Page last updated: 2024-10-18

glycine and Anemia

glycine has been researched along with Anemia in 185 studies

Anemia: A reduction in the number of circulating ERYTHROCYTES or in the quantity of HEMOGLOBIN.

Research Excerpts

ExcerptRelevanceReference
"Roxadustat (FG-4592), an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis, was evaluated in a phase 1b study in patients with end-stage renal disease with anemia on hemodialysis."9.34Oral Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor Roxadustat (FG-4592) for Treatment of Anemia in Chronic Kidney Disease: A Placebo-Controlled Study of Pharmacokinetic and Pharmacodynamic Profiles in Hemodialysis Patients. ( Chou, J; Hemmerich, S; Neff, TB; Provenzano, R; Tumlin, J; Yu, KP; Zabaneh, R, 2020)
"FG-4592 may prove an effective alternative for managing anemia of CKD."9.24Phase 2 studies of oral hypoxia-inducible factor prolyl hydroxylase inhibitor FG-4592 for treatment of anemia in China. ( Besarab, A; Chen, J; Chen, N; Fu, P; Hao, C; He, Q; Hemmerich, S; Jiang, G; Li, X; Lin, H; Liu, C; Mei, C; Neff, TB; Ni, D; Peony Yu, KH; Qian, J; Szczech, L; Valone, FH; Yu, X; Zhang, X; Zuo, L, 2017)
" We conducted two phase 2a studies to explore the relationship between the dose of the hypoxia-inducible factor-prolyl hydroxylase inhibitor GSK1278863 and hemoglobin response in patients with anemia of CKD (baseline hemoglobin 8."9.22Four-Week Studies of Oral Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor GSK1278863 for Treatment of Anemia. ( Cobitz, AR; Holdstock, L; Johnson, BM; Jones, D; Lepore, JJ; Maier, R; Meadowcroft, AM; Rastogi, A; Zeig, S, 2016)
"Ixazomib is approved for use in combination with lenalidomide and dexamethasone (IRd) for patients with multiple myeloma (MM) who received at least one previous therapy."8.12Ixazomib, lenalidomide, and dexamethasone combination in "real-world" clinical practice in patients with relapsed/refractory multiple myeloma. ( Chudej, J; Guman, T; Hlebaskova, M; Kucerikova, M; Sokol, J; Stasko, J; Stecova, N; Valekova, L, 2022)
"Chronic Cyclosporine-A treatment is associated with serious side effects, including kidney toxicity and anemia."8.12Daprodustat prevents cyclosporine-A-mediated anemia and peritubular capillary loss. ( Balcerek, B; Brinkmann, L; Fähling, M; Kulow, VA; Labes, R; Mathia, S; Persson, PB; Roegner, K; Rosenberger, C, 2022)
" PK and adverse events (AEs) were assessed after a single 3 mg dose of ixazomib."6.82A pharmacokinetics and safety phase 1/1b study of oral ixazomib in patients with multiple myeloma and severe renal impairment or end-stage renal disease requiring haemodialysis. ( Badros, A; Berdeja, J; Chari, A; Gupta, N; Hanley, MJ; Harvey, RD; Hui, AM; Kukreti, V; Lipe, B; Qian, M; Venkatakrishnan, K; Yang, H; Zhang, X, 2016)
"GSK1278863 is an orally administered small-molecule PHI."6.82A Novel Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor (GSK1278863) for Anemia in CKD: A 28-Day, Phase 2A Randomized Trial. ( Brigandi, RA; Cross, N; de Zoysa, J; Guptha, V; Johnson, B; Kumar, S; McMahon, L; Oei, C; Olbina, G; Roger, SD; Russ, SF; Sahay, M; Singh, N; Smolyarchuk, EA; Westerman, M, 2016)
" Roxadustat (FG-4592) is an orally bioavailable hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor that promotes coordinated erythropoiesis through HIF-mediated transcription."6.82Roxadustat (FG-4592): Correction of Anemia in Incident Dialysis Patients. ( Besarab, A; Chan, DT; Chernyavskaya, E; Franco, M; Gurevich, K; Hemmerich, S; Kumbar, LM; Leong, R; Motylev, I; Neff, TB; Poole, L; Saikali, KG; Shutov, E; Yu, KH; Zhong, M, 2016)
"Of 116 subjects receiving treatment, 104 completed 4 weeks of dosing and 96 were evaluable for efficacy."6.80Randomized placebo-controlled dose-ranging and pharmacodynamics study of roxadustat (FG-4592) to treat anemia in nondialysis-dependent chronic kidney disease (NDD-CKD) patients. ( Besarab, A; Hemmerich, S; Hertel, J; Klaus, SJ; Lee, T; Leong, R; Neff, TB; Provenzano, R; Yu, KH; Zabaneh, R, 2015)
"We evaluated the efficacy and safety of roxadustat versus epoetin alfa for the treatment of chronic kidney disease-related anemia in patients new to dialysis."5.41Roxadustat for anemia in patients with end-stage renal disease incident to dialysis. ( Besarab, A; Bradley, C; Eremeeva, L; Eyassu, M; Korneyeva, S; Leong, R; Liu, CS; Neff, TB; Poole, L; Provenzano, R; Saha, G; Shutov, E; Szczech, L; Yu, KP, 2021)
"Roxadustat (FG-4592), an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis, was evaluated in a phase 1b study in patients with end-stage renal disease with anemia on hemodialysis."5.34Oral Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor Roxadustat (FG-4592) for Treatment of Anemia in Chronic Kidney Disease: A Placebo-Controlled Study of Pharmacokinetic and Pharmacodynamic Profiles in Hemodialysis Patients. ( Chou, J; Hemmerich, S; Neff, TB; Provenzano, R; Tumlin, J; Yu, KP; Zabaneh, R, 2020)
"Oral roxadustat was noninferior to parenteral epoetin alfa as therapy for anemia in Chinese patients undergoing dialysis."5.30Roxadustat Treatment for Anemia in Patients Undergoing Long-Term Dialysis. ( Cai, GY; Chen, N; Hao, C; Hao, L; Jiang, G; Leong, R; Li, X; Liang, X; Lin, H; Liu, BC; Liu, C; Liu, Z; Luo, L; Neff, T; Szczech, L; Wang, C; Wang, J; Xing, C; Yu, KP; Zhao, MH; Zuo, L, 2019)
"Daprodustat (GSK1278863) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor being developed for treatment of anemia associated with chronic kidney disease (CKD)."5.24Effects of Daprodustat, a Novel Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor on Anemia Management in Japanese Hemodialysis Subjects. ( Akizawa, T; Cobitz, A; Endo, Y; Hara, K; Imai, Y; Kawase, N; Kohno, T; Lepore, J; Nakajima, H; Nangaku, M; Tsubakihara, Y, 2017)
"FG-4592 may prove an effective alternative for managing anemia of CKD."5.24Phase 2 studies of oral hypoxia-inducible factor prolyl hydroxylase inhibitor FG-4592 for treatment of anemia in China. ( Besarab, A; Chen, J; Chen, N; Fu, P; Hao, C; He, Q; Hemmerich, S; Jiang, G; Li, X; Lin, H; Liu, C; Mei, C; Neff, TB; Ni, D; Peony Yu, KH; Qian, J; Szczech, L; Valone, FH; Yu, X; Zhang, X; Zuo, L, 2017)
" We conducted two phase 2a studies to explore the relationship between the dose of the hypoxia-inducible factor-prolyl hydroxylase inhibitor GSK1278863 and hemoglobin response in patients with anemia of CKD (baseline hemoglobin 8."5.22Four-Week Studies of Oral Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor GSK1278863 for Treatment of Anemia. ( Cobitz, AR; Holdstock, L; Johnson, BM; Jones, D; Lepore, JJ; Maier, R; Meadowcroft, AM; Rastogi, A; Zeig, S, 2016)
"Ixazomib is approved for use in combination with lenalidomide and dexamethasone (IRd) for patients with multiple myeloma (MM) who received at least one previous therapy."4.12Ixazomib, lenalidomide, and dexamethasone combination in "real-world" clinical practice in patients with relapsed/refractory multiple myeloma. ( Chudej, J; Guman, T; Hlebaskova, M; Kucerikova, M; Sokol, J; Stasko, J; Stecova, N; Valekova, L, 2022)
"Chronic Cyclosporine-A treatment is associated with serious side effects, including kidney toxicity and anemia."4.12Daprodustat prevents cyclosporine-A-mediated anemia and peritubular capillary loss. ( Balcerek, B; Brinkmann, L; Fähling, M; Kulow, VA; Labes, R; Mathia, S; Persson, PB; Roegner, K; Rosenberger, C, 2022)
"The rate of endogenous carbon monoxide production ( Vco), determined by the closed rebreathing system technique, was elevated above the normal range in four of five patients studied with ineffective erythropoiesis (four patients with primary refractory anemia, one with thalassemia)."3.64Carbon monoxide production associated with ineffective erythropoiesis. ( Coburn, RF; Goldwein, MI; Rother, ML; Shafer, BC; White, P; Williams, WJ, 1967)
" Although TEAEs occurred commonly in both the roxadustat and ESA groups, patients infrequently discontinued the study drug because of an adverse event."3.30Safety of Roxadustat Versus Erythropoiesis-Stimulating Agents in Patients with Anemia of Non-dialysis-Dependent or Incident-to-Dialysis Chronic Kidney Disease: Pooled Analysis of Four Phase 3 Studies. ( Barratt, J; Choukroun, G; De Nicola, L; Dellanna, F; Dimković, N; Portoles, J; Reusch, M; Young, J, 2023)
"Anemia is a common side effect of myelosuppressive chemotherapy; however, chemotherapy-induced anemia (CIA) management options are suboptimal."3.30Open-label, Phase 2 study of roxadustat for the treatment of anemia in patients receiving chemotherapy for non-myeloid malignancies. ( Gabrail, NY; Glaspy, J; Henry, DH; Lee, T; Locantore-Ford, P; Modelska, K; Samal, V, 2023)
" Rates of treatment-emergent and serious adverse events (AEs) were also compared between treatment groups to assess safety and tolerability."3.11Efficacy and Safety of Daprodustat for Treatment of Anemia of Chronic Kidney Disease in Incident Dialysis Patients: A Randomized Clinical Trial. ( Blackorby, A; Carroll, K; Cizman, B; Cobitz, AR; Jha, V; Johansen, KL; Lopes, RD; Macdougall, IC; McMurray, JJV; Meadowcroft, AM; Obrador, GT; Paul, G; Perkovic, V; Ranganathan, P; Sedani, S; Singh, AK; Solomon, S; Stankus, N; Strutz, F; Waikar, SS; Wanner, C; Wheeler, DC; Wiecek, A, 2022)
"Anemia is the predominant cytopenia in myelodysplastic syndromes (MDS) and treatment options are limited."3.11Roxadustat for the treatment of anemia in patients with lower-risk myelodysplastic syndrome: Open-label, dose-selection, lead-in stage of a phase 3 study. ( Bartels, P; Bradley, C; Carraway, HE; Glaspy, J; Harrup, R; Henry, DH; Leong, R; Mittelman, M; Modelska, K; Saha, G; Yu, KP; Zhou, A, 2022)
"Anemia is one of the major complications of chronic kidney disease (CKD)."3.11An evaluation of roxadustat for the treatment of anemia associated with chronic kidney disease. ( Kurata, Y; Nangaku, M; Tanaka, T, 2022)
" This post hoc analysis of a Japanese, open-label, partially randomized, phase 3 study in nondialysis-dependent (NDD) CKD patients treated with traditional erythropoiesis-stimulating agents (ESAs) evaluated dosing trends of roxadustat and darbepoetin alfa (DA) required to maintain target hemoglobin concentrations in patients with risk factors associated with ESA hyporesponsiveness."3.01Factors Affecting Doses of Roxadustat Versus Darbepoetin Alfa for Anemia in Nondialysis Patients. ( Akizawa, T; Otsuka, T; Tanaka-Amino, K; Yamaguchi, Y, 2021)
" The most common adverse events were nasopharyngitis, diarrhea and shunt stenosis, which occurred at similar frequencies in both groups."3.01Efficacy and safety of vadadustat compared with darbepoetin alfa in Japanese anemic patients on hemodialysis: a Phase 3, multicenter, randomized, double-blind study. ( Kaneko, G; Kawaguchi, Y; Kokado, Y; Komatsu, Y; Kondo, K; Matsuda, H; Nangaku, M; Ueta, K, 2021)
" The primary safety end point, assessed in a time-to-event analysis, was the first occurrence of a major adverse cardiovascular event (MACE, a composite of death from any cause, a nonfatal myocardial infarction, or a nonfatal stroke), pooled across the trials (noninferiority margin, 1."3.01Safety and Efficacy of Vadadustat for Anemia in Patients Undergoing Dialysis. ( Agarwal, R; Aswad, A; Awad, A; Bacci, MR; Block, GA; Chertow, GM; Eckardt, KU; Farag, YMK; Fishbane, S; Hubert, H; Jardine, A; Khawaja, Z; Koury, MJ; Lewis, EF; Luo, W; Maroni, BJ; Matsushita, K; McCullough, PA; Parfrey, PS; Pergola, P; Sarnak, MJ; Spinowitz, B; Tumlin, J; Vargo, DL; Walters, KA; Winkelmayer, WC; Wittes, J; Zwiech, R, 2021)
"Anemia is a common complication of chronic kidney disease (CKD), and its prevalence rises as the disease progresses."3.01Roxadustat: Do we know all the answers? ( Fu, H; Li, QY; Liu, F; Mao, J; Peng, WX; Tang, X; Tong, T; Xiong, QW; Yao, X, 2023)
" The most frequent adverse events included nasopharyngitis (29%), catheter-site infection (18%), peritonitis (16%), diarrhea (14%), and nausea (11%)."3.01Efficacy and safety of daprodustat in Japanese peritoneal dialysis patients. ( Cobitz, A; Endo, Y; Kanai, H; Kurata, K; Nagai, R; Nagakubo, T; Nangaku, M; Okuda, N, 2021)
"Anemia is also a leading cause of hospitalization in patients with CKD."3.01The role of roxadustat in chronic kidney disease patients complicated with anemia. ( Li, S; Liu, J; Liu, K; Waheed, Y; Yang, F; Zhou, X, 2023)
" Roxadustat also improved iron utilization, and it was not associated with higher treatment-emergent adverse events, treatment-emergent serious adverse events, and major adverse cardiovascular events when compared to ESAs."3.01The efficacy and safety of roxadustat for anemia in patients with dialysis-dependent chronic kidney disease: a systematic review and meta-analysis. ( Deng, F; Li, J; Mao, M; Zhou, Q, 2023)
"A Study of Intermittent Oral Dosing of ASP1517 in Hemodialysis Chronic Kidney Disease Patients with Anemia, NCT02952092 (ClinicalTrials."2.94Phase 3, Randomized, Double-Blind, Active-Comparator (Darbepoetin Alfa) Study of Oral Roxadustat in CKD Patients with Anemia on Hemodialysis in Japan. ( Akizawa, T; Iwasaki, M; Majikawa, Y; Reusch, M; Yamaguchi, Y, 2020)
" Frequency of adverse events were generally similar between daprodustat and darbepoetin alfa."2.94Efficacy and Safety of Daprodustat Compared with Darbepoetin Alfa in Japanese Hemodialysis Patients with Anemia: A Randomized, Double-Blind, Phase 3 Trial. ( Akizawa, T; Cobitz, AR; Endo, Y; Hara, K; Kawamatsu, S; Nangaku, M; Okuda, N; Onoue, T; Yonekawa, T, 2020)
"These data help inform the appropriate dose conversion ratio to be applied to daily doses to obtain equivalent daprodustat TIW doses and suggest TIW treatment with daprodustat can treat anemia of CKD safely, supporting future long-term studies for this indication using a TIW dosing regimen."2.90A randomized, 29-day, dose-ranging, efficacy and safety study of daprodustat, administered three times weekly in patients with anemia on hemodialysis. ( Bailey, CK; Caltabiano, S; Cobitz, AR; Huang, C; Mahar, KM; Patel, VV, 2019)
" Primary outcomes for both studies were area under the concentration-time curve from the time of dosing extrapolated to infinity and maximum concentration of drug in blood plasma."2.90Evaluation of Food and Spherical Carbon Adsorbent Effects on the Pharmacokinetics of Roxadustat in Healthy Nonelderly Adult Male Japanese Subjects. ( Furihata, K; Katashima, M; Nomura, Y; Shibata, T; Takada, A; Ueno, M; Yazawa, R, 2019)
"GSK1278863 is an orally administered small-molecule PHI."2.82A Novel Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor (GSK1278863) for Anemia in CKD: A 28-Day, Phase 2A Randomized Trial. ( Brigandi, RA; Cross, N; de Zoysa, J; Guptha, V; Johnson, B; Kumar, S; McMahon, L; Oei, C; Olbina, G; Roger, SD; Russ, SF; Sahay, M; Singh, N; Smolyarchuk, EA; Westerman, M, 2016)
" There was no significant difference in the incidence of adverse events (AEs) (OR: 1."2.82Efficacy and safety of roxadustat for anaemia in dialysis-dependent and non-dialysis-dependent chronic kidney disease patients: A systematic review and meta-analysis. ( Fang, X; Liu, D; Liu, Y; Tian, J; Zhang, Y; Zhao, Y; Zheng, L, 2022)
" PK and adverse events (AEs) were assessed after a single 3 mg dose of ixazomib."2.82A pharmacokinetics and safety phase 1/1b study of oral ixazomib in patients with multiple myeloma and severe renal impairment or end-stage renal disease requiring haemodialysis. ( Badros, A; Berdeja, J; Chari, A; Gupta, N; Hanley, MJ; Harvey, RD; Hui, AM; Kukreti, V; Lipe, B; Qian, M; Venkatakrishnan, K; Yang, H; Zhang, X, 2016)
"We concluded that ROX increased Hb level and improved iron utilization parameters in NDD-CKD patients, but ROX was associated with higher serious adverse effects, especially DVT and HTN."2.82The efficacy and safety of roxadustat for the treatment of anemia in non-dialysis dependent chronic kidney disease patients: An updated systematic review and meta-analysis of randomized clinical trials. ( Abbas, KS; Abdelazeem, B; El-Shahat, NA; Eltobgy, M; Kunadi, A; Malik, B; Savarapu, P; Shehata, J, 2022)
" Roxadustat (FG-4592) is an orally bioavailable hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor that promotes coordinated erythropoiesis through HIF-mediated transcription."2.82Roxadustat (FG-4592): Correction of Anemia in Incident Dialysis Patients. ( Besarab, A; Chan, DT; Chernyavskaya, E; Franco, M; Gurevich, K; Hemmerich, S; Kumbar, LM; Leong, R; Motylev, I; Neff, TB; Poole, L; Saikali, KG; Shutov, E; Yu, KH; Zhong, M, 2016)
"Of 116 subjects receiving treatment, 104 completed 4 weeks of dosing and 96 were evaluable for efficacy."2.80Randomized placebo-controlled dose-ranging and pharmacodynamics study of roxadustat (FG-4592) to treat anemia in nondialysis-dependent chronic kidney disease (NDD-CKD) patients. ( Besarab, A; Hemmerich, S; Hertel, J; Klaus, SJ; Lee, T; Leong, R; Neff, TB; Provenzano, R; Yu, KH; Zabaneh, R, 2015)
" No difference was found between roxadustat and control group in terms of oral iron supplementation, adverse events (AEs), serious adverse events (SAEs), infection, myocardial infraction, stroke, heart failure and death."2.72The efficacy and safety of roxadustat treatment for anemia in patients with kidney disease: a meta-analysis and systematic review. ( Duan, K; Jiao, N; Li, J; Liu, G; Liu, Y; Qie, S, 2021)
" As for safety, the incidence of adverse events (AEs) in the roxadustat group was insignificantly different from that of the placebo group [risk ratio (RR) 0."2.72The efficacy and safety of roxadustat for anemia in patients with chronic kidney disease: a meta-analysis. ( Fu, X; Huang, Y; Liu, WJ; Liu, YN; Wang, Y; Wei, R; Yang, H; Zheng, Q, 2021)
" Here, we survey current clinical experience with HIF-PHIs, discuss potential therapeutic advantages, and deliberate over safety concerns regarding long-term administration in patients with renal anemia."2.61Hypoxia-Inducible Factor Activators in Renal Anemia: Current Clinical Experience. ( Haase, VH; Sanghani, NS, 2019)
" One significant concern regarding the long-term use of these agents is their possible effect on tumor growth."2.55Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors: A Potential New Treatment for Anemia in Patients With CKD. ( Gupta, N; Wish, JB, 2017)
"05), and there was no correlation between blood concentration and clinical characteristics such as age, gender, and dosage (P > ."1.91Correlation between blood concentration of roxadustat and clinical efficacy in patients with anemia of chronic kidney disease. ( Jing, Y; Zhang, Y; Zhou, C, 2023)
"Our objective was to develop a population pharmacokinetic (PK) model to describe roxadustat plasma concentrations in Japanese dialysis-dependent chronic kidney disease (DD-CKD) patients with renal anaemia and to identify the covariate factors that affect exposure of roxadustat."1.72Population pharmacokinetics of roxadustat in Japanese dialysis-dependent chronic kidney disease patients with anaemia. ( Groenendaal-van de Meent, D; Komatsu, K; Shibata, T; Shiga, T; Takada, A, 2022)
"Anemia is common in CKD and increases the risk of developing heart disease."1.72Are there advantages of daprodustat over erythropoiesis-stimulating agents (ESAs) in treating anemia associated with chronic kidney disease (CKD)? ( Doggrell, SA, 2022)
" There were no serious adverse events associated with roxadustat were observed."1.72Long-term efficacy, safety, and medication compliance of roxadustat on peritoneal dialysis patients with renal anemia affected by the COVID-19 pandemic: a retrospective study. ( Bao, L; Bian, X; Huang, J; Luo, C; Ren, L; Zhang, A, 2022)
"The efficacy of roxadustat for treatment of anemia after kidney transplantation was analyzed by comparing the change and increase in average hemoglobin levels before and after treatment."1.62Efficacy and safety of roxadustat in the treatment of renal allograft anemia patients: a case series. ( Li, J; Lv, J; Ma, K; Peng, W; Qi, H; Rao, Y; Wang, L, 2021)
"All patients had general muscular hypotonia and 4 had growth retardation."1.42Growth retardation, general hypotonia, and loss of acquired neuromotor skills in the infants of mothers with cobalamin deficiency and the possible role of succinyl-CoA and glycine in the pathogenesis. ( Bicakci, Z, 2015)

