Phase Ib Clinical Study to Assess the Safety, Tolerability and Pharmacokinetic Parameters of CN128 Tablets to Administration in Thalassemia Patients Aged 16 and Above
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Weight (Unit: kg)
研究概览
简要总结
- Primary objectives:
- To study the tolerance and safety of multiple oral administration of CN128 in patients with thalassemia aged 16 years and above.
- To study the pharmacokinetics of CN128 in thalassemia patients aged 16 and above by multiple oral administrations of CN128
- Design:
The study is designed as a safety, tolerability and pharmacokinetic parameters study, phase Ib trial.
The study is consisted of: multiple dose tolerance and safety study; multiple administration pharmacokinetics. 3. Subject inclusion criteria:
- Thalassemia patients with serum ferritin ≥ 500 µg/L
- Patients aged 16 and above
- HB≥80 g/L before administration
- Voluntarily participate in the experiment, and the process of obtaining informed consent met the requirements of GCP.
- Subject exclusion criteria:
- Hepatitis B surface antigen positive, hepatitis B core antibody positive and HBV-DNA positive, hepatitis C anti-HCV positive, HIV positive, Treponema pallidum positive
- History of active digestive tract diseases (including gastric ulcer, duodenal ulcer, gastroesophageal varices, ulcerative colitis, Crohn's disease, digestive tract tumors, familial genetic polyps), history of digestive tract perforation, history of digestive tract surgery and influence on drug absorption, and other investigators believe that patients with potential intestinal complications
- Liver dysfunction (ALT or AST > 2.5×ULN); or renal dysfunction (serum creatinine > 1.5×ULN)
- Uncontrolled active infections
- Patients currently taking CYP3A strong inducer or inhibitor drugs or drugs that may prolong the QT interval without temporary suspension of use or temporary substitution of the said drugs
- ect.
- Usage:
All subjects fasted prior to administration of study drug using 240 ml warm water. The people can not drink water within 1h before administration. 6. Pharmacokinetic assessment of CN128 administration:
PK parameters of CN128 include AUC 0-t, AUC 0-∞, Cmax, Tmax, t1/2, CL/F, Vd/ F, MRT, λz, Css-av, Css-min, Css-max, Accumulation rate, Fluctuation index, etc. 7. Safety and tolerability assessments:
Evaluation was based on the incidence rate of adverse events (AE) after the administration, study termination information, vital signs, physical examination, laboratory tests and ECG. 8. Statistics
详细描述
- Primary objectives:
- To study the tolerance and safety of multiple oral administration of CN128 in patients with thalassemia aged 16 years and above.
- To study the pharmacokinetics of CN128 in thalassemia patients aged 16 and above by multiple oral administrations of CN128
- Design:
The study is designed as a safety, tolerability and pharmacokinetic parameters study, phase Ib trial.
The study is consisted of:
• Multiple dose tolerance and safety study: The trial will start with the lower dose of CN128 given to 8 subjects (20 mg/kg body weight [bw], bid).The dose of second group is 15 mg/kg bw, bid (n=8).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 16 Years 至 60 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
First Dosage
The dose of CN128 is 20 mg/kg bw， bid.
干预措施: CN128 Tablets (Drug)
Second Dosage
The dose of CN128 is 15 mg/kg bw， bid.
干预措施: CN128 Tablets (Drug)
结局指标
主要结局
Weight (Unit: kg)
时间窗: Day 11
The patient's weight will be determined, and it's one kind of Physical examination.
Generally Phisical examination
时间窗: Day 11
The patient's skin, neck, eyes, ears, nose, throat, chest, back, lymph nodes, arms, legs, nervous system, etc. will be observed, and it's one kind of Physical examination.
Pulse (Unit: bpm)
时间窗: Day 1 to Day 11
The patient's pulse will be determined, and it's one kind of vital signs checks.
Respiration (Unit: bpm)
时间窗: Day 1 to Day 11
The patient's respiration will be determined, and it's one kind of vital signs checks.
Temperature (Unit: ℃)
时间窗: Day 1 to Day 11
The patient's temperature will be determined, and it's one kind of vital signs checks.
