MedicalResearch.com Interview with:
Rahul Agrawal MD PhD
VP, Global Medicines Leader
MedicalResearch.com: What is the background for this study?
About the study: HARMONIZE Global is a Phase III, randomized, multicenter, double-blind, placebo-controlled trial involving 267 patients with hyperkalemia (mean potassium levels greater than 5.0 mEq/L) in 47 study locations across the Asia Pacific region, which will support registration in Japan, Taiwan, Korea and Russia.
Study design: The trial design of HARMONIZE Global is similar to HARMONIZE (NCT02088073) but evaluated two doses of LOKELMATM (sodium zirconium cyclosilicate) instead of three, as well as patients in different geographical regions.
MedicalResearch.com: What are the main findings?
Response: HARMONIZE Global investigated the safety and efficacy of LOKELMA compared to placebo in adult patients with hyperkalemia in Japan, Taiwan, Korea and Russia. The trial met its primary endpoint with a statistically significant difference observed with both doses of LOKELMA (5g and 10g) vs. placebo in terms of mean potassium levels during days 8-29 of the maintenance phase.
Patients who achieved normokalemia (mean potassium levels of 3.5-5.0 mEq/L) during the first 48 hours with sodium zirconium cyclosilicate 10g three times daily (93%; N = 248) progressed to the 28-day maintenance phase of the trial. Patients in the maintenance phase were randomized to receive sodium zirconium cyclosilicate 5g or 10g, or placebo, administered once daily. Results show normokalemia was maintained during the maintenance phase, with statistically significant differences observed with both doses of sodium zirconium cyclosilicate vs. placebo in terms of mean potassium levels during 8-29 of the maintenance phase.
The safety profile for sodium zirconium cyclosilicate observed in HARMONIZE Global was consistent with previous trials, in patients with hyperkalemia, with no new or unexpected safety signals identified.
MedicalResearch.com: What should readers take away from your report?
Response: We are committed delivering data that could support physicians’ confidence in treating hyperkalemia promptly and managing potassium levels continuously. The HARMONIZE Global data presented at ASN Kidney Week add to the growing body of evidence supporting LOKELMA and our broader clinical program reinforces our commitment to exploring new patient populations where high unmet medical need remains. This data adds to the body of evidence for LOKELMA and follows the approval of LOKELMA in the US by the Food and Drug Administration (FDA) in May 2018 for the treatment of hyperkalemia in adults.
Hyperkalemia is a serious condition characterized by elevated potassium levels in the blood associated with cardiovascular, renal and metabolic (CVRM) diseases. An estimated 10 million people worldwide experience hyperkalemia in a year and the condition may cause serious or life-threatening consequences if not managed properly.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: LOKELMA is approved for the treatment of hyperkalemia in adult patients in the US and the EU. Registrations in other markets are planned. Data from HARMONIZE Global trial will support registration in Japan, Korea, Taiwan and Russia.
We are committed to exploring the efficacy and optimal use of LOKELMA in other patients with hyperkalemia. For example, multiple studies are underway, including DIALIZE in patients undergoing hemodialysis and ENERGIZE in patients being treated in the emergency department setting. We have started recruitment for PRIORITIZE-HF in patients with heart failure and hyperkalemia, or at high risk of developing hyperkalemia, and are planning to start HARMONIZE-Asia, a companion study evaluating new populations in China and India.
I am an employee of AstraZeneca, which sponsored the study.
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 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.
PLEASE READ FULL PRESCRIBING INFORMATION For LOKELMA.
|Sodium zirconium cyclosilicate for hyperkalemia: results of the randomized, placebo-controlled, multi-dose HARMONIZE-GLOBAL study||Poster #TH-PO1158
Thursday, Oct 25, 10:00 AM to 12:00 PM
Poster session: Late-Breaking Clinical Trials Posters [LB-PO]
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