Research

Studies (185)

TimeframeStudies, this research(%)All Research%
pre-199044 (23.78)18.7374
1990's0 (0.00)18.2507
2000's1 (0.54)29.6817
2010's41 (22.16)24.3611
2020's99 (53.51)2.80

Authors

AuthorsStudies
Csiky, B1
Schömig, M2
Esposito, C2
Barratt, J3
Reusch, M10
Valluri, U3
Sulowicz, W1
Sokol, J1
Guman, T1
Chudej, J1
Hlebaskova, M1
Stecova, N1
Valekova, L1
Kucerikova, M1
Stasko, J1
Akizawa, T12
Tanaka-Amino, K2
Otsuka, T5
Yamaguchi, Y6
Bunn, HF1
Chertow, GM7
Eckardt, KU6
Kurata, Y1
Tanaka, T1
Nangaku, M9
Henry, DH2
Glaspy, J2
Harrup, R1
Mittelman, M1
Zhou, A1
Carraway, HE1
Bradley, C2
Saha, G3
Modelska, K2
Bartels, P1
Leong, R8
Yu, KP6
Singh, AK3
Carroll, K3
Perkovic, V3
Solomon, S3
Jha, V3
Johansen, KL3
Lopes, RD3
Macdougall, IC4
Obrador, GT3
Waikar, SS3
Wanner, C3
Wheeler, DC3
Więcek, A3
Blackorby, A3
Cizman, B3
Cobitz, AR7
Davies, R2
Dole, J1
Kler, L2
Meadowcroft, AM4
Zhu, X1
McMurray, JJV3
DiMino, TL1
Taft, L1
Chen, J5
Li, Z3
Zhang, H2
Hu, J1
Wang, J4
Zhou, H2
Liu, Y4
Liu, J3
Yi, B1
Zhang, W1
Patnaik, MM1
Santini, V1
Allison, SJ1
Li, J4
Ma, K1
Wang, L1
Qi, H1
Lv, J1
Rao, Y1
Peng, W1
Jatho, A1
Zieseniss, A1
Brechtel-Curth, K1
Guo, J1
Böker, KO1
Salinas, G1
Wenger, RH1
Katschinski, DM1
Miki, K1
Nakamura, Y1
Yokoyama, T1
Kamiyama, M1
Ishii, Y1
Abdelazeem, B1
Shehata, J1
Abbas, KS1
El-Shahat, NA1
Malik, B1
Savarapu, P1
Eltobgy, M1
Kunadi, A1
Stankus, N1
Strutz, F1
Paul, G1
Ranganathan, P1
Sedani, S1
Doggrell, SA1
Dai, S1
Chen, Y1
Hao, C4
Ge, X1
Xie, Q1
Shang, D1
Zhu, T1
Sullivan, MK1
Mark, PB1
Labes, R1
Brinkmann, L1
Kulow, VA1
Roegner, K1
Mathia, S1
Balcerek, B1
Persson, PB1
Rosenberger, C1
Fähling, M1
Koury, MJ5
Agarwal, R5
Fishbane, S6
Ganz, T2
Haase, VH5
Hanudel, MR2
Parfrey, PS4
Pergola, PE6
Roy-Chaudhury, P2
Tumlin, JA1
Anders, R1
Farag, YMK4
Luo, W5
Minga, T1
Solinsky, C1
Vargo, DL4
Winkelmayer, WC7
Bao, L1
Bian, X1
Zhang, A2
Huang, J1
Ren, L1
Luo, C1
Hou, YP2
Wang, C6
Mao, XY2
Zhang, MZ1
Li, B2
Zheng, F1
Zhang, P1
Zhao, M1
Xu, X1
Zhang, C1
Zhang, L3
Charytan, C1
Little, DJ1
Tham, S1
Szczech, L6
Yang, F1
Waheed, Y1
Li, S1
Liu, K1
Zhou, X1
Cheng, Y1
Xiang, Q1
Cao, T1
Tang, F1
Qi, D1
Hu, H1
Song, H1
Chang, Z1
Ku, M1
Chen, X2
Chen, C2
Wan, Q1
Gabrail, NY1
Locantore-Ford, P1
Lee, T3
Samal, V1
Li, QY1
Xiong, QW1
Yao, X1
Liu, F1
Tang, X1
Fu, H1
Tong, T1
Mao, J1
Peng, WX1
Dellanna, F1
Portoles, J1
Choukroun, G1
De Nicola, L1
Young, J1
Dimković, N2
Yoshida, S1
Saito, T1
Shibagaki, K1
Hirao, K1
Yuza, T1
Tomosugi, N2
Honda, H1
You, X1
Guo, B1
Wang, Z1
Ma, H1
Liu, L1
Zhou, R1
Zheng, Y1
Zhang, X5
Zhang, Y4
Jing, Y1
Zhou, C1
Berns, JS1
Vishnepolsky, M1
Oluwatosin, Y1
Nolen, J1
Zhu, L1
Cooper, K1
Young, A1
Zhou, Q1
Mao, M1
Deng, F2
Ge, P1
Xu, R1
Ye, Z1
Song, J1
Zhou, L2
Yu, W1
Liu, H1
Yuan, F1
Sanghani, NS1
Maxwell, PH1
Bailey, CK1
Caltabiano, S2
Huang, C1
Mahar, KM2
Patel, VV1
Voit, RA1
Sankaran, VG1
Hayden, JC1
Bhagavathula, AS1
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Wyatt, CM1
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Shi, A1
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Block, GA5
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Lewis, EF3
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Sarnak, MJ4
Farag, YM1
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Kaneko, G2
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Qie, S1
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Liu, G1
Yang, Q1
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Xue, H1
Wang, AY1
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Jiang, F1
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Yang, D1
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Yamamoto, T4
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Korneyeva, S1
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Eyassu, M1
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Sułowicz, W1
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Jung, G1
Qiao, B1
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Zuk, A1
Eleftheriadis, T1
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Liakopoulos, V1
Stefanidis, I1
Cai, KD1
Zhu, BX1
Lin, HX1
Luo, Q1
Aswad, A1
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Jardine, A1
Maroni, BJ5
Pergola, P1
Spinowitz, B2
Zwiech, R1
Arnold, S1
Bako, G1
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Levin, A1
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Wang, H1
Huang, K1
Fang, H1
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Hou, J1
Su, SS1
Xue, S1
Ikeda, Y1
Xu, ZH1
Bu, ZH1
Xu, M1
Zhou, Y1
Ren, Q1
Hu, R1
Zheng, K1
Qin, Y1
Li, X3
Takada, A2
Shibata, T2
Shiga, T1
Groenendaal-van de Meent, D1
Komatsu, K1
Walther, CP1
Zheng, L1
Tian, J1
Liu, D1
Zhao, Y1
Fang, X1
Martin, ER1
Smith, MT1
Zuraw, QC1
deGoma, EM2
Qian, J1
Yu, X1
Mei, C1
Jiang, G2
Lin, H3
Zuo, L3
Fu, P1
Ni, D1
Liu, C3
Peony Yu, KH1
Valone, FH1
Jajosky, RP1
Cook, LO1
Manaloor, E1
Shikle, JF1
Bollag, RJ1
Del Vecchio, L1
Locatelli, F2
Becker, KA1
Jones, JJ1
Wu, Y1
Jiang, Z1
Gu, J1
You, Q1
Nomura, Y1
Ueno, M2
Katashima, M1
Yazawa, R1
Furihata, K1
Xie, D1
Wu, X1
Li, M1
Cygulska, K1
Wejner-Mik, P1
Plewka, M1
Figiel, Ł1
Chrzanowski, Ł1
Kasprzak, JD1
Misumi, T1
Matsushita, H1
Kaplan, J1
Peng, X1
Yin, A1
Hao, L2
Tao, Y1
Liang, X2
Liu, Z3
Xing, C2
Luo, L2
Liao, Y1
Liu, BC2
Neff, T2
Zhao, MH1
Cai, GY1
Flight, MH1
Bouchie, A1
Forristal, CE1
Levesque, JP1
Bisbe, E1
Moltó, L1
Arroyo, R1
Muniesa, JM1
Tejero, M1
Infante, JR1
Weiss, GJ1
Jones, S1
Tibes, R1
Bauer, TM1
Bendell, JC1
Hinson, JM1
Von Hoff, DD1
Burris, HA1
Orlemans, EO1
Ramanathan, RK1
Bicakci, Z1
Hertel, J1
Yu, KH3
Holdstock, L1
Maier, R1
Johnson, BM1
Jones, D1
Rastogi, A1
Zeig, S2
Lepore, JJ1
Chernyavskaya, E1
Motylev, I1
Kumbar, LM1
Gurevich, K1
Chan, DT1
Zhong, M1
Saikali, KG3
Franco, M1
Lenihan, CR1
Brigandi, RA1
Johnson, B1
Oei, C1
Westerman, M1
Olbina, G1
de Zoysa, J1
Roger, SD1
Sahay, M1
Cross, N1
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Guptha, V1
Smolyarchuk, EA1
Singh, N1
Russ, SF1
Kumar, S1
Wright, S1
Dua, S1
Nguyen, P1
Sun, CH1
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Cangiano, JL1
Aiello, JR1
Novak, JE1
Roberts, BK1
Szczech, LA1
Gupta, N2
Hanley, MJ1
Harvey, RD1
Badros, A1
Lipe, B1
Kukreti, V1
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Hui, AM1
Qian, M1
Venkatakrishnan, K1
Chari, A1
Lunetti, P1
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De Benedetto, G1
Siculella, L1
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BROOKS, JW1
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THOMAS, RG1
ALTMAN, KI2
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SALOMON, K1
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LAWRENCE, JH1
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KIM, AY1
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KIM, CH1
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NAKASHIMA, A1
HIRATSUKA, S1
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FUJII, M2
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SUNDBERG, D1
WATSON, CJ1
RUSSELL, ES1
SKANDERBEG, J1
ZIPURSKY, A1
ISRAELS, LG1
BLAUSTEIN, A1
ABBOTT, LD1
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Giordani, L1
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Williams, WJ1
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Samson, D1
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Nicholson, DC1
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Clinical Trials (30)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
A Phase 3 Multi-center, Randomized, Open-label, Active-comparator (Darbepoetin Alfa) Conversion Study of Intermittent Oral Dosing of ASP1517 in Non-dialysis Chronic Kidney Disease Patients With Anemia[NCT02988973]Phase 3334 participants (Actual)Interventional2017-01-12Completed
Roxadustat Combined With Luspatercept Versus Luspatercept Monotherapy in the Treatment of Refractory Myelodysplastic Syndrome With Ring Sideroblasts (MDS-RS): A Prospective Randomized Controlled Study[NCT06006949]Phase 462 participants (Anticipated)Interventional2023-08-31Not yet recruiting
A Phase 3 Randomized Double-Blind Placebo-Controlled Study Investigating the Efficacy and Safety of Roxadustat (FG-4592) for Treatment of Anemia in Patients With Lower Risk Myelodysplastic Syndrome (MDS) With Low Red Blood Cell (RBC) Transfusion Burden (L[NCT03263091]Phase 3140 participants (Actual)Interventional2017-09-07Terminated (stopped due to Study did not meet its primary efficacy endpoint.)
A Phase 3 Randomized, Open-label (Sponsor-blind), Active-controlled, Parallel-group, Multi-center, Event Driven Study in Dialysis Subjects With Anemia Associated With Chronic Kidney Disease to Evaluate the Safety and Efficacy of Daprodustat Compared to Re[NCT02879305]Phase 32,964 participants (Actual)Interventional2016-09-28Completed
A Phase 3 Randomized, Open-label (Sponsor-blind), Active-controlled, Parallel-group, Multi-center, Event Driven Study in Non-dialysis Subjects With Anemia Associated With Chronic Kidney Disease to Evaluate the Safety and Efficacy of Daprodustat Compared t[NCT02876835]Phase 33,872 participants (Actual)Interventional2016-09-27Completed
A 52-week Open-label (Sponsor-blind), Randomized, Active-controlled, Parallel-group, Multi-center Study to Evaluate the Efficacy and Safety of Daprodustat Compared to Recombinant Human Erythropoietin in Subjects With Anemia Associated With Chronic Kidney [NCT03029208]Phase 3312 participants (Actual)Interventional2017-05-11Completed
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 Ch[NCT02689206]Phase 2103 participants (Actual)Interventional2016-02-17Completed
A Single Centre, Single Dose, Open-label, Randomised, 2-way Crossover Study in Healthy Japanese Male Subjects to Evaluate the Bioequivalence of Daprodustat Tablets (2 mg Tablet vs. 4 mg Tablet) (Part 1) and the Food Effect on the Pharmacokinetics of Dapro[NCT03493386]Phase 164 participants (Actual)Interventional2018-04-24Completed
A Phase 3, Multi-center, Randomized, 2-arm Parallel, Double-blind, Active-comparator (Darbepoetin Alfa) Conversion Study of Intermittent Oral Dosing of ASP1517 in Hemodialysis Chronic Kidney Disease Patients With Anemia[NCT02952092]Phase 3303 participants (Actual)Interventional2016-11-30Completed
A 52-week, Phase III, Double-blind, Active-controlled, Parallel-group, Multi-center Study to Evaluate Efficacy and Safety of Daprodustat Compared to Darbepoetin Alfa in Japanese Hemodialysis-dependent Subjects With Anemia Associated With Chronic Kidney Di[NCT02969655]Phase 3271 participants (Actual)Interventional2016-11-21Completed
A Phase III, Open-label Study of MT-6548 in Peritoneal Dialysis Subjects With Anemia Associated With Chronic Kidney Disease in Japan[NCT03402386]Phase 342 participants (Actual)Interventional2018-01-03Completed
A 52-week, Phase III, Open-label, Multi-center Study to Evaluate Efficacy and Safety of GSK1278863 in Japanese Non-dialysis and Peritoneal Dialysis Subjects With Anemia Associated With Chronic Kidney Disease[NCT02791763]Phase 3355 participants (Actual)Interventional2016-06-06Completed
A Phase III, Double Blind, Confirmatory Study of MT-6548 Compared to Darbepoetin Alfa in Hemodialysis Subjects With Anemia Associated With Chronic Kidney Disease in Japan[NCT03439137]Phase 3323 participants (Actual)Interventional2018-02-14Completed
Phase 3, Randomized, Open-Label, Active-Controlled Study Evaluating the Efficacy and Safety of Oral Vadadustat for the Correction or Maintenance Treatment of Anemia in Subjects With Incident Dialysis-Dependent Chronic Kidney Disease (DD-CKD) (INNO2VATE - [NCT02865850]Phase 3369 participants (Actual)Interventional2016-07-31Completed
Phase 3, Randomized, Open-Label, Active-Controlled Study Evaluating the Efficacy and Safety of Oral Vadadustat for the Maintenance Treatment of Anemia in Subjects With Dialysis-Dependent Chronic Kidney Disease (DD-CKD) (INNO2VATE-CONVERSION)[NCT02892149]Phase 33,554 participants (Actual)Interventional2016-08-31Completed
Phase 3, Randomized, Open-Label, Active-Controlled Study Evaluating the Efficacy and Safety of Oral Vadadustat for the Correction of Anemia in Subjects With Non-Dialysis-Dependent Chronic Kidney Disease (NDD-CKD) (PRO2TECT-CORRECTION)[NCT02648347]Phase 31,751 participants (Actual)Interventional2015-12-31Completed
Phase 3, Randomized, Open-label, Active-controlled Study Evaluating the Efficacy and Safety of Oral Vadadustat for the Maintenance Treatment of Anemia in Subjects With Non-dialysis-dependent Chronic Kidney Disease (NDD-CKD) (PRO2TECT-CONVERSION)[NCT02680574]Phase 31,725 participants (Actual)Interventional2016-02-29Completed
A Phase III, Open-label Study of MT-6548 in Hemodialysis Subjects With Anemia Associated With Chronic Kidney Disease in Japan[NCT03461146]Phase 324 participants (Actual)Interventional2018-03-05Completed
Phase 2a Randomized, Double-Blind, Placebo-Controlled, Dose Range Study to Assess the Pharmacodynamic Response, Pharmacokinetics, Safety, and Tolerability of 42-Day Repeat Oral Doses of AKB-6548 in Subjects With Anemia Secondary to Chronic Kidney Disease [NCT01381094]Phase 293 participants (Actual)Interventional2011-06-15Completed
ASP1517 Phase 2 Clinical Trial -A Multi-center, Randomized, Parallel Groups, Placebo-controlled, Double-Blind Study of ASP1517 for the Treatment of Anemia in Chronic Kidney Disease Patients Not on Dialysis-[NCT01964196]Phase 2107 participants (Actual)Interventional2013-09-17Completed
A 24-week, Phase III, Open-label, Non-comparative, Multi-center Study to Evaluate Efficacy and Safety of GSK1278863 in Japanese Hemodialysis Subjects With Anemia Associated With Chronic Kidney Disease Who Are Not Taking Erythropoiesis Stimulating Agents[NCT02829320]Phase 328 participants (Actual)Interventional2016-08-08Completed
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Efficacy and Safety of FG-4592 for Treatment of Anemia in Subjects With Chronic Kidney Disease Not on Dialysis[NCT02652819]Phase 3154 participants (Actual)Interventional2015-12-31Completed
A Randomized Controlled Trial to Evaluate the Safety and Efficacy of Roxadustat in Patients With Acute ST Elevation Myocardial Infarction[NCT04803864]Phase 2158 participants (Anticipated)Interventional2021-06-10Recruiting
Roxadustat Reduces the Incidence of Acute Kidney Injury After Coronary Artery Bypass Grafting: a Multicenter, Randomized, Double-blind, Placebo-controlled Study[NCT05010460]Phase 2318 participants (Anticipated)Interventional2021-09-30Recruiting
A Phase 3, Randomized, Open-Label, Active-Controlled Study of Efficacy and Safety of FG-4592 for Treatment of Anemia in Subjects With Chronic Kidney Disease on Dialysis[NCT02652806]Phase 3305 participants (Actual)Interventional2015-12-31Completed
Efficacy of Intravenous Ferric Carboxymaltose in the Improvement of Anemia in Patients With Postoperative Knee Prosthesis[NCT01913808]Phase 4122 participants (Actual)Interventional2011-01-31Completed
A Randomized, Single-blind, Placebo-controlled, 4-Week Treatment Study of the Safety and Biologic Activity of Escalating Multiple Oral Doses of FG-4592 in Subjects With Chronic Kidney Disease Not Requiring Dialysis[NCT00761657]Phase 2117 participants (Actual)Interventional2006-11-01Completed
A Four-week, Phase IIa, Randomized, Active-controlled, Parallel-group, Multi-center Study to Evaluate the Safety, Efficacy and Pharmacokinetics of Switching Subjects From a Stable Dose of Recombinant Human Erythropoietin to GSK1278863 in Hemodialysis-depe[NCT01587924]Phase 280 participants (Actual)Interventional2012-05-23Completed
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 R[NCT01587898]Phase 272 participants (Actual)Interventional2012-05-17Completed
Phase 2b Randomized, Double-Blind, Placebo-Controlled Study to Assess the Pharmacodynamic Response, Safety, and Tolerability to 20 Weeks of Oral Dosing of AKB-6548 in Participants With Anemia Secondary to Chronic Kidney Disease (CKD), GFR Categories G3a-G[NCT01906489]Phase 2210 participants (Actual)Interventional2013-07-23Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

Blood Pressure (BP) Exacerbation Event Rate Per 100 Participant Years

BP exacerbation was defined (based on post-dialysis) as: SBP >= 25 millimeter of mercury (mmHg) increased from Baseline or SBP >=180 mmHg; DBP >=15 mmHg increased from Baseline or DBP >=110 mmHg. The BP exacerbation events per 100 participant years was estimated using the negative binomial model with treatment, dialysis type and region as covariates and the logarithm of time on-treatment as an offset variable. Data for post-dialysis BP measurements have been presented. (NCT02879305)
Timeframe: Day 1 to end of study (3.9 person-years for follow-up time period)

InterventionEvents per 100 participant years (Number)
Daprodustat207.13
rhEPO206.38

Change From Baseline in On-Treatment EuroQol Visual Analogue Scale (EQ-VAS) at Week 52

The EQ VAS records the respondent's self-rated health on a vertical VAS, ranging from 0 to 100, where 0 represents the worst health one can imagine and 100 represents the best health one can imagine. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. (NCT02879305)
Timeframe: Baseline (Pre-dose on Day 1) and Week 52

InterventionScores on a scale (Least Squares Mean)
Daprodustat-1.0
rhEPO0.8

Change From Baseline in On-Treatment Health Utility EuroQol 5 Dimensions 5 Level (EQ-5D-5L) Questionnaire Score at Week 52

EQ-5D-5L is self-assessment questionnaire,consisting of 5 items covering 5 dimensions (mobility,self care,usual activities,pain/discomfort and anxiety/depression). Each dimension is measured by 5-point Likert scale (1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems). Responses for 5 dimensions together formed a 5-figure description of health state (e.g.11111 indicates no problems in all 5 dimensions). Each of these 5 figure health states were converted to a single index score by applying country-specific value set formula that attaches weights to dimensions and levels. Range for EQ-5D-5L index score is -0.594 (worst health) to 1 (full health state). Change from Baseline was calculated as on-treatment visit value-Baseline value. Baseline was latest non-missing pre-dose assessment on or before randomization date. (NCT02879305)
Timeframe: Baseline (Pre-dose on Day 1) and Week 52

InterventionScores on a scale (Least Squares Mean)
Daprodustat-0.0198
rhEPO-0.0201

Change From Baseline in Post-randomization Hemoglobin Levels at Week 52

Blood samples were collected from participants for hemoglobin measurements. Change from Baseline was defined as post-Baseline value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. Analysis was performed using mixed model repeated measures (MMRM) model fitted from Baseline up to Week 52, excluding values collected during the stabilization period, with factors for treatment, time, dialysis type, region, Baseline hemoglobin and Baseline hemoglobin by time and treatment by time interactions. (NCT02879305)
Timeframe: Baseline (Pre-dose on Day 1) and Week 52

InterventionGrams per deciliter (Least Squares Mean)
Daprodustat0.26
rhEPO0.14

Mean Average Monthly On-treatment IV Iron Dose Per Participant

Average monthly IV iron dose (milligrams) per participant from Day 1 to Week 52 was determined by calculating the total IV iron dose per participant from treatment start date + 1 to the earliest of (Week 52 visit date, first blood (red blood cell [RBC] or whole blood) transfusion date, and treatment stop date + 1 day) which corresponds to the time while the participant was on randomized treatment and before receiving a blood transfusion. This total IV iron dose was divided by (the number of days from treatment start date + 1 to the earliest of (Week 52 visit date, first blood transfusion date (RBC or whole blood), and treatment stop date +1) / 30.4375 days). This endpoint was adjusted for multiplicity using the Holm-Bonferonni method. (NCT02879305)
Timeframe: Day 1 to Week 52

InterventionMilligrams (Least Squares Mean)
Daprodustat90.8
rhEPO99.9

Mean Change From Baseline in Hemoglobin (Hgb) Levels During Evaluation Period (Week 28 to Week 52)

Blood samples were collected from participants for hemoglobin measurements. Hemoglobin during the evaluation period was defined as the mean of all available post-randomization hemoglobin values (on and off-treatment) during the evaluation period (Week 28 to Week 52). For the primary analysis, missing post-Baseline hemoglobin values were imputed using pre-specified multiple imputation methods. Change from Baseline was defined as post-Baseline value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. (NCT02879305)
Timeframe: Baseline (Pre-dose on Day 1) and evaluation period (Week 28 to Week 52)

InterventionGrams per deciliter (Least Squares Mean)
Daprodustat0.28
rhEPO0.10

Number of Hgb Responders in the Hgb Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52)

Mean Hgb during the evaluation period was defined as the mean of all evaluable Hgb values during the evaluation period (Week 28 to Week 52) including any evaluable unscheduled Hgb values that were taken during this time period. Hemoglobin responders were defined as participants with a mean Hgb during the evaluation period that falls within the Hgb analysis range of 10-11.5 g/dL. (NCT02879305)
Timeframe: Week 28 to Week 52

InterventionParticipants (Count of Participants)
Daprodustat903
rhEPO866

Number of Participants With at Least One BP Exacerbation Event During Study

BP exacerbation was defined as: SBP >= 25 mmHg increased from Baseline or SBP >=180 mmHg; DBP >=15 mmHg increased from Baseline or DBP >=110 mmHg. Number of participants with at least one BP exacerbation event is presented. (NCT02879305)
Timeframe: Day 1 to end of study (3.9 person-years for follow-up time period)

InterventionParticipants (Count of Participants)
Daprodustat1191
rhEPO1186

Percentage of Participants Permanently Stopping Randomized Treatment Due to Meeting Rescue Criteria

Percentage of participants permanently stopping randomized treatment due to meeting rescue criteria has been presented. (NCT02879305)
Timeframe: Day 1 to 45.1 months

InterventionPercentage of participants (Number)
Daprodustat3.6
rhEPO3.6

Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52): Non-inferiority Analysis

Percentage of days for which a participant's Hgb was within the analysis range of 10-11.5 g/dL (both inclusive) during the evaluation period (Week 28 to Week 52), including any unscheduled evaluable Hgb values that were taken during this time period was calculated. Percentage of time in the analysis range during evaluation period is calculated as time in range during the evaluation period / [Earlier of (Date of the last evaluable Hgb value, Week 52 visit date) - Later of (Date of the first evaluable Hgb value that between Week 16 and Week 52 inclusive, Week 28 visit date)]. (NCT02879305)
Timeframe: Week 28 to Week 52

InterventionPercentage of days (Median)
Daprodustat60.9
rhEPO59.4

Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52): Superiority Analysis

Percentage of days for which a participant's Hgb was within the analysis range of 10-11.5 g/dL (both inclusive) during the evaluation period (Week 28 to Week 52), including any unscheduled evaluable Hgb values that were taken during this time period was calculated. Percentage of time in the analysis range during evaluation period is calculated as time in range during the evaluation period / [Earlier of (Date of the last evaluable Hgb value, Week 52 visit date) - Later of (Date of the first evaluable Hgb value that between Week 16 and Week 52 inclusive, Week 28 visit date)]. (NCT02879305)
Timeframe: Week 28 to Week 52

InterventionPercentage of days (Median)
Daprodustat60.9
rhEPO59.4

Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Maintenance Period (Week 28 to End of Study): Non-inferiority Analysis

Percentage of days for which a participant's Hgb was within the analysis range of 10-11.5 g/dL (both inclusive) during the maintenance period (Week 28 to end of study), including any unscheduled evaluable Hgb values that were taken during this time period was calculated. Percentage of time in the analysis range during maintenance period is calculated as time in range during the maintenance period / [Earlier of (Date of the last evaluable Hgb value, End of study date)- Later of (Date of the first evaluable Hgb value that is on or after week 16, Week 28 visit date)]. (NCT02879305)
Timeframe: Week 28 to end of study (3.9 person-years for follow-up time period)

InterventionPercentage of days (Median)
Daprodustat60.9
rhEPO57.7

Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Maintenance Period (Week 28 to End of Study): Superiority Analysis

Percentage of days for which a participant's Hgb was within the analysis range of 10-11.5 g/dL (both inclusive) during the maintenance period (Week 28 to end of study), including any unscheduled evaluable Hgb values that were taken during this time period was calculated. Percentage of time in the analysis range during maintenance period is calculated as time in range during the maintenance period / [Earlier of (Date of the last evaluable Hgb value, End of study date)- Later of (Date of the first evaluable Hgb value that is on or after week 16, Week 28 visit date)]. (NCT02879305)
Timeframe: Week 28 to end of study (3.9 person-years for follow-up time period)

