ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on X

Kidney Week

Abstract: SA-OR41

HARMONIZE ASIA: A Phase 3 Study to Investigate the Safety and Efficacy of Sodium Zirconium Cyclosilicate in Patients with Hyperkalemia in China

Session Information

Category: Fluid, Electrolytes, and Acid-Base Disorders

  • 1102 Fluid, Electrolyte, and Acid-Base Disorders: Clinical

Authors

  • Zhao, June, BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, Maryland, United States
  • Yu, Xueqing, Department of Nephrology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
  • Liang, Xinling, Department of Nephrology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
  • Lu, Wanhong, The First Affiliated Hospital of Xi’an Jiaotong University, Xian, China
  • Cheng, Hong, Anzhen Hospital, Capital University of Medical Science, Beijing, China
  • He, Qiang, Sichuan Provincial People's Hospital, Chengdu, China
  • Peng, Qingfeng, Zhuzhou Central Hospital, Zhuzhou, China
  • Ni, Zhaohui, Renji Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China
  • Long, Gang, Tianjin People’s Hospital, Tianjin, China
  • Wang, Lihua, The Second Hospital of Shanxi Medical University, Taiyuan, China
  • Xu, Gang, Tongji Hospital Affiliated to Hua Zhong Technology University, Wuhan, China
  • Chen, Wei, The First Affiliated Hospital Of Sun Yat-Sen University, Guangdong, China
  • Zhang, Yong, AstraZeneca R&D, Shanghai, China
  • Lisovskaja, Vera, Department of Biostatistics, Research and Development, AstraZeneca, Gothenburg, Sweden
  • Tang, Zhiji, AstraZeneca R&D, Shanghai, China

Group or Team Name

  • HARMONIZE ASIA Study Group.
Background

Sodium zirconium cyclosilicate (SZC) is an oral potassium (K+)-lowering therapy for adults with hyperkalemia (HK). HARMONIZE Asia (NCT03528681) evaluated SZC safety and efficacy in patients (pts) with HK in China.

Methods

This Phase 3, randomized, double-blind, placebo (PBO)-controlled study recruited pts with serum K+ (sK+) ≥5.1 mmol/L at 35 sites in China. Pts received SZC 10 g three times daily for 24 or 48 hours in an open-label phase (OLP). Those achieving normokalemia (sK+ 3.5−5.0 mmol/L) entered a 28-day randomized treatment phase (RTP), randomized 2:2:1 to receive SZC 5 g, SZC 10 g, or PBO once daily. The primary endpoint measured mean sK+ level during RTP days 8−29. Secondary endpoints included mean change in sK+ level during the OLP, proportion of pts achieving/maintaining normokalemia during the RTP, and time to recurrence of HK.

Results

In total, 270 pts received SZC during the OLP and 256 (94.8%) completed the OLP. The mean eGFR was 17.9 mL/min/1.73m2. During the OLP, mean sK+ decreased by 1.11 mmol/L from baseline (5.85 mmol/L; P<0.001) and 87.4% of pts achieved normokalemia. During the RTP, SZC 5 g and 10 g (both P<0.001) reduced mean sK+ vs. PBO in a dose-dependent manner; least-squares means (95% confidence interval [CI]) sK+ were 4.86 mmol/L (4.71, 5.01), 4.44 mmol/L (4.30, 4.58), and 5.23 mmol/L (5.06, 5.40), for SZC 5 g, 10 g, and PBO, respectively. At RTP end, 58.8%, 76.5%, and 36.8% of pts maintained normokalemia with SZC 5 g, 10 g, and PBO, respectively. Pts were more likely to maintain normokalemia with SZC 5 g and 10 g vs. PBO (odds ratios: 2.54, 95% CI 1.07, 6.05; P=0.035 and 6.25, 95% CI 2.56, 15.27; P<0.001). Risk of recurrent HK was reduced by 61.0% and 84.0% with SZC 5 g and 10 g (both P<0.001), vs. PBO, respectively. AE incidence during the RTP was higher with SZC 5 g (50.0% of pts) and 10 g (44.0%) vs. PBO (36.0%). The incidence of constipation was higher in the SZC 5 g (7.0%) and 10 g (5.0%) groups compared to the placebo group (0).

Conclusion

Both SZC doses were statistically significant to PBO for all confirmatory sK+ analyses, with dose-dependency observed during the RTP. The safety profile of SZC was generally consistent with previous studies.

Funding

  • Commercial Support – AstraZeneca