A Phase 3 Study of Bardoxolone Methyl in Patients With Diabetic Kidney Disease; AYAME Study

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate the efficacy of multiple oral doses of RTA 402 (5, 10, or 15 mg) administered once daily in patients with diabetic kidney disease (DKD) using the time to onset of a ≥ 30% decrease in estimated glomerular filtration rate calculated from serum creatinine (eGFR) from baseline or end-stage renal disease (ESRD) as an indicator in a randomized, double-blind, placebo-controlled study; the safety of RTA 402 will also be evaluated.

Official Title
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RTA 402 Phase 3 Clinical Trial (A Randomized, Double-blind, Placebo-controlled Clinical Trial in Patients With Diabetic Kidney Disease)

Conditions
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Diabetic Kidney Disease

Intervention / Treatment
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* Drug: Bardoxolone methyl
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with DKD Mean eGFR ≥ 15 and < 60 mL/min/1.73 m² Albumin/creatinine ratio (ACR) ≤ 3500 mg/g Cr Treatment with an angiotensin converting enzyme (ACE) inhibitor and/or an angiotensin II receptor blocker (ARB) with no change in dosage or medication etc. Exclusion Criteria: Diabetes mellitus that is neither type 1 nor type 2 Decreased renal function mainly attributed to a non-diabetic cause History of renal transplantation or upcoming preemptive renal transplantation Confirmed mean systolic blood pressure > 160 mmHg or a confirmed mean diastolic blood pressure > 90 mmHg during the 8-week period before screening Hemoglobin A1c level > 10.0% during screening Serum albumin level ≤ 3.0 g/dL during screening Cardiovascular disease specified in the study protocol History of cardiac failure BNP level > 200 pg/mL during screening etc.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized double-blinded part followed by open label extension part.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RTA 402(Bardoxolone methyl)<br>Patients will receive multiple oral doses of bardoxolone methyl once daily. The starting dose of bardoxolone methyl will be 5 mg. The maximum dose will be 15 mg, and the dose will be increased by 5 mg. | Drug: Bardoxolone methyl<br>* Bardoxolone methyl 5 mg capsules<br>* Other names: RTA 402;|
| Placebo Comparator: Placebo<br>Patients randomized to placebo will remain on placebo throughout the study, undergoing sham titration. | Drug: Placebo<br>* Capsules containing an inert placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to onset of a ≥ 30% decrease in eGFR from baseline or ESRD |  | Through double-blind part completion, approximately 3 to 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to onset of a ≥ 40% decrease in eGFR from baseline or ESRD |  | Through double-blind part completion, approximately 3 to 4 years | 
| Time to onset of a ≥ 53% decrease in eGFR from baseline or ESRD |  | Through double-blind part completion, approximately 3 to 4 years | 
| Time to onset of ESRD |  | Through double-blind part completion, approximately 3 to 4 years | 
| Change in eGFR from baseline at each evaluation time point |  | Through double-blind part completion, approximately 3 to 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bardoxolone Methyl, Diabetic Kidney Disease, Diabetes Mellitus, Kidney Diseases