To evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of HEC53856 capsules on anemia in subjects with chronic kidney disease on dialysis.
The purpose of this multicenter, open-label, dose-increasing, multiple-dose study was to evaluate the safety, tolerability,PK and preliminary efficacy of HEC53856 capsules in renal anemia subjects on dialysis. The study consists of two parts, hemodialysis or peritoneal dialysis . Within each part participants will be administrated for HEC53856. There are three study periods: Screening period :up to 2weeks; Treatment period: 6 weeks(except that 7 weeks in the 100mg cohort in the hemodialysis); Follow-up period: 2weeks.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
60
The 100mg dose cohort in the hemodialysis: D1 single oral administration of the investigation product 2.5h before hemodialysis; Three times a week for 6 weeks starting from D8, oral administration of the test drug 2.5h after hemodialysis. The rest dose cohorts in the hemodialysis: Three times a week for 6 weeks starting from D1, oral administration of the investigation product 2.5h after hemodialysis. The dose cohort in the peritoneal dialysis: Three times a week for 6 weeks starting from D1, oral administration of the investigation product after fasting.
The First Affiliated Hospital, Sun Yat-sen University
Guangzhou, Guangdong, China
Sichuan Provincial People's Hospital
Chengdu, China
The First Affiliated Hospital of Shantou University Medical College
Shantou, China
The First Hospital of China Medical University
Shenyang, China
Incidence of Adverse Events
To assess the safety and tolerability of therapy by incidence of treatment-emergent adverse events after multiple doses of HEC53856 capsule
Time frame: Up to 2 weeks after last dose
AUC0-t
Area under the concentration versus time curve (AUC) from time zero to the time of the last quantifiable concentration
Time frame: Up to 72 hours after single and multiple drug dosing
Cmax
Maximum observed plasma concentration
Time frame: Up to 72 hours after single and multiple drug dosing
Tmax
Time of the maximum observed plasma concentration
Time frame: Up to 72 hours after single and multiple drug dosing
T½
Apparent terminal elimination half-life
Time frame: Up to 72 hours after single and multiple drug dosing
Vz/F
Apparent volume of distribution
Time frame: Up to 72 hours after single and multiple drug dosing
Changes in mean hemoglobin
Changes in mean hemoglobin (Hb) relative to baseline during visit 8 and 9.
Time frame: Up to 2 weeks after the last dose
Hemoglobin response
Percentage of subjects who met the hemoglobin response after dosing
Time frame: Up to 2 weeks after the last dose
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General Hospital of Tianjin Medical University
Tianjin, China
Affiliated Hospital of Guangdong Medical University
Zhanjiang, China
The Fifth Affiliated Hospital Sun Yat-sen University
Zhuhai, China
E-AUC0-t
Area under the EPO concentration versus time curve (AUC) from time zero to the time of the last quantifiable concentration
Time frame: Up to 72 hours after single and multiple drug dosing
Emax
Maximum observed EPO concentration
Time frame: Up to 72 hours after single and multiple drug dosing
E-Tmax
Time of the maximum observed EPO concentration
Time frame: Up to 72 hours after single and multiple drug dosing
Serum lipid
Changes in Serum lipid relative to baseline at visit 8.
Time frame: week 6
Indicators of iron
Changes in the Indicators of iron relative to baseline at visit 8
Time frame: week 6
High-sensitivity C-reactive protein
Changes in the High-sensitivity C-reactive protein relative to baseline at visit 8.
Time frame: week 6
Reticulocytes
Changes in the mean Reticulocytes relative to baseline after doses.
Time frame: Up to week 8
VEGF
Changes in the VEGF relative to baseline after doses.
Time frame: week 6