In Phase IIIb DIALIZE trial, 41.2% of LOKELMA patients maintained normal potassium levels pre-dialysis compared to 1% receiving placebo
AstraZeneca today presented positive results from the Phase IIIb DIALIZE trial which investigated the efficacy and safety of LOKELMA (sodium zirconium cyclosilicate) for the treatment of hyperkalemia in patients with end-stage renal disease (ESRD) on hemodialysis.
Hyperkalemia is a serious condition characterized by elevated potassium levels in the blood.
In the trial, 41.2% of patients with hyperkalemia on stable hemodialysis receiving LOKELMA maintained pre-dialysis normal potassium levels (4-5 mmol/L) on at least three out of four dialysis treatments after the long interdialytic interval and did not require urgent rescue therapy, compared to 1.0% of patients receiving placebo. This was a statistically significant (P<0.001) and clinically meaningful improvement.
The safety profile of LOKELMA observed in DIALIZE was consistent with previous trials.
The results were presented as a late-breaking abstract at the 56th European Renal Association – European Dialysis and Transplant Association (ERA-EDTA) Congress in Budapest, Hungary and were published in the Journal of the American Society of Nephrology.
Elisabeth Björk, Senior Vice President, Head of Late-stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, said, “These positive results show that LOKELMA can normalize potassium levels in between dialysis sessions for patients with hyperkalemia who have end-stage renal disease. There is a high unmet treatment need that affects a large patient population and we believe LOKELMA can play a critical role.”
Steven Fishbane, MD, Zucker School of Medicine at Hofstra/Northwell, Great Neck, NY, and primary investigator in the DIALIZE trial, said, “An estimated two million people worldwide have end-stage renal disease, placing them at a higher risk for hyperkalemia. Despite being on dialysis, many still have high potassium levels, which can be life-threatening if left untreated. These results provide important insights for the clinical community and patients, and have the potential to transform the treatment paradigm.”
Hyperkalemia can be a result of cardiovascular, renal and metabolic diseases, and use of certain medications such as renin-angiotensin-aldosterone system (RAAS) inhibitors. Many patients with ESRD have hyperkalemia despite being on hemodialysis. Prevalence and severity of hyperkalemia is highest after the long interdialytic interval, the longest number of days between dialysis sessions.
LOKELMA is a highly-selective, oral potassium-removing agent currently approved and available in the US for the treatment of adults with hyperkalemia. Data from the DIALIZE trial will support label updates in the US as the dosing regimen used in the trial is not currently approved.
INDICATION AND LIMITATION OF USE FOR LOKELMA™ (sodium zirconium cyclosilicate) 10 g ORAL SUSPENSION
LOKELMA is indicated for the treatment of hyperkalemia in adults.
LOKELMA should not be used as an emergency treatment for life-threatening hyperkalemia because of its delayed onset of action.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS:
- Gastrointestinal Adverse Events in Patients with Motility Disorders: Avoid LOKELMA in patients with severe constipation, bowel obstruction or impaction, including abnormal post-operative bowel motility disorders. LOKELMA has not been studied in patients with these conditions and it may be ineffective and may worsen gastrointestinal conditions
- Edema: Each 5 g dose of LOKELMA contains approximately 400 mg of sodium. In clinical trials of LOKELMA, edema was generally mild to moderate in severity and was more commonly seen in patients treated with 15 g once daily. Monitor for signs of edema, particularly in patients who should restrict their sodium intake or are prone to fluid overload (eg., heart failure (HF) or renal disease). Advise patients to adjust dietary sodium, if appropriate. Increase the dose of diuretics as needed
ADVERSE REACTIONS: The most common adverse reaction with LOKELMA was mild to moderate edema. In placebo-controlled trials up to 28 days, edema was reported in 4.4%, 5.9%, 16.1% of patients treated with 5 g, 10 g and 15 g of LOKELMA once daily, respectively vs 2.4% of patients receiving placebo.
DRUG INTERACTIONS: LOKELMA can transiently increase gastric pH. In general, oral medications with pH-dependent solubility should be administered at least 2 hours before or 2 hours after LOKELMA. Spacing is not needed if it has been determined the concomitant medication does not exhibit pH-dependent solubility.
NOTES TO EDITORS
The risk of hyperkalemia is associated with common comorbidities including chronic kidney disease (CKD), heart failure (HF) and diabetes, and these are the same conditions in which renin-angiotensin-aldosterone system (RAAS) inhibitors are recommended in guidelines. To help prevent the recurrence of hyperkalemia, important guideline-recommended RAAS inhibitor therapy is often modified or discontinued. Hyperkalemia occurs in 23% to 47% of patients with CKD and/or HF, with an estimated 200 million and 64 million people, respectively, living with each condition worldwide.
DIALIZE is the first ever randomized, placebo-controlled trial to evaluate a potassium binder in patients on stable hemodialysis. The Phase IIIb, multicenter, double-blind trial investigated the efficacy of LOKELMA versus placebo in 196 patients on hemodialysis with hyperkalemia. Patients were randomized to receive LOKELMA or placebo once daily on non-dialysis days for a treatment period of 8 weeks. This included a 4 week dose adjustment phase (starting at 5 g and titrated weekly in 5 g increments up to a maximum of 15 g) and a 4 week evaluation phase on stable dose. The dosing regimen used in the DIALIZE trial is not currently approved.
LOKELMA is an insoluble, non-absorbed sodium zirconium silicate, formulated as a powder for oral suspension, that acts as a highly-selective potassium-removing agent. It is administered orally, is odorless, tasteless and stable at room temperature. It has been studied in three double-blind, placebo-controlled trials, which included one 11-month open-label extension and in one separate 12-month open label clinical trial in patients with hyperkalemia.
About AstraZeneca in Cardiovascular, Renal & Metabolism (CVRM)
CV, renal and metabolism together form one of AstraZeneca’s main therapy areas and a key growth driver for the Company. By following the science to understand more clearly the underlying links between the heart, kidneys and pancreas, AstraZeneca is investing in a portfolio of medicines to protect organs and improve outcomes by slowing disease progression, reducing risks and tackling co-morbidities. Our ambition is to modify or halt the natural course of CVRM diseases and potentially regenerate organs and restore function, by continuing to deliver transformative science that improves treatment practices and CV health for millions of patients worldwide.
AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism and Respiratory. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on Twitter @AstraZenecaUS.
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US-30163 Last Updated 6/19