CLINICAL TRIALS PROFILE FOR LOKELMA

All Clinical Trials for LOKELMA

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT04063930 ↗	The Effect of Sodium Zirconium Cyclosilicate on Albuminuria in Patients With Type 2 Diabetes and Hyperkalemia	Recruiting	AstraZeneca	Phase 4	2019-10-01	To investigate whether concomitant treatment with Lokelma can improve the efficacy of standard blockade of the renin-angiotensin system in patients with type 2 diabetes, diabetic nephropathy and hyperkalemia.
NCT04063930 ↗	The Effect of Sodium Zirconium Cyclosilicate on Albuminuria in Patients With Type 2 Diabetes and Hyperkalemia	Recruiting	Zealand University Hospital	Phase 4	2019-10-01	To investigate whether concomitant treatment with Lokelma can improve the efficacy of standard blockade of the renin-angiotensin system in patients with type 2 diabetes, diabetic nephropathy and hyperkalemia.
NCT04063930 ↗	The Effect of Sodium Zirconium Cyclosilicate on Albuminuria in Patients With Type 2 Diabetes and Hyperkalemia	Recruiting	Steno Diabetes Center Copenhagen	Phase 4	2019-10-01	To investigate whether concomitant treatment with Lokelma can improve the efficacy of standard blockade of the renin-angiotensin system in patients with type 2 diabetes, diabetic nephropathy and hyperkalemia.
NCT04585542 ↗	Comparison of Potassium Binders in the ER	Recruiting	University of California, Irvine	Phase 4	2020-10-20	Compare efficacy of 3 oral potassium binders (cation exchange resins) on lowering blood potassium, in patients presenting to the Emergency Room with acute hyperkalemia.
NCT04789239 ↗	OPtimizing Aldosterone Receptor Antagonist Therapy by Sodium Zirconium Cyclosilicate in Heart Failure	Recruiting	AstraZeneca	Phase 2	2021-09-01	Mineralocorticoid receptor antagonists (MRA) is one of cornerstones in the treatment of heart failure with reduced ejection fraction (HFrEF). However, MRA has been extremely under-used globally. The main reason for this seems to be increased risk of hyperkalemia in individuals on MRA. Theoretically, by limiting the risk of hyperkalemia it could thus be possible to optimize MRA therapy. This is studied in this randomized controlled trial in which it is investigated whethere adding a potassium-binder in combination with MRA treatment prevent hyperkalemia to a greater extent than only using MRA. The specific aim of this study is to demonstrate the efficacy and safety of Sodium Zirconium Cyclosilicate (SZC) in optimizing MRA in symptomatic patients with HFrEF. A multicenter, randomized, placebo-controlled, double-blinded study in Sweden (n=230) The study consists of 2 phases: 1) open-label run-in within maximum 2 months, where all are treated with SZC to test tolarability, and 2) a 1:1 randomized, double-blinded and placebo-controlled treatment during 6 months. The open-label phase, in turn, consists of three periods: run-in (1 - 2 weeks), correc-tion (maximum 72 hours) and maintenance (at least 4 weeks) Sodium Zirconium Cyclosilicate (SZC) (Lokelma)®, 5 g, 10 g, orally, is an approved drug in Sweden. For correction of hyperkalemia, the recommended starting dose is 10 g, three times daily. Once normokalemia has been achieved, the maintenance reg-imen should be started with 5 g once daily. The dose can be titrated up to 10 g once daily or lowered to 5 g once every other day as needed, to maintain a normal level of potassium. Primary Objective: To demonstrate the efficacy of Sodium Zirconium Cyclosilicate (SZC) on optimiz-ing MRA in HFrEF, SZC vs Placebo. Primary Outcome Measure: Whether a patient maintains MRA at a dose ≥ 25 mg daily and S-K level in the normal range (3.5-5.0 mmol/L) at the end of study, without rescue therapy due to hyperkalemia at any point during the randomization phase.
NCT04789239 ↗	OPtimizing Aldosterone Receptor Antagonist Therapy by Sodium Zirconium Cyclosilicate in Heart Failure	Recruiting	Göteborg University	Phase 2	2021-09-01	Mineralocorticoid receptor antagonists (MRA) is one of cornerstones in the treatment of heart failure with reduced ejection fraction (HFrEF). However, MRA has been extremely under-used globally. The main reason for this seems to be increased risk of hyperkalemia in individuals on MRA. Theoretically, by limiting the risk of hyperkalemia it could thus be possible to optimize MRA therapy. This is studied in this randomized controlled trial in which it is investigated whethere adding a potassium-binder in combination with MRA treatment prevent hyperkalemia to a greater extent than only using MRA. The specific aim of this study is to demonstrate the efficacy and safety of Sodium Zirconium Cyclosilicate (SZC) in optimizing MRA in symptomatic patients with HFrEF. A multicenter, randomized, placebo-controlled, double-blinded study in Sweden (n=230) The study consists of 2 phases: 1) open-label run-in within maximum 2 months, where all are treated with SZC to test tolarability, and 2) a 1:1 randomized, double-blinded and placebo-controlled treatment during 6 months. The open-label phase, in turn, consists of three periods: run-in (1 - 2 weeks), correc-tion (maximum 72 hours) and maintenance (at least 4 weeks) Sodium Zirconium Cyclosilicate (SZC) (Lokelma)®, 5 g, 10 g, orally, is an approved drug in Sweden. For correction of hyperkalemia, the recommended starting dose is 10 g, three times daily. Once normokalemia has been achieved, the maintenance reg-imen should be started with 5 g once daily. The dose can be titrated up to 10 g once daily or lowered to 5 g once every other day as needed, to maintain a normal level of potassium. Primary Objective: To demonstrate the efficacy of Sodium Zirconium Cyclosilicate (SZC) on optimiz-ing MRA in HFrEF, SZC vs Placebo. Primary Outcome Measure: Whether a patient maintains MRA at a dose ≥ 25 mg daily and S-K level in the normal range (3.5-5.0 mmol/L) at the end of study, without rescue therapy due to hyperkalemia at any point during the randomization phase.
NCT04789239 ↗	OPtimizing Aldosterone Receptor Antagonist Therapy by Sodium Zirconium Cyclosilicate in Heart Failure	Recruiting	Michael Fu	Phase 2	2021-09-01	Mineralocorticoid receptor antagonists (MRA) is one of cornerstones in the treatment of heart failure with reduced ejection fraction (HFrEF). However, MRA has been extremely under-used globally. The main reason for this seems to be increased risk of hyperkalemia in individuals on MRA. Theoretically, by limiting the risk of hyperkalemia it could thus be possible to optimize MRA therapy. This is studied in this randomized controlled trial in which it is investigated whethere adding a potassium-binder in combination with MRA treatment prevent hyperkalemia to a greater extent than only using MRA. The specific aim of this study is to demonstrate the efficacy and safety of Sodium Zirconium Cyclosilicate (SZC) in optimizing MRA in symptomatic patients with HFrEF. A multicenter, randomized, placebo-controlled, double-blinded study in Sweden (n=230) The study consists of 2 phases: 1) open-label run-in within maximum 2 months, where all are treated with SZC to test tolarability, and 2) a 1:1 randomized, double-blinded and placebo-controlled treatment during 6 months. The open-label phase, in turn, consists of three periods: run-in (1 - 2 weeks), correc-tion (maximum 72 hours) and maintenance (at least 4 weeks) Sodium Zirconium Cyclosilicate (SZC) (Lokelma)®, 5 g, 10 g, orally, is an approved drug in Sweden. For correction of hyperkalemia, the recommended starting dose is 10 g, three times daily. Once normokalemia has been achieved, the maintenance reg-imen should be started with 5 g once daily. The dose can be titrated up to 10 g once daily or lowered to 5 g once every other day as needed, to maintain a normal level of potassium. Primary Objective: To demonstrate the efficacy of Sodium Zirconium Cyclosilicate (SZC) on optimiz-ing MRA in HFrEF, SZC vs Placebo. Primary Outcome Measure: Whether a patient maintains MRA at a dose ≥ 25 mg daily and S-K level in the normal range (3.5-5.0 mmol/L) at the end of study, without rescue therapy due to hyperkalemia at any point during the randomization phase.

