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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