Clinical Pharmacology Study of TS-143 in Nondialysis and Hemodialysis Patients with Chronic Kidney Disease

Taisho Pharmaceutical

Status and phase: Completed; Phase 1

Conditions: Chronic Kidney Disease

Treatments: Drug: TS-143

Study type: Interventional

Funder types: Industry

Identifiers

NCT03581071

JapicCTI-163383 (Other Identifier)

TS143-01-02

Details and patient eligibility

About

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.

Enrollment: 29 patients

Sex: All

Ages: 20 to 74 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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29 participants in 5 patient groups

Step1:1mg in non-dialysis subject

Experimental group

Treatment:

Drug: TS-143

Step2-1:1mg in hemodialysis subjects

Experimental group

Treatment:

Drug: TS-143

Step2-2:6mg in non-dialysis subject

Experimental group

Treatment:

Drug: TS-143

Step3-1:11㎎ in hemodialysis subjects

Experimental group

Treatment:

Drug: TS-143

Step3-2:11㎎ in non-dialysis subject

Experimental group

Treatment:

Drug: TS-143