Kidney Week

Abstract: TH-PO1157

Correction of Serum Potassium with Sodium Zirconium Cyclosilicate in Japanese Patients with Hyperkalemia: A Dose-Finding Study

Session Information

• Late-Breaking Clinical Trials Posters
  October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• No subcategory defined

Authors

• Kashihara, Naoki, Kawasaki Medical School, Okayama, Japan

Naoki Kashihara,

• Nishio, Toshiki, Kusatsu General Hospital, Shiga, Japan

Toshiki Nishio,

• Osonoi, Takeshi, Nakakinen Clinic, Ibaraki, Japan

Takeshi Osonoi,

• Saka, Yosuke, Kasugai Municipal Hospital, Aichi, Japan

Yosuke Saka,

• Imasawa, Toshiyuki, Chiba-East-Hospital, Chiba, Japan

Toshiyuki Imasawa,

• Ohtake, Takayasu, Shonankamakura General Hospital, Kanagawa, Japan

Takayasu Ohtake,

• Mizuno, Hiroshi, Inage Hospital, Chiba, Japan

Hiroshi Mizuno,

• Shibagaki, Yugo, St. Marianna University School of Medicine Hospital, Kanagawa, Japan

Yugo Shibagaki,

• Kim, Hyosung, AstraZeneca K.K., Osaka, Japan

Hyosung Kim,

• Yajima, Toshitaka, AstraZeneca K.K., Osaka, Japan

Toshitaka Yajima,

• Sarai, Nobuaki, AstraZeneca K.K., Osaka, Japan

Nobuaki Sarai,

Background

Sodium zirconium cyclosilicate (SZC) is an oral potassium (K) binder approved to treat hyperkalemia (HK) in adults in the US and EU. We evaluated SZC doses for correcting serum K (sK) in Japanese patients (pts) with HK in a multicenter, double-blind, placebo-controlled phase 2/3 trial.

Methods

Pts aged ≥18y with sK ≥5.1–≤6.5mEql/L were randomized 1:1:1 to SZC 5g, SZC 10g, or placebo (PBO) administered (as powder in water) thrice daily for 48h. Primary endpoint was exponential rate of change in sK over 48h. Pts (%) with normokalemia (sK 3.5–5.0mEq/L) at 48h (secondary endpoint), multiple time points (1, 2, 4, 24, 25, 28, and 48h), and adverse events (AEs) were evaluated.

Results

At baseline, the 103 randomized pts (mean age 73y; 75% male) had mean sK of 5.6 mEq/L, mean eGFR of 26.1 mL/min/1.73m² (29%, 40%, 28%, and 3% had eGFR <15, 15–<30, 30–<60, and ≥60, respectively). All pts (34 on SZC 5g; 36 on SZC 10g; 33 on PBO) completed the study except 2 PBO pts discontinued due to HK. Exponential rate of sK change from 0–48h vs PBO was –0.00261/h with SZC 5g and –0.00496/h for SZC10g (Figure; both P<0.0001). At 48h, 85% of pts had normokalemia with SZC 5g, 92% with SZC 10g, and 15% with PBO. More pts had normokalemia with SZC 5g vs PBO at 4h through 48h and with SZC 10g vs PBO at every time point. AEs occurred in 4, 5, and 1 pt in the SZC 5g, 10g, and PBO groups; all AEs were mild and single occurrences in individual patients. sK <3.5 mEq/L occurred in 2 pts in the SZC 10g group, and none in the SZC 5g or PBO groups.

Conclusion

SZC 5g and 10g were well tolerated and corrected HK in most Japanese pts within 48h; SZC 10g had the most rapid sK reduction and highest response rate.

Funding

• Commercial Support – AstraZeneca