InterventionPercentage of days (Median)
Daprodustat60.9
rhEPO57.7

Time to First Occurrence of Adjudicated All-Cause Mortality During Vital Status for Follow-up Time Period

Time to first occurrence of adjudicated all-cause mortality was analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the vital status for follow-up time period. (NCT02879305)
Timeframe: Up to 3.9 person-years for vital status follow-up time period

InterventionEvents per 100 person years (Number)
Daprodustat8.32
rhEPO8.59

Time to First Occurrence of Adjudicated CV Mortality During CV Events Follow-up Time Period

Time to first occurrence of adjudicated CV mortality was analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. (NCT02879305)
Timeframe: Up to 3.9 person-years for CV follow-up time period

InterventionEvents per 100 person years (Number)
Daprodustat3.31
rhEPO3.46

Time to First Occurrence of Adjudicated CV Mortality or Non-Fatal MI During CV Events Follow-up Time Period

Time to first occurrence of adjudicated CV mortality or non-fatal MI was analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. (NCT02879305)
Timeframe: Up to 3.9 person-years for CV follow-up time period

InterventionEvents per 100 person years (Number)
Daprodustat5.98
rhEPO6.79

Time to First Occurrence of Adjudicated Hospitalization for Heart Failure During CV Events Follow-up Time Period

Time to first occurrence of adjudicated hospitalization for heart failure was analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. (NCT02879305)
Timeframe: Up to 3.9 person-years for CV follow-up time period

InterventionEvents per 100 person years (Number)
Daprodustat3.30
rhEPO3.01

Time to First Occurrence of Adjudicated MACE During CV Events Follow-up Time Period: Superiority Analysis

Time to MACE defined as the time to first occurrence of CEC adjudicated MACE was analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariate. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. This endpoint was adjusted for multiplicity using the Holm-Bonferonni method. (NCT02879305)
Timeframe: Up to 3.9 person-years for CV follow-up time period

InterventionEvents per 100 person years (Number)
Daprodustat11.07
rhEPO11.86

Time to First Occurrence of Adjudicated MACE or Hospitalization for Heart Failure During CV Events Follow-up Time Period

Time to first occurrence of adjudicated MACE or hospitalization for heart failure was analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. This endpoint was adjusted for multiplicity using the Holm-Bonferonni method. (NCT02879305)
Timeframe: Up to 3.9 person-years for CV follow-up time period

InterventionEvents per 100 person years (Number)
Daprodustat12.98
rhEPO13.38

Time to First Occurrence of Adjudicated MACE or Hospitalization for Heart Failure or Thromboembolic Events During CV Events Follow-up Time Period

Time to first occurrence of adjudicated MACE or hospitalization for heart failure or thromboembolic events were analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. (NCT02879305)
Timeframe: Up to 3.9 person-years for CV follow-up time period

InterventionEvents per 100 person years (Number)
Daprodustat17.74
rhEPO19.50

Time to First Occurrence of Adjudicated MACE or Thromboembolic Event During CV Events Follow-up Time Period

Time to first occurrence of adjudicated MACE or thromboembolic event (vascular access thrombosis, symptomatic deep vein thrombosis or symptomatic pulmonary embolism) was analyzed using a Cox proportional hazards regression model with with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. This endpoint was adjusted for multiplicity using the Holm-Bonferonni method. (NCT02879305)
Timeframe: Up to 3.9 person-years for CV follow-up time period

InterventionEvents per 100 person years (Number)
Daprodustat15.84
rhEPO17.85

Time to First Occurrence of Adjudicated Major Adverse Cardiovascular Event (MACE) During Cardiovascular (CV) Events Follow-up Time Period: Non-inferiority Analysis

Time to MACE defined as the time to first occurrence of Clinical Events Committee (CEC) adjudicated MACE (composite of all-cause mortality, non-fatal myocardial infarction [MI] and non-fatal stroke) was analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) plus (+) 1. The incidence rate per 100 person years calculated as (100 multiplied by [*] number of participants with at least 1 event) divided by [/] first event person-years) is presented along with 95 percent (%) confidence interval (CI). First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. (NCT02879305)
Timeframe: Up to 3.9 person-years for CV follow-up time period

InterventionEvents per 100 person years (Number)
Daprodustat11.07
rhEPO11.86

Time to First Occurrence of Adjudicated Myocardial Infarction (MI) (Fatal and Non-Fatal) During CV Events Follow-up Time Period

Time to first occurrence of adjudicated MI (fatal and non-fatal) was analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. (NCT02879305)
Timeframe: Up to 3.9 person-years for CV follow-up time period

InterventionEvents per 100 person years (Number)
Daprodustat3.34
rhEPO4.08

Time to First Occurrence of Adjudicated Stroke (Fatal and Non-Fatal) During CV Events Follow-up Time Period

Time to first occurrence of adjudicated stroke (fatal and non-fatal) was analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. (NCT02879305)
Timeframe: Up to 3.9 person-years for CV follow-up time period

InterventionEvents per 100 person years (Number)
Daprodustat1.23
rhEPO1.48

Time to First Occurrence of Adjudicated Thromboembolic Events During CV Events Follow-up Time Period

Time to first occurrence of adjudicated thromboembolic events were analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. (NCT02879305)
Timeframe: Up to 3.9 person-years for CV follow-up time period

InterventionEvents per 100 person years (Number)
Daprodustat5.66
rhEPO6.75

Time to First Occurrence of All-Cause Hospital Re-admission Within 30 Days During CV Events Follow-up Time Period

All-cause hospital re-admissions within 30days are defined as hospital admissions recorded on hospitalization eCRF with hospitalization duration of >=24 hours and admission date within 30days following previous discharge date of all-cause hospitalization event, where previous hospitalization was >=24 hours. Time to first occurrence of all-cause hospital re-admission within 30days was analyzed using Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date)+1. Incidence rate per 100person years calculated as(100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event+cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. (NCT02879305)
Timeframe: Up to 3.9 person-years for CV follow-up time period

InterventionEvents per 100 person years (Number)
Daprodustat8.86
rhEPO9.67

Time to First Occurrence of All-Cause Hospitalization During CV Events Follow-up Time Period

All-cause hospitalization events were hospital admissions recorded on the Hospitalization electronic case report form (eCRF) with a hospitalization duration >=24 hours. Time to first occurrence of all-cause hospitalization was analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. (NCT02879305)
Timeframe: Up to 3.9 person-years for CV follow-up time period

InterventionEvents per 100 person years (Number)
Daprodustat43.92
rhEPO46.03

Change From Baseline in On-Treatment Mental Component Score (MCS) Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52

The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following 8 health domains: physical functioning, role-physical (role limitations caused by physical problems), social functioning, bodily pain, mental health, role-emotional (role limitations caused by emotional problems), vitality and general health. Each domain is scored from 0 (poorer health) to 100 (better health). MCS is an average score derived from 4 domains (vitality, social functioning, role-emotional and mental health) representing overall mental health. MCS ranges from 0 to 100; higher scores represent better health. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. (NCT02879305)
Timeframe: Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52

,
InterventionScores on a scale (Least Squares Mean)
Week 8, n=982,936Week 12, n=990,943Week 28, n=836,819Week 52, n=729,707
Daprodustat-0.38-0.55-1.25-1.63
rhEPO-0.21-0.72-1.23-1.03

Change From Baseline in On-Treatment Patient Global Impression of Severity (PGI-S) at Weeks 8, 12, 28, 52

The PGI-S is a 1-item questionnaire designed to assess participant's impression of disease severity on a 5-point disease severity scale (0=absent, 1=mild, 2=moderate, 3=severe, or 4=very severe). A higher score indicated worse outcome. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. (NCT02879305)
Timeframe: Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52

,
InterventionScores on a scale (Least Squares Mean)
Week 8, n=1102,1064Week 12, n=1102,1073Week 28, n=934,933Week 52, n=826,814
Daprodustat-0.030.020.040.06
rhEPO0.020.060.080.11

Change From Baseline in On-Treatment Physical Component Score (PCS) Using Short Form (SF)-36 Health-related Quality of Life (HRQoL) Questionnaire at Weeks 8, 12, 28, 52

The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following 8 health domains: physical functioning, role-physical (role limitations caused by physical problems), social functioning, bodily pain, mental health, role-emotional (role limitations caused by emotional problems), vitality and general health. Each domain is scored from 0 (poorer health) to 100 (better health). The PCS is an average score derived from 4 domains (physical functioning, role-physical, bodily pain and general health) representing overall physical health. PCS ranges from 0 to 100; higher scores represent better health. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. (NCT02879305)
Timeframe: Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52

,
InterventionScores on a scale (Least Squares Mean)
Week 8, n=982,936Week 12, n=990,943Week 28, n=836,819Week 52, n=729,707
Daprodustat0.300.33-0.23-0.52
rhEPO0.01-0.27-0.57-1.05

Change From Baseline in On-Treatment Physical Functioning Domain Scores Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52

The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following 8 health domains: physical functioning, role-physical (role limitations caused by physical problems), social functioning, bodily pain, mental health, role-emotional (role limitations caused by emotional problems), vitality and general health. Each domain is scored from 0 (poorer health) to 100 (better health). Physical functioning score ranges from 0 to 100; higher scores represent better health. Change from Baseline was calculated as on-treatment visit value minus (-) Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. (NCT02879305)
Timeframe: Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52

,
InterventionScores on a scale (Least Squares Mean)
Week 8, n=982,936Week 12, n=990,943Week 28, n=836,819Week 52, n=729,707
Daprodustat0.480.11-0.20-0.61
rhEPO-0.16-0.45-0.97-1.19

Change From Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52

The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following 8 health domains: bodily pain, general health, mental health, role-emotional (role limitations caused by emotional problems), role-physical (role limitations caused by physical problems), social functioning (Social fun), physical functioning (Phy. fun) and vitality. Each domain is scored from 0 (poorer health) to 100 (better health). Each domain score ranges from 0 to 100, higher score indicates a better health state and better functioning. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. (NCT02879305)
Timeframe: Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52

,
InterventionScores on a scale (Least Squares Mean)
Bodily pain: Week 8, n=982,936Bodily pain: Week 12, n=990,943Bodily pain: Week 28, n=836,819Bodily pain: Week 52, n=729,707General health: Week 8, n=982,936General health: Week 12, n=990,943General health: Week 28, n=836,819General health: Week 52, n=729,707Mental health: Week 8, n=982,936Mental health: Week 12, n=990,943Mental health: Week 28, n=836,819Mental health: Week 52, n=729,707Role-emotional: Week 8, n=982,936Role-emotional: Week 12, n=990,943Role-emotional: Week 28, n=836,819Role-emotional: Week 52, n=729,707Role-physical: Week 8, n=982,936Role-physical: Week 12, n=990,943Role-physical: Week 28, n=836,819Role-physical: Week 52, n=729,707Social functioning: Week 8, n=982,936Social functioning: Week 12, n=990,943Social functioning: Week 28, n=836,819Social functioning: Week 52, n=729,707
Daprodustat-0.130.20-0.70-1.12-0.39-0.59-1.32-1.51-0.43-0.86-1.30-1.97-0.10-0.17-0.95-0.830.400.48-0.10-0.210.240.25-0.61-1.12
rhEPO0.12-0.39-0.74-1.39-0.65-1.04-0.99-1.22-0.47-0.81-1.43-1.16-0.02-0.53-0.90-0.920.320.08-0.39-0.600.38-0.44-0.94-1.14

Change From Baseline in On-Treatment Vitality Scores Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52

The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following 8 health domains: physical functioning, role-physical (role limitations caused by physical problems), social functioning, bodily pain, mental health, role-emotional (role limitations caused by emotional problems), vitality and general health. Each domain is scored from 0 (poorer health) to 100 (better health). Vitality score ranges from 0 to 100; higher scores represent better health. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. (NCT02879305)
Timeframe: Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52

,
InterventionScores on a scale (Least Squares Mean)
Week 8, n=982,936Week 12, n=990,943Week 28, n=836,819Week 52, n=729,707
Daprodustat-0.23-0.17-0.79-1.19
rhEPO-0.26-0.51-1.03-1.04

Change From Baseline in SBP, DBP, MAP at End of Treatment

SBP, DBP and MAP were measured in a semi-supine or seated position in the dialysis chair after at least a 5-minutes of rest. MAP is an average BP in an individual's arteries during a single cardiac cycle. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. This analysis was carried out by using ANCOVA model with terms for treatment group, dialysis type, region and Baseline value. Data for post-dialysis BP measurements have been presented. (NCT02879305)
Timeframe: Baseline (Week -4) and 45.1 months

,
InterventionMillimeter of mercury (Least Squares Mean)
SBPDBPMAP
Daprodustat-0.43-0.92-0.75
rhEPO-0.43-1.37-1.06

Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Blood Pressure (MAP) at Week 52

SBP, DBP and MAP were measured in a semi-supine or seated position in the dialysis chair after at least a 5-minutes of rest. MAP is the average BP in an individual's arteries during a single cardiac cycle. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. Analysis was performed using MMRM model with treatment group + time + dialysis type + region + Baseline value + Baseline value*time + treatment group*time, using an unstructured covariance matrix. Data for post-dialysis BP measurements have been presented. (NCT02879305)
Timeframe: Baseline (Week -4) and Week 52

,
InterventionMillimeter of mercury (Least Squares Mean)
SBPDBPMAP
Daprodustat-0.61-1.04-0.89
rhEPO-0.93-0.58-0.71

Number of Participants With Adjudicated MACE or Hospitalization for Heart Failure (Recurrent Events Analysis)

Number of participants with adjudicated MACE or hospitalization for heart failure (recurrent events analysis) is presented, categorized by number of occurrences of adjudicated MACE or hospitalization for heart failure per participant. (NCT02879305)
Timeframe: Up to 3.9 person-years for CV follow-up time period

,
InterventionParticipants (Count of Participants)
Occurrences per participant: 0Occurrences per participant: 1Occurrences per participant: 2Occurrences per participant: 3Occurrences per participant: 4Occurrences per participant: 5Occurrences per participant: 6Occurrences per participant: 7Occurrences per participant: 8Occurrences per participant: 9Occurrences per participant: 10
Daprodustat106231572253440011
rhEPO1044300882211432111

Blood Pressure (BP) Exacerbation Event Rate Per 100 Participant Years

BP exacerbation event (based on post-dialysis) was defined as: SBP >= 25 millimeter of mercury (mmHg) increased from Baseline or SBP >=180 mmHg; DBP >=15 mmHg increased from Baseline or DBP >=110 mmHg. The BP exacerbation events per 100 participant years was estimated using the negative binomial model with treatment, current ESA use at randomization and region as covariates and the logarithm of time on-treatment as an offset variable. Data for post-dialysis BP measurements have been presented. (NCT02876835)
Timeframe: Day 1 to end of treatment (51.1 months)

InterventionEvents per 100 participant years (Number)
Daprodustat138.50
Darbepoetin Alfa157.35

Change From Baseline in On-treatment EQ Visual Analogue Scale (EQ-VAS) at Week 52

The EQ VAS records the respondent's self-rated health on a vertical VAS, ranging from 0 to 100, where 0 represents the worst imaginable health and 100 represents the best imaginable health. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. (NCT02876835)
Timeframe: Baseline (Pre-dose on Day 1) and Week 52

InterventionScores on a scale (Least Squares Mean)
Daprodustat-0.7
Darbepoetin Alfa-1.4

Change From Baseline in On-treatment Health Utility EuroQol 5 Dimensions 5 Level (EQ-5D-5L) Questionnaire Score at Week 52

EQ-5D-5L is self-assessment questionnaire, consisting of 5 items covering 5 dimensions (mobility, self care, usual activities, pain/discomfort and anxiety/depression). Each dimension is measured by 5-point Likert scale (1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems). Responses for 5 dimensions together formed a 5-figure description of health state (e.g.11111 indicates no problems in all 5 dimensions). Each of these 5 figure health states were converted to a single index score by applying country-specific value set formula that attaches weights to dimensions and levels. Range for EQ-5D-5L index score is -0.594 (worst health) to 1 (full health state). Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was latest non-missing pre-dose assessment on or before randomization date. (NCT02876835)
Timeframe: Baseline (Pre-dose on Day 1) and Week 52

InterventionScores on a scale (Least Squares Mean)
Daprodustat-0.0253
Darbepoetin Alfa-0.0018

Change From Baseline in Post-randomization Estimated Glomerular Filtration Rate (eGFR) at Week 52

