Back to resultsA Phase 3 Study of Bardoxolone Methyl in Patients With Diabetic Kidney Disease; AYAME Study
Primary Purpose
Diabetic Kidney Disease
Status
Terminated
Phase
Phase 3
Locations
Japan
Study Type
Interventional
Intervention
Bardoxolone methyl
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Diabetic Kidney Disease focused on measuring Bardoxolone Methyl, Diabetic Kidney Disease, Diabetes Mellitus, Kidney Diseases
Eligibility Criteria
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.
Sites / Locations
- Japan Community Health care Organization Sendai Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
RTA 402(Bardoxolone methyl)
Placebo
Arm Description
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.
Patients randomized to placebo will remain on placebo throughout the study, undergoing sham titration.
Outcomes
Primary Outcome Measures
Time to onset of a ≥ 30% decrease in eGFR from baseline or ESRD
Secondary Outcome Measures
Time to onset of a ≥ 40% decrease in eGFR from baseline or ESRD
Time to onset of a ≥ 53% decrease in eGFR from baseline or ESRD
Time to onset of ESRD
Change in eGFR from baseline at each evaluation time point
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03550443
Brief Title
A Phase 3 Study of Bardoxolone Methyl in Patients With Diabetic Kidney Disease; AYAME Study
Official Title
RTA 402 Phase 3 Clinical Trial (A Randomized, Double-blind, Placebo-controlled Clinical Trial in Patients With Diabetic Kidney Disease)
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Terminated
Why Stopped
Based on results of double-blind parts, it was determined that it would be difficult to submit a marketing authorization application for RTA 402 for diabetic kidney disease.
Study Start Date
May 30, 2018 (Actual)
Primary Completion Date
November 30, 2022 (Actual)
Study Completion Date
July 31, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kyowa Kirin Co., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetic Kidney Disease
Keywords
Bardoxolone Methyl, Diabetic Kidney Disease, Diabetes Mellitus, Kidney Diseases
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Randomized double-blinded part followed by open label extension part.
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
1323 (Actual)
8. Arms, Groups, and Interventions
Arm Title
RTA 402(Bardoxolone methyl)
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Patients randomized to placebo will remain on placebo throughout the study, undergoing sham titration.
Intervention Type
Drug
Intervention Name(s)
Bardoxolone methyl
Other Intervention Name(s)
RTA 402
Intervention Description
Bardoxolone methyl 5 mg capsules
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Capsules containing an inert placebo
Primary Outcome Measure Information:
Title
Time to onset of a ≥ 30% decrease in eGFR from baseline or ESRD
Time Frame
Through double-blind part completion, approximately 3 to 4 years
Secondary Outcome Measure Information:
Title
Time to onset of a ≥ 40% decrease in eGFR from baseline or ESRD
Time Frame
Through double-blind part completion, approximately 3 to 4 years
Title
Time to onset of a ≥ 53% decrease in eGFR from baseline or ESRD
Time Frame
Through double-blind part completion, approximately 3 to 4 years
Title
Time to onset of ESRD
Time Frame
Through double-blind part completion, approximately 3 to 4 years
Title
Change in eGFR from baseline at each evaluation time point
Time Frame
Through double-blind part completion, approximately 3 to 4 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
Japan Community Health care Organization Sendai Hospital
City
Sendai
State/Province
Miyagi
ZIP/Postal Code
981-3281
Country
Japan
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Phase 3 Study of Bardoxolone Methyl in Patients With Diabetic Kidney Disease; AYAME Study
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