NCT02689206已完成2 期
A 29-day, Randomized, Double-blinded, Placebo-controlled, Parallel-group, Multi-center Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Three-times Weekly Dosing of GSK1278863 in Hemodialysis-dependent Subjects With Anemia Associated With Chronic Kidney Disease Who Are Switched From a Stable Dose of an Erythropoiesis-stimulating Agent
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 103
- 试验地点
- 1
- 主要终点
- Change From Baseline in Hgb Levels at Day 29
研究概览
简要总结
GSK1278863 is an orally available, hypoxia-inducible factor - prolyl hydroxylase inhibitor, currently being investigated as a treatment for anemia associated with chronic kidney disease. GSK1278863 has been given as a once daily regimen in clinical studies to date. However, physicians in countries that use a three-times weekly hemodialysis schedule prefer to give the anemia medicine at the same time as the dialysis session. This study will test how well GSK1278863 can maintain hemoglobin levels when given three-times weekly, for 29 days.
This study will describe the relationship between hemoglobin and GSK1278863 given three-times weekly. The data from this study will allow for conversion of once daily doses to three-times weekly doses.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •More than or equal to 18 years of age, at the time of signing the informed consent.
- •Hemoglobin: Stable Hemoglobin 9.0 - 11.5 gram per deciliter (g/dL).
- •Dialysis frequency: On hemodialysis (HD, hemofiltration or hemodiafiltration) three to five times weekly for at least 4 weeks prior to Day -28 Screening through Day
- •Dialysis adequacy: A single pool Kt/Vurea of >=1.2 based on a historical value obtained within the prior three months in order to ensure the adequacy of dialysis. If Kt/Vurea is not available, then an average of the last 2 values of urea reduction ratio (URR) of at least 65 percent. NOTE: Only needs confirming at Day -
- •Erythropoiesis-stimulating agent (ESA)dose: Treated with the same ESA (epoetins or their biosimilars, or darbepoetin or methoxy polyethylene glycol [PEG]-epoetin beta) with total weekly dose varying by no more than 50 percent during the 4 weeks prior to Day -
- •Iron replacement therapy: Subjects may be on stable maintenance oral or intravenous (IV) (<=100 milligram (mg)/week) iron supplementation. If subjects are on oral or IV iron, then doses must be stable for the 4 weeks prior to Day -28, during the screening phase, and through the 29 days of treatment.
- •Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in study protocol.
排除标准
- •Dialysis modality: Planned change from HD to peritoneal dialysis within the study time period.
- •Renal transplant: Planned for living-related kidney transplant.
- •High ESA dose: An epoetin dose of >=360 international unit (IU)/kilogram (kg)/week IV or >=250 IU/kg/week subcutaneous (SC) or darbepoetin dose of >=1.8 microgram (mcg)/kg/week IV or SC or methoxy PEG-epoetin beta dose of >= 2.2 mcg/kg/week within the prior 8 weeks through Day 1 (randomization).
- •Administration of methoxy PEG-epoetin beta within the prior 4 weeks through Day 1 (randomization).
- •Myocardial infarction or acute coronary syndrome: Within the 8 weeks prior to Screening through Day 1 (randomization).
- •Stroke or transient ischemic attack: Within 8 weeks prior to Screening though Day 1 (randomization).
- •Heart failure: Class IV heart failure, as defined by the New York Heart Association (NYHA) functional classification system diagnosed prior to Screening through Day 1 (randomization).
- •Correction of Q-T Interval using Bazett's formula (QTcB): QTcB >500 millisecond (msec) or QTcB >530 msec in subjects with Bundle Branch Block. There is no correction of Q-T Interval (QTc) exclusion for subjects with a predominantly paced rhythm.
- •Inflammatory disease: Active chronic inflammatory disease that could impact erythropoiesis (e.g., scleroderma, systemic lupus erythematosis, rheumatoid arthritis, celiac disease) diagnosed prior to Screening through Day 1 (randomization).
- •Hematological disease: Any hematological disease including those affecting platelets, white or red blood cells (e.g., sickle cell anemia, myelodysplastic syndromes, hematological malignancy, myeloma, hemolytic anemia and thalassemia), coagulation disorders (e.g., antiphospholipid syndrome, Protein C or S deficiency), or any other cause of anemia of chronic disease other than renal disease diagnosed prior to Screening though Day 1 (randomization).
