A Phase 3 Multicenter, Prospective, Randomized, Double-blind, Placebo-controlled Study to Investigate the Safety and Efficacy of ZS (Sodium Zirconium Cyclosilicate), in Patients With Hyperkalemia-HARMONIZE Asia
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 270
- 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 24 or 48 hours of initial ZS therapy (10g TID).
详细描述
This study will be conducted in approximately 35 centers in China. Before patients are randomized to the double-blind phase, they will receive open-label ZS for 24 or 48 hours during the initial phase. It is expected that approximately 490 patients will need to be enrolled, to have approximately 280 patients entered into the open-label initial phase resulting in 250 patients being randomized in the 28-day treatment study phase. Enrolment will be stopped when 250 patients have been initiated with the 28-day randomized treatment study phase.
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 (pre-screening consent) prior to any study specific procedures
- •Female and male patients aged ≥18 and ≤ 90 years
- •Provision of informed consent prior to any study specific procedures
- •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 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 (from the time they sign consent) and for 3 months after the last dose of ZS/matching placebo to prevent pregnancy. In addition, oral contraceptives, approved contraceptive implant, long-term injectable contraception, intrauterine device, or tubal ligation are allowed. Oral contraception alone is not acceptable; additional barrier methods in conjunction with spermicide must be used
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
- •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
- •Pseudohyperkalemia signs and symptoms, such as hemolyzed blood specimen due to excessive fist clenching to make veins prominent, difficult or traumatic venepuncture, or history of severe leukocytosis or thrombocytosis
- •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
- •Known hypersensitivity or previous anaphylaxis to ZS or to components thereof
- •Patients with cardiac arrhythmias that require immediate treatment
- •History of QT prolongation associated with other medications that required discontinuation of that medication.
- •Congenital long QT syndrome
- •Symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Subjects with atrial fibrillation controlled by medication are permitted
- •QTc(f) > 550 msec
- •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
- •Patients who need hospitalization after taking blood samples on day 1 of the open-label initial phase
研究组 & 干预措施
Sodium Zirconium Cyclosilicate 10g
Suspension administered 10g orally once daily for 28 days after the open label initial phase.
干预措施: Sodium Zirconium Cyclosilicate 10g (Drug)
Sodium Zirconium Cyclosilicate 5g
Suspension administered 5g orally once daily for 28 days after the open label initial phase.
干预措施: Sodium Zirconium Cyclosilicate 5g (Drug)
Matching Placebo
Suspension administered orally placebo once daily for 28 days after the 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: Days 8 to 29 (Randomized treatment study phase) used for model-based least squares mean computation
Comparison between placebo and each SZC treatment group (high to low) with regard to the mean S-K level during the randomized treatment phase days 8-29. Mixed-effects models were used to estimate least-squares means.
次要结局
- Percentage of Patients Who Achieve Normokalemia(Through open label initial phase)
- Exponential Rate of Change in S-K Levels(Through 24 hours post-dose in the initial phase)
- Proportion of Patients Who Remain Normokalemic During RTP(Through 28-day randomized treatment study phase day 8-29)
- Proportion of Normokalemic Patients at the End of RTP(The end of 28-day randomized treatment study phase)
- Absolute Change From Baseline in S-K Levels(Through open label initial phase)
- Days Patients Remain Normokalemic(Through days 8-29 of the randomized treatment phase.)
- Mean Change in S-K Levels(Through 28-day randomized treatment phase.)
- Percentage Change From Baseline in S-K Levels(Through open label initial phase)
- Mean Percent Change in S-K Levels(Through 28-day randomized treatment phase.)
- Least Square Mean Changes in S-Aldo and P-Renin Levels(Through 28 day randomized treatment study phase day 15-29)
- Hyperkalaemia at Day 29(Day 29)
- Percentage of Patients Without Hyperkalemia(Day 29 of randomized treatment phase)