A Phase 3 Multicenter Open-label Maintenance Study to Investigate the Long-term Safety of ZS (Sodium Zirconium Cyclosilicate) in Japanese Subjects With Hyperkalemia
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Number of Patients Who Experienced Adverse Events (AEs) in the MP
研究概览
简要总结
The Open-Label Maintenance Study contains an Correction Phase, in which subjects will be dosed with ZS 10 g three times daily (tid) for 24 to 72 hours, followed by a 12-month long-term Maintenance Phase.
详细描述
The study will start with the screening period, and all baseline parameters should be measured/collected up to 1 day prior to administration of first dose of study drug on Correction Phase Day 1. Subjects with 2 consecutive i-STAT potassium values ≥ 5.1 mmol/L will enter the Correction Phase and receive ZS 10 g TID for up to 72 hours, depending on potassium values. Once normokalemia (i-STAT potassium between 3.5 and 5.0 mmol/L, inclusive) is restored (whether after 24, 48 or 72 hours), subjects will be entered into the Maintenance Phase to be dosed with ZS at a starting dose of 5 g QD. Potassium (i-STAT and Central Laboratory) will be measured Days 1, 2, 5, 12, 19 and 26 throughout the first month of study and every 4 weeks thereafter until Day 362 (Visit 23) then patients will be required to complete the EOS visit which is 7±1 days after the last administration of study medication. For patients who do not enter the Maintenance Phase the last visit will be 7±1 day after the last treatment dose in the Correction Phase. The total expected study duration for an individual patient is approximately 53-54 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Supportive Care
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 130 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.
- •Patients aged ≥
- •For patients aged <20 years, a written informed consent should be obtained from the patient and his or her legally acceptable representative.
- •Two consecutive i-STAT potassium values, measured 60-minutes (± 15 minutes) apart, both ≥ 5.1 mmol/L and measured within 1 day before the first dose of ZS on Correction Phase Study Day
- •Patients who are on peritoneal dialysis (PD) can be enrolled if their SK level is ≥5.5 and ≤ 6.5 mmol/L in two consecutive i-STAT potassium evaluation at least 24 hours apart before Day 1 (in each evaluation, two i-STAT potassium measurements at least 1 hour apart are required). i-STAT potassium measurement should be performed in the morning before breakfast and in the evening before dinner in PD patients on continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD), respectively.
- •Women of childbearing potential must be using 2 forms of medically acceptable contraception (at least 1 barrier method) and have a negative pregnancy test within 1 day prior to the first dose of ZS on Correction Phase Study Day
- •Women who are surgically sterile or those who are postmenopausal for at least 1 year are not considered to be of childbearing potential.
排除标准
- •Patients treated with lactulose, rifaxan (rifaximin), or other non-absorbed antibiotics for hyperammonemia within 7 days prior to first dose of ZS.
- •Patients treated with resins (such as sevelamer hydrochloride, sodium polystyrene sulfonate [SPS; e.g. Kayexalate®] or calcium polystyrene sulfonate [CPS]), calcium acetate, calcium carbonate, or lanthanum carbonate, within 7 days prior to the first dose of study drug. Washout of SPS and CPS for 7 days (or longer) prior to the first dose of ZS is allowed, if termination of CPS or SPS is judged to be clinically acceptable by the investigator. Documented informed consent has to be obtained prior to the washout.
- •Patients with a life expectancy of less than 12 months
- •Female patients who are pregnant, lactating, or planning to become pregnant
- •Patients who have an active or history of diabetic ketoacidosis
- •Known hypersensitivity or previous anaphylaxis to ZS or to components thereof
- •Treatment with a drug or device within the last 30 days that has not received regulatory approval at the time of study entry.
- •Patients with cardiac arrhythmias that require immediate treatment
- •Hemodialysis patients (including those who are on both PD and hemodialysis [HD])
- •Patients who have been on PD less than 6 months or more than 6 months with a history of hypokalemia within 6 months before Correction Phase Day 1
- •Documented Glomerular Filtration Rate (GFR) < 15 mL/min within 90 days prior to study entry (Non peritoneal dialysis (PD) patients only)
- •If patients joined ZS study in the past, the patients cannot join this study within the last 30 days of the last study drug administration day.
研究组 & 干预措施
Sodium Zirconium Cyclosilicate
Correction Phase Dosing: Sodium Zirconium Cyclosilicate 10 g three times daily (TID) from 24 to 72 Extended Dosing: Sodium Zirconium Cyclosilicate 5 g once daily (QD). Sodium Zirconium Cyclosilicate dose increased or decreased in increments/decrements of 5 g QD up to a maximum of 15 g QD or a minimum of 5 g every other day (QOD) (or 2.5 g QD) based on i-STAT potassium measurements up to 12 months.
干预措施: Zirconium Cyclosilicate (Drug)
结局指标
主要结局
Number of Patients Who Experienced Adverse Events (AEs) in the MP
时间窗: First MP dose up to 1 day (2 days for QOD regimen) after last MP dose.
The number of patients who experienced any AE, including those which were serious (SAE), had an outcome of death, were severe, led to discontinuation of ZS or were causally related to ZS are presented for the MP. AEs of special interest are also presented, including oedema-related AEs, cardiac failure and hypertension.
次要结局
- Mean Change From CP Baseline in the Mean S-K Level Over Specified Time Periods in the MP(CP Day 1 to MP Day 362.)
- Mean Number of Normokalemic Days During the MP(MP Day 1 to Day 362.)
- Percentage of Patients Who Were Normokalemic in the MP(MP Day 1 to End of Study visit (up to 12 months).)
- Percentage of Patients Who Were Hypokalemic in the MP(MP Day 1 to End of Study visit (up to 12 months).)
- Mean Change From MP Baseline in the Mean S-K Level Over Specified Time Periods in the MP(MP Day 1 to Day 362.)
- Percentage of Patients With Average S-K Levels of ≤5.1 mmol/L and ≤5.5 mmol/L in the MP(MP Day 2 to Day 362.)
- Mean Change in S-K Level From Last On-treatment MP Visit to the End of Study(MP Day 1 to End of Study visit (up to 12 months).)
- Percentage of Patients Who Were Hyperkalemic in the MP(MP Day 1 to End of Study visit (up to 12 months).)
- Percentage of Patients With Normal S-Aldosterone Levels Over the MP(CP Day 1, MP Day 166 and MP Day 362.)
- Change From CP Baseline in S-Aldosterone Levels Over the MP(CP Day 1, MP Day 166 and MP Day 362.)
- Change From CP Baseline in S-Bicarbonate Levels Over the MP(CP Day 1, and MP Day 1 to End of Study visit (up to 12 months).)
- Baseline and Post-baseline 36-Item Short Form Health Survey Version 2 (SF-36 v2) Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores(CP Day 1 (baseline) and MP Day 362 (post-baseline).)
- Percentage of Patients Who Were Normokalemic in the CP(CP Day 1 to Day 3.)
- Percentage of Patients With Normal S-Bicarbonate Levels Over the MP(CP Day 1 and MP Day 1 to End of Study visit (up to 12 months).)
- Mean Change From CP Baseline in the Mean S-K Levels in the CP(CP Day 1 to Day 3.)
- Number of Patients Who Experienced AEs in the CP(Day 1 of CP to last CP dose + 1 day or first MP dose -1 day, earlier.)