Blood samples were collected to analyze estimated glomerular filtration rate. Change from Baseline was calculated as post-Baseline visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. (NCT02876835)
Timeframe: Baseline (Pre-dose on Day 1) and Week 52

InterventionmL per minute per 1.73 square meter (Least Squares Mean)
Daprodustat-2.88
Darbepoetin Alfa-2.67

Change From Baseline in Post-randomization Hgb Levels at Week 52

Blood samples were collected from participants for Hgb measurements. Change from Baseline was defined as post-randomization value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. Analysis was performed using mixed model repeated measures (MMRM) model fitted from Baseline up to Week 52, excluding values collected during the stabilization period, with factors for treatment, time, current ESA use, region, Baseline Hgb and Baseline Hgb by time and treatment by time interactions. (NCT02876835)
Timeframe: Baseline (Pre-dose on Day 1) and Week 52

InterventionGrams per deciliter (Least Squares Mean)
Daprodustat0.76
Darbepoetin Alfa0.73

Mean Change From Baseline in Hgb Levels Over the Evaluation Period (Week 28 to Week 52)

Blood samples were collected from participants for Hgb measurements. Hgb during the evaluation period was defined as the mean of all available post-randomization Hgb values (on and off-treatment) during the evaluation period (Week 28 to Week 52). For the primary analysis missing post-Baseline Hgb values were imputed using pre-specified multiple imputation methods. Change from Baseline was defined as post-Baseline value minus (-) Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. Analysis was performed using the Analysis of covariance (ANCOVA) model with terms for treatment, Baseline Hgb, current ESA use and region. (NCT02876835)
Timeframe: Baseline (Pre-dose on Day 1) and evaluation period (Week 28 to Week 52)

InterventionGrams per deciliter (Least Squares Mean)
Daprodustat0.74
Darbepoetin Alfa0.66

Number of Hgb Responders in the Hgb Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52)

Mean Hgb during the evaluation period was defined as the mean of all evaluable Hgb values during the evaluation period (Week 28 to Week 52) including any evaluable unscheduled Hgb values that were taken during this time period. Hgb responders were defined as participants with a mean Hgb during the evaluation period that falls within the Hgb analysis range of 10-11.5 g/dL. (NCT02876835)
Timeframe: Week 28 to Week 52

InterventionParticipants (Count of Participants)
Daprodustat1167
Darbepoetin Alfa1063

Number of Participants With at Least One BP Exacerbation Event During Study

BP exacerbation was defined as: SBP >= 25 mmHg increased from Baseline or SBP >=180 mmHg; DBP >=15 mmHg increased from Baseline or DBP >=110 mmHg. Number of participants with at least one BP exacerbation event is presented. (NCT02876835)
Timeframe: Day 1 to end of treatment (51.1 months)

InterventionParticipants (Count of Participants)
Daprodustat939
Darbepoetin Alfa1012

Percentage of Participants Permanently Stopping Randomized Treatment Due to Meeting Rescue Criteria

Percentage of participants permanently stopping randomized treatment due to meeting rescue criteria has been presented. (NCT02876835)
Timeframe: Day 1 to 51.1 months

InterventionPercentage of participants (Number)
Daprodustat2.0
Darbepoetin Alfa3.3

Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Maintenance Period (Week 28 to End of Study): Superiority Analysis

Percentage of days for which a participant's Hgb was within the analysis range of 10-11.5 g/dL (both inclusive) during the maintenance period (Week 28 to end of study), including any unscheduled evaluable Hgb values that were taken during this time period was calculated. Percentage of time in the analysis range during maintenance period is calculated as time in range during the maintenance period / [Earlier of (Date of the last evaluable Hgb value, End of study date)- Later of (Date of the first evaluable Hgb value that is on or after week 16, Week 28 visit date)]. (NCT02876835)
Timeframe: Week 28 to end of study (4.3 person-years for follow-up time period)

InterventionPercentage of days (Median)
Daprodustat66.1
Darbepoetin Alfa62.1

Percentage of Time With Hgb in the Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52): Non-inferiority Analysis

Percentage of days for which a participant's Hgb was within the analysis range of 10-11.5 g/dL (both inclusive) during the evaluation period (Week 28 to Week 52), including any unscheduled evaluable Hgb values that were taken during this time period was calculated. Percentage of time in the analysis range during evaluation period is calculated as time in range during the evaluation period / [Earlier of (Date of the last evaluable Hgb value, Week 52 visit date) - Later of (Date of the first evaluable Hgb value that between Week 16 and Week 52 inclusive, Week 28 visit date)]. (NCT02876835)
Timeframe: Week 28 to Week 52

InterventionPercentage of days (Median)
Daprodustat70.5
Darbepoetin Alfa63.2

Percentage of Time With Hgb in the Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52): Superiority Analysis

Percentage of days for which a participant's Hgb was within the analysis range of 10-11.5 g/dL (both inclusive) during the evaluation period (Week 28 to Week 52), including any unscheduled evaluable Hgb values that were taken during this time period was calculated. Percentage of time in the analysis range during evaluation period is calculated as time in range during the evaluation period / [Earlier of (Date of the last evaluable Hgb value, Week 52 visit date) - Later of (Date of the first evaluable Hgb value that between Week 16 and Week 52 inclusive, Week 28 visit date)]. (NCT02876835)
Timeframe: Week 28 to Week 52

InterventionPercentage of days (Median)
Daprodustat70.5
Darbepoetin Alfa63.2

Percentage of Time With Hgb in the Analysis Range (10 to 11.5 Grams/Deciliter) During Maintenance Period (Week 28 to End of Study): Non-inferiority Analysis

Percentage of days for which a participant's Hgb was within the analysis range of 10-11.5 g/dL (both inclusive) during the maintenance period (Week 28 to end of study), including any unscheduled evaluable Hgb values that were taken during this time period was calculated. Percentage of time in the analysis range during maintenance period is calculated as time in range during the maintenance period / [Earlier of (Date of the last evaluable Hgb value, End of study date)- Later of (Date of the first evaluable Hgb value that is on or after week 16, Week 28 visit date)]. (NCT02876835)
Timeframe: Week 28 to end of study (4.3 person-years for follow-up time period)

InterventionPercentage of days (Median)
Daprodustat66.1
Darbepoetin Alfa62.1

Time to First Occurrence of Adjudicated All-Cause Mortality During Vital Status for Follow-up Time Period

Time to first occurrence of adjudicated all-cause mortality was analyzed using a Cox proportional hazards regression model with treatment group, current ESA use at randomization, and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the vital status follow-up time period. (NCT02876835)
Timeframe: Up to 4.3 person-years for vital status follow-up time period

InterventionEvents per 100 person years (Number)
Daprodustat8.35
Darbepoetin Alfa8.27

Time to First Occurrence of Adjudicated CV Mortality During CV Events Follow-up Time Period

Time to first occurrence of adjudicated CV mortality was analyzed using a Cox proportional hazards regression model with treatment group, current ESA use at randomization, and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. (NCT02876835)
Timeframe: Up to 4.3 person-years for CV follow-up time period

InterventionEvents per 100 person years (Number)
Daprodustat3.02
Darbepoetin Alfa2.55

Time to First Occurrence of Adjudicated CV Mortality or Non-Fatal MI During CV Events Follow-up Time Period

Time to first occurrence of adjudicated CV mortality or non-fatal MI was analyzed using a Cox proportional hazards regression model with treatment group, current ESA use at randomization, and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. (NCT02876835)
Timeframe: Up to 4.3 person-years for CV follow-up time period

InterventionEvents per 100 person years (Number)
Daprodustat5.36
Darbepoetin Alfa4.98

Time to First Occurrence of Adjudicated Hospitalization for Heart Failure During CV Events Follow-up Time Period

Time to first occurrence of adjudicated hospitalization for heart failure was analyzed using a Cox proportional hazards regression model with treatment group, current ESA use at randomization, and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. (NCT02876835)
Timeframe: Up to 4.3 person-years for CV follow-up time period

InterventionEvents per 100 person years (Number)
Daprodustat4.05
Darbepoetin Alfa3.30

Time to First Occurrence of Adjudicated MACE During CV Events Follow-up Time Period (Superiority Analysis)

Time to MACE defined as the time to first occurrence of CEC adjudicated MACE was analyzed using a Cox proportional hazards regression model with treatment group, current ESA use at randomization, and region as covariate. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. This endpoint was adjusted for multiplicity using the Holm-Bonferonni method. (NCT02876835)
Timeframe: Up to 4.3 person-years for CV follow-up time period

InterventionEvents per 100 person years (Number)
Daprodustat10.86
Darbepoetin Alfa10.63

Time to First Occurrence of Adjudicated MACE or Hospitalization for Heart Failure During CV Events Follow-up Time Period

Time to first occurrence of adjudicated MACE or hospitalization for heart failure was analyzed using a Cox proportional hazards regression model with treatment group, current ESA use at randomization, and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. This endpoint was adjusted for multiplicity using the Holm-Bonferonni method. (NCT02876835)
Timeframe: Up to 4.3 person-years for CV follow-up time period

InterventionEvents per 100 person years (Number)
Daprodustat13.16
Darbepoetin Alfa12.22

Time to First Occurrence of Adjudicated MACE or Hospitalization for Heart Failure or Thromboembolic Events During CV Events Follow-up Time Period

Time to first occurrence of adjudicated MACE or hospitalization for heart failure or thromboembolic events were analyzed using a Cox proportional hazards regression model with treatment group, current ESA use at randomization, and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. (NCT02876835)
Timeframe: Up to 4.3 person-years for CV follow-up time period

InterventionEvents per 100 person years (Number)
Daprodustat14.60
Darbepoetin Alfa13.32

Time to First Occurrence of Adjudicated MACE or Thromboembolic Event During CV Events Follow-up Time Period

Time to first occurrence of adjudicated MACE or thromboembolic event (vascular access thrombosis, symptomatic deep vein thrombosis or symptomatic pulmonary embolism) was analyzed using a Cox proportional hazards regression model with with treatment group, current ESA use at randomization, and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. This endpoint was adjusted for multiplicity using the Holm-Bonferonni method. (NCT02876835)
Timeframe: Up to 4.3 person-years for CV follow-up time period

InterventionEvents per 100 person years (Number)
Daprodustat12.34
Darbepoetin Alfa11.77

Time to First Occurrence of Adjudicated Major Adverse Cardiovascular Event (MACE) During Cardiovascular (CV) Events Follow-up Time Period (Non-inferiority Analysis)

Time to MACE defined as time to first occurrence of Clinical Events Committee (CEC) adjudicated MACE (composite of all-cause mortality, non-fatal myocardial infarction [MI] and non-fatal stroke) was analyzed using a Cox proportional hazards regression model with treatment group, current erythropoiesis-stimulating agents (ESA) use at randomization and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) plus (+) 1. The incidence rate per 100 person years calculated as (100 multiplied [*] number of participants with at least 1 event) divided by [/] first event person-years) is presented along with 95 percent (%) confidence interval (CI). First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. (NCT02876835)
Timeframe: Up to 4.3 person-years for CV follow-up time period

InterventionEvents per 100 person years (Number)
Daprodustat10.86
Darbepoetin Alfa10.63

Time to First Occurrence of Adjudicated Myocardial Infarction (MI) (Fatal and Non-Fatal) During CV Events Follow-up Time Period

Time to first occurrence of adjudicated MI (fatal and non-fatal) was analyzed using a Cox proportional hazards regression model with treatment group, current ESA use at randomization, and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. (NCT02876835)
Timeframe: Up to 4.3 person-years for CV follow-up time period

InterventionEvents per 100 person years (Number)
Daprodustat2.94
Darbepoetin Alfa2.76

Time to First Occurrence of Adjudicated Stroke (Fatal and Non-Fatal) During CV Events Follow-up Time Period

Time to first occurrence of adjudicated stroke (fatal and non-fatal) was analyzed using a Cox proportional hazards regression model with treatment group, current ESA use at randomization, and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. (NCT02876835)
Timeframe: Up to 4.3 person-years for CV follow-up time period

InterventionEvents per 100 person years (Number)
Daprodustat1.26
Darbepoetin Alfa0.95

Time to First Occurrence of Adjudicated Thromboembolic Events During CV Events Follow-up Time Period

Time to first occurrence of adjudicated thromboembolic events were analyzed using a Cox proportional hazards regression model with treatment group, current ESA use at randomization, and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. (NCT02876835)
Timeframe: Up to 4.3 person-years for CV follow-up time period

InterventionEvents per 100 person years (Number)
Daprodustat1.81
Darbepoetin Alfa1.43

Time to First Occurrence of All-Cause Hospital Re-admission Within 30 Days During CV Events Follow-up Time Period

All-cause hospital re-admissions within 30days are defined as hospital admissions recorded on hospitalization electronic case record form with hospitalization duration of >=24 hours and admission date within 30days following previous discharge date of all-cause hospitalization event, where previous hospitalization was >=24hours.Time to first occurrence of all-cause hospital re-admission within 30days was analyzed using Cox proportional hazards regression model with treatment group, current ESA use at randomization and region as covariates.Time to the first occurrence was computed as(event date - randomization date)+1. Incidence rate per 100 person years calculated as(100*number of participants with at least 1event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event+cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. (NCT02876835)
Timeframe: Up to 4.3 person-years for CV follow-up time period

InterventionEvents per 100 person years (Number)
Daprodustat7.78
Darbepoetin Alfa7.55

Time to First Occurrence of All-Cause Hospitalization During CV Events Follow-up Time Period

All-cause hospitalization events were hospital admissions recorded on the hospitalization electronic case report form (eCRF) form with a hospitalization duration >=24 hours. Time to first occurrence of all-cause hospitalization was analyzed using a Cox proportional hazards regression model with treatment group, current ESA use at randomization, and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. (NCT02876835)
Timeframe: Up to 4.3 person-years for CV follow-up time period

InterventionEvents per 100 person years (Number)
Daprodustat41.13
Darbepoetin Alfa38.99

Time to First Occurrence of Chronic Dialysis During CV Events Follow-up Time Period

Time to first occurrence of chronic dialysis was analyzed using a Fine & Gray's proportional subdistribution hazard regression model with treatment group, Baseline ESA use and region as covariates. Chronic dialysis is defined by either initiating dialysis for >=90 days or not initiating chronic dialysis when dialysis is indicated. Time to the first occurrence was computed as (event date minus randomization date)+1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. (NCT02876835)
Timeframe: Up to 4.3 person-years for CV follow-up time period

InterventionEvents per 100 person years (Number)
Daprodustat12.20
Darbepoetin Alfa12.06

Time to First Occurrence of Chronic Kidney Disease (CKD) Progression During CV Events Follow-up Time Period

Progression of CKD defined as: 40% decline in estimated glomerular filtration rate (eGFR) from Baseline or end stage renal disease (ESRD) as defined by either initiating chronic dialysis for >=90 days or not initiating chronic dialysis when dialysis is indicated or kidney transplantation. Time to first occurrence of CKD progression was analyzed using Fine and Gray's proportional subdistribution hazard regression model with treatment group, Baseline ESA use and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) +1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event+cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. (NCT02876835)
Timeframe: Up to 4.3 person-years for CV follow-up time period

InterventionEvents per 100 person years (Number)
Daprodustat17.55
Darbepoetin Alfa17.76

Time to First Occurrence of Confirmed 40% Decline in eGFR During CV Events Follow-up Time Period

Time to first occurrence of confirmed 40% decline in eGFR was analyzed using a Fine & Gray's proportional subdistribution hazard regression model with treatment group, Baseline ESA use and region as covariates. Time to the first occurrence was computed as (event date minus randomization date)+1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. (NCT02876835)
Timeframe: Up to 4.3 person-years for CV follow-up time period

InterventionEvents per 100 person years (Number)
Daprodustat8.21
Darbepoetin Alfa8.90

Time to First Occurrence of Kidney Transplant During CV Events Follow-up Time Period

Time to first occurrence of kidney transplant were analyzed using a Fine & Gray's proportional subdistribution hazard regression model with treatment group, Baseline ESA use and region as covariates. Time to the first occurrence was computed as (event date minus randomization date)+1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. (NCT02876835)
Timeframe: Up to 4.3 person-years for CV follow-up time period

InterventionEvents per 100 person years (Number)
Daprodustat1.00
Darbepoetin Alfa1.14

Change From Baseline in On-treatment Chronic Kidney Disease- Anemia Symptoms Questionnaire (CKD-AQ) at Weeks 8, 12, 28, 52