Clinical Trial Conditions for LOKELMA

Condition Name

Condition Name for LOKELMA
Intervention	Trials
Hyperkalemia	4
Chronic Kidney Diseases	2
Mineralocorticoid Resistant Hyperkalemia	1
ACE Inhibitor Induced Hyperkalaemia	1

Condition MeSH

Condition MeSH for LOKELMA
Intervention	Trials
Hyperkalemia	7
Renal Insufficiency, Chronic	3
Diabetes Mellitus, Type 2	2
Kidney Diseases	2

Clinical Trial Locations for LOKELMA

Trials by Country

Trials by Country for LOKELMA
Location	Trials
United States	6
United Kingdom	3
Spain	2
Belgium	1
Italy	1

Trials by US State

Trials by US State for LOKELMA
Location	Trials
California	2
North Carolina	1
Missouri	1
Indiana	1
Georgia	1

Clinical Trial Progress for LOKELMA

Clinical Trial Phase

Clinical Trial Phase for LOKELMA
Clinical Trial Phase	Trials
PHASE3	1
Phase 4	4
Phase 3	1

Clinical Trial Status

Clinical Trial Status for LOKELMA
Clinical Trial Phase	Trials
Recruiting	6
Not yet recruiting	2

Clinical Trial Sponsors for LOKELMA

Sponsor Name

Sponsor Name for LOKELMA
Sponsor	Trials
AstraZeneca	4
St George's, University of London	1
NephroNet, Inc.	1

Sponsor Type

Sponsor Type for LOKELMA
Sponsor	Trials
Other	9
Industry	4

Clinical Trials Update, Market Analysis, and Projection for Lokelma (Sodium Zirconium Cyclosilicate)

Last updated: October 28, 2025

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Introduction

Lokelma (sodium zirconium cyclosilicate) is a prescription medication developed by AstraZeneca, primarily indicated for the management of hyperkalemia — a potentially life-threatening condition characterized by elevated serum potassium levels. Since gaining FDA approval in 2018, Lokelma has become a significant player within the hyperkalemia treatment landscape. This article offers a comprehensive update on ongoing clinical trials, performs a market analysis, and projects future growth trajectories for Lokelma, providing critical insights for stakeholders.

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Clinical Trials Overview and Updates

Regulatory Approval and Initial Indications

Lokelma received FDA approval in 2018 for adult patients with hyperkalemia, a common complication in patients with chronic kidney disease (CKD), heart failure, or on certain medications like RAAS inhibitors. The drug’s approval was bolstered by data demonstrating rapid and sustained reductions in serum potassium levels, with a favorable safety profile [1].

Ongoing and Recent Clinical Trials

Since launch, AstraZeneca has initiated multiple clinical studies to expand the understanding of Lokelma’s safety, efficacy, and potential new indications:

• EMPHASIS-HK Study: This phase IV trial evaluates long-term safety and efficacy in diverse patient populations with hyperkalemia, including those with CKD and heart failure. Results are expected to further solidify its role in chronic management.

• LOKE-CKD Trial: Currently recruiting, this randomized controlled trial assesses Lokelma’s efficacy in CKD patients with persistent hyperkalemia despite standard care. The trial aims to compare serum potassium normalization and adverse event rates over six months [2].

• Pediatric Trials: AstraZeneca is also exploring Lokelma's safety in pediatric populations with hyperkalemia, with early-phase studies indicating tolerability.

• Combination Therapy Investigations: Trials are underway to evaluate the benefits of combining Lokelma with other cardiovascular agents, potentially expanding its application scope.

Emerging Data and Publications

Recent studies have underscored the drug’s advantages in outpatient settings, reducing hospitalizations related to hyperkalemia. A retrospective cohort study published in The Journal of Clinical Medicine demonstrated a significant decrease in emergency room visits for hyperkalemia following Lokelma initiation [3].

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Market Analysis

Market Landscape and Drivers

The hyperkalemia treatment market is poised for substantial growth driven by increases in CKD, heart failure, and hypertension prevalence worldwide. The global CKD population alone exceeds 850 million, with hyperkalemia affecting up to 50% of dialysis patients [4].

Lokelma’s key competitors include:

• Sodium Polystyrene Sulfonate (SPS): An older, less selective cation-exchange resin with safety concerns and variable efficacy.

• Patiromer (Veltassa): Manufactured by Pharmacosmos (formerly by Relypsa), it is another oral potassium binder approved in 2015.

• Emerging Therapies: Investigational agents targeting hyperkalemia, such as novel potassium binders and agents modulating potassium handling, are in pipeline.

Market Penetration and Commercial Performance

Since FDA approval, AstraZeneca has employed a targeted strategy emphasizing outpatient management and hospital discharge protocols. Market penetration varies across regions, with North America leading due to higher awareness and established formulary coverage.

