NCT03409107已完成3 期
A 28-week, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multi-center, Study in Recombinant Human Erythropoietin (rhEPO) naïve Non-dialysis Participants With Anemia Associated With Chronic Kidney Disease to Evaluate the Efficacy, Safety and Effects on Quality of Life of Daprodustat Compared to Placebo
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 614
- 试验地点
- 1
- 主要终点
- Mean Change in Hemoglobin From Baseline and Over the Evaluation Period (Mean Over Week 24 and 28)
研究概览
简要总结
The purpose of this multi-center study in non-dialysis participants with anemia associated with CKD is to evaluate safety, efficacy and quality of life of daprodustat compared to placebo.
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)
盲法说明
This will be a double-blind study. The participant, investigator, site staff, and study team will be blinded to the assigned study treatment.
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
- •>=18 years of age at the time of signing the informed consent.
- •Have CKD, confirmed at screening: Kidney Disease Outcomes Quality Initiative (KDOQI) CKD stages 3, 4, or 5 defined by Estimated glomerular filtration rate (eGFR) using the CKD Epidemiology Collaboration (CKD-EPI) formula.
- •Participants with Stable HemoCue Hgb from 8.5 to 10.5 at screening visit (Week -4) and from 8.5 to 10.0 g/dL at randomization (Day 1).
- •Participants may receive up to one intravenous (IV) iron dose within the 8 weeks prior to screening and NO IV iron use between screening visit and randomization (Day 1).
- •If needed, participant may be on stable maintenance oral iron supplementation. There should be <50% change in overall dose and no change in type of iron prescribed in the 4 weeks prior to Day 1 randomization visit.
- •Male and female participants are eligible. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential (WOCBP) or WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 4 weeks after the last dose of study treatment.
- •Capable of giving signed informed consent.
排除标准
- •Participants who are on dialysis or clinical evidence of impending need to initiate dialysis within 180 days after randomization (Day 1).
- •Planned living-related or living-unrelated kidney transplant within 28 weeks after randomization (Day 1).
- •Transferrin saturation (TSAT) <15 percent (Screening only).
- •Ferritin <50 nanograms per milliliter (ng/mL) (Screening only).
- •History of rhEPO or rhEPO analogue use within the 8 weeks prior to screening and rhEPO use between screening and randomization (Day 1).
- •History of transfusion within the 8 weeks prior to screening and transfusion between screening and randomization (Day 1).
- •History of bone marrow aplasia or pure red cell aplasia (PRCA).
- •Participants with Megaloblastic anemia (untreated pernicious anemia and folate deficiency), thalassemia major, sickle cell disease or myelodysplastic syndrome.
- •Evidence of actively bleeding gastric, duodenal, or esophageal ulcer disease or clinically significant gastrointestinal (GI) bleeding <= 8 weeks prior to screening through to randomization (Day 1).
- •History of severe allergic or anaphylactic reactions or hypersensitivity to excipients in the investigational product.
- •Use of strong inhibitor of CYP2C8 (for example, gemfibrozil) or strong inducers of CYP2C8 (for example, rifampin/rifampicin).
- •Ferric citrate use within 4 weeks prior to randomization (Day 1).
- •Use of other investigational agent or device prior to screening through to randomization (Day 1).
- •Any prior treatment with daprodustat for a treatment duration of >30 days.
- •MI or acute coronary syndrome within the 8 weeks prior to screening through to randomization. (Day 1).
- •Stroke or transient ischemic attack within the 8 weeks prior to screening through to randomization. (Day 1).
- •Chronic Class IV heart failure, as defined by the New York Heart Association (NYHA) functional classification system.
- •QT interval corrected by Bazett's formula (QTcB) >500 milliseconds (msec) or QTcB >530 msec in participants with bundle branch block. There is no corrected QT interval (QTc) exclusion for participants with a predominantly paced rhythm.
- •Alanine transaminase (ALT) >2x upper limit of normal (ULN) at screening (Week -4).
- •Bilirubin >1.5xULN at screening (Week -4).
- •Current unstable liver or biliary disease per investigator assessment, generally defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis.
- •History of malignancy within the 2 years prior to screening through to randomization (Day 1), or currently receiving treatment for cancer, or complex kidney cyst (for example, Bosniak Category II F, III or IV) > 3 centimeters (cm).
- •Any other condition, clinical or laboratory abnormality, or examination finding that the investigator considers would put the participant at unacceptable risk, which may affect study compliance or prevent understanding of the aims or investigational procedures or possible consequences of the study.
- •Current uncontrolled hypertension as determined by the investigator.
