Trial to Determine the Effects of Bardoxolone Methyl on eGFR in Patients With Type 2 Diabetes and Chronic Kidney Disease

NCT00811889 | Completed Phase 2 DMC

• 1 other identifier: RTA 402-C-0804
• Study Type: interventional
• Target: 227
• Locations: 1 country
• Sites: 42

Brief Summary

This study assesses the effects of bardoxolone methyl (RTA 402) in patients with type 2 diabetes and chronic kidney disease.

Conditions

Chronic Kidney Disease; Type 2 Diabetes; Diabetic Nephropathy

Outcome Measures

Primary Outcomes (2)

• To determine the change in eGFR from baseline in patients with type 2 diabetes and CKD (baseline eGFR = 20 - 45 mL/min/1.73m2) after receiving bardoxolone methyl for 6 months (24 weeks) following randomization

  6 months (24 weeks)

• To determine the safety and tolerability of bardoxolone methyl when administered for 12 months (52 weeks)following randomization to type 2 diabetic patients with CKD (eGFR 20 - 45 mL/min/1.73m2).

  1 year (52 weeks)

Secondary Outcomes (2)

• To quantify the effects of bardoxolone methyl at two different dosing levels relative to placebo on: Hemoglobin A1c, Serum Creatinine, Urine, Intact PTH albumin/creatinine ratio, Serum Phosphorus, Blood Urea Nitrogen, Uric Acid

  6 months (24 weeks) and 1 year (52 weeks)

• To determine the change in eGFR from baseline in patients with type 2 diabetes and CKD (baseline eGFR = 20 - 45 mL/min/1.73m2) after receiving bardoxolone methyl for 12 months (52 weeks) following randomization.

  12 months (52 weeks)

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Other: Placebo

Bardoxolone Methyl (RTA 402): 75mg

EXPERIMENTAL

Drug: Bardoxolone Methyl (RTA 402)

Bardoxolone Methyl (RTA 402): 150mg

EXPERIMENTAL

Drug: Bardoxolone Methyl (RTA 402)

Bardoxolone Methyl (RTA 402): 25mg

EXPERIMENTAL

Drug: Bardoxolone Methyl (RTA 402)

Interventions

Placebo OTHER

Placebo

Placebo

Bardoxolone Methyl (RTA 402) DRUG

Oral, Once Daily

Bardoxolone Methyl (RTA 402): 150mg; Bardoxolone Methyl (RTA 402): 25mg; Bardoxolone Methyl (RTA 402): 75mg

Eligibility Criteria

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

You may qualify if:

• Male or female patient, at least 18 years of age with known type 2 diabetes, diagnosis of type 2 diabetes should have been made at \> 30 years of age (if diabetes developed at a younger age, C-peptide level may be obtained to confirm diagnosis)
• The average of two eGFR values collected during screening must be within 20 - 45 mL/min/1.73m2, inclusive
• Patient must be receiving an angiotensin converting enzyme (ACE) inhibitor and/or an angiotensin II receptor blocker (ARB) for at least 3 months prior to screening, where the dose of the ACE inhibitor or the ARB is considered appropriate for that patient, and has been stable and maintained on that dose for at least 8 weeks prior to the Randomization visit
• For male and female subjects, agreement to use effective contraception during the entire study period and for at least 2 months after the last dose of study drug, unless documentation of infertility exists
• Women of child-bearing potential, she must have a negative serum pregnancy test at screening and a negative urine pregnancy test confirmed within 72 hours prior to the first dose of study medication
• Patient is willing and able to cooperate with all aspects of the protocol
• Patient is willing and able to give written informed consent for study participation.

You may not qualify if:

• Type 1 (insulin-dependent; juvenile onset) diabetes, or any history of diabetic ketoacidosis
• Patients with known non-diabetic renal disease or patients with a history of a renal transplant
• Patients with a Hemoglobin A1c \>10% collected at the Screening A visit
• Cardiovascular disease as follows: Unstable angina pectoris within 3 months prior to study randomization; Myocardial infarction, coronary artery bypass graft surgery, or percutaneous transluminal coronary angioplasty/stent within 3 months prior to study randomization; Transient ischemic attack within 3 months of study randomization; Cerebrovascular accident within 3 months of study randomization; Obstructive valvular heart disease or hypertrophic cardiomyopathy; Diagnosis of Class III or IV congestive heart failure at any time
• Systolic blood pressure (BP) \>160 mmHg and diastolic blood pressure \> 90 determined by the average of three seated readings taken at least 5 minutes apart, at each of two time-points at least 5 days apart during the screening period
• QTc Fredericia interval \> 450 milliseconds determined by the average of values reported by a central reader from three ECGs taken at the Screening A visit. Each of the three ECGs will be obtained using only equipment provided by the Sponsor, and the ECGs shall be obtained at least ten minutes apart.
• Second or third degree atrioventricular block not successfully treated with a pacemaker
• Need for chronic (\>2 weeks) immunosuppressive therapy, or need for corticosteroids (excluding intraarticular injections,inhaled or nasal steroids) within 3 months of study randomization
• Evidence of hepatic or biliary dysfunction including total bilirubin \>1.0 mg/dL (\>17 micromol/L), aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> upper limit of normal (ULN), or alkaline phosphatase \>2.0 ULN on ANY screening lab
• If female, patient is pregnant, nursing or planning a pregnancy
• Patient has any concurrent clinical conditions that in the judgment of the investigator could either potentially pose a health risk to the patient while involved in the study or could potentially influence the study outcome
• Patient has known hypersensitivity to any component of the study drug
• Patient has undergone a diagnostic or interventional procedure requiring a contrast agent within 30 days prior to randomization
• Change or dose adjustment in any of the following medications within 8 weeks prior to randomization into the study or anticipated change in dose within 30 days following randomization into the study: ACE inhibitors, angiotensin II receptor blockers.
• Change or dose adjustment of any other anti-hypertensive, and other anti-diabetic medications within 8 weeks prior to randomization or anticipated change in dose within 30 days following randomization into the study

Sponsors & Collaborators

• Biogen: lead

Study Sites (42)

Unknown Facility

Birmingham, Alabama, 35294, United States

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Montgomery, Alabama, 36106, United States

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Chula Vista, California, 91910, United States

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La Mesa, California, 91942, United States

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Mission Viejo, California, 92691, United States

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Orange, California, 92868, United States

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Riverside, California, 92505, United States

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San Dimas, California, 91773, United States

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Middlebury, Connecticut, 06762, United States

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Washington D.C., District of Columbia, 20036, United States

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Brandon, Florida, 33511, United States

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Miami, Florida, 33173, United States

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Pembroke Pines, Florida, 33028, United States

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Port Charlotte, Florida, 33952, United States

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West Palm Beach, Florida, 33401, United States

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Marietta, Georgia, 30060, United States

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Chicago, Illinois, 60616, United States

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Peoria, Illinois, 61603, United States

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Baton Rouge, Louisiana, 70809, United States

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Portland, Maine, 04102, United States

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Baltimore, Maryland, 21237, United States

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Flint, Michigan, 48504, United States

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Brooklyn Center, Minnesota, 55430, United States

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Flushing, New York, 11355, United States

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Springfield Gardens, New York, 11413, United States

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Morehead City, North Carolina, 28557, United States

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Winston-Salem, North Carolina, 27103, United States

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Roseburg, Oregon, 97471, United States

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Allentown, Pennsylvania, 18103, United States

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Pittsburgh, Pennsylvania, 15224, United States

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Pittsburgh, Pennsylvania, 15240, United States

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Providence, Rhode Island, 02904, United States

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Nashville, Tennessee, 37205, United States

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Corpus Christi, Texas, 78404, United States

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Dallas, Texas, 75390, United States

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El Paso, Texas, 79935, United States

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Fort Worth, Texas, 76104, United States

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San Antonio, Texas, 78205, United States

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San Antonio, Texas, 78215, United States

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San Antonio, Texas, 78229, United States

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Salem, Virginia, 24153, United States

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Federal Way, Washington, 98003, United States

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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

• Pergola PE, Raskin P, Toto RD, Meyer CJ, Huff JW, Grossman EB, Krauth M, Ruiz S, Audhya P, Christ-Schmidt H, Wittes J, Warnock DG; BEAM Study Investigators. Bardoxolone methyl and kidney function in CKD with type 2 diabetes. N Engl J Med. 2011 Jul 28;365(4):327-36. doi: 10.1056/NEJMoa1105351. Epub 2011 Jun 24.

  PMID: 21699484 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 2
• 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 18, 2008
• First Posted: December 19, 2008
• Study Start: April 30, 2009
• Primary Completion: May 31, 2010
• Study Completion: December 31, 2010
• Last Updated: May 29, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

US (42)