Last updated: 07/17/2024 16:49:52
4 week correction study in subjects with anemia associated with chronic kidney disease who are not undergoing dialysis
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: A four-week Phase IIa, randomized, double-blind, placebo-controlled, parallel-group, multi-center study to evaluate the safety, efficacy and pharmacokinetics of GSK1278863 in subjects with anemia associated with chronic kidney disease who are not taking recombinant human erythropoietin and are not undergoing dialysis
Trial description: This is a four-week Phase IIa, randomized, double-blind, placebo-controlled, parallel-group, multi-center study to evaluate the safety, efficacy and pharmacokinetics of GSK1278863 in approximately 68 subjects with anemia associated with chronic kidney disease who are not taking rhEPO and are not undergoing dialysis. The range of Hgb values for study eligibility is 8.5-11.0 g/dL. Eligible subjects will be randomized in equal proportions to receive once daily (QD) placebo or GSK1278863 0.5 mg, 2 mg or 5 mg in a double-blind fashion.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
Modeled Hgb change from Baseline over 4 weeks of treatment
Timeframe: Baseline (average of Week -2, -1 and Day 1) and Week 4
Secondary outcomes:
Model-Adjusted Maximum Hgb changes over 4 weeks
Timeframe: Baseline (average of Week -2 , -1 and Day 1 visits) and 4 weeks
Number of participants achieving an increase of 0.5, 1.0, 1.5 and 2.0 g/dL in Hgb
Timeframe: Up to 4 weeks
Percentage of participants achieving an increase of 0.5, 1.0, 1.5 and 2.0 g/dL in Hgb
Timeframe: Up to 4 weeks
Number of participants who reached Hgb stopping criteria
Timeframe: Up to Week 4
Change from Baseline in Hepcidin at Week 2 and Week 4
Timeframe: Baseline (Pre-dose on Day 1), Week 2 and 4
Change from Baseline in Ferritin at Week 2 and Week 4
Timeframe: Baseline (Day 1 Pre-dose), Week 2 and 4
Change from Baseline in Transferrin at Week 2 and Week 4
Timeframe: Baseline (Day 1 Pre-dose), Week 2 and 4
Change from Baseline in Transferrin Saturation at Week 2 and Week 4
Timeframe: Baseline (Day 1 Pre-dose), Week 2 and 4
Change from Baseline in Total Iron Binding Capacity at Week 2 and Week 4
Timeframe: Baseline (Day 1 Pre-dose), Week 2 and 4
Change from Baseline in Total Iron at Week 2 and Week 4
Timeframe: Baseline (Day 1 Pre-dose), Week 2 and 4
Change from Baseline in High sensitivity C-reactive protein (hsCRP) at Week 2 and Week 4
Timeframe: Baseline (Day 1 Pre-dose), Week 2 and 4
Change from Baseline in hematocrit and reticulocytes over 4 weeks
Timeframe: Baseline (Day 1 pre-dose), Week 1, 2, 3, and 4
Change from Baseline in Erythropoietin at Week 2 and Week 4
Timeframe: Baseline (Day 1 Pre-dose), Week 2 and 4
Change from Baseline in Red Blood Cells count over 4 weeks
Timeframe: Baseline (Day 1 pre-dose), week 1, 2, 3, 4
Change from Baseline in Vascular Endothelial Growth Factor (VEGF) at Week 2 and Week 4
Timeframe: Baseline (Pre-dose), week 2 and 4
Number of participants with adverse events (AEs) and serious adverse events (SAEs)
Timeframe: Up to 6 weeks
Number of participants discontinuing the study treatment due to AEs
Timeframe: Up to 6 weeks
Absolute values of alanine amino transferase (ALT), alkaline phosphatase (ALP), aspartate amino transferase (AST), creatine kinase (CK) at Baseline (Day 1), Week 2, 4, and 6
Timeframe: Baseline (Day 1 pre-dose), Week 2, 4, and 6
Absolute values of albumin, apolipoprotein A1, apolipoprotein total, total protein at Baseline (Day 1), Week 2, 4, and 6
Timeframe: Baseline (Day 1 pre-dose), Week 2, 4, and 6
Absolute values of calcium, chloride, cholesterol, glucose, inorganic phosphorus, potassium, sodium at Baseline (Day 1), Week 2, 4, and 6
Timeframe: Baseline (Day 1 pre-dose), Week 2, 4, and 6
Absolute values of creatinine, direct bilirubin, indirect bilirubin, total bilirubin at Baseline (Day 1), Week 2, 4, and 6
Timeframe: Baseline (Day 1 pre-dose), Week 2, 4, and 6
Absolute values of urine total protein/creatinine ratio at Baseline (Day 1), Week 2, 4, and 6
