E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
moderate to severe chronic kidney disease |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 6.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10038444 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1) 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 DEVELOPMENT OF A COMPONENT OF A TRIPLE COMPOSITE ENDPOINT (INITIATION OF DIALYSIS, KIDNEY TRANSPLANT, OR DOUBLING OF sCR; AND 2) TO DEMONSTRATE THE GENERAL SAFETY AND TOLERABILITY OF LONG-TERM AST-120 THERAPY IN CKD PATIENTS |
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E.2.2 | Secondary objectives of the trial |
- 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 Pe'ROTEIN EXCRETION, CREATINE CLEARANCE, UREA CLEARANCE, AND 24 HR URINARY CREATINE EXCRETION; AND -TO ASSESS THE EFFECTS OF AST-120 VERSUUS PLACEBO, ON FAT-SOLUBLE VITAMIN LEVELS (A, D, E AND K), VITAMIN B-12, AND FOLATE LEVELS |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1) Age 18 years or older; 2) Moderate to severe CKD (sCr >= 2.0 mg/dL (>=177 umol/L) and <= 5.0 mg/dL (<= 442 umol/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 >= 2.0 mg/dL (>= 177 umol/L) and <= 5.0 mg/dL (<= 442 umol/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 <0.5, then the patient may return for a second Screening visit 3 months later. If the sCr value at the second Screening visit is >10% higher than the first Screening visit but not > 5.0 mg/dL (> 442 umol/L) or if the urinary total protein to urinary total creatinine ratio is > 0.5, then the patient may be enrolled 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 if medically indicated, a stable dose of either an ACEI or ARB; 8) Stable nutritional status; and 9) Willingness to comply with the study and sign a written informed consent. |
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E.4 | Principal exclusion criteria |
1) Obstructive or reversible cause of kidney disease; 2) Severe 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, 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); |
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E.5 End points |
E.5.1 | Primary end point(s) |
THE PRIMARY ENDPOINT WILL BE THE OCCURRENCE OF ONE COMPONENT OF TRIPLE COMPOSITE ENDPOINT 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 WILL BE VERIFIED 5-10 DAYS LATER WITH ANOTHER sCR SAMPLING. IF THIS RESULT RAMAINS DOUBLED, A CONFIRMATORY MEASUREMENT OF sCR DOUBLING WILL OCCURR 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 COMMITEE (EAC) WILL REVIEW AND ADJUDICATE ALL POTENTIAL ENDPOINT EVENTS |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |