Pilot PK/PD Study of DS-1093a in Patients With Chronic Kidney Disease

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02299661
• Date of registration: 18/11/2014
• Prospective Registration: No
• Primary sponsor: Daiichi Sankyo, Inc.
• Public title: Pilot PK/PD Study of DS-1093a in Patients With Chronic Kidney Disease
• Scientific title: An Open-Label, Randomised, Parallel Group Pilot Study to Assess the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Single Doses of DS-1093a in Patients With Chronic Kidney Disease
• Date of first enrolment: November 2014
• Target sample size: 31
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02299661
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Basic Science. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Czech Republic, Czechia, Hungary

Contacts

• Name: Mendel Jansen, BSc
• Affiliation: Daiichi Sankyo Development

Key inclusion & exclusion criteria

Inclusion Criteria:

- Male and female patients aged 18 - 70 years (inclusive).

- Female patients must be of non-childbearing potential (post-menopause or surgical
sterilization). In women younger than 60 years a follicle-stimulating hormone (FSH)
test will be conducted to confirm post-menopausal status (i.e., FSH = 30 mU/mL).

- Part A: CKD stage 3b (eGFR: < 45 to = 30 mL/min) or stage 4 (eGFR: < 30 to = 15
mL/min). The CKD-EPI equation will be used for the eGFR estimation.

- Part B: Patients on chronic haemodialysis for at least 6 months and stable Hb levels
(i.e., +/- 1 g/dL) for the last 6 months.

- Patient can be washed out from ESAs for at least 3 weeks (2 weeks prior to dosing and
1 week post-dose).

- Baseline Hb level =10 g/dL.

- Willingness to give written consent to participate after reading the ICF, and after
having the opportunity to discuss the trial with the Investigator or his delegate.

- Male patients must be willing to use a reliable method of contraception during the
trial, and for 4 months afterwards

Exclusion Criteria:

- Use of ESAs within 2 weeks prior to dosing.

- Uncontrolled hypertension despite optimal medical therapy, defined as > 160/100 mmHg
after 10 minutes of rest at screening, and > 180/110 mmHg after 10 minutes of rest on
Day -1 pre-dose.

- Known haemoglobinopathy.

- Acute renal failure (as judged by the Investigator).

- History of kidney transplant regardless of functionality.

- Start of any new medication or any changes to a current dosage within 7 days prior to
study drug administration.

- Chronic liver disease.

- Positive hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibody test.

- Positive test for human immunodeficiency virus (HIV)-1 or HIV-2.

- A history of gastrointestinal bleeding.

- History of a thrombotic event (e.g., myocardial infarction, stroke or transient
ischemic attack, peripheral embolism, venous thromboembolism, etc.)

- Patients with poorly controlled diabetes despite optimal medical therapy.

- A history of cancer, except basal cell skin cancer, squamous cell skin cancer, or
cervical cancer (if judged by the Investigator to be in full remission).

- Hypersensitivity to any components of the study drug.

- Requirement for any concomitant medication that cannot be withheld on Day 1 until 4
hours post-dose (insulin is allowed to cover the breakfast, if necessary).

- Clinically relevant abnormal medical history, physical findings, ECG, or laboratory
values at the screening assessments that could interfere with the objectives of the
trial or the safety of the patient.

- Participation in another investigational drug trial within 30 days prior to dosing (or
5 times the half-life of the drug, whichever is longer) or exposure to more than three
new investigational agents within 12 months prior to enrolment.

- Abuse of drugs or alcohol during the 2 years before the first dose of trial
medication.

- Ingestion of alcohol within 72 hours prior to dosing and during confinement. Outside
the in-house period, regular alcohol consumption must not exceed 16 units for males
and 7 units for females per week (1 unit equals 340 mL of beer, 115 mL of wine or 43
mL of spirits).

- Positive drug screen (if not due to concomitant medication) or alcohol breath test at
screening and/or Day -1.

- Patients who smoke more than 10 cigarettes per day (or equivalent), and who would not
be able to abstain from smoking during the in-house period.

- Concomitant use of medications known to affect the elimination of serum creatinine
(e.g., trimethoprim or cimetidine) and competitors of renal tubular secretion (e.g.,
probenecid) within 30 days before dosing.

- Use of a strong inducer or inhibitor of CYP enzymes, during the 30 days before dosing.

- Use of any other prohibited medication.

- Loss of more than 400 mL blood, or donation of blood, plasma, platelets, or any other
blood components, during the 3 months before the trial, or unwilling to abstain from
donating during the study and for 3 months after receipt of the final dose of trial
medication.

- Possibility that the patient will not cooperate with the requirements of the protocol



Age minimum: 18 Years
Age maximum: 70 Years
Gender: All

Health Condition(s) or Problem(s) studied

Chronic Renal Disease

Renal Anemia

Intervention(s)

Drug: DS-1093a

Primary Outcome(s)

Change in serum erythropoietin concentrations [Time Frame: 6 days]

Plasma concentrations of DS-1093a [Time Frame: 28 days]

Secondary Outcome(s)

Change from baseline for composite iron metabolism parameters [Time Frame: 7 days]

Change from baseline for serum concentrations of vascular endothelial growth factor [Time Frame: 7 days]

Number and severity of adverse events [Time Frame: 28 days]

Change from baseline for composite haematology parameters [Time Frame: 28 days]

Secondary ID(s)

2014-002331-33

DS1093-A-E103

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

PRA Health Sciences