An Exploratory Study of Vadadustat on Metabolic Parameters in Patients with Anemia in Non-dialysis Dependent Chronic Kidney Disease complicated with Type 2 Diabetes

JRCT ID: jRCTs041210143

Registered date:14/02/2022

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Patients with anemia in non-dialysis dependent chronic kidney disease complicated with type 2 diabet
• Date of first enrollment: 25/10/2022
• Target sample size: 41
• Study type: Interventional
• Intervention(s): The starting dose of vadadustat is 300 mg orally once a day

Outcome(s)

• Primary Outcome: Change in HbA1c from baseline to 24 weeks follow-up

Secondary Outcome

- HbA1c, glycoalbumin (GA), fasting blood glucose, fasting plasma insulin, HOMA-IR (insulin resistance index)
- Fasting plasma triglycerides, plasma cholesterol (total, LDL, HDL)
- Fasting plasma triglycerides, plasma cholesterol (total, LDL, HDL), eGFR (calculated from serum creatinine level), urine albumin/creatinine ratio
- Plasma adiponectin level
- Body weight, blood pressure
- Proportion of patients who changed (increased, remained the same, or decreased) the dose of anti-diabetic and anti-dyslipidemic drugs from baseline
- Dose of study drug
- Iron dosage (calculated as the iron content in mg)
- Hemoglobin and hematocrit levels
- Iron dosage (calculated as iron content (mg)) , Hemoglobin and hematocrit levels, MCV, MCH, MCHC, RDW, iron-related indices (serum iron, TIBC, TSAT, and serum ferritin levels)
- hsCRP
- Serum potassium, uric acid
- Heart failure markers (NT-proBNP, BNP)
- Renal tubular damage markers (urinary L-FABP, NGAL, KIM-1, NAG, MCP-1)

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1) Patients who have given written consent to participate in this study.
2) Patients who are 20 years old or older on the date of obtaining written consent (gender is not required)
3) Patients who have been diagnosed with type 2 diabetes
4) Patients who have been diagnosed with chronic kidney disease (CKD) based on the evidence-based CKD treatment guidelines 2018 (edited by the Japanese Society of Nephrology) on the date of obtaining written consent.
5) Patients with an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m^2 during the screening period.
The eGFR is calculated by the following formula using the patient's age at the date of obtaining consent.
eGFR (mL/min/1.73 m^2) = 194 x serum creatinine level^(-1.094) x age ^(-0.287) (female: x 0.739)
6) Patients who have not undergone dialysis treatment since 8 weeks prior to the date of documented consent and are not expected to start dialysis treatment during the treatment period
7) Patients with HbA1c >= 6.5% and < 8.0% during the screening period.
8) Patients who have not changed the type and dosage of glucose-lowering drugs (including insulin) since 8 weeks prior to the date of document consent, and are not expected to change during the treatment period.
9) Patients who have not changed the type and dosage of their dyslipidemia medication since 8 weeks prior to the date of obtaining written consent, and are expected to remain unchanged during the treatment period.
10) Patients who have not received an ESA since 8 weeks prior to the date of document consent.
11) Patients with an average Hb level (average of the two most recent Hb levels) corresponds to the following during the screening period. The interval of blood collection for multiple measurements should be at least one week.
Untreated group: 8.0 g/dL to less than 11.0 g/dL
Switching group: 8.0 g/dL to less than 13.0 g/dL
12) Patients with a difference of less than 1.5 g/dL between the two most recent Hb levels in the screening period. However, patients whose difference between the two most recent Hb levels during the screening period was 1.5 g/dL or higher may participate in the study if the difference is confirmed to be less than 1.5 after multiple Hb measurements. The interval of blood collection for multiple measurements should be at least one week.
13) Patients with a serum ferritin level of 100 ng/mL or higher or transferrin saturation (TSAT) of 20% or higher during the screening period.

Exclude criteria

1) Patients with anemia caused by factors other than CKD (sickle cell disease, myelodysplastic syndrome, myelofibrosis, hematopoietic malignancy, myeloma, hemolytic anemia, thalassemia, and locus coeruleus, etc.)
2) Patients with anemia due to CKD other than diabetes and hypertension (nephrosclerosis), such as IgA nephropathy, lupus nephritis, and polycystic kidney disease.
3) In the Untreated group, patients who have received at least one ESA in the 8 weeks or later prior to the date of obtaining documented consent
4) Patients who have had active bleeding or blood loss since 8 weeks prior to the date of document consent
5) Patients who have received red blood cell transfusion after 8 weeks prior to the date of document consent
6) Patients who have received testosterone enanthate or mepitiostane after 8 weeks prior to the date of document consent.
7) Patients who, in the judgment of the principal investigator, are likely to require immediate rescue treatment or withdrawal of study drug after the start date of study drug administration.
8) Patients with nephrotic syndrome (urine protein/urine creatinine ratio of 3.5 g/gCr or higher and serum albumin level of 3.0 g/dL or lower)
9) Patients whose AST, ALT, or total bilirubin during the screening period exceeded 2.5 times the upper limit of the reference value. This does not apply to patients with Gilbert's syndrome.
10) Patients with poorly controlled hypertension (defined as systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg) during the screening period.
11) Patients with severe heart failure {class IV on the New York Heart Association (NYHA) heart failure severity scale} during the screening period
12) Patients with cerebrovascular disease or acute coronary syndrome (e.g. hospitalization for unstable angina or myocardial infarction) after 12 weeks prior to the date of documented consent.
13) Patients who required hospitalization for urgent coronary revascularization or heart failure after 12 weeks prior to the date of documented consent.
14) Patients with concomitant malignancy or a history of malignancy. However, patients with a history of malignancy who have not had a recurrence of malignancy for more than 5 years (patients who have not had a recurrence of malignancy for more than 5 years after the last administration of anticancer drugs, if any) are excluded.
15) Patients at high risk of developing retinal hemorrhage (patients with complications such as proliferative diabetic retinopathy)
16) Patients who have developed or recurred deep vein thrombosis or pulmonary embolism within 12 weeks prior to the date of obtaining written consent
17) Patients with complications or history of hemosiderin deposition or hemochromatosis
18) Patients who have had or plan to have an organ transplant (this does not apply to patients on the kidney transplant waiting list) or who have had a hematopoietic stem cell or bone marrow transplant
19) Patients who are allergic to the study drug.
20) Patients who participated in another clinical trial and received the study drug within 12 weeks prior to the date of obtaining written consent or within 5 times the half-life of the study drug in another study (whichever is longer)
21) Patients who have a history of taking hypoxia-inducible factor proline hydroxylase (hereafter referred to as HIF-PH) inhibitors and have been found to be refractory to treatment, or who have received HIF-PH inhibitors and developed serious side effects
22) Female patients who are pregnant, lactating, or who may become pregnant, or who wish to become pregnant during the study period
23) Other patients who are judged by the principal investigator to be ineligible for this study.

Related Information

• Primary Sponsor: Toyama Tadashi
• Secondary Sponsor: NPO HEART