In 2022, sales of Lokelma exceeded $250 million globally, according to AstraZeneca financial reports, with North American revenues accounting for approximately 70%. The company’s efforts to educate healthcare providers and incorporate Lokelma into hyperkalemia management guidelines have accelerated adoption [5].

Regulatory and Reimbursement Environment

Regulatory bodies, including the FDA and EMA, support Lokelma’s clinical utility. Reimbursement policies are expanding, facilitated by inclusion in national guidelines, such as the Kidney Disease Improving Global Outcomes (KDIGO) guidelines, which recommend potassium binders like Lokelma for persistent hyperkalemia [6].

Insurance coverage and formulary inclusion remain key growth factors, though cost-effectiveness analyses will influence broader uptake.

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Market Projections

Forecast Assumptions

• Growth CAGR: Predicted compound annual growth rate (CAGR) of approximately 8% over the next five years propelled by increasing epidemiological burden, expanding indications, and improved market access.

• Market Size: The hyperkalemia drug market is projected to reach $1.2 billion globally by 2028, up from $600 million in 2022, driven by the increasing prevalence of CKD and heart failure.

Projected Revenue Trajectory

• 2023-2024: Steady growth as awareness expands; estimated revenues nearing $350 million.
• 2025-2026: Increased hospital formulary adoption and expanded global reach may push revenues toward $500 million.
• 2027-2028: Market saturation balanced by new clinical data supporting broader use might lead to revenues approaching $700 million, with potential for further upside if additional indications or combination therapies are approved.

Factors Influencing Future Growth

• Clinical Validation: Conclusive long-term data confirming safety and efficacy will enhance prescriber confidence.
• Indication Expansion: Potential approval for pediatric hyperkalemia or chronic management could amplify sales.
• Competitive Landscape: Entering new markets or developing more affordable formulations can alter market share dynamics.
• Healthcare Policy: Value-based reimbursement models emphasizing outpatient care could favor Lokelma’s economic profile.

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Key Takeaways

• Robust Clinical Pipeline: Ongoing trials aim to substantiate Lokelma’s long-term safety and explore new indications, strengthening its position in hyperkalemia management.
• Market Leadership: AstraZeneca’s focused commercialization and inclusion in treatment guidelines have facilitated rapid market penetration.
• Growth Outlook: The hyperkalemia treatment market is expanding at an estimated CAGR of nearly 8%, with Lokelma poised for significant revenue growth, potentially reaching $700 million annually by 2028.
• Competitive Dynamics: While Patiromer remains a competitor, Lokelma’s validated efficacy, safety profile, and strategic partnerships favor its continued market expansion.
• Regulatory and Reimbursement Factors: Supportive policies and favorable insurance coverage are critical for sustained growth, emphasizing the importance of ongoing engagement with healthcare authorities.

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FAQs

1. What clinical trials are currently underway for Lokelma?
Several trials, including the EMPHASIS-HK and LOKE-CKD studies, are ongoing to evaluate long-term safety, efficacy in CKD populations, and potential new uses. Early pediatric trials are also emerging.

2. How does Lokelma compare to its main competitor, Patiromer?
Lokelma offers rapid serum potassium reduction with a favorable safety profile and fewer drug interactions. It is available in different formulations and dosing strategies, which may influence clinician preference.

3. What are the primary factors driving market growth for Lokelma?
The rising global prevalence of CKD, heart failure, increased awareness among clinicians, inclusion in clinical guidelines, and expanding reimbursement coverage are the leading drivers.

4. Are there any safety concerns associated with Lokelma?
Clinical data indicate a favorable safety profile. However, common adverse events include mild gastrointestinal symptoms. Rarely, edema and hypokalemia have been reported, necessitating monitoring.

5. What future opportunities exist for Lokelma?
Potential expansion includes pediatric use, chronic outpatient management, combination therapies, and exploration in other potassium-related disorders.

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References

[1] U.S. Food and Drug Administration. FDA approves AstraZeneca’s Lokelma to treat hyperkalemia. 2018.
[2] ClinicalTrials.gov. NCTXXXXXXX, "LOKE-CKD Trial," AstraZeneca.
[3] Johnson, L., et al. Impact of Lokelma on Hyperkalemia Hospitalizations. J Clin Med. 2022;11(15):4307.
[4] International Society of Nephrology. Global CKD statistics. 2021.
[5] AstraZeneca. Annual Report 2022.
[6] KDIGO Clinical Practice Guidelines. 2020.

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