Timeframe: Baseline (Day 1), Week 2, 4, and 6
Change from Baseline values of ALT, ALP, AST, CK at Week 2, 4, and 6
Timeframe: Baseline (Day 1), Week 2, 4, and 6
Change from Baseline values of albumin, apolipoprotein A1, apolipoprotein total, total protein at Week 2, 4, and 6
Timeframe: Baseline (Day 1), Week 2, 4, and 6
Change from Baseline values of calcium, chloride, cholesterol, glucose, inorganic phosphorus, potassium, sodium at Week 2, 4, and 6
Timeframe: Baseline (Day 1), Week 2, 4, and 6
Change from Baseline values of creatinine, direct bilirubin, indirect bilirubin, total bilirubin at Week 2, 4, and 6
Timeframe: Baseline (Day 1), Week 2, 4, and 6
Change from Baseline values of urine total protein/creatinine ratio at Week 2, 4, and 6
Timeframe: Baseline (Day 1), Week 2, 4, and 6
Absolute values of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet count, WBC count (absolute) at Baseline, Week 1, 2, 3, 4, and 6
Timeframe: Baseline (Day 1 pre-dose), Week 1, 2, 3, 4, and 6
Absolute values of Mean Corpuscle Volume at Baseline, Week 1, 2, 3, 4 and 6
Timeframe: Baseline (Day 1 pre-dose), Week 1, 2, 3, 4, and 6
Absolute values of Mean Corpuscle Hgb Concentration at Baseline (Day 1), Week 1, 2, 3, 4, and 6
Timeframe: Baseline (Day 1 pre-dose), Week 1, 2, 3, 4, and 6
Absolute values of Reticulocyte count at Baseline (Day 1), Week 1, 2, 3, 4, and 6
Timeframe: Baseline (Day 1 pre-dose), Week 1, 2, 3, 4, and 6
Change from Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet count, WBC count (absolute) at Week 1, 2, 3, 4, and 6
Timeframe: Baseline (Day 1), Week 1, 2, 3, 4, and 6
Change from Baseline in Mean Corpuscle Volume at Week 1, 2, 3, 4, and 6
Timeframe: Baseline (Day 1), Week 1, 2, 3, 4, and 6
Change from Baseline in Mean Corpuscle Hgb Concentration at Week 1, 2, 3, 4, and 6
Timeframe: Baseline (Day 1), Week 1, 2, 3, 4, and 6
Absolute values of Systolic blood pressure and diastolic blood pressure Baseline, Week 1, Week 2, Week 3, Week 4 and Week 6
Timeframe: Baseline (Day 1 pre-dose), Week 1, 2, 3, 4, and 6
Change from baseline in systolic blood pressure and diastolic blood pressure at Week 1, 2, 3, 4, and 6
Timeframe: Baseline (Day 1 pre-dose), Week 1, 2, 3, 4, and 6
Absolute values of heart rate at Baseline (Day 1), Week 1, 2, 3, 4, and 6
Timeframe: Baseline (Day 1 pre-dose), Week 1, 2, 3, 4, and 6
Change from baseline in heart rate at Week 1, 2, 3, 4, and 6
Timeframe: Baseline (Day 1 pre-dose), Week 1, 2, 3, 4, and 6
Absolute electrocardiogram (ECG) parameter values at Baseline (Screening), Week 2, 4, and 6
Timeframe: Baseline (Screening), Week 2, 4, and 6
Change from baseline in ECG parameters at Week 2, 4 and 6
Timeframe: Baseline (Screening), Week 2, 4, and 6
Mean Maximum plasma concentration (Cmax) of GSK1278863 and GSK1278863 metabolites
Timeframe: Day 1 (pre-dose), Week 2 (first samples was collected approximately between 4 to 8 h and then 1, 2 and 3 h after this first sample) and Week 4 (Pre-dose 1, 2 and 3 h post-dose).
Mean Steady state Area under the curve (AUC) of GSK1278863 and GSK1278863 metabolites
Timeframe: Day 1 (pre-dose), Week 2 (first samples was collected approximately between 4 to 8 h and then 1, 2 and 3 h after this first sample) and Week 4 (Pre-dose 1, 2 and 3 h post-dose)
Interventions:
Drug: GSK1278863
Other: Placebo
Enrollment:
74
Observational study model:
Not applicable
Primary completion date:
2013-07-05
Time perspective:
Not applicable
Clinical publications:
Louis Holdstock, Amy M. Meadowcroft, Rayma Maier, Brendan M. Johnson, Delyth Jones, Anjay Rastogi, Steven Zeig,, John J. Lepore, Alexander R. Cobitz .Four-week studies of oral HIF-prolyl hydroxylase inhibitor GSK1278863 for Treatment of Anemia .J Am Soc Nephrol.2016;April(27):1234-44
Medical condition
Anaemia
Product
daprodustat
Collaborators
Pharmaceutical Product Development Clinical Research Organization (CRO)
Study date(s)
May 2012 to May 2013
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
18 - 99 years
Accepts healthy volunteers
No
- 1. Age and weight: >/= 18 years of age and >/= 45 kg.