研究组 & 干预措施
Daprodustat receivers
Experimental
Participants will receive oral daprodustat once daily
干预措施: Daprodustat (GSK1278863) (Drug)
Daprodustat receivers
Experimental
Participants will receive oral daprodustat once daily
干预措施: Iron therapy (Drug)
Placebo receivers
Placebo Comparator
Participants will receive oral placebo once daily
干预措施: Placebo (Drug)
Placebo receivers
Placebo Comparator
Participants will receive oral placebo once daily
干预措施: Iron therapy (Drug)
结局指标
主要结局
Mean Change in Hemoglobin From Baseline and Over the Evaluation Period (Mean Over Week 24 and 28)
时间窗: Baseline (Day 1) and Week 24 to Week 28
Blood samples were collected at given time points from participants for hemoglobin measurements. Evaluation period hemoglobin value was defined as the mean of all available post-randomization hemoglobin values (on and off-treatment) during the evaluation period (Week 24 to Week 28 inclusive). For the primary analysis, the missing post-Baseline hemoglobin values were imputed using pre-specified multiple imputations. Change from Baseline was defined as the average of post-randomization values during the evaluation period minus Baseline value. Baseline value was the latest non-missing pre-dose assessment on or before the randomization date. Analysis was performed using the Analysis of Covariance (ANCOVA) model with terms for treatment, Baseline hemoglobin, and region.
次要结局
- Percentage of Participants With Hemoglobin Increase of >=1.0 Grams Per Deciliter From Baseline to Evaluation Period(Baseline (Day 1) and Week 24 to Week 28)
- Change From Baseline in Post-randomization Hgb at Week 28(Baseline (Day 1) and Week 28)
- Change From Baseline in Patient Global Impression of Severity (PGI-S)(Baseline (Day 1) and Week 28)
- Number of Participants Currently Employed as Per Work Productivity and Activity Impairment Questionnaire: Anemic Symptoms Clinical Practice Version (WPAI-ANS-CPV)(Week 8, Week 12 and Week 28)
- Rate of Participants Permanently Stopping Randomized Treatment Due to Meeting Rescue Criteria(Up to Week 28)
- Change From Baseline in WPAI-ANS-CPV: Mean Hours Missed From Work in the Past 7 Days(Baseline (Day 1), Week 8, Week 12 and Week 28)
- Change From Baseline in EuroQol 5 Dimension 5 Level Health Utility Index (EQ-5D-5L) Utility Score(Baseline (Day 1) and Week 28)
- Change From Baseline in EuroQol Visual Analogue Scale (EQ-VAS) Score(Baseline (Day 1) and Week 28)
- Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Mean Arterial Pressure (MAP) at Week 28(Baseline (Day 1) and Week 28)
- Percentage of Time With Hgb Within the Target Range (11-12 Grams Per Deciliter) During Evaluation Period (Week 24 to Week 28 Inclusive) (Hodges-Lehmann Estimate)(Week 24 to Week 28)
- Percentage of Time With Hgb Within the Target Range (11-12 Grams Per Deciliter) During Evaluation Period (Week 24 to Week 28 Inclusive) (Mann-Whitney Estimate)(Week 24 to Week 28)
- Change From Baseline in the SF-36 Physical Functioning Domain(Baseline (Day 1) and Week 28)
- Change From Baseline in Short Form-36 (SF-36) Questionnaire Vitality Domain Score by Traditional Scoring at Week 28(Baseline (Day 1) and Week 28)
- Percentage of Participants With Hgb Response (Hgb in the 11-12 Grams/Deciliter Range) During Evaluation Period (Week 24 to Week 28 Inclusive)(Week 24 to Week 28)
- Change From Baseline in WPAI-ANS-CPV: Percent Time Missed From Work(Baseline (Day 1), Week 8, Week 12 and Week 28)
- Change From Baseline by Domain and Single Item Scores on the Chronic Kidney Disease -Anemia Questionnaire (CKD-AQ) Symptom Questionnaire(Baseline (Day 1) and Week 28)
- Change From Baseline of the SF-36 Individual Items in the Vitality Domain(Baseline (Day 1) and Week 28)
- Change From Baseline in WPAI: Percent Regular Daily Activity Impairment(Baseline (Day 1), Week 8, Week 12 and Week 28)
- Change From Baseline in WPAI: Percent Impairment at Work(Baseline (Day 1), Week 8, Week 12 and Week 28)
- Change From Baseline in WPAI: Percent Overall Work Impairment(Baseline (Day 1), Week 8, Week 12 and Week 28)
- Percentage of Participants With at Least One Blood Pressure (BP) Exacerbation Event(Up to Week 28)
研究者
研究点 (1)
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