AP301 Efficacy and Safety in Chinese Dialysis Patients With Hyperphosphatemia

Alebund Pharmaceuticals474 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

Conditions

ESRD (End Stage Renal Disease)Chronic Kidney Disease(CKD)Hyperphosphatemia Hyperphosphatemia in Chronic Kidney Disease Dialysis Chronic Kidney Disease, Receiving Dialysis

Interventions

AP301DRUG

Three times a day, administered orally with three meals at a daily dose level from 2.1g to 9.1g

Sevelamer carbonate (Renvela®)DRUG

Three times a day, administered orally with three meals at a daily dose level from 2.4g to 9.6g

AP301 Low DoseDRUG

Three times a day, administered orally with three meals at a daily dose level of 0.375g.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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: 1. Screening: 1.13 mmol/L (3.5 mg/dL) ≤ serum phosphate \< 2.58 mmol/L (8.0 mg/dL) 2. 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: 1. 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

Locations (50)

Outcomes

Primary Outcomes

Change in serum phosphorus levels between AP301 and AP301 low dose groups in hyperphosphatemic patients

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.

Time frame: From the end of Week 24 to the end of Week 27

Change in serum phosphorus levels between AP301 and sevelamer carbonate groups in hyperphosphatemic patients

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.

Time frame: From Baseline to the end of Week 12

Secondary Outcomes

The achievement rate of serum phosphorus in the target range 1.13-1.78 mmol/L (3.5-5.5 mg/dL) (both inclusive).

The serum phosphorus will be measured with a standard laboratory test.

Time frame: From Baseline to the end of Week 52.

Changes in serum calcium

The serum calcium in the blood will be measured with a standard laboratory test.

Time frame: From Baseline to the end of Week 52

Changes in serum calcium times phosphorus product

The serum calcium and phosphorus in the blood will be measured with standard laboratory tests.

Time frame: From Baseline to the end of Week 52

Changes in intact parathyroid hormone

The intact parathyroid hormone in the blood will be measured with a standard laboratory test.

Time frame: From Baseline to the end of Week 52

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Beijing Anzhen Hospital, Capital Medical University