NCT02299661已完成1 期
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
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 2
- 主要终点
- Plasma concentrations of DS-1093a
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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-
- •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 -
- •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
研究组 & 干预措施
50mg DS-1093a
Experimental
DS-1093a, single oral dose of 50 mg
干预措施: DS-1093a (Drug)
7.5mg DS-1093a
Experimental
DS-1093a, single oral dose of 7.5 mg
干预措施: DS-1093a (Drug)
25mg DS-1093a
Experimental
DS-1093a, single oral dose of 25 mg
干预措施: DS-1093a (Drug)
结局指标
主要结局
Plasma concentrations of DS-1093a
时间窗: 28 days
Plasma concentrations of DS-1093a and derived PK parameters up to 28 days post-dose.
Change in serum erythropoietin concentrations
时间窗: 6 days
Change in serum erythropoietin concentrations compared to baseline, and derived EPO parameters, up to 6 days post-dose
次要结局
- Number and severity of adverse events(28 days)
- Change from baseline for serum concentrations of vascular endothelial growth factor(7 days)
- Change from baseline for composite iron metabolism parameters(7 days)
- Change from baseline for composite haematology parameters(28 days)
研究者
研究点 (2)
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