AnaemiaPhase 2NCT02689206
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
A Phase 2 study testing GSK1278863 in people with Anaemia, run by GlaxoSmithKline at 38 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Anaemia
- What is being tested?
- GSK1278863
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 103 participants
- Where
- 38 sitesin 5 countries
- Study dates
- 17 Feb 2016to 25 Jan 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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) (<=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.
Who cannot join
- 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).
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- 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.
Trial locations and contacts
38 sites in 5 countries.
38 sites in 5 countries
Spain15 sites
GSK Investigational Site
Almería, 04009
GSK Investigational Site
Badalona, 08916
GSK Investigational Site
Barcelona, 08003
GSK Investigational Site
Granollers, Barcelona, 08041
GSK Investigational Site
L'Hospitalet de Llobregat, 08907
GSK Investigational Site
Lleida, 25198
GSK Investigational Site
Madrid, 28040
GSK Investigational Site
Madrid, 28041
GSK Investigational Site
Madrid, 28100
GSK Investigational Site
Málaga, 29010
GSK Investigational Site
Manises (Valencia), 46940
GSK Investigational Site
San Sebastián de los Reyes, 28702
GSK Investigational Site
Santander, 39008
GSK Investigational Site
Santiago de Compostela, 15706
GSK Investigational Site
Valladolid, 47005
Russia8 sites
GSK Investigational Site
Krasnodar, 350029
GSK Investigational Site
Moscow, 129327
GSK Investigational Site
Mytischi, 141009
GSK Investigational Site
Omsk, 644112
GSK Investigational Site
Penza, 440034
GSK Investigational Site
Saint Petersburg, 194354
GSK Investigational Site
Saint Petersburg, 197110
GSK Investigational Site
Yaroslavl, 150062
United States7 sites
GSK Investigational Site
Greenbelt, Maryland, 20770
GSK Investigational Site
Kansas City, Missouri, 64111
GSK Investigational Site
Northridge, California, 91324
GSK Investigational Site
Pembroke Pines, Florida, 33028
GSK Investigational Site
Roseville, Michigan, 48066
GSK Investigational Site
San Dimas, California, 91773
GSK Investigational Site
The Bronx, New York, 10461
Canada4 sites
GSK Investigational Site
Calgary, Alberta, T2R 0X7
GSK Investigational Site
Greenfield Park, Quebec, J4V 2H1
GSK Investigational Site
Ottawa, Ontario, K1H 7W9
GSK Investigational Site
Toronto, Ontario, M3M 0B2
Germany4 sites
GSK Investigational Site
Darmstadt, 64295
GSK Investigational Site
Kiel, Schleswig-Holstein, 24105
GSK Investigational Site
Stuttgart, Baden-Wurttemberg, 70376
GSK Investigational Site
Villingen-Schwenningen, Baden-Wurttemberg, 78054
About this study
Official title: 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
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.
- Conditions
- Anaemia
- Being tested
- GSK1278863, GSK1278863 matching Placebo
- Keywords
- Chronic kidney disease, Efficacy, Erythropoiesis-stimulating agent, GSK1278863, Safety, Hemodialysis-dependent anemia, Pharmacokinetics
- Medical subject headings
- Anemia, Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK1278863Drug
GSK1278863 will be supplied as a round, biconvex, 10 millimeter (mm) white film coated tablet with the unit dose strength of 5 mg and 25 mg.
GSK1278863 matching PlaceboDrug
GSK1278863 matching placebo will be supplied as a round, biconvex, 10 mm white film coated tablet.
| Study group | Role | What they receive |
|---|---|---|
| GSK1278863 10 mg | Experimental | Subject will receive 10 mg of GSK1278863 three-times weekly for 4 weeks (up to 29 days). Receives: Drug: GSK1278863 |
| GSK1278863 15 mg | Experimental | Subject will receive 15 mg of GSK1278863 three-times weekly for 4 weeks (up to 29 days). Receives: Drug: GSK1278863 |
| GSK1278863 25 mg | Experimental | Subject will receive 25 mg of GSK1278863 three-times weekly for 4 weeks (up to 29 days). Receives: Drug: GSK1278863 |
| GSK1278863 30 mg | Experimental | Subject will receive 30 mg of GSK1278863 three-times weekly for 4 weeks (up to 29 days). Receives: Drug: GSK1278863 |
| Placebo | Placebo comparator | Subject will receive GSK1278863 matching placebo three-times weekly for 4 weeks (up to 29 days). Receives: Drug: GSK1278863 matching Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Hgb Levels at 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.
