Chronic Kidney Disease
Conditions
Keywords
Dialysis, CKD
Brief summary
To evaluate the safety, pharmacokinetics, and pharmacodynamics in nondialysis (ND) and hemodialysis (HD) subjects with Chronic Kidney Disease (CKD) who receive a single administration of TS-143.
Interventions
DRUGTS-143
Sponsors
Taisho Pharmaceutical Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
* Serum concentration of erythropoietin (EPO): \<50 mIU/mL at screening test 1, 2, or 3 * Transferrin saturation ≥ 20% or ferritin ≥ 100 ng/mL at screening test 1 * Subjects meeting any of the following criteria 1. Subjects who has not used erythropoiesis-stimulating agent (ESA) ≥ eight weeks from screening test 1 2. Subjects who has used ESA, other than epoetin beta pegol, ≥ four weeks from screening test 1 and has met all of the following criteria A) to C). A)The total ESA dosage for each week could be changed within a range of 50%, compared to the total ESA dosage for one week before screening test 1, for four weeks before screening test 1 B)Acceptable to discontinue ESA the day following screening test 1 to Follow-up 2 C)The fluctuating range of Hb concentration between screening tests 1 and 2 is within ±0.5 g/dL per week (the same criteria applied between screening test 2 and 3) * Subjects who receive an explanation about the study before participating in the study and can understand the contents and are willing and able to provide written consent. \<Criteria for ND subjects\> * CKD subjects who never received dialysis and do not need to receive dialysis during the study period. * Subjects with an Hb concentration at screening test 1 (ESA present at screening test 2) ≥ 10.0 g/dL to \< 13.0 g/dL. * Subjects with an eGFR at screening test 1 ≥ 15 mL/min/1.73m\^2 to \< 45 mL/min/1.73m\^2. \<Criteria for HD subjects\> * Subjects who received hemodialysis (including diafiltration) three times per week ≥ 12 weeks from acquisition consent. * Subjects with an Hb concentration at screening test 1 (ESA present at screening test 2) ≥ 10.0 g/dL to \< 12.0 g/dL.
Exclusion criteria
* Subjects with anemia other than that caused by CKD. * Subjects who have severe infection, systemic hematopathy (e.g. myelodysplastic syndrome, hemoglobinopathy), peptic ulcer or clear hemorrhagic lesion such as gastrointestinal hemorrhage * Subjects with immune disorder with severe inflammation * Subjects with uncontrolled secondary hyperparathyroidism * Subjects who already had or will have a kidney transplantation * Subjects who have a complication which requires treatment such as proliferative retinopathy, macular edema, or macular degeneration. Or, subjects who had a complication which required treatment such as proliferative retinopathy, macular edema, or macular degeneration within 12 months from screening test 1 * Subjects with congestive heart failure * Subjects with a medical history of thrombotic disease in the six months from screening test 1 * Subjects with uncontrolled blood pressure; SBP \> 170 mmHg or DBP \> 100 mmHg at screening test 1 (ESA present, screening tests 1 and 2), (HD subject, evaluated before dialysis)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events | 8 days | To evaluate the safety of TS-143 given single administration in CKD patients by incidence of adverse events which include abnormal electrocardiograms, vital signs, and clinical laboratory parameters. |
| Plasma concentrations of unchanged form (ng/mL) | 7 days | The descriptive statistics (e.g., number of subjects, arithmetic mean, standard deviation) were calculated by dose group and evaluation timing. |
| Urinary excretions of unchanged form (ng/mL) | 24 hours | The descriptive statistics (e.g., number of subjects, arithmetic mean, standard deviation) for the total urinary excretion (amount and fraction) were summarized by dose group. |
| Serum EPO concentration | 4 days | — |
| Reticulocyte count | 7 days | — |
| Plasma vascular endothelial growth factor (VEGF) concentration | 4 days | — |
Countries
Japan
Outcome results
None listed