Chronic Kidney Disease(CKD), Chronic Kidney Disease, Receiving Dialysis, Dialysis, ESRD (End Stage Renal Disease), Hyperphosphatemia, Hyperphosphatemia in Chronic Kidney Disease
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGAP301
Three times a day, administered orally with three meals at a daily dose level from 2.1g to 9.1g
Three times a day, administered orally with three meals at a daily dose level from 2.4g to 9.6g
DRUGAP301 Low Dose
Three times a day, administered orally with three meals at a daily dose level of 0.375g.
Sponsors
Alebund Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in serum phosphorus levels between AP301 and AP301 low dose groups in hyperphosphatemic patients | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in serum calcium | From Baseline to the end of Week 52 | The serum calcium in the blood will be measured with a standard laboratory test. |
| Changes in serum calcium times phosphorus product | From Baseline to the end of Week 52 | The serum calcium and phosphorus in the blood will be measured with standard laboratory tests. |
| Changes in intact parathyroid hormone | From Baseline to the end of Week 52 | The intact parathyroid hormone in the blood will be measured with a standard laboratory test. |
| Changes in serum bone-specific alkaline phosphatase | From Baseline to the end of Week 52 | The serum bone-specific alkaline phosphatase in the blood will be measured with standard laboratory tests. |
| 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 | The serum iron parameters will be measured with standard laboratory tests. |
| Change in QT intervals measured by 12-lead electrocardiogram test over time | From Baseline to the end of Week 52 | The duration of QT intervals will be measured with a standard 12-lead electrocardiogram test. |
| Number of participants with abnormal vital signs | From Baseline to the end of Week 52 | The vital sign will consist of pulse rate and blood pressure with standard measurements. |
| Number of participants with abnormal laboratory tests results | From Baseline to the end of Week 52 | The laboratory tests will be measured with standard validated methods, involving hematology, biochemistry, bone markers, iron parameters and others. |
| Changes in osteocalcin | From Baseline to the end of Week 52 | The serum osteocalcin in the blood will be measured with a standard laboratory test. |
| 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. | The serum phosphorus will be measured with a standard laboratory test. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Changes in average serum phosphorus levels | From the end of Week 48 to the end of Week 52 | The serum phosphorus will be measured with a standard laboratory test. |
| Number of adverse events | From the end of Week 48 to the end of Week 52 | — |
Countries
China
Outcome results
None listed