Measured: Baseline and Day 29
Secondary outcomes (39)
Maximum Observed Change From Baseline in Plasma Erythropoietin (EPO)
Blood samples were collected at Day 1, Day 15 and Day 29 for pharmacodynamic analysis of effect of dapro three times weekly dose regimens on EPO. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. The change from Baseline at each given post-Baseline time point was calculated and the maximum change from Baseline was determined.
Measured: Baseline and up to Day 29
Maximum Observed Percent Change From Baseline in Vascular Endothelial Growth Factor (VEGF)
Blood samples were collected at Day 1, Day 15 and Day 29 for pharmacodynamic analysis of effect of dapro three times weekly dose regimens on VEGF. Day 1 values were considered as Baseline values. The percent change from Baseline at each given post-Baseline time point was calculated (expressed as geometric mean) and the maximum percent change from Baseline was determined.
Measured: Baseline and up to Day 29
Percent Change From Baseline in Hepcidin at Day 29
Blood samples were collected at Day 1, Day 15 and Day 29 for pharmacodynamic analysis of effect of dapro three times weekly dose regimens on hepcidin. Day 1 values were considered as Baseline values. The Percent change from Baseline at Day 29 post-Baseline time point was calculated and expressed as geometric mean and the maximum change from Baseline was determined.
Measured: Baseline and Day 29
Change From Baseline in Hematocrit Levels
Blood samples were collected at Day 1, Day 15 and Day 29 for pharmacodynamic analysis of effect Dapro three times weekly dose regimens on hematocrit. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-dose visit values minus Baseline value. The change from Baseline at Day 29 post-Baseline time point was calculated.
Measured: Baseline and Day 29
Change From Baseline in Red Blood Cell (RBC) Count
Blood samples were collected at Day 1, Day 15 and Day 29 for pharmacodynamic analysis of effect Dapro three times weekly dose regimens on RBC count. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-dose visit values minus Baseline value. The change from Baseline at Day 29 post-Baseline time point was calculated.
Measured: Baseline and Day 29
Change From Baseline in Reticulocyte Count
Blood samples were collected at Day 1, Day 15 and Day 29 for pharmacodynamic analysis of effect Dapro three times weekly dose regimens on reticulocyte count. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. The change from Baseline at Day 29 post-Baseline time point was calculated.
Measured: Baseline and Day 29
Change From Baseline in Reticulocyte Hemoglobin (CHr)
Blood samples were collected at Day 1, Day 15 and Day 29 for pharmacodynamic analysis of effect Dapro three times weekly dose regimens on CHr. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. The change from Baseline at Day 29 post-Baseline time point was calculated.
Measured: 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
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of dapro. The data from each PK sampling day was combined to generate a single profile, and normalized to a 24-hour period to create a "Day 1" profile for non-compartmental analysis (NCA). Metabolite plasma concentrations were analyzed but PK parameters could not be calculated as the metabolites were partially eliminated through dialysis and the dialysis start and end times were not consistent on both PK days. Therefore, a representative metabolite PK profile could not be generated. The analysis was performed on PK Population, which comprised of all participants from whom a PK sample has been obtained and analyzed. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Measured: 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
Maximum Observed Concentration of Dapro in Plasma (Cmax)
Blood samples were collected at indicated time points for PK analysis of dapro. The data from each PK sampling day was combined to generate a single profile, and normalized to a 24-hour period to create a "Day 1" profile for NCA. Metabolite plasma concentrations were analyzed but PK parameters could not be calculated as the metabolites were partially eliminated through dialysis and the dialysis start and end times were not consistent on both PK days. Therefore, a representative metabolite PK profile could not be generated.