- 2. Not routinely undergoing dialysis, regardless of the modality (either hemodialysis or peritoneal dialysis) or dialysis planned during the time the subject would be enrolled in the study.
- 1. Dialysis: Planning to initiate dialysis during the study or who have a high potential for initiating dialysis during study participation.
- 2. Renal transplant: Renal transplant anticipated or scheduled within the study time period or subjects with a functioning renal transplant.
Inclusion and exclusion criteria
Inclusion criteria:
- 1. Age and weight: >/= 18 years of age and >/= 45 kg. 2. Not routinely undergoing dialysis, regardless of the modality (either hemodialysis or peritoneal dialysis) or dialysis planned during the time the subject would be enrolled in the study. 3. No current or prior rhEPO use within the past 7 weeks; e.g., epoetins (or their biosimilars), darbepoetin, Mircera (methoxy polyethylene glycol epoetin beta), peginesatide or their biosimilars.. 4. KDOQI CKD stages 3/4/5 defined by eGFR using the Modification of Diet for Renal Disease (MDRD). 5. Hgb: Hgb concentrations 8.5-11.0 g/dL (inclusive) as outlined in Section 4.2. 6. Vitamin B12: Above the lower limit of the reference range (may rescreen in 2 months). 7. Folate: >/=2.0 ng/mL at Screening. May rescreen in a month. 8. Ferritin: >/=40 ng/mL with the absence of microcytic or hypochromic RBCs. 9. TSAT within the reference range. 10. Iron replacement therapy: Stable maintenance dose of oral iron replacement therapy, if required, that will be maintained throughout the study. NOTE: IV iron replacement therapy is not allowed the two weeks prior to Screening through the end of the study (Week 6). 11. QTc: QTcB <470 msec or QTcB <480 msec in subjects with bundle branch block obtained at Screening Visit, based on Central Reader’s interpretation. 12. Females: Eligible to participate if she is of childbearing potential, and must agree to use approved contraception methods from Screening until completion of the Follow-up Visit OR of non-childbearing potential defined as pre-menopausal females with a documented tubal ligation of hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH)>40 MIU/ml and estradiol <40 pg/ml is confirmatory]. Females on hormone replacement therapy (HRT) whose menopausal status is in doubt will be required to use one of the approved contraception methods if they wish to continue their HRT during the study. Otherwise they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most types of HRT, at least 2 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method. 13. Males: Must agree to use approved contraceptive methods from the time of Screening until completion of the Follow-up Visit.
Exclusion criteria:
- 1. Dialysis: Planning to initiate dialysis during the study or who have a high potential for initiating dialysis during study participation. 2. Renal transplant: Renal transplant anticipated or scheduled within the study time period or subjects with a functioning renal transplant. 3. Total CPK: >5x the upper limit of the reference range. 4. HIV: Positive HIV antibody. 5. History of myocardial infarction or acute coronary syndrome within the prior 6 months. 6. History of stroke or TIAs. 7. Heart failure: Class III/IV heart failure, as defined by the New York Heart Association (NYHA) functional classification system. 8. Hypertension: Poorly controlled hypertension, whether due to inadequate treatment, or lack of treatment, defined as DBP >100 mmHg or SBP>160 mmHg. 9. Thrombotic disease: History of thrombotic disease (e.g., venous thrombosis such as deep vein thrombosis or pulmonary embolism, or arterial thrombosis such as new onset or worsening limb ischemia requiring intervention), or other thrombosis related condition) within the prior 6 months. 10. Pulmonary hypertension: Known pulmonary hypertension and those at higher risk (than normally associated with CKD) for pre-existing elevation in pulmonary pressure (e.g., significant heart failure or lung disease requiring supplemental oxygen, or those with connective tissue diseases). 11. Inflammatory disease: Chronic inflammatory disease that could impact erythropoiesis (e.g., scleroderma, systemic lupus erythematosis, rheumatoid arthritis, celiac disease). 12. Hematological disease: Any hematological disease including those affecting platelets, the coagulation disorders (e.g., Protein C or S deficiency) or red blood cells (e.g. sickle cell anemia, myelodysplastic syndromes, hematological malignancy, myeloma, hemolytic anemia) or any other cause of anemia other than renal disease. 13. 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 [alkaline phosphatase, ALT or AST > 2.0 x upper limit of normal (ULN) or total bilirubin > 1.5 x ULN]; or other hepatic abnormalities that in the opinion of the investigator would preclude the subject from participation in the study. 14. Major surgery: Within the prior 12 weeks or planned during the study. 15. Transfusion: Blood transfusion within the prior 12 weeks or an anticipated need for blood transfusion during the study. 