A phase 3 multicenter open-label maintenance study to investigate the long-term safety of sodium zirconium cyclosilicate in Japanese subjects with hyperkalemia

Naoki Kashihara, Yoshimitsu Yamasaki, Takeshi Osonoi, Hiromasa Harada, Yugo Shibagaki, June Zhao, Hyosung Kim, Toshitaka Yajima, Nobuaki Sarai, Naoki Kashihara, Yoshimitsu Yamasaki, Takeshi Osonoi, Hiromasa Harada, Yugo Shibagaki, June Zhao, Hyosung Kim, Toshitaka Yajima, Nobuaki Sarai

Abstract

Background: Hyperkalemia is associated with many chronic diseases and renin-angiotensin-aldosterone system inhibitor therapy. Sodium zirconium cyclosilicate (SZC), an oral, highly selective cation-exchanger, is approved for the treatment of hyperkalemia.

Methods: This phase 3, multicenter, open-label, single-arm, flexible-dose study assessed the safety and efficacy of SZC in Japanese patients with hyperkalemia during a correction phase of up to 3 days and long-term (1 year) maintenance phase (NCT03172702).

Results: Overall, 150 patients received treatment during both study phases; the study population was generally representative of hyperkalemic Japanese patients in clinical practice. Most patients (78.7%) had three doses of SZC during the correction phase. All but one patient received SZC for ≤ 48 h before transitioning to the maintenance phase. In the maintenance phase, mean (standard deviation; SD) exposure to the study drug was 319.4 (98.1) days and mean (SD) dose was 7.38 (2.85) g/day. Adverse events (AEs) were reported in 131 patients (87.3%); most were mild. The most common treatment-related AEs as evaluated by investigators were constipation (6.7%), peripheral edema (4.0%), and hypertension (2.7%). In the correction phase, 78.7% of patients were normokalemic at 24 h and 98.7% within 48 h; ≥ 65.5% maintained normokalemia throughout the maintenance phase.

Conclusion: After a year of exposure, SZC treatment was well tolerated by Japanese patients and potassium levels were well controlled.

Keywords: Hyperkalemia; Japanese; Long-term safety study; Sodium zirconium cyclosilicate.

Conflict of interest statement

N Kashihara has received consulting fees from AstraZeneca, Gilead, Kyowa-Kirin, and GlaxoSmithKline, and has received honoraria for lectures from Daiichi-Sankyo, Takeda, Astellas, Otsuka, and Kyowa-Kirin, and has received research grants from Tanabe-Mitsubishi, Tore, Baxter, Cyugai-Seiyaku, Kyowa-Kirin, Bayer-Yakuhin, Ono-Yakuhin, Daiichi-Sankyo, Nihon-Boehringer Ingelheim, Astellas-Seiyaku, and Takeda-Yakuhin-Kogyo. J Zhao, H Kim, T Yajima, and N Sarai are employees of AstraZeneca. Y Yamasaki, T Osonoi, H Harada, and Y Shibagaki have no conflicts of interest to declare. This work was supported by AstraZeneca.

Figures

Fig. 1
Fig. 1
Trial design. K+ potassium, Max maximum, QD once daily, QOD every other day
Fig. 2
Fig. 2
Study flow diagram. ECG electrocardiogram
Fig. 3
Fig. 3
Mean serum potassium (mmol/L) over time (± standard deviation) (full analysis set, maintenance phase)

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