Measured: 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
Time to Reach Cmax (Tmax) and Apparent Terminal Half-life (t1/2) of Dapro
Blood samples were collected at indicated time points for PK analysis of dapro. The data from each PK sampling day was combined to generate a single profile, and normalized to a 24-hour period to create a "Day 1" profile for NCA. Metabolite plasma concentrations were analyzed but PK parameters could not be calculated as the metabolites were partially eliminated through dialysis and the dialysis start and end times were not consistent on both PK days. Therefore, a representative metabolite PK profile could not be generated. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Measured: 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
Number of Participants Who Discontinued Study Treatment
Reasons of study treatment discontinuation included adverse events (AEs), protocol deviation, participants reached protocol defined stopping criteria, physician decision and withdrawal by participants. Number of participants who discontinued study treatment are presented. Analysis was performed on Safety Population which comprised of all participants who received at least one dose of study treatment.
Measured: Up to Day 43
Number of Participants With AEs and Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/ birth effect, other situations and is associated with liver injury or impaired liver function.
Measured: Up to Day 43
Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points
Serum sodium, potassium, glucose, corrected calcium and phosphate levels were assessed as a clinical chemistry laboratory parameter from Baseline up to follow up visit at Day 43. Day 1 values were considered as Baseline values. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Measured: Up to Day 43
Albumin and Protein Levels in Blood at Indicated Tme Points
Serum albumin and protein levels were assessed as a clinical chemistry laboratory parameter from Baseline up to follow up visit at Day 43. Day 1 values were considered as Baseline values. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Measured: Up to Day 43
Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points
Serum ALT, AST and alk. phosph. levels were assessed as a clinical chemistry laboratory parameter from Baseline up to follow up visit at Day 43. Day 1 values were considered as Baseline values. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Measured: Up to Day 43
Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points
Serum bilirubin, direct bilirubin and indirect bilirubin levels were assessed as a clinical chemistry laboratory parameter from Baseline up to follow up visit at Day 43. Day 1 values were considered as Baseline values. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Measured: Up to Day 43
Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels
Blood samples were collected from participants to evaluate clinical chemistry parameters including sodium, potassium, glucose, calcium and phosphate. Change from Baseline in clinical chemistry parameters at Day 15, Day 29 and Day 43 are presented. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Measured: Baseline and up to Day 43
Change From Baseline in Albumin and Protein Levels
Blood samples were collected from participants to evaluate clinical chemistry parameters including albumin and protein. Change from Baseline in clinical chemistry parameters at Day 15, Day 29 and Day 43 are presented. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Measured: Baseline and up to Day 43
Change From Baseline in ALT, AST, Alk. Phosph. Levels
Blood samples were collected from participants to evaluate clinical chemistry parameters including ALT, AST, Alk. phosph. Change from Baseline in clinical chemistry parameters at Day 15, Day 29 and Day 43 are presented. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Measured: Baseline and up to Day 43
Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels
Blood samples were collected from participants to evaluate clinical chemistry parameters including bilirubin, direct bilirubin and indirect bilirubin. Change from Baseline in clinical chemistry parameters at Day 15, Day 29 and Day 43 are presented. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Measured: Baseline and up to Day 43
Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points
Serum leukocytes, neutrophils, basophils, eosinophils, lymphocytes, monocytes and platelet levels were assessed as a clinical hematology laboratory parameter from Baseline up to follow up visit at Day 43. Day 1 values were considered as Baseline values. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Measured: Up to Day 43
Mean Corpuscular Hemoglobin (MCH) Levels in Blood at Indicated Time Points
Serum MCH levels were assessed as a clinical hematology laboratory parameter from Baseline up to follow up visit at Day 43. Day 1 values were considered as Baseline values. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Measured: Up to Day 43
Mean Corpuscular Hemoglobin Concentration (MCHC) Levels in Blood at Indicated Time Points
Serum MCHC levels were assessed as a clinical hematology laboratory parameter from Baseline up to follow up visit at Day 43. Day 1 values were considered as Baseline values. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Measured: Up to Day 43
Mean Corpuscular Volume (MCV) Levels in Blood at Indicated Time Points
Serum MCV levels were assessed as a clinical hematology laboratory parameter from Baseline up to follow up visit at Day 43. Day 1 values were considered as Baseline values. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Measured: Up to Day 43
Erythrocyte Distribution Width Levels in Blood at Indicated Time Points
Erythrocyte distribution width levels were assessed as a clinical hematology laboratory parameter from Baseline up to follow up visit at Day 43. Day 1 values were considered as Baseline values. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Measured: Up to Day 43
