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

NCT03550443 | Terminated Phase 3 DMC

• 1 other identifier: RTA 402-006
• Study Type: interventional
• Target: 1,323
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetic Kidney Disease

Keywords

Bardoxolone Methyl; Diabetic Kidney Disease; Diabetes Mellitus; Kidney Diseases

Outcome Measures

Primary Outcomes (1)

• Time to onset of a ≥ 30% decrease in eGFR from baseline or ESRD

  Through double-blind part completion, approximately 3 to 4 years

Secondary Outcomes (4)

• 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

Study Arms (2)

RTA 402(Bardoxolone methyl)

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

Patients randomized to placebo will remain on placebo throughout the study, undergoing sham titration.

Drug: Placebo

Interventions

Bardoxolone methyl DRUG

Bardoxolone methyl 5 mg capsules

Also known as: RTA 402

RTA 402(Bardoxolone methyl)

Placebo DRUG

Capsules containing an inert placebo

Placebo

Eligibility Criteria

• Age: 20 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Kyowa Kirin Co., Ltd.: lead

Study Sites (1)

Japan Community Health care Organization Sendai Hospital

Sendai, Miyagi, 981-3281, Japan

Location

Related Publications (1)

• Yoshioka K, Kaneko H, Haruyama W, Tomiyama T, Takami A, Kitayama T, Yamasaki K. Multi-Omics Reveal Antioxidant Effects of Bardoxolone Methyl in the Phase 2 Study of Bardoxolone Methyl in Patients with CKD and Type 2 Diabetes Study. Kidney360. 2025 Nov 1;6(11):1880-1889. doi: 10.34067/KID.0000000853. Epub 2025 Jun 11.

  PMID: 40498549 DERIVED

MeSH Terms

Conditions

Diabetic Nephropathies; Diabetes Mellitus; Kidney Diseases

Interventions

bardoxolone methyl

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications; Endocrine System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

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

Model Details: Randomized double-blinded part followed by open label extension part.

Study Record Dates

• First Submitted: May 14, 2018
• First Posted: June 8, 2018
• Study Start: May 30, 2018
• Primary Completion: November 30, 2022
• Study Completion: July 31, 2023
• Last Updated: September 26, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

JP (1)