CKD-AQ is 21-item patient reported outcome measure assessing symptoms and symptom impact in participants with anemia associated with CKD. It had 3 domains: 1.Tired/Low Energy (LE)/Weak scale consisting of 10 items; 2.Chest Pain (CP)/Shortness of Breath (SOB) scale consisting of 4 items; and 3.Cognitive (Cog) scale consisting of 3 items. The 4 CKD-AQ single items are: shortness of breath, no activity; severity-short breath (S-SB), resting; difficulty standing (diff. std.)for long time (LT) and difficulty sleeping (diff sleep). Single-item were recorded based on a 0-100 scoring with 0=worst possible and 100=best possible score. Three domains scores were calculated as average of items in each domain and ranged from 0-100 where 0=worst possible and 100=best possible score. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. (NCT02876835)
Timeframe: Baseline (Day 1) and Weeks 8, 12, 28, 52

,
InterventionScores on a scale (Least Squares Mean)
Tired/Low energy/Weak domain: Week 8,n=1340,1294Tired/Low energy/Weak domain: Week 12,n=1341,1360Tired/Low energy/Weak domain: Week 28,n=1053,1047Tired/Low energy/Weak domain: Week 52,n=870,865Chest pain/SOB domain: Week 8,n=1340,1294Chest pain/ SOB domain: Week 12,n=1341,1360Chest pain/ SOB domain: Week 28,n=1053,1047Chest pain/ SOB domain: Week 52,n=870,865Cognitive domain: Week 8,n=1340,1294Cognitive domain: Week 12,n=1341,1360Cognitive domain: Week 28,n=1053,1047Cognitive domain: Week 52,n=870,865SOB, no activity: Week 8,n=1340,1294SOB, no activity: Week 12,n=1341,1360SOB, no activity: Week 28,n=1053,1047SOB, no activity: Week 52,n=870,865Severity-short breath, Resting: Week 8,n=1340,1294Severity-short breath, Resting:Week 12,n=1341,1360Severity-short breath, Resting:Week 28,n=1053,1047Severity-short breath, Resting:Week 52,n=870,865Diff std for long time: Week 8,n=1340,1294Diff std for long time: Week 12,n=1341,1360Diff std for long time: Week 28,n=1053,1047Diff std for long time: Week 52,n=870,865Difficulty sleeping: Week 8,n=1340,1294Difficulty sleeping: Week 12,n=1341,1360Difficulty sleeping: Week 28,n=1053,1047Difficulty sleeping: Week 52,n=870,865
Daprodustat1.722.111.270.200.630.880.01-0.710.13-0.17-0.40-2.00-0.10.1-1.1-1.7-0.3-0.3-1.1-2.01.00.70.4-2.11.60.5-0.7-2.6
Darbepoetin Alfa2.943.081.871.771.831.530.530.470.891.010.37-0.351.00.4-0.2-1.60.80.0-0.7-0.52.51.61.71.21.12.0-0.3-0.3

Change From Baseline in On-treatment Mental Component Score (MCS) Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52

The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following 8 health domains: physical functioning, role-physical (role limitations caused by physical problems), social functioning, bodily pain, mental health, role-emotional (role limitations caused by emotional problems), vitality and general health. Each domain is scored from 0 (poorer health) to 100 (better health). MCS is an average score derived from 4 domains (vitality, social functioning, role-emotional and mental health) representing overall mental health. MCS ranges from 0 to 100; higher scores represent better health. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. (NCT02876835)
Timeframe: Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52

,
InterventionScores on a scale (Least Squares Mean)
Week 8, n=1238,1187Week 12, n=1237,1227Week 28, n=968,956Week 52, n=804,780
Daprodustat0.080.02-0.35-0.71
Darbepoetin Alfa0.370.18-0.02-0.35

Change From Baseline in On-treatment Patient Global Impression of Severity (PGI-S) at Weeks 8, 12, 28, 52

The PGI-S is a 1-item questionnaire designed to assess participant's impression of disease severity on a 5-point disease severity scale (0=absent, 1=mild, 2=moderate, 3=severe, or 4=very severe). A higher score indicated more disease severity. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. (NCT02876835)
Timeframe: Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52

,
InterventionScores on a scale (Least Squares Mean)
Week 8, n=1341,1295Week 12, n=1341,1362Week 28, n=1054,1051Week 52, n=871,865
Daprodustat0.000.030.050.11
Darbepoetin Alfa-0.02-0.020.090.06

Change From Baseline in On-treatment Physical Component Score (PCS) Using Short Form (SF)-36 Health-related Quality of Life (HRQoL) Questionnaire at Weeks 8, 12, 28, 52

The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following 8 health domains: physical functioning, role-physical (role limitations caused by physical problems), social functioning, bodily pain, mental health, role-emotional (role limitations caused by emotional problems), vitality and general health. Each domain is scored from 0 (poorer health) to 100 (better health). The PCS is an average score derived from 4 domains (physical functioning, role-physical, bodily pain and general health) representing overall physical health. PCS ranges from 0 to 100; higher score represents better health. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. (NCT02876835)
Timeframe: Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52

,
InterventionScores on a scale (Least Squares Mean)
Week 8, n=1238,1187Week 12, n=1237,1227Week 28, n=968,956Week 52, n=804,780
Daprodustat0.420.600.16-0.32
Darbepoetin Alfa0.780.710.04-0.12

Change From Baseline in On-treatment Physical Functioning Domain Scores Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52

The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following 8 health domains: physical functioning, role-physical (role limitations caused by physical problems), social functioning, bodily pain, mental health, role-emotional (role limitations caused by emotional problems), vitality and general health. Each domain is scored from 0 (poorer health) to 100 (better health). Physical functioning score ranges from 0 to 100; higher scores represent better health. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. (NCT02876835)
Timeframe: Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52

,
InterventionScores on a scale (Least Squares Mean)
Week 8, n=1238,1187Week 12, n=1237,1227Week 28, n=968,956Week 52, n=804,780
Daprodustat0.510.650.05-0.69
Darbepoetin Alfa0.830.52-0.10-0.37

Change From Baseline in On-treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52

The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following 8 health domains: bodily pain (b pain), general health (GH), mental health (MH), role-emotional (RE) (role limitations caused by emotional problems), role-physical (RP) (role limitations caused by physical problems), social functioning (SF), physical functioning and vitality. Each domain is scored from 0 (poorer health) to 100 (better health). Each domain score ranges from 0 to 100, higher score indicates a better health state and better functioning. Change from Baseline (BL) was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. (NCT02876835)
Timeframe: Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52

,
InterventionScores on a scale (Least Squares Mean)
Bodily pain: Week 8, n=1238,1187Bodily pain: Week 12, n=1237,1227Bodily pain: Week 28, n=968,956Bodily pain: Week 52, n=804,780General health: Week 8, n=1238,1187General health: Week 12, n=1237,1227General health: Week 28, n=968,956General health: Week 52, n=804,780Mental health: Week 8, n=1238,1187Mental health: Week 12, n=1237,1227Mental health: Week 28, n=968,956Mental health: Week 52, n=804,780Role-emotional: Week 8, n=1238,1187Role-emotional: Week 12, n=1237,1227Role-emotional: Week 28, n=968,956Role-emotional: Week 52, n=804,780Role-physical: Week 8, n=1238,1187Role-physical: Week 12, n=1237,1227Role-physical: Week 28, n=968,956Role-physical: Week 52, n=804,780Social functioning: Week 8, n=1238,1187Social functioning: Week 12, n=1237,1227Social functioning: Week 28, n=968,956Social functioning: Week 52, n=804,780
Daprodustat0.110.35-0.48-0.340.360.280.14-0.27-0.19-0.07-0.67-0.850.450.17-0.30-0.900.330.400.06-0.630.190.210.04-0.58
Darbepoetin Alfa0.450.500.020.130.430.480.04-0.190.12-0.09-0.37-0.610.540.430.07-0.380.830.730.00-0.440.820.530.17-0.20

Change From Baseline in On-treatment Vitality Scores Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52

The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following 8 health domains: physical functioning, role-physical (role limitations caused by physical problems), social functioning, bodily pain, mental health, role-emotional (role limitations caused by emotional problems), vitality and general health. Each domain is scored from 0 (poorer health) to 100 (better health). Vitality score ranges from 0 to 100; higher scores represent better health. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. (NCT02876835)
Timeframe: Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52

,
InterventionScores on a scale (Least Squares Mean)
Week 8, n=1238,1187Week 12, n=1237,1227Week 28, n=968,956Week 52, n=804,780
Daprodustat0.350.620.22-0.14
Darbepoetin Alfa0.900.740.320.35

Change From Baseline in SBP, DBP, MAP at End of Treatment

SBP, DBP and MAP were measured in a seated position after at least a 5-minutes of rest. MAP is an average BP in an individual's arteries during a single cardiac cycle. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. Analysis was performed using ANCOVA model with terms for treatment group, current ESA use at randomization, region and Baseline value. Data for post-dialysis BP measurements have been presented. (NCT02876835)
Timeframe: Baseline (Week -4) and 51.1 months

,
InterventionMillimeter of mercury (Least Squares Mean)
SBP, n=1919, 1884DBP, n=1918, 1884MAP, n=1918, 1884
Daprodustat-1.19-0.26-0.57
Darbepoetin Alfa-1.10-0.38-0.62

Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Blood Pressure (MAP) at Week 52

SBP, DBP and MAP were measured in a seated position after at least a 5-minutes of rest. MAP is the average (BP) in an individual's arteries during a single cardiac cycle. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. Analysis was performed using MMRM model with treatment group + time + current ESA use at randomization + region + Baseline value + Baseline value*time + treatment group*time, using an unstructured covariance matrix. Data for post-dialysis BP measurements have been presented. (NCT02876835)
Timeframe: Baseline (Week -4) and Week 52

,
InterventionMillimeter of mercury (Least Squares Mean)
SBP, n=1913, 1884DBP, n=1912, 1884MAP, n=1912, 1884
Daprodustat-0.620.06-0.17
Darbepoetin Alfa-1.17-0.59-0.77

Number of Participants With Adjudicated MACE or Hospitalization for Heart Failure (Recurrent Events Analysis)

Number of participants with adjudicated MACE or hospitalization for heart failure (recurrent events analysis) is presented, categorized by number of occurrences of adjudicated MACE or hospitalization for heart failure per participant. (NCT02876835)
Timeframe: Up to 4.3 person-years for CV follow-up time period

,
InterventionParticipants (Count of Participants)
Occurrences per participant: 0Occurrences per participant: 1Occurrences per participant: 2Occurrences per participant: 3Occurrences per participant: 4Occurrences per participant: 5Occurrences per participant: 6Occurrences per participant: 7Occurrences per participant: 8
Daprodustat14933187626145140
Darbepoetin Alfa1518317642293011

Average Monthly Intravenous Iron Dose (Milligrams) From Baseline to Week 52

Total IV iron dose per participant was calculated from Day 1 to the earliest of (Week 52 visit date, first blood [red blood cells or whole blood] transfusion date and treatment stop date plus [+] 1 day) which corresponds to the time while the participant was on randomized treatment and before receiving a blood transfusion. Average monthly IV iron dose was calculated by Total IV iron dose divided by (/) (the number of days from Day 1 to the earliest of [Week 52 visit date, first blood transfusion date and treatment stop date +1] /30.4375 days). Data for participants until they underwent a red blood cells or whole blood transfusion was included in the analysis. (NCT03029208)
Timeframe: Baseline (Day 1) to Week 52

InterventionMilligram (Least Squares Mean)
Daprodustat144.7
Darbepoetin Alfa125.3

Blood Pressure (BP) Exacerbation Events Rate Per 100 Participant Years

BP exacerbation event is defined (based on post-dialysis BP) as SBP >=25 millimeter of mercury (mmHg) increased from Baseline or SBP >=180 mmHg; or DBP >=15 mmHg increased from Baseline or DBP >=110 mmHg. The BP exacerbation events per 100 participant years was estimated using the Negative Binomial Model. (NCT03029208)
Timeframe: Up to Week 52

InterventionEvents per 100 participant year (Number)
Daprodustat352.50
Darbepoetin Alfa350.00

Change From Baseline in EQ Visual Analogue Scale (EQ-VAS) at Week 52

The EQ-5D-5L consists of 2 concepts -EQ-5D-5L descriptive system and EQ-VAS. The EQ-5D-5L is a self-assessment questionnaire, consisting of five items covering five dimensions (mobility, self care, usual activities, pain/discomfort and anxiety/depression). Each dimension is measured by a five-point Likert scale (no problems, slight problems, moderate problems, severe problems, and extreme problems). The range for the EQ-5D-5L index score is 0 to 1 with '0' is worst health and '1' is full health. The EQ VAS records the respondent's self-rated health on a vertical VAS, ranging from 0 to 100, where 0 represents the worst health one can imagine and 100 represents the best health one can imagine. Change from Baseline was calculated as post-dose visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. (NCT03029208)
Timeframe: Baseline (Day 1) and Week 52

InterventionScores on a scale (Least Squares Mean)
Daprodustat3.4
Darbepoetin Alfa6.8

Change From Baseline in Health Utility EuroQol 5 Dimensions 5 Level (EQ-5D-5L) Questionnaire Score at Week 52

EQ-5D-5L consists of 2 concepts-EQ-5D-5L descriptive system and EQ Visual Analogue Scale (EQ-VAS). EQ-5D-5L is self-assessment questionnaire, consisting of 5items covering 5 dimensions (mobility,self care, usual activities, pain/discomfort and anxiety/depression). Each dimension is measured by 5-point Likert scale(no problems, slight problems, moderate problems, severe problems and extreme problems). Responses for 5 dimensions together formed a 5-figure description of health state(e.g.11111 indicates no problems in all 5 dimensions). Each of these 5 figure health states were converted to a single index score by applying country-specific value set formula that attaches weights to dimensions and levels. Range for EQ-5D-5L index score is -0.594 (worst health) to 1 (full health), higher the score better the health status. Change from Baseline was calculated as post-dose visit value-Baseline value. Baseline was latest non-missing pre-dose assessment on or before randomization date. (NCT03029208)
Timeframe: Baseline (Day 1) and Week 52

InterventionScores on a scale (Least Squares Mean)
Daprodustat0.00
Darbepoetin Alfa-0.03

Change From Baseline in Post-randomization Hgb at Week 52

Blood samples were collected from participants for Hgb measurements. Change from Baseline was calculated as post-dose visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. (NCT03029208)
Timeframe: Baseline (Day 1) and Week 52

InterventionGrams per deciliter (Least Squares Mean)
Daprodustat1.17
Darbepoetin Alfa1.13

Mean Change From Baseline in Hemoglobin (Hgb) During Evaluation Period (Week 28 to Week 52)

Blood samples were collected from participants for Hgb measurement. Hgb during the evaluation period was defined as the mean of all available post-randomization Hgb values (on and off-treatment) during the evaluation period (Week 28 to Week 52). For the primary analysis missing post-Baseline Hgb values were imputed using pre-specified multiple imputations. Change from Baseline was defined as the average of post-randomization values during the evaluation period minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. An analysis of covariance (ANCOVA) model including randomization stratification factors Baseline Hgb and treatment was performed to obtain a point estimate and two-sided 95 percent (%) confidence interval (CI) for the treatment difference (daprodustat-darbepoetin alfa). (NCT03029208)
Timeframe: Baseline (Pre-dose on Day 1) and evaluation period (Week 28 to Week 52)

InterventionGrams per deciliter (Least Squares Mean)
Daprodustat1.02
Darbepoetin Alfa1.12

Number of Hgb Responders (Hgb in the Analysis Range of 10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52)

Mean Hgb during the evaluation period was defined as the mean of all evaluable Hgb values during the evaluation period (Week 28 to Week 52) including any evaluable unscheduled Hgb values that were taken during this time period. Hgb responders were defined as number of participants with a mean Hgb during the evaluation period that falls within the Hgb analysis range of 10-11.5 g/dL. (NCT03029208)
Timeframe: Weeks 28 to 52

InterventionParticipants (Count of Participants)
Daprodustat86
Darbepoetin Alfa87

Number of Participants Permanently Stopping Randomized Treatment Due to Meeting Rescue Criteria

Number of participants permanently stopping randomized treatment due to meeting rescue criteria has been presented. (NCT03029208)
Timeframe: Up to Week 52

InterventionParticipants (Count of Participants)
Daprodustat5
Darbepoetin Alfa5

Number of Participants With at Least One Blood Pressure Exacerbation Event During Study

BP exacerbation was defined (based on post-dialysis BP) as: SBP >=25 mmHg increased from Baseline or SBP >=180 mmHg; DBP >=15 mmHg increased from Baseline or DBP >=110 mmHg. Number of participants with at least one blood pressure exacerbation event is presented. (NCT03029208)
Timeframe: Up to Week 52

InterventionParticipants (Count of Participants)
Daprodustat91
Darbepoetin Alfa100

Percentage of Time for Which Hgb Was Within the Analysis Range (10 to 11.5 g/dL) During Evaluation Period (Week 28 to Week 52): Non-inferiority Analysis

