臨床研究等提出・公開システム

ZG-801 Phase III Trial
- Randomized, Double-blind, Placebo-controlled Trial of ZG-801 in patients with Hyperkalemia -

A comparative study of ZG-801 and placebo in patients with Hyperkalemia

85

The demographic and other baseline characteristics of the double-blind-period were generally well-balanced between the ZG-801 group and the placebo group.

85 patients were determined eligible and entered the run-in-period. Of the 85 patients, 67 entered the double-blind-period. Of the 67 patients who entered the double-blind-period, 34 were assigned to the ZG-801 group and 33 to the placebo group. 55 patients completed the study (30 in the ZG-801 group, 25 in the placebo group), and 12 patients discontinued the study.

During the run-in-period, the incidence of AEs was 32.9%, the incidence of ADRs was 12.9%, the incidence of serious AEs was 2.4%, and the incidence of serious ADRs was 1.2%. During the double-blind-period, the incidence of AEs was 32.4% and 24.2%, of ADRs was 8.8% and 0.0%, and of serious AEs was 5.9% and 0.0% in the ZG-801 group and the placebo group, respectively. No serious ADRs were observed in any group. No deaths occurred in this study. Furthermore, there were no serious AEs that occurred in multiple patients, and serious ADR was only "decreased appetite (1/85 patients)" in the run-in-period. The ADR that occurred in 5% or more during the total study period was only "constipation (10.6%, 9/85 patients)", none of which were serious.

As a result of the primary analysis, the change of sK-level LSMean (95%CI) from the baseline to the week 4 in the double-blind-period, was -0.02 (-0.19, 0.15) mmol/L in the patiromer group, and 0.78 (0.60, 0.96) mmol/L in the placebo group, with a statistically significant difference between the two treatment groups (p < 0.001). The least squares mean change (95% CI) from baseline to week 1 of the double-blind-period in sK values was 0.08 (-0.04, 0.20) mmol/L in the patiromer group and 0.55 (0.43, 0.67) mmol/L in the placebo group, demonstrating a statistically significant difference between the two groups at week 1. Similarly, statistically significant differences were observed between the two groups at week 2 and 3. The proportion of patients whose sK-level were maintained within the normal range at week 1 of the double-blind-period was 82.4% and 57.6%, and that at week 4 was 76.5% and 37.5%, respectively in the patiromer group and in the placebo group. The proportion of patients whose sK-level were maintained within the normal range, were statistically significantly higher in the patiromer group than in the placebo group at all time points, including week 2 and 3. The change in serum potassium level from baseline during the run-in-period was -0.61 mmol/L at the week 1, -0.94 mmol/L at the week 2, and -1.16 mmol/L at the week 3, -1.29 mmol/L at the week 4, and -1.35 mmol/L at the week 5 of the run-in-period. The proportion of patients whose sK-level became normal was 32.9% at the week 1, 74.0% at the week 2, 83.1% at the week 3, 85.9% at the week 4, and 91.7% at the week 5 of the run-in-period. Furthermore, the proportion of patients whose sK-level became normal at the final timing of each patient during the run-in-period was 97.3%.

During the run-in period, when all patients were administered ZG-801, the effect of ZG-801 in lowering sK levels was suggested. In addition, during the double-blind period, when patients whose sK levels had normalized during the run-in period were randomly assigned to the ZG-801 group or the placebo group, the increase in sK levels was significantly suppressed in the ZG-801 group compared to the placebo group (primary endpoint). No adverse events requiring particular attention were observed.

Feb. 20, 2025

https://link.springer.com/article/10.1007/s10157-025-02637-4

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2031210188

Tomioka Yuusuke

Zeria Pharmaceutical Co., Ltd.

10-11, Nihonbashi Kobuna-cho, Chuo-ku, Tokyo

801registry@zeria.co.jp

Division R&D

Zeria Pharmaceutical Co., Ltd.

10-11, Nihonbashi Kobuna-cho, Chuo-ku, Tokyo

+81-3-3661-0276

801registry@zeria.co.jp

Complete

Aug. 01, 2021

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

treatment purpose

1) Patients whose serum potassium value (local) at the Run-in period baseline is >=5.5mEq/L, < 6.5 mEq/L
2) Age 20 - 80 years old at informed consent
3) Patients who understand an overview of the study and voluntarily consented to participate in the study by documents.

1) Patients determined to require emergency treatment for hyperkalemia at the Run-in period baseline
2) Patients with poorly controlled blood pressure
3) Patients with heart failure in New York Heart Association Class IV
4) Patients who have experienced heart transplant, liver transplant or kidney transplant or who are predicted that the need for them will occur during the study
5) Patients who have taken any of the following medication within 7 days prior to the Run-in period baseline or currently administrated.
a) Sodium polystyrene sulfonate
b) Calcium polystyrene sulfonate
c) Sodium zirconium cyclosilicate hydrate
d) Potassium supplement
6) Patients whose last measured eGFR within 90 days prior to the Run-in period baseline is >= 60mEq/L (calculated by using the serum creatinine value measured at local laboratory). When eGFR has not been measured within 90 days prior to the Run-in period baseline, it must be measured until the Run-in period baseline.
7) Patients with or who have experienced a severe swallowing disorder, moderate to severe gastroparesis, severe constipation, bowel obstruction, incarceration, abnormal post-operative bowel motility disorders or severe gastrointestinal disorders. In addition, patients who have experienced bariatric surgery or major gastrointestinal surgery (e.g., bowel resection).
8) Patients suspected to be with transient high potassium value.(ex. caused by dietary effects only)

Both

Hyperkalemia

1) Run-in period
Subject takes ZG-801 once daily. The starting dose of ZG-801 is 8.4 g/day. From the Run-in period week 1 to week 3, the dose will be adjusted based on the serum potassium value (local) at prescribed visit. Only for subjects who do not meet the transition criteria at the Run-in period week 4, the dose can be adjusted at the Run-in period week 4. The dose titration range of ZG-801 is 8.4 g/day to 25.2g/day.
2) Double-blind period
Subjects take a randomly assigned ZG-801 or placebo once daily. The dose in the Double-blind period shall be the dose at the transition to the Double-blind period and shall not be changed during the Double-blind period.

Change in serum potassium value at Double-blind period week4

+81-3-5213-0028

June. 18, 2021

none