A Phase 1, Single and Multiple Dosing Study to Evaluate Pharmacokinetics and Pharmacodynamics of ASP3325 in Patients With Chronic Kidney Disease and Hyperphosphatemia Undergoing Hemodialysis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 5
- 主要终点
- Safety assessed by vital signs: Part 2
研究概览
简要总结
The objective of this study is to assess PK, safety and tolerability of a single oral dose of ASP3325 and to assess PD, PK and safety of repeated oral doses of ASP3325 administered t.i.d. before or just after each meal
详细描述
[Part 1] This part is an open-label, uncontrolled study to evaluate PK and safety with single dosing of ASP3325 in hemodialysis patients. After washout period of therapeutic medication for hyperphosphatemia, six subjects will receive single oral administration of ASP3325 (Tablet A) on a non-dialysis day (Day 1).
[Part 2] This part is a 2-arm, open-label, uncontrolled study to evaluate PD, PK and safety with dosing ASP3325 Tablet B t.i.d. before or just after each meal.
Eligible subjects at screening will be entered into the washout period for stopping their phosphate-binding treatment. 20 subjects with serum inorganic phosphorus (Pi) level between ≥6.0 and <10.0 mg/dL during the washout period (washout period week 1 or washout period week 2) will be randomized to each treatment group and ASP3325 will be administered for 2 weeks until Day 14.
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
- 20 Years 至 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject who has received maintenance hemodialysis 3 times a week for at least 12 weeks (84 days) prior to the scheduled first day of the washout period.
- •Subject who can receive morning dialysis from the start of the washout period to the end of follow-up period. (Part 2)
- •Subject with pre-dialysis serum Pi level between ≥6.0 and <10.0 mg/dL and be confirmed increase in serum Pi of ≥1.5 mg/dL after the maximum dialysis interval at the washout period week 1 or
- •Subject who did not change the type or dose of any phosphate binder(s), any nutritional supplements or any other drugs with phosphorus reducing action for at least 4 weeks (28 days) prior to the scheduled first day of the washout period.
- •Subject who did not receive calcimimetics (e.g., cinacalcet HCl) for at least 12 weeks (84 days) prior to the scheduled first day of the washout period.
- •Subject taking native or active vitamin D (including vitamin D analogues), calcitonin agents or PTH agents must be on stable dose for at least 4 weeks (28 days) prior to the scheduled first day of the washout period.
排除标准
- •Subject who has a history of severe gastrointestinal disorder, major gastrointestinal surgery, malabsorption considered influential on the absorption of the drug and nutrition in the gastrointestinal tract.
- •Subject who has a history of parathyroid intervention (e.g., parathyroidectomy [PTx], percutaneous ethanol injection therapy [PEIT]).
- •Subject whose dry weight loss >5% within 12 weeks (84 days) prior to the scheduled start day of the washout period.
- •Confirmed serum intact PTH >1000 pg/mL at the start of the washout period (only applicable for Part 2).
- •Subject whose last 3 measurement values at the separate day of pre-dialysis systolic/diastolic blood pressure before the scheduled start day of the washout period or during the washout period are all 180 mmHg or higher and 120 mmHg or higher.
- •Subject who has severe congestive heart failure (i.e., NYHA cardiac function classification Class III or severer).
- •Subject who experienced a myocardial infarction or major surgery excluding vascular access surgery within 12 weeks (84 days) prior to the informed consent signing.
- •Subject who has any of liver function tests (ALT, AST, T-Bil) out of range as indicated below at the screening (Part 1) or during the washout period, or patients with a complication of serious hepatic disease (e.g., acute and active chronic hepatitis, liver cirrhosis). AST: >2×ULN, ALT: >2×ULN, T-Bil: >1.25×ULN
- •Subject with history or complication of malignant tumor (considered eligible if recurrence has not been observed for at least 5 years).
- •Subject with history of serious drug hypersensitivity, such as anaphylactic shock.
研究组 & 干预措施
Part1, ASP3325 Tablet A
ASP3325 tablets A will be orally administered with 150 mL of water in fasting condition on non-dialysis day in Day 1
干预措施: ASP3325 (Drug)
Part2, ASP3325 Tablet B group 1
ASP3325 tablets B will be orally administered t.i.d. 30 minutes before each meal for 2 weeks
干预措施: ASP3325 (Drug)
Part2, ASP3325 Tablet B group 2
ASP3325 tablets B will be orally administered t.i.d. 30 minutes just after each meal for 2 weeks
干预措施: ASP3325 (Drug)
结局指标
主要结局
Safety assessed by vital signs: Part 2
时间窗: Up to Day 22
Vital signs include body temperature, blood pressure and pulse rate)
Safety assessed by 12-Lead ECG: Part 1
时间窗: Up to Day 7
ECG: electrocardiogram
Safety assessed by adverse events: Part 2
时间窗: Up to Day 22
Safety assessed by clinical laboratory test: Part 1
时间窗: Up to Day 7
Clinical laboratory tests include hematology and biochemistry
Safety assessed by adverse events: Part 1
时间窗: Up to Day 7
Safety assessed by vital signs: Part 1
时间窗: Up to Day 7
Vital signs include body temperature, blood pressure and pulse rate)
Safety assessed by clinical laboratory test: Part 2
时间窗: Up to Day 22
Clinical laboratory tests include hematology and biochemistry
Safety assessed by 12-Lead ECG: Part 2
时间窗: Up to Day 22
ECG: electrocardiogram
次要结局
- AUClast of ASP3325(Part 1 Before administration, Day 1, 2, 4, 5 and 7)
- Serum Calcium (adjusted for albumin)(Part 2 Day -21, -14, and -7 in washout period, Day 1, 8, 15 and 22)
- Cmax of unchanged ASP3325(Part 1 Before administration, Day 1, 2, 4, 5 and 7)
- t1/2 of ASP3325(Part 1 Before administration, Day 1, 2, 4, 5 and 7)
- Serum concentration of intact PTH before dialysis(Part 2 Day -21 in washout period, Day 1, 8, 15 and 22)
- tmax of unchanged ASP3325(Part 1 Before administration, Day 1, 2, 4, 5 and 7)
- AUCinf of ASP3325(Part 1 Before administration, Day 1, 2, 4, 5 and 7)
- Vz/F of ASP3325(Part 1 Before administration, Day 1, 2, 4, 5 and 7)
- CL/F of ASP3325(Part 1 Before administration, Day 1, 2, 4, 5 and 7)
- Ctrough of ASP3325(Part 2 Before administration, Day 3, 5, 8, 10, 12, 15 and 22)
- Serum Pi of ASP3325(Part 2 Day -21, -14, and -7 in washout period, Day 1, 8, 15 and 22)
- Serum concentration of FGF23(Part 2 Day -21 in washout period, Day 1, 8, 15 and 22)