Percentage of days for which a participant's Hgb was within the analysis range of 10-11.5 g/dL (both inclusive) during the evaluation period (Week 28 to Week 52), including any unscheduled evaluable Hgb values that were taken during this time period was calculated. Percentage of time for which Hgb was within range for a participant was calculated by dividing 'the total number of days that Hgb was within range during Weeks 28 to 52' by 'the total number of days the participant remained on treatment during Weeks 28 to 52'. (NCT03029208)
Timeframe: Weeks 28 to 52

InterventionPercentage of days (Median)
Daprodustat57.0
Darbepoetin Alfa54.7

Percentage of Time for Which Hgb Was Within the Analysis Range (10 to 11.5 g/dL) During Evaluation Period (Week 28 to Week 52): Superiority Analysis

Percentage of days for which a participant's Hgb was within the analysis range of 10-11.5 g/dL (both inclusive) during the evaluation period (Week 28 to Week 52), including any unscheduled evaluable Hgb values that were taken during this time period was calculated. Percentage of time for which Hgb was within range for a participant was calculated by dividing 'the total number of days that Hgb was within range during Weeks 28 to 52' by 'the total number of days the participant remained on treatment during Weeks 28 to 52'. (NCT03029208)
Timeframe: Weeks 28 to 52

InterventionPercentage of days (Median)
Daprodustat57.0
Darbepoetin Alfa54.7

Change From Baseline in Chronic Kidney Disease- Anemia Symptoms Questionnaire (CKD-AQ) at Week 52

CKD-AQ is 21-item patient reported outcome measure assessing symptoms and symptom impact in participants with anemia associated with CKD. It had 3 domains: 1.Tired/Low Energy/Weak scale consisting of 10 items; 2.Chest Pain/Shortness of Breath scale consisting of 4 items; and 3.Cognitive scale consisting of 3 items. The 4 CKD-AQ single items are: (shortness of breath, no activity), (severity-short breath, resting), (difficulty standing for long time) and (difficulty sleeping). Single-item were recorded based on a 0-100 scoring with 0=worst possible and 100=best possible score. Three domains scores were calculated as average of items in each domain and ranged from 0-100 where 0=worst possible and 100=best possible score. Change from Baseline was calculated as post-dose visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. (NCT03029208)
Timeframe: Baseline (Day 1) and Week 52

,
InterventionScores on a scale (Least Squares Mean)
Tired/Low energy/Weak domainChest pain/Shortness of breath domainCognitive domainShortness of breath, no activitySeverity-short breath, RestingDifficulty standing for long timeDifficulty sleeping
Daprodustat-2.36-1.83-4.17-1.90-4.16-2.00-5.27
Darbepoetin Alfa4.072.282.431.140.123.301.26

Change From Baseline in Mental Component Score (MCS) Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52

The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following 8 health domains: physical functioning, role-physical (role limitations caused by physical problems), social functioning, bodily pain, mental health, role-emotional (role limitations caused by emotional problems), vitality and general health. Each domain is scored from 0 (poorer health) to 100 (better health). MCS is an average score derived from 4 domains (vitality, social functioning, role-emotional and mental health) representing overall mental health. MCS ranges from 0 to 100; higher scores represent better health. Change from Baseline was calculated as post-dose visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. (NCT03029208)
Timeframe: Baseline (Day 1), Weeks 8, 12, 28 and 52

,
InterventionScores on a scale (Least Squares Mean)
Week 8, n=88,86Week 12, n=88,88Week 28, n=80,74Week 52, n=67,65
Daprodustat0.100.08-0.02-0.95
Darbepoetin Alfa0.761.600.30-0.72

Change From Baseline in Patient Global Impression of Severity (PGI-S)

The PGI-S is a 1-item questionnaire designed to assess participant's impression of disease severity on a 5-point disease severity scale (0=absent, 1=mild, 2=moderate, 3=severe, or 4=very severe). A higher score indicated worse outcome. Change from Baseline was calculated as post-dose visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. (NCT03029208)
Timeframe: Baseline (Day 1), Weeks 8, 12, 28 and 52

,
InterventionScores on a scale (Least Squares Mean)
Week 8, n=100,100Week 12, n=100,103Week 28, n=92,85Week 52, n=75,77
Daprodustat0.160.020.090.22
Darbepoetin Alfa-0.11-0.03-0.070.04

Change From Baseline in Physical Component Score (PCS) Using Short Form (SF)-36 Health-related Quality of Life (HRQoL) Questionnaire at Weeks 8, 12, 28, 52

The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following 8 health domains: physical functioning, role-physical (role limitations caused by physical problems), social functioning, bodily pain, mental health, role-emotional (role limitations caused by emotional problems), vitality and general health. Each domain is scored from 0 (poorer health) to 100 (better health). The PCS is an average score derived from 4 domains (physical functioning, role-physical, bodily pain and general health) representing overall physical health. PCS ranges from 0 to 100; higher scores represent better health. Change from Baseline was calculated as post-dose visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. (NCT03029208)
Timeframe: Baseline (Day 1), Weeks 8, 12, 28 and 52

,
InterventionScores on a scale (Least Squares Mean)
Week 8, n=88,86Week 12, n=88,88Week 28, n=80,74Week 52, n=67,65
Daprodustat0.791.670.940.61
Darbepoetin Alfa1.180.540.451.93

Change From Baseline in Physical Functioning Domain Scores Using SF-36 HRQoL Questionnaire at Weeks 28, 52

The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following 8 health domains: physical functioning, role-physical (role limitations caused by physical problems), social functioning, bodily pain, mental health, role-emotional (role limitations caused by emotional problems), vitality and general health. Each domain is scored from 0 (poorer health) to 100 (better health). Physical functioning ranges from 0 to 100; higher scores represent better health. Change from Baseline was calculated as post-dose visit value minus (-) Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. (NCT03029208)
Timeframe: Baseline (Day 1), Weeks 28 and 52

,
InterventionScores on a scale (Least Squares Mean)
Week 28, n=80,74Week 52, n=67,65
Daprodustat0.550.14
Darbepoetin Alfa0.831.58

Change From Baseline in SBP, DBP, MAP at End of Treatment

SBP, DBP and MAP were measured in a semi-supine or seated position in the dialysis chair after at least a 5-minutes of rest. MAP is an average BP in an individual's arteries during a single cardiac cycle. End of treatment value for the blood pressure parameters were defined as the latest value on or before the last non-zero dose date plus (+) 1 day. Change from Baseline was calculated as post-dose visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. This analysis was carried out by using ANCOVA model. (NCT03029208)
Timeframe: Baseline (Day 1) and end of treatment (last on-treatment value until Week 52)

,
InterventionMillimeter of mercury (Least Squares Mean)
SBPDBPMAP
Daprodustat-3.230.60-0.68
Darbepoetin Alfa-3.14-1.39-1.97

Change From Baseline in SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52

The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following 8 health domains: bodily pain, general health, mental health, role-emotional (role limitations caused by emotional problems), role-physical (role limitations caused by physical problems), social functioning, physical functioning and vitality. Each domain is scored from 0 (poorer health) to 100 (better health). Each domain score ranges from 0 to 100, higher score indicates a better health state and better functioning. Change from Baseline was calculated as post-dose visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. (NCT03029208)
Timeframe: Baseline (Day 1), Weeks 8, 12, 28 and 52

,
InterventionScores on a scale (Least Squares Mean)
Bodily pain: Week 8, n=88,86Bodily pain: Week 12, n=88,88Bodily pain: Week 28, n=80,74Bodily pain: Week 52, n=67,65General health: Week 8, n=88,86General health: Week 12, n=88,88General health: Week 28, n=80,74General health: Week 52, n=67,65Mental health: Week 8, n=88,86Mental health: Week 12, n=88,88Mental health: Week 28, n=80,74Mental health: Week 52, n=67,65Role-emotional: Week 8, n=88,86Role-emotional: Week 12, n=88,88Role-emotional: Week 28, n=80,74Role-emotional: Week 52, n=67,65Role-physical: Week 8, n=88,86Role-physical: Week 12, n=88,88Role-physical: Week 28, n=80,74Role-physical: Week 52, n=67,65Social functioning: Week 8, n=88,86Social functioning: Week 12, n=88,88Social functioning: Week 28, n=80,74Social functioning: Week 52, n=67,65
Daprodustat-0.41-0.131.08-2.000.800.870.630.40-0.900.01-0.69-0.530.830.550.91-1.601.342.390.621.490.520.981.030.39
Darbepoetin Alfa-0.55-0.06-1.260.610.750.590.370.580.251.42-0.21-0.270.50-0.070.39-0.112.641.691.492.221.552.150.95-0.33

Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Mean Arterial Blood Pressure (MAP) at Week 52

SBP, DBP and MAP were measured in a semi-supine or seated position in the dialysis chair after at least a 5-minutes of rest. MAP is an average BP in an individual's arteries during a single cardiac cycle. Change from Baseline was calculated as post-dose visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. This analysis was carried out by using mixed model repeated measures (MMRM) model. (NCT03029208)
Timeframe: Baseline (Day 1) and Week 52

,
InterventionMillimeter of mercury (Least Squares Mean)
SBPDBPMAP
Daprodustat-3.570.21-0.95
Darbepoetin Alfa-6.80-4.01-5.05

Change From Baseline in Vitality Scores Using SF-36 HRQoL Questionnaire at Weeks 28, 52

The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following 8 health domains: physical functioning, role-physical (role limitations caused by physical problems), social functioning, bodily pain, mental health, role-emotional (role limitations caused by emotional problems), vitality and general health. Each domain is scored from 0 (poorer health) to 100 (better health). Vitality ranges from 0 to 100; higher scores represent better health. Change from Baseline was calculated as post-dose visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. (NCT03029208)
Timeframe: Baseline (Day 1), Weeks 28 and 52

,
InterventionScores on a scale (Least Squares Mean)
Week 28, n=80,74Week 52, n=67,65
Daprodustat-0.080.16
Darbepoetin Alfa0.951.61

Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2506104 (M3), and GSK2531401 (M13)

Pharmacokinetic samples were collected at pre-dose, 0.5, 1, 2 and 3 hours post-dose on Week 4 or 8 or 12 for pharmacokinetic analysis of daprodustat (GSK1278863) and its metabolites GSK2391220 (M2), GSK2506104 (M3), and GSK2531401 (M13). GSK2391220, GSK2506104 and GSK2531401 are the metabolites of Daprodustat (GSK1278863). Protocol allowed participants to provide pharmacokinetic samples on Week 4 or 8 or 12. (NCT03029208)
Timeframe: Pre-Dose, 0.5, 1, 2 and 3 hours post-dose; each pharmacokinetic sample was taken at Week 4 or 8 or 12

,,,,,
InterventionNanogram per milliliter (Mean)
DaprodustatGSK2391220GSK2506104GSK2531401
Daprodustat 1 mg21.742.1602.4772.283
Daprodustat 10 mg145.016.6022.0010.20
Daprodustat 2 mg32.294.1395.2123.565
Daprodustat 4 mg76.925.7807.0755.328
Daprodustat 6 mg100.210.3611.607.836
Daprodustat 8 mg32.006.09010.105.760

Observed Concentration at Dosing Interval (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2506104 (M3), and GSK2531401 (M13)

Pharmacokinetic samples were collected at pre-dose, 0.5, 1, 2 and 3 hours post-dose on Week 4 or 8 or 12 for pharmacokinetic analysis of daprodustat (GSK1278863) and its metabolites GSK2391220 (M2), GSK2506104 (M3), and GSK2531401 (M13). GSK2391220, GSK2506104 and GSK2531401 are the metabolites of Daprodustat (GSK1278863). Protocol allowed participants to provide pharmacokinetic samples on Week 4 or 8 or 12. (NCT03029208)
Timeframe: Pre-Dose, 0.5, 1, 2 and 3 hours post-dose; each pharmacokinetic sample was taken at Week 4 or 8 or 12

,,,,,
InterventionNanogram per milliliter (Mean)
DaprodustatGSK2391220GSK2506104GSK2531401
Daprodustat 1 mg2.1180.71061.2701.642
Daprodustat 10 mg0.10906.5609.5007.760
Daprodustat 2 mg1.0152.1243.5082.729
Daprodustat 4 mg0.57872.0873.8793.750
Daprodustat 6 mg2.8673.5605.9215.111
Daprodustat 8 mg0.10304.4508.7105.660

Plasma Concentration of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2506104 (M3), and GSK2531401 (M13)

Pharmacokinetic samples were collected at pre-dose, 0.5, 1, 2 and 3 hours post-dose on Week 4 or 8 or 12 for pharmacokinetic (PK) analysis of daprodustat (GSK1278863) and its metabolites GSK2391220 (M2), GSK2506104 (M3), and GSK2531401 (M13). GSK2391220, GSK2506104 and GSK2531401 are the metabolites of Daprodustat (GSK1278863). Protocol allowed participants to provide pharmacokinetic samples on Week 4 or 8 or 12. Pharmacokinetic Population comprised of participants for whom a pharmacokinetic sample was obtained and analyzed. (NCT03029208)
Timeframe: Pre-dose, 0.5, 1, 2 and 3 hours post-dose; each pharmacokinetic sample was taken at Week 4 or 8 or 12

InterventionNanogram per milliliter (Mean)
Daprodustat: Pre-Dose, n=19,26,20,18,1,1,0,0,0Daprodustat: 1 hour, n=19,26,20,18,1,1,0,0,0Daprodustat: 2 hours, n=19,26,20,18,1,1,0,0,0Daprodustat: 3 hours, n=19,26,19,18,1,1,0,0,0GSK2391220: Pre-Dose, n=19,26,20,18,1,1,0,0,0GSK2391220: 0.5 hour, n=19,25,20,18,1,1,0,0,0GSK2391220: 1 hour, n=18,26,20,18,1,1,0,0,0GSK2391220: 2 hours, n=19,26,20,18,1,1,0,0,0GSK2391220: 3 hours, n=19,26,19,18,1,1,0,0,0GSK2506104: Pre-Dose, n=19,26,20,18,1,1,0,0,0GSK2506104: 0.5 hour, n=19,26,20,18,1,1,0,0,0GSK2506104: 1 hour, n=19,26,20,18,1,1,0,0,0GSK2506104: 2 hours, n=19,26,20,18,1,1,0,0,0GSK2506104: 3 hours, n=19,26,19,18,1,1,0,0,0GSK2531401: Pre-Dose, n=19,26,20,18,1,1,0,0,0GSK2531401: 0.5 hour, n=19,26,20,18,1,1,0,0,0GSK2531401: 1 hour, n=19,26,20,18,1,1,0,0,0GSK2531401: 2 hours, n=19,26,20,18,1,1,0,0,0GSK2531401: 3 hours, n=19,26,19,18,1,1,0,0,0
Daprodustat 8 mg0.10300.912032.0025.304.4503.9503.9004.7006.0908.7107.7407.4608.93010.105.6604.9604.8105.1905.760

Plasma Concentration of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2506104 (M3), and GSK2531401 (M13)

Pharmacokinetic samples were collected at pre-dose, 0.5, 1, 2 and 3 hours post-dose on Week 4 or 8 or 12 for pharmacokinetic (PK) analysis of daprodustat (GSK1278863) and its metabolites GSK2391220 (M2), GSK2506104 (M3), and GSK2531401 (M13). GSK2391220, GSK2506104 and GSK2531401 are the metabolites of Daprodustat (GSK1278863). Protocol allowed participants to provide pharmacokinetic samples on Week 4 or 8 or 12. Pharmacokinetic Population comprised of participants for whom a pharmacokinetic sample was obtained and analyzed. (NCT03029208)
Timeframe: Pre-dose, 0.5, 1, 2 and 3 hours post-dose; each pharmacokinetic sample was taken at Week 4 or 8 or 12

