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

Phase 3

Terminated

• Conditions: Diabetic Kidney Disease
• Interventions: Drug: Placebo; Drug: Bardoxolone methyl

• Registration Number: NCT03550443
• Lead Sponsor: Kyowa Kirin Co., Ltd.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-05-14
• Study Start: 2018-05-30
• Study First Submitted QC: 2018-06-07
• Study First Posted: 2018-06-08
• Primary Completion: 2022-11-30
• Study Completion: 2023-07-31
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-22
• Last Update Posted: 2023-09-26

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 1323

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Patients randomized to placebo will remain on placebo throughout the study, undergoing sham titration.
RTA 402(Bardoxolone methyl)	Bardoxolone methyl	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Time to onset of ESRD	Through double-blind part completion, approximately 3 to 4 years
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
Change in eGFR from baseline at each evaluation time point	Through double-blind part completion, approximately 3 to 4 years

Trial Locations

Locations (1)

Japan Community Health care Organization Sendai Hospital; 🇯🇵 Sendai, Miyagi, Japan