Anaemia associated with chronic kidney disease
Conditions
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Age 1. = 18 years of age at the time of signing the informed consent. Type of Participant and Disease Characteristics 2. CKD: 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 [Levey, 2009]. 3. Hgb: 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) (Section 9.1 of the study protocol). 4. IV Iron: Participants may receive up to one IV iron dose within the 8 weeks prior to screening and NO IV iron use between screening visit and randomization (Day 1). 5. Oral Iron: If needed, participant may be on stable maintenance oral iron supplementation. There should be =65 years) no F.1.3.1 Number of subjects for this age range 300
Exclusion criteria
Exclusion criteria: CKD Related Criteria 1. Dialysis: On dialysis or clinical evidence of impending need to initiate dialysis within 180 days after randomization (Day 1). 2. Kidney Transplant: Planned living-related or living-unrelated kidney transplant within 28 weeks after randomization (Day 1). Anemia-Related Criteria 3. Transferrin saturation (TSAT) 30 days. Cardiovascular Disease-Related Criteria 15. MI or acute coronary syndrome: within the 8 weeks prior to screening through to randomization. (Day 1) 16. Stroke or transient ischemic attack: within the 8 weeks prior to screening through to randomization. (Day 1) 17. Heart failure: Chronic Class IV heart failure, as defined by the New York Heart Association (NYHA) functional classification system 18. QTcB (Day 1): QTcB >500 msec or QTcB >530 msec in participants with bundle branch block. There is no QTc exclusion for participants with a predominantly paced rhythm. Other Disease Related Criteria 19. Liver Disease-Related Criteria: Alanine transaminase (ALT) >2x upper limit of normal (ULN) at screening(Week -4). Bilirubin >1.5xULN at screening (Week -4). NOTE: Isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%. Current unstable liver or biliary disease per investigator assessment, generally defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. NOTE: Stable chronic liver disease (including asymptomatic gallstones, chronic hepatitis B or C, or Gilbert’s syndrome) is acceptable if participant otherwise meets entry criteria. 20. Malignancy: History of malignancy within the 2 years prior to screening through to randomization (Day 1), or currently receiving treatment for cancer, or complex kidney cy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the efficacy of daprodustat to placebo on mean change in Hgb levels;Secondary Objective: To compare the proportion of participants achieving increases in Hgb when treated with daprodustat versus placebo. To compare daprodustat to placebo for health related quality-of-life To compare daprodustat to placebo on additional Hgb endpoints To compare daprodustat to placebo on the time to rescue To compare daprodustat to placebo for improving symptoms of anemia of CKD To compare daprodustat to placebo on the severity and change in symptoms To compare daprodustat to placebo for improving health related quality-of-life To compare daprodustat to placebo on improving work productivity and regular daily activity impairment To compare daprodustat to placebo on improving health status To compare daprodustat to placebo on BP;Primary end point(s): Mean change in Hgb between baseline and the Evaluation Period(EP, mean over week 24 to week 28 inclusive);Timepoint(s) of evaluation of this end point: Evaluation period is mean over week 24 to week 28 inclusive | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): % of participants having a Hgb increase of =1.0 g/dL from baseline to EP. Mean Change in SF-36 Vitality domain between baseline and Week 28 N (%) responders, defined as mean Hgb within range. % time Hgb in range Mean change in Hgb from baseline. Time to stopping study treatment due to meeting rescue criteria Mean change from baseline by domain and overall symptom score on the Chronic Kidney Disease - Anemia Questionnaire (CKD-AQ) symptom questionnaire Change from baseline in PGI-S Mean Change in individual items of the SF-36 Vitality Domain from baseline. Mean Change in SF-36 Physical Function domain from baseline. N (%) of patients currently employed on the WPAI-ANS-CPV Change from baseline in percent and mean hours work time missed on the WPAI-ANS-CPV Change from baseline in percent impaired (equivalent) on the WPAI-ANS-CPV Change from baseline in overall percent work impairment (equivalent) on the WPAI-ANS-CPV Change from baseline in percent activity impairment on the WPAI-ANS-CPV Change in EQ-5D-5L utility score from baseline. Change in EQ-VAS score from baseline. Change from baseline in SBP, DBP, and MAP at week 28 N (%) with at least one BP exacerbation event during the study;Timepoint(s) of evaluation of this end point: 1. from baseline at any post-baseline visit. 2. between baseline and Week 28 | — |
Countries
Argentina, Australia, Brazil, Canada, France, Italy, Korea, Republic of, Mexico, Poland, Romania, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trials Helpdesk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed