Vitamin K Levels |  | Baseline, Week 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, Early Term/Discontinuation (Mean: 441.826 Days), Final Visit (Mean: 946.463 Days) | 
| Serum Folate Levels |  | Baseline, Week 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, Early Term/Discontinuation (Mean: 423.024 Days), Final Visit (Mean: 946.074 Days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kidney Diseases