A Phase 2b, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety, Tolerability, and Serum Phosphate Lowering Effect of Fixed Dose AP306 in Participants With Hyperphosphatemia Receiving Maintenance Hemodialysis
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 168
- 试验地点
- 38
- 主要终点
- To evaluate the efficacy of AP306 assessed by serum phosphate lowering
研究概览
简要总结
This study is being conducted to characterize the safety, tolerability, and efficacy of AP306 at fixed doses in adults with hyperphosphatemia receiving maintenance hemodialysis.
详细描述
Hyperphosphatemia, one of the most common complications of advanced chronic kidney disease, becomes increasingly prevalent as kidney function declines and is found almost universally in patients with end-stage kidney disease requiring dialysis. Hyperphosphatemia is an independent risk factor for cardiovascular outcomes, fractures, and mortality in patients with chronic kidney disease, especially in patients receiving dialysis.
AP306 is a pan-phosphate transporter inhibitor that may stop phosphate absorption in the gut, controlling hyperphosphatemia.
This is a randomized, double-blind, placebo-controlled, study to characterize the safety, tolerability, and efficacy of AP306 given daily for 8 weeks at fixed doses in adults with hyperphosphatemia receiving maintenance hemodialysis.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Important Inclusion Criteria:
- •Signs a written informed consent form (ICF) and is willing to comply with all study requirements in the study
- •Receiving a stable hemodialysis (including hemodialysis, hemodiafiltration, and hemoadsorption) regimen, which is defined as a frequency of three times per week for at least 12 weeks before signing the ICF, and does not plan to change in the study
- •Who has a blood phosphate level within the study-required range
- •Who has a dialysis adequacy, assessed by single pooled Kt/V (SpKt/V, estimated with blood urea) ≥1.20, at screening or any documented value ≥1.20 within 12 weeks prior to signing the ICF
- •If the participant is receiving etelcalcetide, their doses must be unchanged for at least 4 weeks prior to signing the ICF
- •If the participant is receiving any of the following therapies, their doses are stable for at least 14 days prior to signing the ICF: phosphate-lowering products other than tenapanor or phosphate binders, active vitamin D and analogs, cinacalcet, calcitonin, and P-glycoprotein inhibitors
- •Agreement to use highly effective contraception for women of childbearing potentially and non-sterile sexually active males throughout the study and for 90 days after the final dose of study drug
排除标准
- •Pregnant or breastfeeding
- •Scheduled for a living donor kidney transplant in the next 6 months, planned change to peritoneal dialysis or home hemodialysis in the study; planned relocation to another dialysis center in the study
- •Any history of a non-pharmacological parathyroid intervention within 6 months prior to the ICF sign off, or planned parathyroid intervention in the study
- •Blood calcium or blood intact parathyroid hormone abnormality
- •Adequate organ and bone marrow function
- •Acute hepatitis or significant chronic liver disease
- •Any clinically significant GI disorders within 4 weeks prior to signing the ICF; or any history of gastrectomy; or any GI tract surgery (excluding appendectomy and polypectomy), within 12 weeks of signing the ICF
- •Uncontrolled hypertension
- •Hospitalization for cardiac or cardiocerebrovascular disease within 24 weeks prior to signing the ICF
- •Significant abnormalities of QT interval and heart rhythm on an electrocardiograph (ECG) test
- •Any clinically significant active infection or infestation or any treatment with systemic antimicrobial treatment within 2 weeks prior to signing the ICF
- •History or presence of malignancy within 3 years prior to signing the ICF, except basal cell skin cancer, in-situ carcinoma of the cervix, and in-situ prostate cancer
- •Taking moderate or strong cytochrome P450 (CYP) 3A inhibitors within 2 weeks or 5 half-lives, whichever is longer, prior to signing the ICF (topical use is allowed)
- •Treatment with any investigational medication or medical device within 30 days prior to signing the ICF
- •Life expectancy less than 12 months
研究组 & 干预措施
Cohort 7
干预措施: Placebo (Drug)
Cohort 2
干预措施: AP306 125 mg BID (Drug)
Cohort 3
干预措施: AP306 150 mg BID (Drug)
Cohort 1
干预措施: AP306 75 mg BID (Drug)
Cohort 5
干预措施: AP306 100 mg TID (Drug)
Cohort 4
干预措施: AP306 75 mg TID (Drug)
Cohort 6
干预措施: AP306 125 mg TID (Drug)
结局指标
主要结局
To evaluate the efficacy of AP306 assessed by serum phosphate lowering
时间窗: 12 weeks
The change in serum phosphate from the baseline to the end of treatment or before the initiation of rescue therapy
To investigate the ability of AP306 at different fixed doses to lower serum phosphate in participants with hyperphosphatemia receiving maintenance hemodialysis
时间窗: 8 weeks
The change in serum phosphate from baseline to the end of treatment or before the initiation of rescue therapy, or before the interruption of study drug due to serum phosphate \<2.5 mg/dL (0.81 mmol/L)
次要结局
- To assess the proportion of participants with serum phosphate in the target range(8 weeks)
- To assess the change in serum phosphate from baseline to the end of the Treatment Period(8 weeks)
- To assess the time to response on serum phosphate reduction(8 weeks)