Moderate to Severe Chronic Kidney Disease MedDRA version: 14.0 Level: LLT Classification code 10064848 Term: Chronic kidney disease System Organ Class: 10038359 - Renal and urinary disorders
Conditions
Interventions
Product Name: AST-120
Product Code: AST-120
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: N/A
CAS Number: 90597-58-3
Current Sponsor code: AST-120
Other descriptive name: AST-120 Drug Subs
Sponsors
Mitsubishi Tanabe Pharma Corporation
KUREHA CORPORATION
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients that meet all of the following Inclusion Criteria may be enrolled into the study: 1) Age 18 years or older; 2) Moderate to severe CKD (in men: sCr = 2.0 mg/dL[= 177 µmol/L] and = 5.0 mg/dL[= 442 µmol/L]; in women: sCr = 1.5 mg/dL[= 133 µmol/L] and = 5.0 mg/dL [= 442 µmol/L] ), not anticipated to require dialysis or renal transplant within the next 6 months; 3) Patient survival expected to be no less than one year; 4) 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 the initial Screening visit; 5) Proteinuria / Progressive deterioration in renal function: Urinary total protein to urinary total creatinine ratio (both values measured as mg/dL, or other like units) must be = 0.5 on a spot void obtained at the Screening visit OR If the urinary total protein to urinary total creatinine ratio is 10% higher than the first Screening visit but not > 5.0 mg/dL [= 442 µmol/L] or if the urinary total protein to urinary total creatinine ratio is = 0.5, then the patient may be enrolled (See Appendix E in the Protocol for a listing of qualifying sCr values based on initial and second Screening visit values). 6) Sitting 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; 7) In patients being treated for hypertension, they should be on a stable anti-hypertensive regimen, defined as no changes in anti-hypertensive medications or doses in the last 3 months prior to the Baseline visit, and to include a stable dose of either an ACEI or ARB unless contraindicated; 8) Stable nutritional status; and 9) Willingness to comply with the study and sign a written informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 980 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 980
Exclusion criteria
Exclusion criteria: Patients that meet any of the following Exclusion Criteria must not be enrolled into the study: 1) Obstructive or reversible cause of kidney disease; 2) Nephrotic syndrome defined as a ratio of urinary total protein to urinary creatinine (both components measured as mg/dL or other like units) of > 6.0 as measured on a spot void; 3) Adult polycystic kidney disease; 4) History of previous kidney transplant; 5) History of alcohol or drug abuse within the past 12 months; 6) Known human immunodeficiency virus (HIV) infection; 7) Received immunosuppressive therapy (including systemic corticosteroids for more than 5 days at a daily dose in excess of 0.1 mg/kg, prednisone equivalent) in the past 3 months, or anticipated to require such treatment during the study course; 8) History of recent (within the past 6 months) accelerated or malignant hypertension; 9) Patients who are likely to require changes in ACEI or ARB regimens during the course of this study; 10) Uncontrolled arrhythmia or severe cardiac disease (New York Heart Association Class III -IV), including myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, cerebrovascular accident, or transient ischemic attack within the past 6 months; 11) History of malabsorption, inflammatory bowel disease, hiatal hernia, active peptic ulcer, or severe GI dysmotility, not attributable to the use of a phosphate binder; 12) History of cancer within the past 5 years (cervical carcinoma in situ, low-grade cutaneous malignancy, or other low grade malignancy are exemptions); 13) Alanine transaminase (ALT) or aspartate transaminase (AST) values > 2.5 times the upper limit of normal (ULN); 14) Received any investigational agent or participated in a clinical study within the previous 3 months; 15) 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; or 16) For women of childbearing potential, a positive pregnancy test result of serum beta human chorionic gonadotropin (ßHCG) or unwillingness to use approved single barrier or oral contraception, or unwillingness to be sexually abstinent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To demonstrate AST-120, added to standard-of-care therapy in moderate to severe CKD, reduces the risk of progression of CKD as assessed by the development of a component of a triple composite endpoint (initiation of dialysis, kidney transplant, or doubling of sCr), when compared with placebo; and • To demonstrate the general safety and tolerability of long-term AST-120 therapy in CKD patients.;Secondary Objective: • To evaluate the efficacy of AST-120 in reducing the risk of developing a component of a quadruple composite endpoint (initiation of dialysis, kidney transplant, doubling of sCr, or death) compared with placebo; • To evaluate the effects of AST-120 versus placebo, on other measures of renal function i.e. sCr, 24 hr urinary protein excretion, creatinine clearance, urea clearance, and 24 hr urinary creatinine excretion; and • To assess the effects of AST-120 versus placebo, on fat-soluble vitamin levels (A, D, E, and K), vitamin B-12, and folate levels. ;Primary end point(s): The primary endpoint will be the occurrence of one component of a triple composite of renal outcomes: initiation of dialysis, kidney transplantation, or doubling of sCr from the value obtained at the Baseline visit (Visit 2). The initial doubled (from Baseline) sCr result will be verified 5-10 days later with another sCr sampling. If this result remains doubled, a confirmatory measurement of sCr doubling will occur at 4-6 weeks after the initial doubled result was reported. If the Baseline value is not available for comparison, the value obtained at the Screening visit (Visit 1) will be used, If a second screening visit is performed then that screening value will be used. An Endpoint Adjudication Committee (EAC) will review and adjudicate all potential endpoint events. ;Timepoint(s) of evaluation of this end point: NA | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): NA;Timepoint(s) of evaluation of this end point: NA | — |
Countries
Argentina, Brazil, Canada, Czech Republic, European Union, France, Italy, Mexico, Russian Federation, Ukraine, United States
Outcome results
None listed