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

NCT02299661 | Completed Phase 1

• 2 other identifiers: DS1093-A-E1032014-002331-33
• Study Type: interventional
• Target: 31
• Locations: 2 countries
• Sites: 3

Brief Summary

DS-1093a is an inhibitor of hypoxia-inducible factor prolyl hydroxylases, and is expected to produce transient dose / exposure dependent increases in erythropoietin levels in subjects with chronic kidney disease (CKD). This study will be conducted in 2 parts. Part A will involve subjects with stage 3b or 4 CKD, and will be an open, non-controlled parallel group investigation of three single doses of DS-1093a (6 subjects/dose), in which allocation to dose will be randomised. On completion of this part of the study an optional fourth dose may be tested to gain a more complete understanding of the PK/PD behaviour of DS-1093a. Part B will be an open, non-controlled investigation of a single dose of DS-1093a in CKD subjects (n=6) receiving haemodialysis. The dose for Part B will be determined based on the data from Part A.

Conditions

Chronic Renal Disease; Renal Anemia

Keywords

Hypoxia inducible factor prolyl hydroxylase inhibitor.; Erythropoietin stimulating agent; Chronic renal disease; renal anemia

Outcome Measures

Primary Outcomes (2)

• Plasma concentrations of DS-1093a

  Plasma concentrations of DS-1093a and derived PK parameters up to 28 days post-dose.

  28 days

• Change in serum erythropoietin concentrations

  Change in serum erythropoietin concentrations compared to baseline, and derived EPO parameters, up to 6 days post-dose

  6 days

Secondary Outcomes (4)

• Change from baseline for composite haematology parameters

  28 days

• Change from baseline for composite iron metabolism parameters

  7 days

• Change from baseline for serum concentrations of vascular endothelial growth factor

  7 days

• Number and severity of adverse events

  28 days

Study Arms (3)

7.5mg DS-1093a

EXPERIMENTAL

DS-1093a, single oral dose of 7.5 mg

Drug: DS-1093a

25mg DS-1093a

EXPERIMENTAL

DS-1093a, single oral dose of 25 mg

Drug: DS-1093a

50mg DS-1093a

EXPERIMENTAL

DS-1093a, single oral dose of 50 mg

Drug: DS-1093a

Interventions

DS-1093a DRUG

DS-1093a, single oral doses up to 50 mg

25mg DS-1093a; 50mg DS-1093a; 7.5mg DS-1093a

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Daiichi Sankyo: lead
• PRA Health Sciences: collaborator

Study Sites (3)

: Hemodialysis Center, Teaching Hospital Hradec Králove

Hradec Králové, 500 05, Czechia

Location

PRA Clinical Pharmacology Unit

Prague, 170 00 Prague 7, Czechia

Location

PRA Clinical Pharmacology Unit

Budapest, H-1077, Hungary

Location

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Mendel Jansen, BSc

  Daiichi Sankyo Development

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2014
• First Posted: November 24, 2014
• Study Start: November 1, 2014
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: December 24, 2018

Record last verified: 2015-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.

Locations

CZ (2); HU (1)