Chronic Renal DiseasePhase 1NCT02299661
Pilot PK/PD Study of DS-1093a in Patients With Chronic Kidney Disease
A Phase 1 study testing DS-1093a in people with Chronic Renal Disease and Renal Anemia, run by Daiichi Sankyo at 3 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Chronic Renal Disease, Renal Anemia
- What is being tested?
- DS-1093a
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 3 sitesin 2 countries
- Study dates
- Nov 2014to May 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
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- 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
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
Czechia2 sites
: Hemodialysis Center, Teaching Hospital Hradec Králove
Hradec Králové, 500 05
PRA Clinical Pharmacology Unit
Prague, 170 00 Prague 7
About this study
Official 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
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
- Being tested
- DS-1093a
- Keywords
- Hypoxia inducible factor prolyl hydroxylase inhibitor., Erythropoietin stimulating agent, Chronic renal disease, renal anemia
- Medical subject headings
- Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DS-1093aDrug
DS-1093a, single oral doses up to 50 mg
| Study group | Role | What they receive |
|---|---|---|
| 7.5mg DS-1093a | Experimental | DS-1093a, single oral dose of 7.5 mg Receives: Drug: DS-1093a |
| 25mg DS-1093a | Experimental | DS-1093a, single oral dose of 25 mg Receives: Drug: DS-1093a |
| 50mg DS-1093a | Experimental | DS-1093a, single oral dose of 50 mg Receives: Drug: DS-1093a |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma concentrations of DS-1093a
Plasma concentrations of DS-1093a and derived PK parameters up to 28 days post-dose.
Measured: 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
Measured: 6 days
Secondary outcomes (4)
Change from baseline for composite haematology parameters
Change from baseline for haematology parameters (reticulocyte count, haemoglobin concentration, haematocrit, red blood cell count) up to 28 days post-dose.
Measured: 28 days
Change from baseline for composite iron metabolism parameters
Change from baseline for iron metabolism parameters (serum concentrations of iron, transferrin, transferrin saturation, hepcidin-25) up to 7 days post-dose.
Measured: 7 days
Change from baseline for serum concentrations of vascular endothelial growth factor
Change from baseline for serum concentrations of vascular endothelial growth factor up to 7 days post-dose
Measured: 7 days
Number and severity of adverse events
Safety and tolerability up to 28 days post-dose
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Nov 2014 (estimated)
- Study startNov 2014
- Primary completionMay 2015
- Study completionMay 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Renal DiseaseStudies of the same condition, open and under way.
- More trials run by Daiichi SankyoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Daiichi Sankyo
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- PRA Health Sciences
- Responsible party
- Sponsor
- Investigators
- Mendel Jansen, BSc, Study director, Daiichi Sankyo Development
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02299661
- Sponsor's protocol ID
- DS1093-A-E103
- Other IDs
- 2014-002331-33, 2014
- Status last verified
- Jun 2015
- First submitted
- 18 Nov 2014
- Last updated
- 24 Dec 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
Study at a glance
From the registry record, last updated by the sponsor on 24 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT02299661
- Acronym / sponsor ID
- DS1093-A-E103
- Conditions
- Chronic Renal Disease, Renal Anemia
- Keywords
- Hypoxia inducible factor prolyl hydroxylase inhibitor., Erythropoietin stimulating agent, Chronic renal disease, renal anemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Daiichi SankyoIndustry (pharma, biotech, devices)
- Collaborators
- PRA Health Sciences
- Study start
- Nov 2014
- Primary completion
- May 2015 (actual)
- Study completion
- May 2015 (actual)
- First posted
- 24 Nov 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 7.5mg DS-1093a | Experimental | Drug: DS-1093aDS-1093a, single oral dose of 7.5 mg |
| 25mg DS-1093a | Experimental | Drug: DS-1093aDS-1093a, single oral dose of 25 mg |
| 50mg DS-1093a | Experimental | Drug: DS-1093aDS-1093a, single oral dose of 50 mg |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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).
Key exclusion criteria (26 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DS-1093aDS-1093a, single oral doses up to 50 mg | Drug | 25mg DS-1093a, 50mg DS-1093a, 7.5mg DS-1093a |
Primary outcome
Plasma concentrations of DS-1093a
Time frame: 28 days
Plasma concentrations of DS-1093a and derived PK parameters up to 28 days post-dose.
Change in serum erythropoietin concentrations
Time frame: 6 days
Change in serum erythropoietin concentrations compared to baseline, and derived EPO parameters, up to 6 days post-dose
4 secondary outcomes
Change from baseline for composite haematology parameters
Time frame: 28 days
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Dec 2018.
- Individual participant dataSharing planned: Yes. De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mendel Jansen, BSc study director
Daiichi Sankyo Development
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing DS-1093a in people with Chronic Renal Disease and Renal Anemia, run by Daiichi Sankyo at 3 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Czechia, Hungary. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasma concentrations of DS-1093a (time frame: 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Dec 2018.