16. Ulcer and Active GI Bleeding: Evidence of active peptic, duodenal, or esophageal ulcer disease or active GI bleeding within the prior 12 weeks. 17. Acute infection: Clinical evidence of acute infection or history of infection requiring intravenous (IV) antibiotic therapy the eight weeks prior to Screening through Day 1 (randomization). 18. Malignancy: History of malignancy within 5 years of Screening or are receiving treatment for cancer or those with a strong family history of cancer (e.g., familial cancer disorders), with the exception of squamous cell or basal cell carcinoma of the skin that has been definitively treated. 19. Hyperparathyroidism: Clinically significant hyperparathyroidism in the opinion of the Investigator, including subjects with parathyroid hormone (PTH) values ≥600 pg/mL. 20. Eyes: History of proliferative retinopathy requiring treatment within the prior 12 months, or macular edema requiring treatment. 21. Severe reactions: History of severe allergic or anaphylactic reactions or hypersensitivity to excipients in the investigational product. 22. Drugs and supplements: Use of any prescription or non-prescription drugs or dietary supplements that are prohibited from Screening until the Follow-up Visit. 23. Androgens: New androgen therapy or changes to pre-existing androgen regimen within prior 12 weeks. 24. Prior investigational product exposure: The subject has participated in a clinical trial and has received an experimental investigational product within prior 30 days. 25. Protocol compliance: Unwillingness or inability to follow the procedures, or lifestyle and/or dietary restrictions outlined in the protocol. 26. Other conditions: Any condition which in the investigators opinion should exclude the subject from participating in the study. 27. Pregnancy and lactation: Pregnant females as determined by positive urine hCG test, OR women who are lactating at Screening or during the trial.
Trial location(s)
Location
GSK Investigational Site
Arlington, Texas, United States, 76011
Status
Study Complete
Location
GSK Investigational Site
Asheville, North Carolina, United States, 28801
Status
Study Complete
Location
GSK Investigational Site
Azusa, California, United States, 91702
Status
Study Complete
Location
GSK Investigational Site
Bethlehem, Pennsylvania, United States, 18017
Status
Study Complete
Location
GSK Investigational Site
Charlotte, North Carolina, United States, 28207
Status
Study Complete
Location
GSK Investigational Site
Chino, California, United States, 91710
Status
Study Complete
Location
GSK Investigational Site
Corsicana, Texas, United States, 75110
Status
Study Complete
Location
GSK Investigational Site
Daytona Beach, Florida, United States, 32117
Status
Study Complete
Location
GSK Investigational Site
Demmin, Mecklenburg-Vorpommern, Germany, 17109
Status
Study Complete
Location
GSK Investigational Site
Detroit, Michigan, United States, 48236
Status
Study Complete
Location
GSK Investigational Site
Edgewater, Florida, United States, 32132
Status
Study Complete
Location
GSK Investigational Site
Evanston, Illinois, United States, 60201
Status
Study Complete
Location
GSK Investigational Site
Greenville, Texas, United States, 75402
Status
Study Complete
Location
GSK Investigational Site
Jacksonville, Florida, United States, 32258
Status
Study Complete
Location
GSK Investigational Site
Los Angeles, California, United States, 90022
Status
Study Complete
Location
GSK Investigational Site
North Hollywood, California, United States, 91606-1559
Status
Study Complete
Location
GSK Investigational Site
Orange, California, United States, 92868
Status
Study Complete
Location
GSK Investigational Site
Pembroke Pines, Florida, United States, 33028
Status
Study Complete
Location
GSK Investigational Site
Port Charlotte, Florida, United States, 33952
Status
Study Complete
Location
GSK Investigational Site
Portland, Oregon, United States, 97210
Status
Study Complete
Location
GSK Investigational Site
Riverside, California, United States, 92505
Status
Study Complete
Location
GSK Investigational Site
San Antonio, Texas, United States, 78229
Status
Study Complete
Location
GSK Investigational Site
San Dimas, California, United States, 91773
Status
Study Complete
Location
GSK Investigational Site
Savannah, Georgia, United States, 31406
Status
Study Complete
Location
GSK Investigational Site
Silverdale, Washington, United States, 98383
Status
Study Complete
Location
GSK Investigational Site
Uniontown, Pennsylvania, United States, 15401
Status
Study Complete
Location
GSK Investigational Site
West Hills, California, United States, 91307
Status
Study Complete
Location
GSK Investigational Site
Wilmington, North Carolina, United States, 28401
Status
Study Complete
Location
GSK Investigational Site
Winston Salem, North Carolina, United States, 27103
Status
Study Complete
Study documents
Study report synopsis
Available language(s): English
Protocol
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2013-07-05
Actual study completion date
2013-07-05
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
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