- •Liver disease: Current liver disease, known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones) or evidence at Screening of abnormal liver function tests [alanine transaminase (ALT) or aspartate transaminase (AST) >2x upper limit of normal (ULN) or total bilirubin >1.5xULN]; or other hepatic abnormalities that in the opinion of the investigator would preclude the subject from participating in the study.
- •NOTE: Those with Hepatitis B or Hepatitis C are eligible provided these exclusions are not met.
- •Major surgery: Major surgery (excluding vascular access surgery) within the 8 weeks prior to Screening, during the Screening phase, or planned during the study.
- •Transfusion: Blood transfusion within the 8 weeks prior to Screening, during the Screening phase or an anticipated need for blood transfusion during the study.
- •Gastrointestinal (GI) Bleeding: Evidence of actively bleeding peptic, duodenal, or esophageal ulcer disease OR clinically significant GI bleeding within the 8 weeks prior to Screening through Day 1 (randomization).
- •Acute Infection: Clinical evidence of acute infection or history of infection requiring IV antibiotic therapy within the 4 weeks prior to Screening through Day 1 (randomization). NOTE: IV antibiotics as prophylaxis are allowed.
- •Malignancy: History of malignancy within the two years prior to randomization or currently receiving treatment for cancer, or has a known >=4 centimeter complex kidney cyst (i.e. Bosniak Category II F, III of IV). NOTE: ONLY exception is squamous cell or basal cell carcinoma of the skin that has been definitively treated >=8 weeks prior to Screening.
- •Severe allergic reactions: History of severe allergic or anaphylactic reactions or hypersensitivity to excipients in the investigational product
- •Drugs and supplements: Use of any prescription or non-prescription drugs or dietary supplements that are prohibited (as per protocol) from Screening until the Follow-up Visit.
- •Prior investigational product exposure: The Subject has participated in a clinical trial and has received an experimental investigational product within the prior 30 days from Screening through Day 1 (randomization).
- •Other conditions: Any other condition, clinical or laboratory abnormality, or examination finding that the investigator considers would put the subject at unacceptable risk, which may affect study compliance or prevent understanding of the aims or investigational procedures or possible consequences of the study.
- •Females ONLY: A female subject is not eligible to participate if she is pregnant [as confirmed by a positive serum human chorionic gonadotrophin (hCG) test for females of reproductive potential (FRP) only], breastfeeding, and if of reproductive potential does not agree to follow one of the options listed in the GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in FRP.
- •Vitamin B12: At or below the lower limit of the reference range (may rescreen in a minimum of 8 weeks).
- •Folate: <2.0 nanogram (ng) per millilitre (mL) (4.5 nanomole/liter [L]) (may rescreen in a minimum of 4 weeks).
- •Ferritin: <100 ng/mL (<100 mcg/L).
- •Transferrin saturation (TSAT): <20 percent.
研究组 & 干预措施
GSK1278863 10 mg
Experimental
Subject will receive 10 mg of GSK1278863 three-times weekly for 4 weeks (up to 29 days).
干预措施: GSK1278863 (Drug)
GSK1278863 15 mg
Experimental
Subject will receive 15 mg of GSK1278863 three-times weekly for 4 weeks (up to 29 days).
干预措施: GSK1278863 (Drug)
GSK1278863 25 mg
Experimental
Subject will receive 25 mg of GSK1278863 three-times weekly for 4 weeks (up to 29 days).
干预措施: GSK1278863 (Drug)
GSK1278863 30 mg
Experimental
Subject will receive 30 mg of GSK1278863 three-times weekly for 4 weeks (up to 29 days).
干预措施: GSK1278863 (Drug)
Placebo
Placebo Comparator
Subject will receive GSK1278863 matching placebo three-times weekly for 4 weeks (up to 29 days).
