Phase IIa Trial to Determine the Effects of Bardoxolone Methyl on Renal Function in Patients With Diabetic Nephropathy

NCT00664027 | Completed Phase 2

• 1 other identifier: RTA 402-C-0801
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 3

Brief Summary

To determine the effects of three different doses of bardoxolone methyl administered orally on the kidney function (glomular filtration rate) in patients with diabetic nephropathy.

Conditions

Diabetic Nephropathy

Outcome Measures

Primary Outcomes (2)

• To determine the effects of RTA 402 administered orally at three dose strengths on the glomerular filtration rate (as estimated by the MDRD formula) in patients with diabetic nephropathy (stratum 1).

  28 days

• To determine the effects of RTA 402 on glomerular filtration rate (as estimated by the MDRD formula) when administered for 28 days at dose of 25 mg followed by a dose of 75 mg for another 28 days in patients with diabetic nephropathy (stratum 2).

  56 days

Secondary Outcomes (5)

• To evaluate the safety and tolerability of oral RTA 402 administered orally at three dose strengths in patients with diabetic nephropathy.

  28 days

• To evaluate the effects of RTA 402 on the serum creatinine level, iohexol serum clearance (one study center only), creatinine clearance, and urine albumin/creatinine ratio in patients with diabetic nephropathy.

  28 days (stratum 1), 56 days (stratum 2)

• To evaluate the effects of RTA 402 on hemoglobin A1c in all patients enrolled and on insulin response by the hyperinsulinemic euglycemic clamp test in patients enrolled at only one of the study centers.

  28 days (stratum 1), 56 days (stratum 2)

• To evaluate the effects of RTA 402 on a panel of markers of inflammation, renal injury, oxidative stress, and endothelial cell dysfunction.

  28 days (stratum 1), 56 days (stratum 2)

• To determine the safety and tolerability of RTA 402 when the dose is escalated after 28 days in patients with diabetic nephropathy from 25 mg to 75 mg and continued for another 28 consecutive days.

  28 days (stratum 1), 56 days (stratum 2)

Study Arms (4)

25 mg

EXPERIMENTAL

25 mg RTA 402 (Bardoxolone methyl)/Stratum 1

Drug: RTA 402 (Bardoxolone Methyl)

75 mg

EXPERIMENTAL

75 mg RTA 402 (Bardoxolone methyl)/Stratum 1

Drug: RTA 402 (Bardoxolone Methyl)

150 mg

EXPERIMENTAL

150 mg RTA 402 (Bardoxolone methyl)/Stratum 1

Drug: RTA 402 (Bardoxolone Methyl)

25/75 mg

EXPERIMENTAL

25 mg -\> 75 mg RTA 402 (Bardoxolone methyl)/Stratum 2

Drug: RTA 402 (Bardoxolone Methyl)

Interventions

RTA 402 (Bardoxolone Methyl) DRUG

Stratum 1: 25, 75, 150mg/day, orally, 28 consecutive days Stratum 2: 25 mg/day, orally, 28 consecutive days followed by 75 mg/day, orally, 28 consecutive days

150 mg; 25 mg; 25/75 mg; 75 mg

Eligibility Criteria

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

You may qualify if:

• Diagnosis of type 2 diabetes;
• Serum creatinine in women 1.3 - 3.0 mg/dL (115-265 μmol/L), inclusive, and in men 1.5 - 3.0 mg/dL (133-265 μmol/L), inclusive;
• Patient must agree to practice effective contraception.
• Patient must have a negative urine pregnancy test within 72 hours prior to the first dose of study medication.
• Patient is willing and able to cooperate with all aspects of the protocol and is able to communicate effectively.
• Patient is willing and able to provide written informed consent to participate in this clinical study.

You may not qualify if:

• Type 1 (insulin-dependent; juvenile onset) diabetes.
• Patients with known non-diabetic renal disease (nephrosclerosis superimposed on diabetic nephropathy acceptable), or with renal allograft.
• Cardiovascular disease as follows: unstable angina pectoris within 3 mo of study entry; myocardial infarction, coronary artery bypass graft surgery, or percutaneous transluminal coronary angioplasty/stent within 3 mo of study entry; transient ischemic attack within 3 mo of study entry; cerebrovascular accident within 3 mo of study entry; obstructive valvular heart disease or hypertrophic cardiomyopathy; second or third degree atrioventricular block not successfully treated with a pacemaker.
• Need for chronic (\>2 weeks) immunosuppressive therapy, including corticosteroids (excluding inhaled or nasal steroids) within 3 mo of study entry.
• Evidence of hepatic dysfunction including total bilirubin \>1.5 mg/dL (\>26 micromole/L); elevation of liver transaminase (aspartate aminotransferase \[AST\] or alanine transferase \[ALT\])above the upper limit of normal(ULN) within the 14-day screening period; documented elevation (above ULN) of AST or ALT within 3 months prior to screening; elevation of alkaline phosphatase (ALP) above 1.5 x ULN; documented elevation of gamma-glutamyl transpeptidase (GGT) above 1.5 X ULN.
• 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 known allergy to iodine;
• Patient has undergone diagnostic or intervention procedure requiring a contrast agent within the last 30 days prior to entry into the study;
• Change or dose-adjustment in any of the following medications: ACE inhibitors, angiotensin II blockers, non-steroidal anti inflammatory drugs (NSAIDs), or COX-2 inhibitors within 3 months; other anti-hypertensive, and other anti-diabetic medications within 6 weeks prior to entry into the study;
• Patient has a history of drug or alcohol abuse or has positive test results for any drug of abuse (positive urine drug test and/or alcohol breathalyzer test).
• Patients who are unable or unwilling to discontinue the following medications until 1 week following last dose of study treatment: Nicotinic acid, Isoniazid, Dantrolene, Labetalol, Pemoline, Felbamate, Zileutan, Tolcapone, Trovafloxacin, Vitamin D, Vitamin D analogues (such as Calcitriol, paricalcitol, doxercalciferol), or multivitamins containing vitamin D or related analogs, or Fenofibrate. Patient must have been off the aforementioned medications for a minimum of two weeks prior to enrollment.
• Patient with an intact parathyroid hormone (iPTH) level \> 300 pg/mL.
• Patient has participated in another clinical study involving investigational or marketed products within 30 days prior to entry into the study or would concomitantly participate in such a study.

Sponsors & Collaborators

• Biogen: lead

Study Sites (3)

West Houston Clinical Research Services

Houston, Texas, 77055, United States

Location

Renal Associates, PA

San Antonio, Texas, 78215, United States

Location

DGD Research

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Diabetic Nephropathies

Interventions

bardoxolone methyl

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2008
• First Posted: April 22, 2008
• Study Start: April 30, 2008
• Primary Completion: May 31, 2009
• Study Completion: May 31, 2009
• Last Updated: May 29, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

US (3)