A Double-Blind, Randomized, Placebo-Controlled Safety Study Evaluating the Effects of Residual Renal Function (RFF) in Patients With End-Stage Renal Disease and Type 2 Diabetes Mellitus on Peritoneal Dialysis

This study has been withdrawn prior to enrollment.
(IDMC recommendation for safety concerns)
Sponsor:
Information provided by (Responsible Party):
Reata Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01576887
First received: March 30, 2012
Last updated: November 1, 2012
Last verified: November 2012
  Purpose

This study is a multi-center, double-blinded, randomized, study of bardoxolone methyl treatment in patients with End-Stage Renal Disease (ERSD) and Type 2 Diabetes Mellitus (T2DM) on peritoneal dialysis.


Condition Intervention Phase
End-Stage Renal Disease
Type 2 Diabetes Mellitus
Drug: Bardoxolone Methyl 20 mg
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

Resource links provided by NLM:


Further study details as provided by Reata Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Number of Adverse Events [ Time Frame: Approximately 17 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Type of Adverse Events [ Time Frame: Approximately 17 months ] [ Designated as safety issue: Yes ]
  • Change in Residual Renal Function [ Time Frame: Baseline to 6 months ] [ Designated as safety issue: No ]
  • Maximum observed concentration [ Time Frame: Day 0, 30, 60, 90, 120, 150, 180, 210 ] [ Designated as safety issue: No ]
  • Time to maximum observed concentration [ Time Frame: Day 0, 30, 60, 90, 120, 150, 180, 210 ] [ Designated as safety issue: No ]
  • Area under the plasma concentration-time curve [ Time Frame: 2, 4, 8, 24 hours, 30, 60, 90, 120, 150 and 180 days ] [ Designated as safety issue: No ]
    Only the first 8 patients randomized will have the PK drawn and hours 2, 4, 8, and 24. All patients will have the PK drawn at 30, 60, 90, 120, 150 and 180 days.

  • Area under the curve [ Time Frame: 2, 4, 8 and 24 hours ] [ Designated as safety issue: No ]
    Only the first 8 patients randomized


Enrollment: 0
Study Start Date: July 2012
Estimated Study Completion Date: October 2013
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Drug: Placebo
Oral, once daily
Experimental: Bardoxolone Methyl Drug: Bardoxolone Methyl 20 mg
Oral, once daily

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

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:

    1. Unstable angina pectoris within 12 weeks before study randomization
    2. Myocardial infarction, coronary artery bypass graft surgery, or percutaneous transluminal coronary angioplasty/stent within 12 weeks before study randomization
    3. Cerebrovascular accident, including transient ischemic attack within 12 weeks before study randomization
  12. History of a 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 or 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 prior to study randomization or anticipated need for more than 15 days of immunosuppression during the study
  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 and 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 methyl in any form
  29. Female patients who are pregnant, intend to become pregnant during this study, or are nursing
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Reata Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01576887     History of Changes
Other Study ID Numbers: 402-C-1201, 2012-001563-78
Study First Received: March 30, 2012
Last Updated: November 1, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Kidney Diseases
Kidney Failure, Chronic
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency

ClinicalTrials.gov processed this record on August 25, 2014