Clinical trial NCT03581071: Clinical Pharmacology Study of TS-143 in Nondialysis and Hemodialysis Patients with Chronic Kidney Disease
Official title: Clinical Pharmacology Study of TS-143 in Nondialysis and Hemodialysis Patients with Chronic Kidney Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chronic Kidney Disease
Keywords: Dialysis, CKD
Lead sponsor: Taisho Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2018-07-10
Enrollment: 29
Sex: ALL
Minimum age (years): 20
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Incidence of adverse events
timeFrame: 8 days
measure: Plasma concentrations of unchanged form (ng/mL)
timeFrame: 7 days
measure: Urinary excretions of unchanged form (ng/mL)
timeFrame: 24 hours
measure: Serum EPO concentration
timeFrame: 4 days
measure: Reticulocyte count
timeFrame: 7 days
measure: Plasma vascular endothelial growth factor (VEGF) concentration
timeFrame: 4 days
Secondary outcomes:
Other outcomes:
Locations:
city: Tokyo and other Japanese city
country: Japan
facility: Taisho Pharmaceutical Co., Ltd selected site
Study officials:
affiliation: Taisho Pharmaceutical Co., Ltd.
name: Shigeru Okuyama
role: STUDY_DIRECTOR
References:
citation: 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.