A Study of AST-120 for Evaluating Prevention of Progression In Chronic Kidney Disease Including Assessment of Quality of Life (EPPIC-2)

Chronic Kidney Disease Clinical Trial

Official title:

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 Including Assessment of Quality of Life

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00501046
• Other study ID #: KRM-307
• Status: Completed
• Phase: Phase 3
• Start date: July 2007
• Est. completion date: October 2011

Study information

• Verified date: May 2022
• Source: Mitsubishi Tanabe Pharma Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 and quality of life.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1015
• Est. completion date: October 2011
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 obtained at Screening

• Blood pressure <= 160/90 mmHg at both Screening and Baseline visits. 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

Related Conditions & MeSH terms

• Chronic Kidney Disease
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• Placebo
9g /day (3 times a day)
• AST-120
9g /day (3 times a day)

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Mitsubishi Tanabe Pharma Corporation	Kureha Corporation

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Canada,  Czechia,  Germany,  Mexico,  Poland,  Puerto Rico,  Russian Federation,  Spain,  Ukraine, 

References & Publications (1)

Schulman G, Berl T, Beck GJ, Remuzzi G, Ritz E, Arita K, Kato A, Shimizu M. Randomized Placebo-Controlled EPPIC Trials of AST-120 in CKD. J Am Soc Nephrol. 2015 Jul;26(7):1732-46. doi: 10.1681/ASN.2014010042. Epub 2014 Oct 27. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Number of Participants With Treatment-emergent Adverse Events and Treatment-emergent Serious Adverse Events		Approximately 42 months
Secondary	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
Secondary	Vitamin A Levels		Baseline, Week 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, Early Term/Discontinuation (Mean: 430.293 Days), Final Visit (Mean: 908.486 Days)
Secondary	Vitamin B12 Levels		Baseline, Week 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, Early Term/Discontinuation (Mean: 425.112 Days), Final Visit (Mean: 910.988 Days)
Secondary	25-Hydroxyvitamin D Levels		Baseline, Week 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, Early Term/Discontinuation (Mean: 429.695 Days), Final Visit (Mean: 908.601 Days)
Secondary	Vitamin E Levels		Baseline, Week 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, Early Term/Discontinuation (Mean: 427.067 Days), Final Visit (Mean: 908.715 Days)
Secondary	Vitamin K Levels		Baseline, Week 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, Early Term/Discontinuation (Mean: 432.942 Days), Final Visit (Mean: 910.448 Days)
Secondary	Serum Folate Levels		Baseline, Week 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, Early Term/Discontinuation (Mean: 420.569 Days), Final Visit (Mean: 909.848 Days)