Phase 2
Completed N=103
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
Source: ClinicalTrials.gov NCT02689206 ↗Enrolled (actual)
103
Serious AEs
9.7%
Results posted
May 2018
Primary outcomePrimary: Change From Baseline in Hgb Levels at Day 29 — -0.61; -0.19; -0.13; 0.64 g/dL
Summary
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in Hgb Levels at Day 29 |
-0.61; -0.19; -0.13; 0.64; 0.55 | — |
| SECONDARY Maximum Observed Change From Baseline in Plasma Erythropoietin (EPO) |
53.761; 2.255; 73.369; 302.529; 477.644 | — |
| SECONDARY Maximum Observed Percent Change From Baseline in Vascular Endothelial Growth Factor (VEGF) |
20.35; 43.75; 32.16; 53.34; 76.09 | — |
| SECONDARY Percent Change From Baseline in Hepcidin at Day 29 |
27.81; 35.37; 3.83; -36.74; -36.09 | — |
| SECONDARY Change From Baseline in Hematocrit Levels |
-0.0218; -0.0127; -0.0149; 0.0150; 0.0215 | — |
| SECONDARY Change From Baseline in Red Blood Cell (RBC) Count |
-0.19; -0.12; -0.13; 0.12; 0.15 | — |
| SECONDARY Change From Baseline in Reticulocyte Count |
-0.08; -0.11; -0.04; 0.43; 0.09 | — |
| SECONDARY Change From Baseline in Reticulocyte Hemoglobin (CHr) |
-0.15; 0.23; 0.26; 0.23; 0.59 | — |
| SECONDARY 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 |
311.7; 416.7; 513.9; 1010; 348.2; 383.5 | — |
| SECONDARY Maximum Observed Concentration of Dapro in Plasma (Cmax) |
140.0; 141.4; 246.9; 387.3 | — |
| SECONDARY Time to Reach Cmax (Tmax) and Apparent Terminal Half-life (t1/2) of Dapro |
2.456; 2.106; 2.297; 1.718; 2.086; 1.886 | — |
| SECONDARY Number of Participants Who Discontinued Study Treatment |
0; 0; 1; 0; 1; 1 | — |
| SECONDARY Number of Participants With AEs and Serious Adverse Events (SAEs) |
10; 10; 6; 7; 7; 4 | — |
| SECONDARY Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points |
138.8; 138.1; 138.7; 139.4; 138.4; 137.7 | — |
| SECONDARY Albumin and Protein Levels in Blood at Indicated Tme Points |
37.6; 38.6; 38.7; 38.8; 38.1; 38.1 | — |
| SECONDARY Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points |
12.6; 13.4; 14.6; 10.7; 11.5; 16.5 | — |
| SECONDARY Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points |
6.6; 7.8; 6.6; 6.5; 7.2; 6.7 | — |
| SECONDARY Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels |
-0.9; -0.6; -0.5; -1.4; -1.0; -1.1 | — |
| SECONDARY Change From Baseline in Albumin and Protein Levels |
0.8; -0.5; 0.2; -0.5; -1.0; -0.5 | — |
| SECONDARY Change From Baseline in ALT, AST, Alk. Phosph. Levels |
3.6; 0.5; -3.1; 1.1; -3.4; 11.8 | — |
| SECONDARY Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels |
0.2; -0.7; 0.8; 0.0; 0.5; 0.2 | — |
| SECONDARY Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points |
6.28; 6.07; 5.88; 6.44; 5.90; 7.01 | — |
| SECONDARY Mean Corpuscular Hemoglobin (MCH) Levels in Blood at Indicated Time Points |
31.19; 30.95; 30.19; 30.70; 31.46; 30.83 | — |
| SECONDARY Mean Corpuscular Hemoglobin Concentration (MCHC) Levels in Blood at Indicated Time Points |
322.9; 321.7; 319.5; 321.5; 327.6; 321.5 | — |
| SECONDARY Mean Corpuscular Volume (MCV) Levels in Blood at Indicated Time Points |
96.7; 96.4; 94.7; 95.7; 96.1; 95.9 | — |
| SECONDARY Erythrocyte Distribution Width Levels in Blood at Indicated Time Points |
15.13; 16.40; 15.41; 15.81; 15.68; 15.05 | — |
| SECONDARY Change From Baseline in MCH Levels |
0.16; 0.19; 0.27; 0.16; 0.25; 0.16 | — |
| SECONDARY Change From Baseline in MCHC Levels |
2.6; 3.0; 3.5; -3.2; -5.0; 5.6 | — |
| SECONDARY Change From Baseline in MCV Levels |
-0.4; -0.2; -0.3; 1.3; 2.2; -1.4 | — |
| SECONDARY Change From Baseline in Erythrocyte Distribution Width Levels |
-0.18; -0.48; -0.09; 0.54; 1.06; -0.31 | — |
| SECONDARY Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels |
0.47; -0.21; 0.40; -0.03; -0.03; 0.49 | — |
| SECONDARY Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Indicated Time Points |
10; 15; 18; 12; 16; 0 | — |
| SECONDARY Change From Baseline in ECG Mean Heart Rate |
-2.0; 0.5; 1.1; 2.2; 0.9 | — |
| SECONDARY Change From Baseline in ECG Parameters Including PR Interval, QRS Duration, QT Interval and QTcB |
7.8; 7.3; -3.3; 2.1; -11.5; -1.4 | — |
| SECONDARY Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis |
142.5; 136.6; 149.2; 144.1; 144.1; 138.8 | — |
| SECONDARY Pulse Rate Values at Pre-dialysis and Post-dialysis |
68.5; 69.9; 66.7; 71.4; 76.5; 76.1 | — |
| SECONDARY Weight Values at Post-dialysis |
82.38; 80.04; 78.83; 79.38; 76.03; 84.24 | — |
| SECONDARY Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis |
-2.9; 1.7; -5.6; 2.5; -1.4; -0.6 | — |
| SECONDARY Change From Baseline in Pulse Rate Value at Pre-dialysis and Post-dialysis |
7.0; -2.6; 2.3; 0.7; -1.4; 2.4 | — |
| SECONDARY Change From Baseline in Weight at Post-dialysis |
-0.16; 0.16; -0.01; 0.06; -0.31; -0.11 | — |
Eligibility Criteria
Inclusion Criteria
- 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 29.
- 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 -28.
- 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 -28.
- Iron replacement therapy: Subjects may be on stable maintenance oral or intravenous (IV) ( =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 thr
Data sourced from ClinicalTrials.gov (NCT02689206). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.