The purpose of this study is to characterize the safety and tolerability of repeat doses of compound 1278863A in healthy subjects.
Compound 1278863A is a novel small molecule agent, which stimulates erythropoiesis through inhibition of hypoxia-inducible factor (HIF)-prolyl hydroxylases (EGLNs). This compound is being developed for the treatment of anemia. Compound 111427 was the first administration of compound 1278863A to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single oral doses up to 300 mg in healthy adult subjects. This study, PHI112842, will be the first administration of compound 1278863A to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of repeat oral doses up to 300 mg for 14 days in healthy adult subjects. At least 6 subjects will complete each cohort. Multiple blood samples for pharmacokinetic analyses will be obtained post-dose in each cohort. Safety will be assessed by measurement of vital signs, cardiac monitoring, collection of adverse event assessments and laboratory safety tests. Blood samples will be collected for pharmacodynamic analyses.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
SINGLE
Enrollment
24
GSK Investigational Site
Melbourne, Victoria, Australia
adverse events reporting
Time frame: throughout study
Safety Labs (hematology)
Time frame: Screening, Days -1, 1-3, 5, 7, 9, 11, 14-18, 21, 25, 28
vital signs (blood pressure and heart rate)
Time frame: Days 1-15, 28
12-lead ECG
Time frame: Screening, Days 1-2, 4, 6, 8, 10, 12, 14, 28
dual-lead cardiac monitoring (telemetry monitoring)
Time frame: Days -1 to 3, 14
clinical monitoring/observation
Time frame: throughout
Safety Labs (Chemistry)
Time frame: Screening, Days -1, 1-3, 7, 10, 14-15, 17, 21, 28
Safety Labs (Urinalysis)
Time frame: Screening, Days -1, 1-3, 7, 10, 14-15, 17, 21, 28
AUC(0-∞) on Day 1, AUC(0-τ), Cmax, tmax and t1/2, on Days 1 and 14
Time frame: Days 1-2, 4, 6, 8, 10, 12, 14-18
Trough plasma concentrations at the end of the dosing interval
Time frame: Days 2, 4, 6, 8, 10 and 12
Hemoglobin actual values, rate of rise, maximum change from baseline, and rate of decline following stopping of dosing
Time frame: Days 1, 7, 14, 21, 28
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Fetal hemoglobin actual values, change from baseline, and percent of total hemoglobin
Time frame: Days 1, 7, 14, 21, 28
Actual values and change from baseline in erythropoietin
Time frame: Days 1-4, 7, 14-15, 18, 21
Actual values and change from baseline in absolute VEGF
Time frame: Days 1-2, 14-15, 18, 21
Actual values and change from baseline in hepcidin
Time frame: Days 1-2, 7, 14-15, 18, 21
Actual values and change from baseline in total iron binding capacity (TIBC)
Time frame: Screening, Days 1, 7, 14, 18, 21
Actual values and change from baseline in transferring saturation (%)
Time frame: Days 1, 7, 14, 18, 21