Conditions: Anaemia
Keywords: Renal Impairment Anemia pharmacokinetics hemodialysis Chronic kidney disease GSK1278863 hemoglobin Prolyl hydroxylase inhibitor recombinant human erythropoietin erythropoiesis stimulating agents Dialysis, Renal
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 80
Healthy volunteers: no

Brief summary:
This is a four-week, Phase IIa, randomized, active-controlled, parallel-group, multi-center study to evaluate the safety, efficacy and pharmacokinetics of switching subjects from stable rhEPO to GSK1278863 in approximately 68 hemodialysis-dependent subjects with anemia associated with chronic kidney disease. The study consists of a screening phase of 2 weeks, a 4-week treatment phase and a 2-week follow-up phase. The range of Hgb values for study eligibility is 9.5-12.0 g/dL and the subjects must have received the same rhEPO product with total weekly doses that varied by no more than 50% during the 4 weeks prior to the Screening visit (Week -1. This study aims to estimate the relationship between dose of GSK1278863 and Hgb response in hemodialysis-dependent (HDD) subjects with anemia associated with chronic kidney disease after switching from a stable maintenance dose of recombinant human erythropoetin (rhEPO).

Detailed description:
This is a four-week, Phase IIa, randomized, active-controlled, parallel-group, multi-center study to evaluate the safety, efficacy and pharmacokinetics of switching subjects from stable rhEPO to GSK1278863 in approximately 68 hemodialysis-dependent subjects with anemia associated with chronic kidney disease. The study consists of a screening phase of 2 weeks, a 4-week treatment phase and a 2-week follow-up phase. The range of Hgb values for study eligibility is 9.5-12.0 g/dL and the subjects must have received the same rhEPO product with total weekly doses that varied by no more than 50% during the 4 weeks prior to the Screening visit (Week -1. Eligible subjects, stratified by their prior rhEPO dose will be randomized in equal proportions to receive double-blind GSK1278863 0.5 mg, 2 mg or 5 mg QD (after discontinuing their rhEPO), or to continue to receive their existing type and dose of rhEPO (epoetins or their biosimilars, or darbepoetin). Study treatment will be stopped if Hgb values fall outside of the protocol pre-specified ranges. Subject completion is defined as completion of all study phases including the follow-up phase.

This study aims to estimate the relationship between dose of GSK1278863 and Hgb response in hemodialysis-dependent (HDD) subjects with anemia associated with chronic kidney disease after switching from a stable maintenance dose of recombinant human erythropoetin (rhEPO). In addition, the study will characterize the effect of GSK1278863 on various pharmacokinetic (PK)/pharmacodynamic (PD) markers, and will investigate the safety and tolerability of GSK1278863.

An early interim analysis of the Hgb data is planned after approximately 20 subjects from cohort 1 have completed 3 weeks of treatment. Depending upon the interim findings, a second cohort of subjects may be added to investigate an additional GSK1278863 dose arm. Recruitment to the first cohort will continue during the interim analysis.

A second interim analysis is planned after approximately 48 subjects from cohort 1 have completed 4 weeks treatment. The purpose of this interim is three-fold, to investigate if a second cohort of subjects may be added, to facilitate early development of dose-response and PK/PD statistical models, and to generate interim results to facilitate design and dosing decisions for the next trial.

Arms:
arm 1: once daily arm 2: once daily arm 3: once daily arm 4: as required

Interventions: intervention 1: GSK1278863 intervention 2: rhEPO
Intervention descriptions: intervention 1: tablet intervention 2: injection

Protocol document: