CLINICAL TRIALS PROFILE FOR SODIUM ZIRCONIUM CYCLOSILICATE

All Clinical Trials for Sodium Zirconium Cyclosilicate

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT02088073 ↗	Safety & Efficacy of Zirconium Silicate Dosed for 28 Days in Hyperkalemia.	Completed	ZS Pharma, Inc.	Phase 3	2014-03-31	It is hypothesized that ZS is more effective than placebo control (alternative hypothesis) in maintaining mean double-blind randomized maintenance phase (DBRMP) Day 8-29 serum potassium levels (3.5 - 5.0 mmol/l, inclusive) among hyperkalemic subjects in whom normokalemia was established during the open-label acute phase versus no difference between each ZS dose (highest to lowest) versus placebo control (null hypothesis).
NCT02107092 ↗	Open-label Safety & Efficacy of ZS (Sodium Zirconium Cyclosilicate)10g qd to Extend Study ZS-004 in Hyperkalemia.	Completed	ZS Pharma, Inc.	Phase 3	2014-05-31	Subjects who completed the Double-blind Randomized Maintenance Phase (DBRMP) Study Day 29 visit in ZS-004 (NCT 02088073) and have an i-STAT potassium value that is 3.5 to 6.2 mmol/l inclusive or who discontinued during ZS-004 due to hypo- or hyperkalemia in the DBRMP and have a mean i-STAT potassium value from two consecutive measurements at 0 and 60 minutes on Acute Phase Day 1/Maintenance Phase Day 1 that is 3.5 to 6.2 mmol/l inclusive may have the option to participate in ZS-004E (NCT 021070920). Subjects who discontinued from study ZS-004 due to any other reasons (e.g. adverse events, poor compliance, investigator decision) will not be entered into study ZS-004E. All subjects who continue into the extension study must begin dosing within two (2) days after the last dose of investigational product in ZS-004.
NCT02163499 ↗	Open-label Safety and Efficacy of Sodium Zirconium Cyclosilicate for up to 12 Months	Completed	ZS Pharma, Inc.	Phase 3	2014-06-30	The Open-Label Maintenance Study contains an Acute Phase, in which subjects will be dosed with ZS 10 g three times daily (tid) for 24 to 72 hours, followed by a long-term Maintenance Phase.
NCT03127644 ↗	ZS Ph2/3 Dose-response Study in Japan	Completed	AstraZeneca	Phase 2/Phase 3	2017-06-14	To assess efficacy of 5 g three times daily (TID) and 10 g TID ZS versus placebo in Japanese patients with hyperkalemia (serum potassium [S-K] ≥ 5.1 mmol/L and ≤ 6.5 mmol/L).
NCT03172702 ↗	Open-label Safety of Sodium Zirconium Cyclosilicate for up to 12 Months in Japanese Subjects With Hyperkalemia	Completed	AstraZeneca	Phase 3	2017-09-04	The Open-Label Maintenance Study contains an Correction Phase, in which subjects will be dosed with ZS 10 g three times daily (tid) for 24 to 72 hours, followed by a 12-month long-term Maintenance Phase.

Clinical Trial Conditions for Sodium Zirconium Cyclosilicate

Condition Name

Condition Name for Sodium Zirconium Cyclosilicate
Intervention	Trials
Hyperkalemia	18
Hyperkalaemia	6
Chronic Kidney Disease	2
Chronic Kidney Diseases	2

Condition MeSH

Condition MeSH for Sodium Zirconium Cyclosilicate
Intervention	Trials
Hyperkalemia	26
Renal Insufficiency, Chronic	5
Kidney Diseases	4
Heart Failure	4

Clinical Trial Locations for Sodium Zirconium Cyclosilicate

Trials by Country

Trials by Country for Sodium Zirconium Cyclosilicate
Location	Trials
United States	180
Canada	14
United Kingdom	9
Australia	9
Russian Federation	6

Trials by US State

Trials by US State for Sodium Zirconium Cyclosilicate
Location	Trials
California	13
New York	12
Texas	11
Missouri	11
Florida	9

Clinical Trial Progress for Sodium Zirconium Cyclosilicate

Clinical Trial Phase

Clinical Trial Phase for Sodium Zirconium Cyclosilicate
Clinical Trial Phase	Trials
Phase 4	6
Phase 3	13
Phase 2/Phase 3	1

Clinical Trial Status

Clinical Trial Status for Sodium Zirconium Cyclosilicate
Clinical Trial Phase	Trials
Recruiting	12
Completed	10
Not yet recruiting	3

Clinical Trial Sponsors for Sodium Zirconium Cyclosilicate

Sponsor Name

Sponsor Name for Sodium Zirconium Cyclosilicate
Sponsor	Trials
AstraZeneca	19
ZS Pharma, Inc.	3
Guangdong Provincial People's Hospital	1

Sponsor Type

Sponsor Type for Sodium Zirconium Cyclosilicate
Sponsor	Trials
Industry	23
Other	10

Sodium Zirconium Cyclosilicate: Clinical Trials, Market Analysis, and Projections

Introduction

Sodium zirconium cyclosilicate (SZC), marketed as Lokelma, is a significant advancement in the treatment of hyperkalemia, a condition characterized by elevated potassium levels in the blood. This article delves into the current state of clinical trials, market analysis, and future projections for this drug.

Clinical Trials Overview

Phase IV Trials

A notable Phase IV, double-blind, placebo-controlled, randomized-withdrawal trial (D9480C00018) is underway to evaluate the efficacy and safety of SZC in managing hyperkalemia in patients with symptomatic heart failure and reduced ejection fraction who are receiving spironolactone. This trial involves two cohorts: one for patients who are hyperkalemic at study entry and another for those who develop hyperkalemia during spironolactone uptitration. The trial aims to maintain normokalemia using SZC, with dose adjustments as necessary[1].

Discontinuation of Phase III Trials

AstraZeneca has discontinued the STABILIZE-CKD and DIALIZE-Outcomes Phase III evidence trials for Lokelma due to prolonged enrollment timelines and low event rates, which made it impractical to deliver meaningful results within a feasible timeframe[4].

Long-Term Safety and Efficacy

Previous Phase 3 studies, such as Study ZS-005, have provided valuable long-term (up to 12 months) safety and efficacy data for SZC. These studies have shown that SZC effectively reduces potassium levels to normal within 48 hours and maintains this effect over the long term, with a favorable safety profile[3].

Efficacy and Safety

Rapid Potassium Reduction

SZC has been clinically proven to reduce serum potassium levels to normal within 48 hours, even in patients with chronic kidney disease (CKD) or heart failure (HF) who are receiving renin–angiotensin–aldosterone system inhibitors (RAASi)[2].

Long-Term Maintenance

The drug's ability to sustain normokalemia over extended periods is a significant advantage. It allows patients to continue their RAASi therapy without the need to adjust or discontinue these critical medications[2].

Safety Profile

SZC has a mild-to-moderate adverse event profile, which is manageable and does not typically require treatment discontinuation. This favorable safety profile makes it a viable option for long-term management of hyperkalemia[2].

Market Analysis

Cost-Effectiveness

Studies have shown that SZC is a cost-effective alternative for treating chronic hyperkalemia in patients with CKD or HF. When compared to standard treatments like calcium polystyrene sulfonate and lifestyle modifications, SZC offers significant benefits from the perspective of health systems, such as the Spanish National Health System[2].

Comparison with Other Treatments

A cost comparison analysis between SZC and patiromer in Saudi Arabia indicated that while patiromer might offer some cost savings under certain dosing schedules, SZC remains a competitive option due to its efficacy and safety profile. The analysis highlighted that hospitalization rates for heart failure and dosing schedules are key drivers of cost outcomes[5].

Market Projections

Growing Demand

The demand for effective hyperkalemia treatments is expected to grow, driven by the increasing prevalence of CKD and HF. As more patients require long-term management of potassium levels, the market for SZC is likely to expand.

Competitive Landscape

Despite the discontinuation of some Phase III trials, SZC remains a strong contender in the market for hyperkalemia treatments. Its unique mechanism of action and favorable safety and efficacy profile position it well against other potassium-lowering agents.

Regulatory and Clinical Momentum

While the discontinuation of certain trials may impact the immediate expansion of clinical evidence, the existing body of research and ongoing trials continue to support the use of SZC. Regulatory approvals and positive clinical outcomes will be crucial in maintaining and growing market share.

Key Takeaways

• Clinical Efficacy: SZC is effective in rapidly reducing and maintaining normal potassium levels in patients with hyperkalemia, including those with CKD or HF.
• Safety Profile: The drug has a favorable safety profile with manageable adverse events.
• Cost-Effectiveness: SZC is a cost-effective option compared to standard treatments, particularly from the perspective of national health systems.
• Market Competition: While other treatments like patiromer may offer some cost advantages, SZC's efficacy and safety make it a competitive choice.
• Future Projections: The market for SZC is expected to grow due to increasing demand for effective hyperkalemia treatments.

FAQs

What is sodium zirconium cyclosilicate (SZC)?

SZC, marketed as Lokelma, is an oral medication used to treat hyperkalemia by binding to potassium ions in the gastrointestinal tract.

How quickly does SZC reduce potassium levels?

SZC can reduce serum potassium levels to normal within 48 hours.

Is SZC safe for long-term use?

Yes, SZC has been shown to be safe for long-term use, with a favorable safety profile and manageable adverse events.

How does SZC compare to other hyperkalemia treatments in terms of cost?

SZC is generally cost-effective compared to standard treatments, although cost comparisons can vary based on dosing schedules and specific patient populations.

What are the implications of the discontinued Phase III trials for SZC?

The discontinuation of certain Phase III trials may delay the expansion of clinical evidence but does not significantly impact the current use and efficacy of SZC, which is supported by existing research.

Sources

1. AstraZeneca Clinical Trials: Study to assess efficacy and safety of SZC for the Management of Hyperkalaemia in Patients with Symptomatic Heart Failure with Reduced Ejection Fraction and Receiving Spironolactone.
2. Nefrología: Cost-effectiveness of sodium zirconium cyclosilicate for the treatment of hyperkalemia in patients with chronic kidney disease or heart failure.
3. FDA: LOKELMA (sodium zirconium cyclosilicate) - New Drug Application.
4. AstraZeneca: Update on CRYSTALIZE evidence trials.
5. ISPOR: Cost comparison analysis of patiromer versus sodium zirconium cyclosilicate for the treatment of hyperkalemia in Saudi Arabia.