Change From Baseline in MCH Levels
Blood samples were collected from participants to evaluate clinical hematology parameters including MCH. Change from Baseline in clinical hematology parameters at Day 15, Day 29, Day 43 are presented. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Measured: Baseline and up to Day 43
Change From Baseline in MCHC Levels
Blood samples were collected from participants to evaluate clinical hematology parameters including MCHC. Change from Baseline in clinical hematology parameters at Day 15, Day 29, Day 43 are presented. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Measured: Baseline and up to Day 43
Change From Baseline in MCV Levels
Blood samples were collected from participants to evaluate clinical hematology parameters including MCV. Change from Baseline in clinical hematology parameters at Day 15, Day 29, Day 43 are presented. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Measured: Baseline and up to Day 43
Change From Baseline in Erythrocyte Distribution Width Levels
Blood samples were collected from participants to evaluate clinical hematology parameters including erythrocyte distribution width. Change from Baseline in clinical hematology parameters at Day 15, Day 29, Day 43 are presented. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Measured: Baseline and up to Day 43
Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels
Blood samples were collected from participants to evaluate clinical hematology parameters including leukocytes, neutrophils, basophils, eosinophils, lymphocytes, monocytes, platelets. Change from Baseline in clinical hematology parameters at Day 15, Day 29, Day 43 are presented. Day 1 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Measured: Baseline and up to Day 43
Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Indicated Time Points
Single measurements of 12-lead ECG were obtained in supine position using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT interval. Number of participants who had abnormal non clinically significant (NCS) and abnormal clinically significant (CS) ECG findings at Baseline (Week -4) and Day 29 are presented.
Measured: Up to Day 29
Change From Baseline in ECG Mean Heart Rate
Single measurements of 12-lead ECG were obtained in supine position using an ECG machine to measure HR. Week -4 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values at Day 29 minus Baseline value.
Measured: Baseline and Day 29
Change From Baseline in ECG Parameters Including PR Interval, QRS Duration, QT Interval and QTcB
Single measurements of 12-lead ECG were obtained in supine position using an ECG machine to measure PR interval, QRS duration, QT interval and QTcB. Week -4 values were considered as Baseline values. Change from Baseline was calculated by subtracting post-Baseline visit values at Day 29 minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Measured: Baseline and Day 29
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis
Vital sign measurements including SBP and DBP were taken in a seated or semi-supine position in the dialysis chair at specific time points. SBP and DBP were measured pre-dialysis and post-dialysis. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Measured: Up to Day 43
Pulse Rate Values at Pre-dialysis and Post-dialysis
Vital sign measurements including pulse rate values were taken in a seated or semi-supine position in the dialysis chair. Pulse rate was measured pre-dialysis and post-dialysis. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Measured: Up to Day 43
Weight Values at Post-dialysis
Vital sign measurements including weight values were taken in a seated or semi-supine position in the dialysis chair. Weight was measured post-dialysis. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Measured: Up to Day 43
Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis
Vital sign measurements including SBP and DBP were taken in a seated or semi-supine position in the dialysis chair. SBP and DBP were measured pre-dialysis and post-dialysis. Pre-dialysis Baseline value was defined as SBP and DBP value obtained pre-dialysis on Day 1. Post-dialysis Baseline value was defined as SBP and DBP value obtained post-dialysis at Week -2. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Measured: Up to Day 43
Change From Baseline in Pulse Rate Value at Pre-dialysis and Post-dialysis
Vital sign measurements including pulse rate were taken in a seated or semi-supine position in the dialysis chair. Pulse rate was measured pre-dialysis and post-dialysis. Pre-dialysis Baseline value was defined as pulse rate value obtained pre-dialysis on Day 1. Post-dialysis Baseline value was defined as pulse rate value obtained post-dialysis at Week -2. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Measured: Up to Day 43
Change From Baseline in Weight at Post-dialysis
Vital sign measurements including weight were taken in a seated or semi-supine position in the dialysis chair. Weight was measured post-dialysis. Post-dialysis Baseline value was defined as SBP and DBP value obtained post-dialysis at Week -2. Change from Baseline was calculated by subtracting post-Baseline visit values minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Measured: Up to Day 43
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2016 (estimated)
- Study start17 Feb 2016
- Primary completion25 Jan 2017
- Study completion25 Jan 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for AnaemiaStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 103 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02689206
- Sponsor's protocol ID
- 204836
- Other IDs
- 2015-004790-32, 2015
- Status last verified
- Feb 2020
- First submitted
- 11 Feb 2016
- Last updated
- 25 Feb 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: IPD for this study will be made available via the Clinical Study Data Request site.
