AP301 Efficacy and Safety in Chinese Dialysis Patients With Hyperphosphatemia

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.

B) The starting dose of sevelamer carbonate will be one to two 800 mg capsules 3 times daily. The dosage is to be adjusted based on their serum phosphorus level every and safety assessments two or four weeks. The maximal dose is to be 12 capsules daily.

Then, a 2-week safety observation will be followed after the last dosing.

Key Inclusion Criteria:

• 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)

Key Exclusion Criteria:

• 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