A Randomized, Open-Label, Multi-Center, Phase 3 Study to Evaluate the Efficacy and Safety of AP301 on Serum Phosphorus Control in Chronic Kidney Disease Patients Receiving Maintenance Dialysis With Hyperphosphatemia
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 474
- 试验地点
- 50
- 主要终点
- Change in serum phosphorus levels between AP301 and AP301 low dose groups in hyperphosphatemic patients
研究概览
简要总结
This Phase 3 clinical trial is the pivotal study of AP301 aiming to evaluate the efficacy and safety of AP301 for controlling serum phosphorus in chronic kidney disease receiving hemodialysis and peritoneal dialysis in Chinese patients with hyperphosphatemia.
详细描述
This study has two primary efficacy objectives. The primary efficacy objective 1 is to evaluate the superiority of maintenance dose versus low dose of AP301 on serum P control in dialysis patients with hyperphosphatemia. The primary efficacy objective 2 is to evaluate the non-inferiority of AP301 versus sevelamer carbonate on serum phosphorus control. Besides these two primary efficacy objectives, this study will also evaluate the serum phosphorus control equivalence and the safety for AP301 produced from two APIs (Active Pharmaceutical Ingredient) in the last 8 weeks of drug exposure.
Patients will start dosed after eligibility confirmation. The treatment period will last 52 weeks in total, including:
A) A 24-week sevelamer carbonate active control phase in which serum phosphorus level at the end of Week 12 will be measured for the analysis of primary efficacy endpoint 2, B) A 3-week AP301 low dose control phase in which serum phosphorus level at the end of Week 27 will be measured for the analysis of primary efficacy endpoint 1, and C) A 25 or 28-week extension treatment phase
The investigational treatments will be AP301. Sevelamer carbonate will be provided as active control in active control and extension treatment phase and AP301 125 mg as ineffective control in low dose control phase.
A) The starting dose of AP301 is one 700 mg capsule 3 times daily. The dosage is to be adjusted based on their serum phosphorus level and safety assessmentsevery two or four weeks. The maximal dose is to be 10 capsules daily.
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
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provision of signed and dated ICF
- •Adult when signing the ICF
- •Patients on dialysis for ≥ 3 months before signing the ICF and throughout the study
- •For HD patients, spKt/V ≥ 1.2; for PD patients, total Kt/V ≥ 1.7/week
- •For patients who receive phosphate binders and their serum phosphate level is:
- •Screening: 1.13 mmol/L (3.5 mg/dL) ≤ serum phosphate < 2.58 mmol/L (8.0 mg/dL)
- •After washout: 1.94 mmol/L (6.0 mg/dL) ≤ serum phosphate < 3.23 mmol/L (10.0 mg/dL)
- •For patients who do not receive phosphate binders over 2 weeks and their serum phosphate level is:
- •Screening: 1.94 mmol/L (6.0 mg/dL) ≤ serum phosphate < 3.23 mmol/L (10.0 mg/dL)
排除标准
- •History or plan of kidney transplantation
- •History or plan of parathyroid intervention 6 months before signing the ICF
- •Serum calcium < 1.9 mmol/L (7.6 mg/dL) or > 2.75 mmol/L (11 mg/dL) at screening
- •Serum intact parathyroid hormone > 110 pmol/L (1000 pg/mL) at screening
- •Presence of clinically significant gastrointestinal (GI) disorder
- •History of gastrectomy or duodenectomy, or GI surgery within 3 months before signing the ICF
- •Known allergic to any ingredient of AP301 or Sevelamer Carbonate, or known history of severe allergies leading to emergency medical care
- •Female who are breastfeeding
研究组 & 干预措施
AP301
A blood phosphate-lowering medication containing iron
干预措施: AP301 (Drug)
Sevelamer Carbonate
A marketed blood phosphate-lowering medication
干预措施: Sevelamer carbonate (Renvela®) (Drug)
AP301 Low Dose
A blood phosphate-lowering medication containing iron, but with a low dose considered as ineffective
干预措施: AP301 Low Dose (Drug)
结局指标
主要结局
Change in serum phosphorus levels between AP301 and AP301 low dose groups in hyperphosphatemic patients
时间窗: From the end of Week 24 to the end of Week 27
The serum phosphorus will be measured with a standard laboratory test. The change in serum phosphorus levels will be compared between the group receiving AP301 and the group receiving AP301 low dose.
Change in serum phosphorus levels between AP301 and sevelamer carbonate groups in hyperphosphatemic patients
时间窗: From Baseline to the end of Week 12
The serum phosphorus will be measured with a standard laboratory test. The change in serum phosphorus levels will be compared between the group receiving AP301 and the group receiving sevelamer carbonate.
次要结局
- The achievement rate of serum phosphorus in the target range 1.13-1.78 mmol/L (3.5-5.5 mg/dL) (both inclusive).(From Baseline to the end of Week 52.)
- Changes in serum calcium(From Baseline to the end of Week 52)
- Changes in serum calcium times phosphorus product(From Baseline to the end of Week 52)
- Changes in intact parathyroid hormone(From Baseline to the end of Week 52)
- Changes in serum bone-specific alkaline phosphatase(From Baseline to the end of Week 52)
- Changes in osteocalcin(From Baseline to the end of Week 52)
- Number of adverse events(From Baseline to Follow-up (up to 54 weeks))
- Changes in serum iron parameters(From Baseline to the end of Week 52)
- Change in QT intervals measured by 12-lead electrocardiogram test over time(From Baseline to the end of Week 52)
- Number of participants with abnormal vital signs(From Baseline to the end of Week 52)
- Number of participants with abnormal laboratory tests results(From Baseline to the end of Week 52)