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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease
• Intervention / Treatment: Drug: TS-143

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Multiple Locations, Japan
    • Taisho Pharmaceutical Co., Ltd selected site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Step1:1mg in non-dialysis subject	Drug: TS-143
Experimental: Step2-1:1mg in hemodialysis subjects	Drug: TS-143
Experimental: Step2-2:6mg in non-dialysis subject	Drug: TS-143
Experimental: Step3-1:11㎎ in hemodialysis subjects	Drug: TS-143
Experimental: Step3-2:11㎎ in non-dialysis subject	Drug: TS-143

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	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.	8 days
Plasma concentrations of unchanged form (ng/mL)	The descriptive statistics (e.g., number of subjects, arithmetic mean, standard deviation) were calculated by dose group and evaluation timing.	7 days
Urinary excretions of unchanged form (ng/mL)	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.	24 hours
Serum EPO concentration		4 days
Reticulocyte count		7 days
Plasma vascular endothelial growth factor (VEGF) concentration		4 days

Collaborators and Investigators

• Sponsor: Taisho Pharmaceutical Co., Ltd.

Publications and helpful links

General Publications

• Shinfuku A, Shimazaki T, Fujiwara M, Sato F, Watase H, Numazaki T, Kawakita Y, Mutoh M, Yamasaki H, Takayama N, Kato S, Sugimoto T, Maruyama J. Novel Compound Induces Erythropoietin Secretion through Liver Effects in Chronic Kidney Disease Patients and Healthy Volunteers. Am J Nephrol. 2018;48(3):157-164. doi: 10.1159/000492181. Epub 2018 Sep 3.

Study record dates

Study Major Dates

• Study Start (Actual): October 6, 2016
• Primary Completion (Actual): July 6, 2017
• Study Completion (Actual): July 6, 2017

Study Registration Dates

• First Submitted: April 18, 2018
• First Submitted That Met QC Criteria: July 6, 2018
• First Posted (Actual): July 10, 2018

Study Record Updates

• Last Update Posted (Actual): October 6, 2022
• Last Update Submitted That Met QC Criteria: October 4, 2022
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Dialysis, CKD
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: TS143-01-02; JapicCTI-163383 (Other Identifier: JapicCTI)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No