Publications
Bailey CK, Caltabiano S, Cobitz AR, Huang C, Mahar KM, Patel VV. A randomized, 29-day, dose-ranging, efficacy and safety study of daprodustat, administered three times weekly in patients with anemia on hemodialysis. BMC Nephrol. 2019 Oct 16;20(1):372. doi: 10.1186/s12882-019-1547-z.
PubMed 31619187Natale P, Palmer SC, Jaure A, Hodson EM, Ruospo M, Cooper TE, Hahn D, Saglimbene VM, Craig JC, Strippoli GF. Hypoxia-inducible factor stabilisers for the anaemia of chronic kidney disease. Cochrane Database Syst Rev. 2022 Aug 25;8(8):CD013751. doi: 10.1002/14651858.CD013751.pub2.
PubMed 36005278
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02689206
- Acronym / sponsor ID
- 204836
- Conditions
- Anaemia
- Keywords
- Chronic kidney disease, Efficacy, Erythropoiesis-stimulating agent, GSK1278863, Safety, Hemodialysis-dependent anemia, Pharmacokinetics
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 103 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 17 Feb 2016 (actual)
- Primary completion
- 25 Jan 2017 (actual)
- Study completion
- 25 Jan 2017 (actual)
- First posted
- 23 Feb 2016 (estimated)
- Results
- Posted 21 May 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| GSK1278863 10 mg | Experimental | Drug: GSK1278863Subject will receive 10 mg of GSK1278863 three-times weekly for 4 weeks (up to 29 days). |
| GSK1278863 15 mg | Experimental | Drug: GSK1278863Subject will receive 15 mg of GSK1278863 three-times weekly for 4 weeks (up to 29 days). |
| GSK1278863 25 mg | Experimental | Drug: GSK1278863Subject will receive 25 mg of GSK1278863 three-times weekly for 4 weeks (up to 29 days). |
| GSK1278863 30 mg | Experimental | Drug: GSK1278863Subject will receive 30 mg of GSK1278863 three-times weekly for 4 weeks (up to 29 days). |
| Placebo | Placebo comparator | Drug: GSK1278863 matching PlaceboSubject will receive GSK1278863 matching placebo three-times weekly for 4 weeks (up to 29 days). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (26 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GSK1278863GSK1278863 will be supplied as a round, biconvex, 10 millimeter (mm) white film coated tablet with the unit dose strength of 5 mg and 25 mg. | Drug | GSK1278863 10 mg, GSK1278863 15 mg, GSK1278863 25 mg, GSK1278863 30 mg |
| GSK1278863 matching PlaceboGSK1278863 matching placebo will be supplied as a round, biconvex, 10 mm white film coated tablet. | Drug | Placebo |
Primary outcome
Change From Baseline in Hgb Levels at Day 29
Time frame: 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.
