A Study to Evaluate the Effect of Sodium Zirconium Cyclosilicate on Chronic Kidney Disease (CKD) Progression in Participants With CKD and Hyperkalaemia or at Risk of Hyperkalaemia

Summary

The purpose of this study is to evaluate the effect of Sodium Zirconium Cyclosilicate (SZC), as adjunct to ACEi/ARB therapy (lisinopril or valsartan), on slowing CKD progression (assessed as the reduction in participant's glomerular filtration rate \[eGFR\] decline over time) in participants with hyperkalaemia or at high risk of hyperkalaemia.

Conditions

• Renal Insufficiency, Chronic
• Hyperkalemia

Interventions

DRUG

Sodium Zirconium Cyclosilicate (SZC)

Powder for oral suspension in a sachet. Unit dose strength: 5 or 10 g SZC. Single dose will consist of 1-3 sachets. During Initiation Phase: * S-K \> 5 to ≤ 6.5 mmol/L (measured by L-Lab): Single dose contains 10 g SZC that should be suspended in 45 mL of water. The 10 g SZC single dose should be administered three times daily for up to 72 hours until normokalaemic (S-K 3.5-5.0 mmol/L); the total daily dose is 30 g SZC. * S-K ≥ 3.5 to ≤ 5 mmol/L (measured by L-Lab): Single dose contains 5 g SZC that should be suspended in 45 mL of water and administered once daily for 48 hours. During Run-in and Maintenance Phases: \- Single dose contains 5 g SZC administered every other day or 5, 10, or 15 g SZC administered once daily that should be suspended in 45 mL of water.

DRUG

Placebo

Powder for oral suspension in a sachet. Placebo to match 5 or 10 g. Single dose will consist of 1-3 sachets. During Maintenance Phase: \- Single dose contains 5 g placebo administered every other day or 5, 10, or 15 g placebo administered once daily that should be suspended in 45 mL of water.

DRUG

Lisinopril

Tablet for oral administration. Unit dose strength: 2.5, 5, 10 or 20 mg. Dosage level: 5, 10, 20, or 40 mg administered once daily.

DRUG

Valsartan

Tablet or capsule for oral administration. Unit dose strength: 40, 80 or 160 mg. Dosage level: 40, 80, 160, or 320 mg administered once daily.

DRUG

Irbesartan

Tablet for oral administration. Unit dose strength: 75, 150 or 300 mg. Dosage level: 75, 150, or 300 mg administered once daily. The study is designed to use valsartan as the selected ARB therapy adjunct to SZC. However, if an actual shortage of valsartan in a local market jeopardises the ability of participants to enter or continue in the study, valsartan can be temporarily substituted with irbesartan until the shortage of valsartan is resolved.

Sponsors & Collaborators

• AstraZeneca

  lead INDUSTRY

Principal Investigators

• Glenn M. Chertow, MD, MPH · Stanford University School of Medicine, Stanford, CA USA

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

130 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-09-30

Primary Completion

2024-02-07

Completion

2024-02-07

FDA Drug

Yes

Countries

• United States
• Argentina
• Brazil
• Bulgaria
• Canada
• China
• India
• Italy
• Japan
• Malaysia
• Mexico
• Philippines
• Poland
• Puerto Rico
• Russia
• Spain
• Taiwan
• Thailand
• Turkey (Türkiye)
• Ukraine
• Vietnam

Study Locations