A Phase 3 Multicenter, Prospective, Randomized, Double-blind, Placebo-controlled Study to Investigate the Safety and Efficacy of ZS, in Patients With Hyperkalemia-HARMONIZE Global
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 267
- 试验地点
- 1
- 主要终点
- Least Square Mean S-K Level on Days 8-29
研究概览
简要总结
To evaluate the efficacy of two different doses (5 and 10 g) of ZS orally administered once daily (qd) vs placebo in maintaining normokalemia in initially hyperkalemic patients having achieved normokalemia following two days of initial ZS therapy (10g TID).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provision of informed consent prior to any study specific procedures
- •Female and male patients aged ≥18 and ≤ 90 years
- •Two consecutive i-STAT potassium values, measured 60-minutes (± 10 minutes) apart, both ≥ 5.1 mmol/l and measured within 1 day of the first ZS dose on 48-hour open-label initial phase Day 1
- •Ability to have repeated blood draws or effective venous catheterization
- •Female patients must be 1 year post-menopausal, surgically sterile, or using an acceptable method of contraception for the duration of the study and for 3 months after the last dose of ZS/matching placebo to prevent pregnancy.
排除标准
- •Involvement in the planning and/or conduct of the study
- •Participation in another clinical study with an investigational product during the last 3 months
- •Pseudohyperkalemia signs and symptoms
- •Patients treated with lactulose, xifaxan (rifaximin) or other non-absorbed antibiotics for hyperammonemia within 7 days prior to the first dose of study drug
- •Patients treated with resins,calcium acetate,calcium carbonate, or lanthanum carbonate,within 7 days prior to the first dose of study drug
- •Patients with a life expectancy of less than 3 months
- •Patients who are severely physically or mentally incapacitated and who in the opinion of investigator are unable to perform the subjects' tasks associated with the protocol
- •Female patients who are pregnant, lactating, or planning to become pregnant
- •Patients with diabetic ketoacidosis
- •Presence of any condition which, in the opinion of the investigator, places the patient at undue risk or potentially jeopardizes the quality of the data to be generated
- •Known hypersensitivity or previous anaphylaxis to ZS or to components thereof
- •Patients with cardiac arrhythmias that require immediate treatment
- •Patients on dialysis
- •Patients who are blood donors should not donate blood during the study and for 3 months following their last dose of ZS
研究组 & 干预措施
Sodium Zirconium Cyclosilicate (ZS) 5g
Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.
干预措施: Sodium Zirconium Cyclosilicate (ZS) 5g (Drug)
Sodium Zirconium Cyclosilicate (ZS) 10g
Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase.
干预措施: Sodium Zirconium Cyclosilicate (ZS) 10g (Drug)
Placebo
Suspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase.
干预措施: Placebo (Drug)
结局指标
主要结局
Least Square Mean S-K Level on Days 8-29
时间窗: Through 28-day randomized treatment study phase day 8-29.
Comparison between placebo and the active ZS treatment groups (each dose group will be sequentially compared with placebo, starting with the highest and ending with the lowest dose) with regard to the mean S-K level during the 28-day randomized treatment study phase Days 8-29. The results in the table below are presented for RTP.
次要结局
- Proportion of Patients Achieving Normokalemia(Through 48-hour initial phase.)
- Exponential Rate of Change in S-K Levels(Through 48-hour initial phase.)
- Absolute Change From Baseline in S-K Levels(Through 48-hour initial phase.)
- Percentage Change From Baseline in S-K Levels(Through 48-hour initial phase.)
- Proportion of Patients Remaining Normokalemic(Through 28-day randomized treatment study phase day 8-29.)
- Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit(Through 28-day randomized treatment phase.)
- Days Patients Remain Normokalemic(Through 28-day randomized treatment phase.)
- Mean Change in S-K Levels(Through 28-day randomized treatment phase.)
- Mean Percentage Change in S-K Levels(Through 28-day randomized treatment phase.)
- Number of Hyperkalemic Patients(Through 28-day randomized treatment phase.)
- Mean Changes in S-Aldosterone and P Renin Levels(Through 28-day randomized treatment phase.)
- Patient Reported Health State (EQ-5D) Questionnaire(Through study completion, an average of 37 days.)