Bardoxolone Methyl Evaluation in Patients With Chronic Kidney Disease and Type 2 Diabetes

NCT01351675 | Terminated Phase 3 DMC

• 1 other identifier: 402-C-0903
• Study Type: interventional
• Target: 2,185
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study assesses the efficacy of bardoxolone methyl relative to placebo in delaying progression to end-stage renal disease (ESRD) and cardiovascular deaths in patients with Stage 4 Chronic Kidney Disease (CKD) and type 2 diabetes receiving standard of care.

Conditions

Renal Insufficiency, Chronic; Diabetes Mellitus, Type 2

Keywords

Chronic kidney disease; Type 2 diabetes; Diabetic nephropathy

Outcome Measures

Primary Outcomes (1)

• Time-to-first event of the composite endpoint

  Time-to-first event of the composite endpoint consisting of: * ESRD (need for chronic dialysis or renal transplantation) * Cardiovascular death

  Approximately 24 months

Secondary Outcomes (4)

• Rate of change in estimated glomerular filtration rate (eGFR) over the duration of the study

  Approximately 24 months

• Time to first hospitalization for heart failure

  Approximately 24 months

• Time to first event in the composite cardiorenal endpoint

  Approximately 24 months

• Frequency, intensity, and relationship to study drug of adverse events and serious adverse events, as well as clinical and laboratory test abnormalities.

  Approximately 24 months

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Bardoxolone Methyl

EXPERIMENTAL

Drug: Bardoxolone Methyl: 20 mg

Interventions

Placebo DRUG

Oral, once daily

Placebo

Bardoxolone Methyl: 20 mg DRUG

20 mg, oral, once daily

Also known as: RTA-402

Bardoxolone Methyl

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Screening eGFR ≥ 15.0 and \< 30.0 mL/min/1.73 m2;
• A history of type 2 diabetes; diagnosis should have been made at ≥ 30 years of age;
• Male or female at least 18 years of age;
• Treatment with an angiotensin converting enzyme (ACE)inhibitor and/or an angiotensin II receptor blocker (ARB)for at least 6 weeks prior to and during screening. Stable dose 2 weeks prior to and during screening. Patients not taking an ACE inhibitor and/or ARB because of a medical contraindication must have discontinued treatment at least 8 weeks prior to Screening Visit A;
• Mean systolic blood pressure (SBP) must be ≤ 160 mmHg and ≥ 105 mmHg and mean diastolic blood pressure (DBP) must be \< 90 mm Hg during screening; both mean SBP and mean DBP (determined as the average of three readings) must be within this range at two separate time points measured at least 4 days apart during the screening period (blood pressure may be re-evaluated once during an unscheduled visit);
• Willing to practice methods of birth control (both male and female patients) during the entire study period and for at least 30 days after the last dose of the study drug is ingested;
• Serum magnesium level must be ≥ 1.3 mEq/L (0.65 mmol/L) at Screening Visit B or during subsequent unscheduled visit during screening (serum magnesium level may be re-evaluated once during an unscheduled visit);
• Willing and able to cooperate with all aspects of the protocol;
• Willing and able to give written informed consent for study participation and provide consent for access to medical data according to appropriate local data protection legislation, allowing authorization to access medical records and describe events captured in the endpoints

You may not qualify if:

• Type 1 diabetes mellitus (juvenile onset). If a history of diabetic ketoacidosis exists, a C-peptide level must confirm type 2 diabetes;
• Known non-diabetic renal disease (e.g., polycystic kidney disease, focal segmental glomerulosclerosis) \[nephrosclerosis superimposed on diabetic kidney disease is acceptable\];
• Ongoing clinical evidence suggesting non-diabetic renal disease other than nephrosclerosis;
• History of a renal transplant or a planned transplant from a living donor during the study;
• Albumin to creatinine ratio (ACR) greater than 3500 mg/g (395.5 mg/mmol);
• Hemoglobin A1c level \> 11.0% (97 mmol/mol) during screening;
• Acute dialysis or acute kidney injury within 12 weeks prior to screening or during screening;
• Clinical signs and/or symptoms of uremia and expected need for renal replacement therapy within 12 weeks following randomization, as assessed by the investigator;
• Recently active cardiovascular disease defined as: a. Unstable angina pectoris within 12 weeks before study randomization; b. Myocardial infarction, coronary artery bypass graft surgery, or percutaneous transluminal coronary angioplasty/stent within 12 weeks before study randomization; c. Cerebrovascular accident, including transient ischemic attack within 12 weeks before study randomization; d. Current diagnosis of Class III or IV New York Heart Association (NYHA) congestive heart failure;
• Clinical diagnosis of severe obstructive valvular heart disease or severe obstructive hypertrophic cardiomyopathy;
• Atrioventricular block, 2o or 3o, not successfully treated with a pacemaker;
• DAdministration of a contrast agent that may induce nephropathy within 30 days prior to study randomization or planned during the study;
• Systemic immunosuppression for a total of \> 2 weeks, cumulatively, within the 12 weeks prior to randomization or planned during the study;
• Total bilirubin, aspartate aminotransaminase (AST) or alanine aminotransaminase (ALT) levels greater than the upper limit of normal (ULN), or alkaline phosphatase level greater than two times the ULN on ANY screening laboratory test result;
• Female patients who are pregnant, intend to become pregnant during the study, or are nursing;

Sponsors & Collaborators

• Biogen: lead

Related Publications (3)

• Colombijn JM, Hooft L, Jun M, Webster AC, Bots ML, Verhaar MC, Vernooij RW. Antioxidants for adults with chronic kidney disease. Cochrane Database Syst Rev. 2023 Nov 2;11(11):CD008176. doi: 10.1002/14651858.CD008176.pub3.

  PMID: 37916745 DERIVED

• Conley MM, McFarlane CM, Johnson DW, Kelly JT, Campbell KL, MacLaughlin HL. Interventions for weight loss in people with chronic kidney disease who are overweight or obese. Cochrane Database Syst Rev. 2021 Mar 30;3(3):CD013119. doi: 10.1002/14651858.CD013119.pub2.

  PMID: 33782940 DERIVED

• de Zeeuw D, Akizawa T, Audhya P, Bakris GL, Chin M, Christ-Schmidt H, Goldsberry A, Houser M, Krauth M, Lambers Heerspink HJ, McMurray JJ, Meyer CJ, Parving HH, Remuzzi G, Toto RD, Vaziri ND, Wanner C, Wittes J, Wrolstad D, Chertow GM; BEACON Trial Investigators. Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease. N Engl J Med. 2013 Dec 26;369(26):2492-503. doi: 10.1056/NEJMoa1306033. Epub 2013 Nov 9.

  PMID: 24206459 DERIVED

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Diabetes Mellitus, Type 2; Diabetic Nephropathies

Interventions

bardoxolone methyl

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Diabetes Complications

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2010
• First Posted: May 11, 2011
• Study Start: June 30, 2011
• Primary Completion: October 31, 2012
• Study Completion: December 31, 2012
• Last Updated: May 29, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share