干预措施: GSK1278863 matching Placebo (Drug)
结局指标
主要结局
Change From Baseline in Hgb Levels at Day 29
时间窗: Baseline and Day 29
Blood samples were collected from participants for measurement of Hgb values. Baseline is the average of Hgb measured at Week -2 and Day 1 visits. Change from Baseline at Day 29 was defined as post dose value at Day 29 minus Baseline value. The analysis was performed on intent-to-treat (ITT) Population which comprised of all randomized participants who received at least one dose of study treatment, had a Baseline and at least one corresponding on treatment assessment, including Hgb.
次要结局
- Change From Baseline in Reticulocyte Count(Baseline and Day 29)
- Change From Baseline in Hematocrit Levels(Baseline and Day 29)
- Area Under the Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration (AUC[0-t]) and AUC From Time Zero to Infinity (AUC[0-inf]) of Dapro(Pre-dose on Day 1; 6-10 hours, 7-11 hours, 8-12 hours, 9-13 hours post dose on Day 15; pre-dose and 1, 2, 3 hours post-dose on Day 29)
- Change From Baseline in Reticulocyte Hemoglobin (CHr)(Baseline and Day 29)
- Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels(Baseline and up to Day 43)
- Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Indicated Time Points(Up to Day 29)
- Change From Baseline in Weight at Post-dialysis(Up to Day 43)
- Maximum Observed Change From Baseline in Plasma Erythropoietin (EPO)(Baseline and up to Day 29)
- Percent Change From Baseline in Hepcidin at Day 29(Baseline and Day 29)
- Change From Baseline in Red Blood Cell (RBC) Count(Baseline and Day 29)
- Number of Participants With AEs and Serious Adverse Events (SAEs)(Up to Day 43)
- Maximum Observed Percent Change From Baseline in Vascular Endothelial Growth Factor (VEGF)(Baseline and up to Day 29)
- Maximum Observed Concentration of Dapro in Plasma (Cmax)(Pre-dose on Day 1; 6-10 hours, 7-11 hours, 8-12 hours, 9-13 hours post dose on Day 15; pre-dose and 1, 2, 3 hours post-dose on Day 29)
- Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points(Up to Day 43)
- Albumin and Protein Levels in Blood at Indicated Tme Points(Up to Day 43)
- Time to Reach Cmax (Tmax) and Apparent Terminal Half-life (t1/2) of Dapro(Pre-dose on Day 1; 6-10 hours, 7-11 hours, 8-12 hours, 9-13 hours post dose on Day 15; pre-dose and 1, 2, 3 hours post-dose on Day 29)
- Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points(Up to Day 43)
- Mean Corpuscular Hemoglobin (MCH) Levels in Blood at Indicated Time Points(Up to Day 43)
- Mean Corpuscular Hemoglobin Concentration (MCHC) Levels in Blood at Indicated Time Points(Up to Day 43)
- Number of Participants Who Discontinued Study Treatment(Up to Day 43)
- Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points(Up to Day 43)
- Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels(Baseline and up to Day 43)
- Change From Baseline in Albumin and Protein Levels(Baseline and up to Day 43)
- Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points(Up to Day 43)
- Change From Baseline in Erythrocyte Distribution Width Levels(Baseline and up to Day 43)
- Change From Baseline in ECG Mean Heart Rate(Baseline and Day 29)
- Change From Baseline in ALT, AST, Alk. Phosph. Levels(Baseline and up to Day 43)
- Mean Corpuscular Volume (MCV) Levels in Blood at Indicated Time Points(Up to Day 43)
- Erythrocyte Distribution Width Levels in Blood at Indicated Time Points(Up to Day 43)
- Change From Baseline in MCHC Levels(Baseline and up to Day 43)
- Change From Baseline in MCV Levels(Baseline and up to Day 43)
- Weight Values at Post-dialysis(Up to Day 43)
- Change From Baseline in Pulse Rate Value at Pre-dialysis and Post-dialysis(Up to Day 43)
- Change From Baseline in MCH Levels(Baseline and up to Day 43)
- Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels(Baseline and up to Day 43)
- Change From Baseline in ECG Parameters Including PR Interval, QRS Duration, QT Interval and QTcB(Baseline and Day 29)
- Pulse Rate Values at Pre-dialysis and Post-dialysis(Up to Day 43)
- Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis(Up to Day 43)
- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis(Up to Day 43)
研究者
研究点 (1)
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