39 secondary outcomes
Maximum Observed Change From Baseline in Plasma Erythropoietin (EPO)
Time frame: Baseline and up to Day 29
Maximum Observed Percent Change From Baseline in Vascular Endothelial Growth Factor (VEGF)
Time frame: Baseline and up to Day 29
Percent Change From Baseline in Hepcidin at Day 29
Time frame: Baseline and Day 29
Change From Baseline in Hematocrit Levels
Time frame: Baseline and Day 29
Change From Baseline in Red Blood Cell (RBC) Count
Time frame: Baseline and Day 29
Change From Baseline in Reticulocyte Count
Time frame: Baseline and Day 29
Change From Baseline in Reticulocyte Hemoglobin (CHr)
Time frame: 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
Time frame: 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
Maximum Observed Concentration of Dapro in Plasma (Cmax)
Time frame: 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
Time to Reach Cmax (Tmax) and Apparent Terminal Half-life (t1/2) of Dapro
Time frame: 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
Number of Participants Who Discontinued Study Treatment
Time frame: Up to Day 43
Number of Participants With AEs and Serious Adverse Events (SAEs)
Time frame: Up to Day 43
Sodium, Potassium, Glucose, Calcium, Phosphate Levels in Blood at Indicated Time Points
Time frame: Up to Day 43
Albumin and Protein Levels in Blood at Indicated Tme Points
Time frame: Up to Day 43
Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (Alk. Phosph) Levels in Blood at Indicated Time Points
Time frame: Up to Day 43
Bilirubin, Direct Bilirubin and Indirect Bilirubin Levels in Blood at Indicated Time Points
Time frame: Up to Day 43
Change From Baseline in Sodium, Potassium, Glucose, Calcium and Phosphate Levels
Time frame: Baseline and up to Day 43
Change From Baseline in Albumin and Protein Levels
Time frame: Baseline and up to Day 43
Change From Baseline in ALT, AST, Alk. Phosph. Levels
Time frame: Baseline and up to Day 43
Change From Baseline in Bilirubin, Direct Bilirubin, Indirect Bilirubin Levels
Time frame: Baseline and up to Day 43
Leukocytes, Neutrophils, Basophils, Eosinophils,Lymphocytes, Monocytes, Platelet Levels in Blood at Indicated Time Points
Time frame: Up to Day 43
Mean Corpuscular Hemoglobin (MCH) Levels in Blood at Indicated Time Points
Time frame: Up to Day 43
Mean Corpuscular Hemoglobin Concentration (MCHC) Levels in Blood at Indicated Time Points
Time frame: Up to Day 43
Mean Corpuscular Volume (MCV) Levels in Blood at Indicated Time Points
Time frame: Up to Day 43
Erythrocyte Distribution Width Levels in Blood at Indicated Time Points
Time frame: Up to Day 43
Change From Baseline in MCH Levels
Time frame: Baseline and up to Day 43
Change From Baseline in MCHC Levels
Time frame: Baseline and up to Day 43
Change From Baseline in MCV Levels
Time frame: Baseline and up to Day 43
Change From Baseline in Erythrocyte Distribution Width Levels
Time frame: Baseline and up to Day 43
Change From Baseline in Leukocytes, Neutrophils, Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Levels
Time frame: Baseline and up to Day 43
Number of Participants With Abnormal Electrocardiogram (ECG) Findings at Indicated Time Points
Time frame: Up to Day 29
Change From Baseline in ECG Mean Heart Rate
Time frame: Baseline and Day 29
Change From Baseline in ECG Parameters Including PR Interval, QRS Duration, QT Interval and QTcB
Time frame: Baseline and Day 29
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Values at Pre-dialysis and Post-dialysis
Time frame: Up to Day 43
Pulse Rate Values at Pre-dialysis and Post-dialysis
Time frame: Up to Day 43
Weight Values at Post-dialysis
Time frame: Up to Day 43
Change From Baseline in SBP and DBP Values at Pre-dialysis and Post-dialysis
Time frame: Up to Day 43
Change From Baseline in Pulse Rate Value at Pre-dialysis and Post-dialysis
Time frame: Up to Day 43
Change From Baseline in Weight at Post-dialysis
Time frame: Up to Day 43
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 31619187Bailey CK, Caltabiano S, Cobitz AR, Huang C, Mahar KM, Patel VV. A randomized, 29-day, dose-ranging, efficacy and safety study of daprodustat, administered three times weekly in patients with anemia on hemodialysis. BMC Nephrol. 2019 Oct 16;20(1):372. doi: 10.1186/s12882-019-1547-z.
- Derived from this study: PubMed 36005278Natale P, Palmer SC, Jaure A, Hodson EM, Ruospo M, Cooper TE, Hahn D, Saglimbene VM, Craig JC, Strippoli GF. Hypoxia-inducible factor stabilisers for the anaemia of chronic kidney disease. Cochrane Database Syst Rev. 2022 Aug 25;8(8):CD013751. doi: 10.1002/14651858.CD013751.pub2.
- Individual participant dataSharing planned: Yes. IPD for this study will be made available via the Clinical Study Data Request site.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
38 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GSK1278863 in people with Anaemia, run by GlaxoSmithKline at 38 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 38 sites in Spain, Russia, United States, Canada, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 May 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Hgb Levels at Day 29 (time frame: Baseline and Day 29). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02689206, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Feb 2020.