Comparing the effects (safety and efficacy) of the study drug, bardoxolone methyl, against placebo for patients with End-Stage Renal Disease and Type 2 diabetes on peritoneal dialysis

• Conditions: Chronic Kidney Disease in patients with type 2 diabetes mellitus on peritoneal dialysis; Therapeutic area: Diseases [C] - Male diseases of the urinary and reproductive systems [C12]; MedDRA version: 14.1Level: SOCClassification code 10038359Term: Renal and urinary disordersSystem Organ Class: 10038359 - Renal and urinary disorders

• Registration Number: EUCTR2012-001563-78-GB
• Lead Sponsor: Reata UK Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-05-22
• Last Update Posted: 3 December 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 45

Inclusion Criteria

1. Patients must have ESRD and been on PD for longer than 3
months.
2. Patients must have had a diagnosis of T2DM prior to starting
dialysis.
3. Patients must have RRF, as defined by the mean of urea and
creatinine clearance on a 24 hour urine collection, = 25 Liters/week/1.73 m2 documented in the four months prior to the Screen A visit.
4. Patients must have RRF, as defined by the mean of urea and
creatinine clearances on a 24 hour urine collection, = 25
Liters/week/1.73 m2 at both the Screen A and Screen B visits.
5. The RRF value obtained at the Screen B visit must not be less
than 50% of the RRF value obtained at the Screen A visit.
6. Patients must be at least 18 years of age.
7. Patients must have a mean systolic blood pressure (SBP) on three readings at both Screen A and Screen B visits = 160 mmHg and = 90 mmHg.
8. Patients must have a mean diastolic blood pressure (DBP) on
three readings at both Screen A and Screen B visits < 100
mmHg and = 40 mmHg.
9. Patients must be willing to practice methods of birth control (both males who have partners of childbearing potential and females of childbearing potential) during screening, while taking study drug and for at least 30 days after the last dose of study drug is ingested.
10. Patients must be willing and able to cooperate with all aspects of the protocol.
11. Patients must be willing and able to give written informed
consent to participate in the study. They must provide consent
for access to medical data according to appropriate local data
protection legislation and allow authorization to access medical
records that describe events captured in the endpoints.
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 45
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. History of Autosomal Dominant Polycystic Kidney Disease
2. Currently active Systemic Lupus Erythematosus
3. History of Hepatitis B Surface Antigen +
4. History of Hepatitis C Antibody + being treated with antiviral therapy
5. History of an organ transplant
6. A planned renal transplant from a living donor during the study
7. History of hospitalization for congestive heart failure or pulmonary edema within 12 weeks before study randomization
8. History of cirrhosis of the liver
9. History of amyloidosis or light chain nephropathy
10. History of Hemoglobin A1c level > 11.0% (97 mmol/mol) within 12 weeks before study randomization
11. History of recently active cardiovascular disease defined as:
• Unstable angina pectoris within 12 weeks before study randomization
• Myocardial infarction, coronary artery bypass graft surgery, or
percutaneous transluminal coronary angioplasty/stent within 12
weeks before study randomization
• Cerebrovascular accident, including transient ischemic attack within 12 weeks before study randomization
12. History of diagnostic or interventional procedure that required
intravenous administration of an iodinated contrast agent or gadolinium within 12 weeks before study randomization
13. History of known severe obstructive valvular heart disease or severe obstructive hypertrophic cardiomyopathy
14. History of known 2o or 3o Atrioventricular block not successfully treated with a pacemaker
15. History of resuscitated sudden cardiac death
16. History of an automatic implantable defibrillator
17. QTc greater than 0.50 seconds on an ECG obtained during either Screen A or Screen B visits
18. A serum magnesium level less than 1.4 meq/L on either Screen A or Screen B visit laboratory test results
19. History of systemic immunosuppression for more than 15 days, cumulatively, within the 12 weeks before study randomization or anticipated need for more than 15 days of immunosuppression during the study (see section 5.4)
20. Total bilirubin, aspartate transaminase (AST), or alanine transaminase (ALT) level greater than the upper limit of normal (ULN) or alkaline phosphatase level greater than two times the ULN on either the Screen A or Screen B visit laboratory test results
21. Known hypersensitivity to any component of the study drug
22. Current history of drug or alcohol abuse, as assessed by the investigator
23. History of clinically significant infection requiring intravenous
administration of antibiotics or hospitalization within 12 weeks before study randomization
24. In patients who have been on peritoneal dialysis for = 6 months, two or more episodes of peritonitis in the 6 months before study randomization. In patients who have been on peritoneal dialysis for <6 months, one episode of peritonitis before study randomization
25. History of a diagnosis or treatment of a malignancy in the past 5 years, excluding non-melanoma skin cancer and carcinoma in situ of the cervix
26. History of a clinical condition that, in the judgment of the investigator, could potentially pose a health risk to the patient while involved in the study
27. Patient is unable to communicate or cooperate with the investigator due to language problems, poor mental development, or impaired cerebral function
28. Participation in a clinical study involving any intervention within 30 days prior to Screen A visit, concurrent participation in such a study, or participation in a prior clinical study involving bardoxolone

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the safety and pharmacokinetic profile of 20 mg bardoxolone in patients with ESRD and T2DM on PD.;Secondary Objective: To assess the effect of bardoxolone methyl relative to placebo on RRF in patients with ESRD and T2DM on PD.;Primary end point(s): SAFETY ENDPOINTS<br>Frequency, intensity and relationship of study drug to adverse events and serious adverse events, as well as clinical and laboratory test result abnormalities.<br><br>PK ENDPOINTS<br>Assessment of bardoxolone methyl plasma concentration-time data.<br>;Timepoint(s) of evaluation of this end point: SAFETY ENDPOINTS<br>Throughout study from study randomization (SR) visit until post treatment visit (V7)<br><br>PK ENDPOINTS<br>From visit 1 (V1) through visit 6 (V6)<br><br>

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): EFFICACY ENDPOINTS<br>The mean change in RRF from baseline to month 6 as analyzed by the repeated measures model.;Timepoint(s) of evaluation of this end point: EFFICACY ENDPOINTS<br>Screening visits A and B and from visit 1 (V1) until visit 7 (V7)