A Phase 3b, Multicentre, Prospective, Randomized, Double-Blind, Placebo-Controlled Study to Reduce Incidence of Pre-Dialysis Hyperkalaemia With Sodium Zirconium Cyclosilicate in Chinese Subjects
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 134
- 试验地点
- 1
- 主要终点
- Percentage of Responders
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of Sodium Zirconium Cyclosilicate (SZC), as well as the appropriateness of the dosing mechanism, in Chinese end-stage renal disease (ESRD) patients on chronic haemodialysis.
详细描述
This is a randomized, double-blind, placebo-controlled study to determine the safety and efficacy of SZC in ESRD subjects with hyperkalaemia and on stable haemodialysis. This study consists of a screening period, an 8-week randomized treatment period, and a follow-up period. Approximately 134 stable haemodialysis subjects with persistent pre-dialysis hyperkalaemia will be enrolled in the study across research sites in China.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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 signed and dated, written informed consent form prior to any mandatory study specific procedures, sampling, and analyses.
- •Subject must be ≥ 18 years of age inclusive, at the time of signing the informed consent form.
- •Subjects must have haemodialysis access consisting of an arteriovenous fistula, AV graft, or tunnelled (permanent) catheter which is expected to remain in place for the entire duration of the study.
- •Receiving haemodialysis (or hemodiafiltration) 3 times a week for treatment of end-stage renal disease (ESRD) for at least 3 months before randomization.
- •Pre-dialysis S-K > 5.4 mmol/L after long inter-dialytic interval and > 5.0 mmol/L after at least one short inter-dialytic interval during screening (as assessed by central lab).
- •Prescribed dialysate K concentration ≤ 3 mmol/L during screening.
- •Sustained Qb ≥ 200 ml/min and spKt/V ≥ 1.2 (or URR ≥ 63) on stable haemodialysis / haemodiafltration prescription during screening with prescription (time, dialyzer, blood flow [Qb], dialysate flow rate [Qd] and bicarbonate concentration) expected to remain unchanged during study.
- •Subjects must be receiving dietary counselling appropriate for ESRD subjects treated with haemodialysis / haemodiafiltration as per local guidelines, which includes dietary potassium restriction.
排除标准
- •Myocardial infarction, acute coronary syndrome, stroke, seizure or a thrombotic / thromboembolic event (e.g., deep vein thrombosis or pulmonary embolism, but excluding vascular access thrombosis) within 12 weeks prior to randomization.
- •Pseudohyperkalaemia secondary to haemolyzed blood specimen (this situation is not considered screening failure, sampling or full screening can be postponed to a later time as applicable).
- •Diagnosis of rhabdomyolysis during the 4 weeks preceding randomization.
- •Presence of cardiac arrhythmias or conduction defects that require immediate treatment.
- •Any medical condition, including active, clinically significant infection or liver disease, that in the opinion of the investigator or Sponsor may pose a safety risk to a subject in this study, which may confound safety or efficacy assessment and jeopardize the quality of the data, or may interfere with study participation.
- •History of QT prolongation associated with other medications that required discontinuation of that medication; congenital long QT syndrome or QTc(f) > 550 msec; uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Subjects with atrial fibrillation controlled by medication or with transient atrial fibrillation associated with dialysis or peridialytic period are permitted.
- •Subjects treated with sodium polystyrene sulfonate (e.g. SPS, Kayexalate, Resonium), calcium polystyrene sulfonate (CPS, Resonium calcium) or patiromer (Veltassa) within 7 days before screening or anticipated in requiring any of these agents during the study.
- •Participation in another clinical study with an investigational product administered in the last 1 month before screening.
- •Haemoglobin < 9 g/dL on screening (as assessed on Visit 1).
- •Laboratory diagnosis of hypokalaemia (K < 3.5 mmol/L), hypocalcemia (Ca < 8.2 mg/d or albumin-corrected Ca < 8.0 mg/dL if the latter is used in local practice), hypomagnesemia (Mg < 1.7 mg/dL) or severe acidosis (serum bicarbonate 16 mEq/L or less) in the 4 weeks preceding randomization.
- •Severe leukocytosis (> 20 × 109/L) or thrombocytosis (≥ 450 × 109/L) during screening.
- •Polycythaemia (Hb > 14 g/dL) during screening.
- •Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
- •Judgment by the investigator that the subject should not participate in the study if the subject is unlikely to comply with study procedures, restrictions and requirements.
- •Previous randomisation in the present study.
- •For women only - currently pregnant (confirmed with positive pregnancy test or uterine ultrasound if pregnancy test is questionable) or breast-feeding.
- •Females of childbearing potential, unless using contraception as detailed in the protocol or sexual abstinence.
- •Lack of compliance with haemodialysis prescription (both number and duration of treatments) during the two-week period preceding screening (100% compliance required).
- •Subjects unable to take investigational product drug mix.
- •Scheduled date for living donor kidney transplant.
- •Subjects with a life expectancy of less than 6 months.
- •Known hypersensitivity or previous anaphylaxis to SZC or to components thereof.
- •History of alcohol or drug abuse within 2 years prior to randomization.
研究组 & 干预措施
Sodium Zirconium Cyclosilicate (SZC)
Suspension administered orally for a treatment period of eight weeks (4 weeks of dose adjustment, 4 weeks in stable dose) Single dose contains from 1 to 3 sachets of SZC 5g depending on dose level assigned to a patient per non-dialysis days.
干预措施: Sodium Zirconium Cyclosilicate (Drug)
Placebo
Suspension administered orally for a treatment period of eight weeks (4 weeks of dose adjustment, 4 weeks in stable dose) Single dose contains from 1 to 3 sachets of Placebo depending on dose level assigned to a patient per non-dialysis days.
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Responders
时间窗: Evaluation period runs over the last 4 weeks of the treatment period up to 8 weeks.
A subject was considered to be a responder if, during the evaluation period, they maintained a pre-dialysis serum potassium (S-K) between 4.0 and 5.0 mmol/L on at least 3 out of 4 dialysis treatments following the long inter-dialytic interval (LIDI) and did not receive rescue therapy. Subjects with no data during the evaluation period were classified as non-responders. The S-K levels used for this analysis were based on the measurements obtained by the central laboratory.
次要结局
- Maximum Pre-dialysis S-K Values After SIDI and LIDI Below or Equal to 5.5 mmol/L During Evaluation Period(Evaluation period runs over the last 4 weeks of the treatment period up to 8 weeks.)
- Pre-dialysis S-K After LIDI Between 3.5 and 5.5 mmol/L During the Evaluation Period(Evaluation period runs over the last 4 weeks of the treatment period up to 8 weeks.)
- Instances of Pre-dialysis S-K After LIDI Between 4.0 and 5.0 mmol/L During the Evaluation Period(Evaluation period runs over the last 4 weeks of the treatment period up to 8 weeks.)
- Expected Number of Normokalaemic (S-K 4.0-5.0 mmol/L) Instances(Evaluation period runs over the last 4 weeks of the treatment period up to 8 weeks.)
- Instances of Potassium Gradient of < 3.0 mmol/L After LIDI During the Evaluation Period(Evaluation period runs over the last 4 weeks of the treatment period up to 8 weeks.)