WBC (Unit: 10E9/L), RBC (Unit: 10E9/L), NEUT (Unit: 10E9/L), BASO (Unit: 10E9/L)
时间窗: Day 3, Day 7, Day 11
The patient's blood examination（WBC (Unit: 10E9/L), RBC (Unit: 10E9/L), NEUT (Unit: 10E9/L), BASO (Unit: 10E9/L), etc.）will be determined at Day 3, Day 7, Day 11 respectively, and it's one kind of laboratory test.
ALT (Unit: U/L), AST (Unit: U/L)
时间窗: Day 3, Day 7, Day 11
The patient's blood biochemical examination（ALT (Unit: U/L), AST (Unit: U/L), etc.）will be determined at Day 3, Day 7, Day 11 respectively，and it's one kind of laboratory test.
Electrocardiogram: P-R (Unit: ms), QRS (Unit: ms), QTc (Unit: ms), etc
时间窗: Day 1 to Day 11
The patient's electrocardiogram will be measured, and it's one kind of laboratory test.
Height (Unit: m)
时间窗: Day 11
The patient's height will be determined, and it's one kind of Physical examination.
Blood pressure (Unit: mmHg)
时间窗: Day 1 to Day 11
Both patient's systolic and diastolic blood pressure will be measured, and it's one kind of vital signs checks.
Urine appearance
时间窗: Day 3, Day 7, Day 11
The appearance of urine will be observed at Day 3, Day 7, Day 11 respectively，and it's one kind of laboratory test.
Css-av of CN128
时间窗: Day 1, Day 2, Day 3, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11
Pharmacokinetics parameters
Tmax of CN128
时间窗: Day 1, Day 2, Day 3, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11
Pharmacokinetics parameters
CL/F of CN128
时间窗: Day 1, Day 2, Day 3, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11
Pharmacokinetics parameters
Fibrinogen (Unit: g/L), Prothrombin time (Unit: s), APTT (Unit: s)
时间窗: Day 11
The patient's blood coagulation function ( fibrinogen (Unit: g/L), prothrombin time (Unit: s), APTT (Unit: s) , etc.) will be determined at Day 11, and it's one kind of laboratory test.
Serum iron (Unit: umol/L)
时间窗: Day 11
The patient's serum iron will be determined at Day 11, and it's one kind of laboratory test.
AUC0-t of CN128
时间窗: Day 1, Day 2, Day 3, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11
Pharmacokinetics parameters
AUC0-∞ of CN128
时间窗: Day 1, Day 2, Day 3, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11
Pharmacokinetics parameters
Urine colour
时间窗: Day 3, Day 7, Day 11
The colour of urine will be observed at Day 3, Day 7, Day 11 respectively，and it's one kind of laboratory test.
Urine glucose (Unit: mmol/L)
时间窗: Day 3, Day 7, Day 11
The glucose of urine will be determined at Day 3, Day 7, Day 11 respectively，and it's one kind of laboratory test.
Urine protein (Unit: g/L)
时间窗: Day 3, Day 7, Day 11
The protein of urine will be determined at Day 3, Day 7, Day 11 respectively，and it's one kind of laboratory test.
λz of CN128
时间窗: Day 1, Day 2, Day 3, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11
Pharmacokinetics parameters
Number of subjects with adverse events
时间窗: Day 1 to Day 11
It's the number of subjects with adverse events after administration.
Cmax of CN128
时间窗: Day 1, Day 2, Day 3, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11
Pharmacokinetics parameters
Vd/F of CN128
时间窗: Day 1, Day 2, Day 3, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11
Pharmacokinetics parameters
MRT of CN128
时间窗: Day 1, Day 2, Day 3, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11
Pharmacokinetics parameters
t1/2 of CN128
时间窗: Day 1, Day 2, Day 3, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11
Pharmacokinetics parameters
Css-min of CN128
时间窗: Day 1, Day 2, Day 3, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11
Pharmacokinetics parameters
Css-max of CN128
时间窗: Day 1, Day 2, Day 3, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11
Pharmacokinetics parameters
Accumulation rate of CN128
时间窗: Day 1, Day 2, Day 3, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11
Pharmacokinetics parameters
Fluctuation index of CN128
时间窗: Day 1, Day 2, Day 3, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11
Pharmacokinetics parameters
次要结局
未报告次要终点