,,,,
InterventionNanogram per milliliter (Mean)
Daprodustat: Pre-Dose, n=19,26,20,18,1,1,0,0,0Daprodustat: 0.5 hour, n=19,26,20,18,0,1,0,0,0Daprodustat: 1 hour, n=19,26,20,18,1,1,0,0,0Daprodustat: 2 hours, n=19,26,20,18,1,1,0,0,0Daprodustat: 3 hours, n=19,26,19,18,1,1,0,0,0GSK2391220: Pre-Dose, n=19,26,20,18,1,1,0,0,0GSK2391220: 0.5 hour, n=19,25,20,18,1,1,0,0,0GSK2391220: 1 hour, n=18,26,20,18,1,1,0,0,0GSK2391220: 2 hours, n=19,26,20,18,1,1,0,0,0GSK2391220: 3 hours, n=19,26,19,18,1,1,0,0,0GSK2506104: Pre-Dose, n=19,26,20,18,1,1,0,0,0GSK2506104: 0.5 hour, n=19,26,20,18,1,1,0,0,0GSK2506104: 1 hour, n=19,26,20,18,1,1,0,0,0GSK2506104: 2 hours, n=19,26,20,18,1,1,0,0,0GSK2506104: 3 hours, n=19,26,19,18,1,1,0,0,0GSK2531401: Pre-Dose, n=19,26,20,18,1,1,0,0,0GSK2531401: 0.5 hour, n=19,26,20,18,1,1,0,0,0GSK2531401: 1 hour, n=19,26,20,18,1,1,0,0,0GSK2531401: 2 hours, n=19,26,20,18,1,1,0,0,0GSK2531401: 3 hours, n=19,26,19,18,1,1,0,0,0
Daprodustat 10 mg0.1090145.079.6027.6011.006.5606.74010.0016.2016.609.5008.11012.4019.6022.007.7606.4606.6308.29010.20
Daprodustat 2 mg1.0154.66421.4520.3615.582.1241.8071.7522.9693.5353.5082.7882.6103.5834.1452.7292.1701.9792.3382.734
Daprodustat 4 mg0.578710.2736.7854.6843.342.0871.8221.9654.0085.5533.8793.3153.2684.9896.5033.7503.2633.1463.7114.715
Daprodustat 6 mg2.86712.5845.4855.6256.493.5602.4103.1406.3369.3725.9214.0154.3337.1309.9425.1113.8003.7764.8926.631
Daprodustat 1 mg2.1185.67512.3412.747.7190.71060.76021.1231.7451.9111.2701.1971.3641.9662.1901.6421.4271.3991.6901.847

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. (NCT02689206)
Timeframe: Baseline and Day 29

InterventionBeats per minute (Mean)
Placebo-2.0
Dapro 10 mg0.5
Dapro 15 mg1.1
Dapro 25 mg2.2
Dapro 30 mg0.9

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. (NCT02689206)
Timeframe: Baseline and Day 29

InterventionProportion of red blood cells in blood (Mean)
Placebo-0.0218
Dapro 10 mg-0.0127
Dapro 15 mg-0.0149
Dapro 25 mg0.0150
Dapro 30 mg0.0215

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. (NCT02689206)
Timeframe: Baseline and Day 29

Interventiong/dL (Mean)
Placebo-0.61
Dapro 10 mg-0.19
Dapro 15 mg-0.13
Dapro 25 mg0.64
Dapro 30 mg0.55

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. (NCT02689206)
Timeframe: Baseline and Day 29

Intervention10^12 cells/L (Mean)
Placebo-0.19
Dapro 10 mg-0.12
Dapro 15 mg-0.13
Dapro 25 mg0.12
Dapro 30 mg0.15

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. (NCT02689206)
Timeframe: Baseline and Day 29

InterventionPercentage of reticulocyte (Mean)
Placebo-0.08
Dapro 10 mg-0.11
Dapro 15 mg-0.04
Dapro 25 mg0.43
Dapro 30 mg0.09

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. (NCT02689206)
Timeframe: Baseline and Day 29

InterventionPicograms (pg) (Mean)
Placebo-0.15
Dapro 10 mg0.23
Dapro 15 mg0.26
Dapro 25 mg0.23
Dapro 30 mg0.59

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. (NCT02689206)
Timeframe: Baseline and up to Day 29

InterventionInternational unit per liter (IU/L) (Mean)
Placebo53.761
Dapro 10 mg2.255
Dapro 15 mg73.369
Dapro 25 mg302.529
Dapro 30 mg477.644

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." (NCT02689206)
Timeframe: 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

Interventionng/mL (Geometric Mean)
Dapro 10 mg140.0
Dapro 15 mg141.4
Dapro 25 mg246.9
Dapro 30 mg387.3

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. (NCT02689206)
Timeframe: Baseline and up to Day 29

InterventionNanograms per liter (ng/L) (Geometric Mean)
Placebo20.35
Dapro 10 mg43.75
Dapro 15 mg32.16
Dapro 25 mg53.34
Dapro 30 mg76.09

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. (NCT02689206)
Timeframe: Baseline and Day 29

InterventionMicrograms per liter (µg/L) (Geometric Mean)
Placebo27.81
Dapro 10 mg35.37
Dapro 15 mg3.83
Dapro 25 mg-36.74
Dapro 30 mg-36.09

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). (NCT02689206)
Timeframe: Up to Day 43

,,,,
InterventionIU/L (Mean)
ALT; Day 1; n= 18, 20, 20, 22, 22ALT; Day 15; n= 17, 20, 18, 22, 20ALT; Day 29; n= 17, 19, 18, 19, 17ALT; Day 43; n= 15, 20, 18, 21, 21AST; Day 1; n= 18, 20, 20, 22, 22AST; Day 15; n= 17, 20, 18, 22, 20AST; Day 29; n= 17, 19, 18, 19, 17AST; Day 43; n= 15, 20, 18, 21, 21Alk. phosph; Day 1; n= 18, 20, 20, 22, 22Alk. phosph; Day 15; n= 17, 20, 18, 22,20Alk. phosph.; Day 29; n= 17, 19, 18, 19,17Alk. phosph.; Day 43; n= 15, 20, 18, 21,21
Dapro 10 mg13.413.912.813.814.214.313.814.9112.3115.4120.2117.6
Dapro 15 mg14.612.412.212.817.215.016.017.2106.8114.5109.2113.8
Dapro 25 mg10.711.910.913.114.415.415.015.799.4101.593.5116.2
Dapro 30 mg11.58.48.611.213.612.413.514.3115.4110.0120.4108.6
Placebo12.616.524.414.314.917.126.815.997.0102.494.196.5

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). (NCT02689206)
Timeframe: Up to Day 43

,,,,
Interventiongrams per liter (g/L) (Mean)
Albumin; Day 1; n= 18, 20, 20, 22, 22Albumin; Day 15; n= 17, 20, 18, 22, 20Albumin; Day 29; n= 17, 19, 18, 19, 17Albumin; Day 43; n= 15, 20, 18, 21, 21Protein; Day 1; n= 18, 20 ,20, 22, 22Protein; Day 15; n= 17, 20, 18, 22, 20Protein; Day 29; n= 17, 19, 18, 19, 17Protein; Day 43; n= 15, 20, 18, 21, 21
Dapro 10 mg38.638.137.238.166.966.565.767.4
Dapro 15 mg38.738.437.637.967.467.366.066.8
Dapro 25 mg38.838.437.439.066.465.665.566.7
Dapro 30 mg38.137.236.937.565.764.365.366.6
Placebo37.638.136.537.167.368.166.167.2

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)." (NCT02689206)
Timeframe: 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

,,,
Interventionhour into nanograms/milliliter (h*ng/mL) (Geometric Mean)
AUC (0-t); n= 19, 15, 16, 14AUC (0-inf); n= 12, 9, 8, 11
Dapro 10 mg311.7348.2
Dapro 15 mg416.7383.5
Dapro 25 mg513.91214
Dapro 30 mg10101369

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). (NCT02689206)
Timeframe: Up to Day 43

,,,,
InterventionMicromoles per liter (µmol/L) (Mean)
Bilirubin; Day 1; n= 18, 20, 20, 22, 22Bilirubin; Day 15; n= 17, 20, 18, 22, 20Bilirubin; Day 29; n= 17, 19, 18, 19, 17Bilirubin; Day 43; n= 15, 20 ,18, 21, 21Direct bilirubin; Day 1; n= 18, 20, 20, 22, 22Direct bilirubin; Day 15; n= 17, 20, 18, 22, 20Direct bilirubin; Day 29; n= 17, 19, 18, 19,17Direct bilirubin; Day 43; n= 15, 20, 18, 21,21Indirect bilirubin; Day 1; n= 18, 20, 20, 22, 22Indirect bilirubin; Day 15; n= 17, 20, 18, 22, 20Indirect bilirubin; Day 29; n= 17, 19, 18, 19, 17Indirect bilirubin; Day 43; n= 15, 20, 18, 21, 21
Dapro 10 mg7.87.16.97.01.92.21.61.95.94.95.45.1
Dapro 15 mg6.67.27.67.22.02.42.72.34.64.84.94.9
Dapro 25 mg6.56.56.56.51.91.81.81.74.64.74.74.8
Dapro 30 mg7.27.87.87.52.42.62.42.34.85.25.45.2
Placebo6.66.76.86.01.81.52.51.34.85.24.44.7

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). (NCT02689206)
Timeframe: Baseline and up to Day 43

,,,,
Interventiong/L (Mean)
Albumin; Day 15; n= 17, 20, 18, 22, 20Albumin; Day 29; n= 17, 19, 18, 19, 17Albumin; Day 43; n= 15, 20, 18, 21, 21Protein; Day 15; n= 17, 20, 18, 22, 20Protein; Day 29; n= 17, 19, 18, 19, 17Protein; Day 43; n= 15, 20, 18, 21, 21
Dapro 10 mg-0.5-1.3-0.6-0.4-0.80.6
Dapro 15 mg0.2-0.7-0.70.3-1.2-0.9
Dapro 25 mg-0.5-1.30.1-0.7-1.00.3
Dapro 30 mg-1.0-0.9-0.3-1.50.11.2
Placebo0.8-0.50.10.8-1.1-0.1

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). (NCT02689206)
Timeframe: Baseline and up to Day 43

,,,,
InterventionIU/L (Mean)
ALT; Day 15; n= 17, 20, 18, 22, 20ALT; Day 29; n= 17, 19, 18, 19, 17ALT; Day 43; n= 15, 20, 18, 21, 21AST; Day 15; n= 17, 20, 18, 22, 20AST; Day 29; n= 17, 19, 18, 19, 17AST; Day 43; n= 15, 20, 18, 21, 21Alk.phosph.; Day 15; n= 17, 20, 18, 22, 20Alk.phosph.; Day 29; n= 17, 19, 18, 19, 17Alk.phosph.; Day 43; n= 15, 20, 18, 21, 21
Dapro 10 mg0.5-0.90.40.1-0.30.73.25.15.4
Dapro 15 mg-3.1-3.4-2.5-2.7-1.8-0.62.7-0.92.7
Dapro 25 mg1.1-0.22.21.00.91.52.10.918.0
Dapro 30 mg-3.4-3.6-0.4-1.6-0.30.7-4.7-1.2-8.4
Placebo3.611.80.92.311.50.63.2-0.4-1.5

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). (NCT02689206)
Timeframe: Baseline and up to Day 43

,,,,
Interventionµmol/L (Mean)
Bilirubin; Day 15; n= 17, 20, 18, 22, 20Bilirubin; Day 29; n= 17, 19, 18, 19, 17Bilirubin; Day 43; n= 15, 20, 18, 21, 21Direct bilirubin; Day 15; n= 17, 20, 18, 22, 20Direct bilirubin; Day 29; n= 17, 19, 18, 19, 17Direct bilirubin; Day 43; n= 15, 20, 18, 21, 21Indirect bilirubin; Day 15; n= 17, 20, 18, 22, 20Indirect bilirubin; Day 29; n= 17, 19, 18, 19, 17Indirect bilirubin; Day 43; n= 15, 20, 18, 21, 21
Dapro 10 mg-0.7-0.3-0.80.3-0.30.0-1.00.0-0.8
Dapro 15 mg0.81.00.60.60.70.30.20.30.2
Dapro 25 mg0.00.10.1-0.1-0.1-0.20.10.20.3
Dapro 30 mg0.50.20.40.2-0.1-0.10.30.40.5
Placebo0.20.2-0.1-0.10.7-0.10.4-0.50.0

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). (NCT02689206)
Timeframe: Baseline and Day 29

,,,,
InterventionMilliseconds (msec) (Mean)
PR interval; n= 17, 18, 18, 17, 16QRS duration; n= 17, 19, 18, 19, 17QT interval; n= 17, 19, 18, 19, 17QTcB; n= 17, 19, 18, 19, 17
Dapro 10 mg7.3-5.70.75.6
Dapro 15 mg-3.3-4.7-19.2-3.7
Dapro 25 mg2.11.7-1.41.1
Dapro 30 mg-11.52.5-8.2-5.7
Placebo7.8-1.410.50.0

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). (NCT02689206)
Timeframe: Baseline and up to Day 43

,,,,
InterventionPercentage of width (Mean)
Day 15; n= 17, 19, 17, 21, 21Day 29; n= 16, 19, 17, 18, 17Day 43; n= 16, 20, 19, 21, 20
Dapro 10 mg-0.48-0.64-0.74
Dapro 15 mg-0.09-0.23-0.50
Dapro 25 mg0.540.580.23
Dapro 30 mg1.060.40-0.22
Placebo-0.18-0.310.18

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). (NCT02689206)
Timeframe: Baseline and up to Day 43

,,,,
Intervention10^12 cells/L (Mean)
Leukocytes; Day 15; n= 17, 19, 17, 21, 21Leukocytes; Day 29; n= 16, 19, 17, 18, 17Leukocytes; Day 43; n= 16, 20, 19, 20, 19Neutrophils; Day 15; n= 17, 19, 17, 21, 21Neutrophils; Day 29; n= 16, 18, 17, 17, 15Neutrophils; Day 43; n= 16, 20, 19, 19, 19Basophils; Day 15; n= 17, 19, 17, 21, 21Basophils; Day 29; n= 16, 18, 17, 17, 15Basophils; Day 43; n= 16, 20, 19, 19, 19Eosinophils; Day 15; n= 17, 19, 17, 21, 21Eosinophils; Day 29; n= 16, 18, 17, 17, 15Eosinophils; Day 43; n= 16, 20, 19, 19, 19Lymphocytes; Day 15; n= 17, 19, 17, 21, 21Lymphocytes; Day 29; n= 16, 18, 17, 17, 15Lymphocytes; Day 43; n= 16, 20, 19, 19, 19Monocytes; Day 15; n= 17, 19, 17, 21, 21Monocytes; Day 29; n= 16, 18, 17, 17, 15Monocytes; Day 43; n= 16, 20, 19, 19, 19Platelet; Day 15; n= 17, 18, 17, 20, 21Platelet; Day 29; n= 16, 18, 17, 17, 17Platelet; Day 43; n= 15, 19, 19, 21, 20
Dapro 10 mg-0.210.401.08-0.1460.4690.9040.0090.0060.001-0.017-0.0020.030-0.0190.0260.061-0.0420.0530.065-16.2-12.84.4
Dapro 15 mg0.400.000.230.280-0.0210.112-0.002-0.004-0.004-0.006-0.0060.0510.1060.0190.007-0.016-0.0310.026-3.2-18.1-10.4
Dapro 25 mg-0.03-0.140.210.259-0.0090.504-0.0020.000-0.001-0.0060.0250.021-0.208-0.074-0.064-0.0680.077-0.021-3.31.3-1.6
Dapro 30 mg-0.030.200.670.3440.2730.6910.0070.0120.007-0.0530.007-0.024-0.236-0.154-0.041-0.0370.0150.023-10.8-2.4-7.1
Placebo0.470.490.540.3910.2370.4230.0050.0130.0060.0090.0200.0610.0820.1940.018-0.0050.0270.033-14.2-17.1-4.9

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). (NCT02689206)
Timeframe: Baseline and up to Day 43

,,,,
InterventionPg (Mean)
Day 15; n= 17, 19, 17, 21, 21Day 29; n= 16, 19, 17, 18, 17Day 43; n= 16, 20, 19, 21, 20
Dapro 10 mg0.190.580.13
Dapro 15 mg0.270.420.34
Dapro 25 mg0.160.410.11
Dapro 30 mg0.250.150.29
Placebo0.160.160.11

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). (NCT02689206)
Timeframe: Baseline and up to Day 43

,,,,
Interventiong/L (Mean)
Day 15; n= 17, 19, 17, 21, 21Day 29; n= 16, 19, 17, 18, 17Day 43; n= 16, 20, 19, 21, 20
Dapro 10 mg3.07.33.0
Dapro 15 mg3.57.66.0
Dapro 25 mg-3.20.8-1.0
Dapro 30 mg-5.0-4.4-0.3
Placebo2.65.63.9

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). (NCT02689206)
Timeframe: Baseline and up to Day 43

,,,,
InterventionfL (Mean)
Day 15; n= 17, 19, 17, 21, 21Day 29; n= 16, 19, 17, 18, 17Day 43; n= 16, 20, 19, 21, 20
Dapro 10 mg-0.2-0.5-0.7
Dapro 15 mg-0.3-0.9-0.8
Dapro 25 mg1.30.90.6
Dapro 30 mg2.21.60.9
Placebo-0.4-1.4-0.8

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). (NCT02689206)
Timeframe: Up to Day 43

,,,,
InterventionBeats per minute (Mean)
Pre-dialysis; Day 15; n= 17, 20, 18, 22, 21Pre-dialysis; Day 29; n= 17, 19, 18, 19, 17Pre-dialysis; Day 43; n= 16, 20, 19, 21, 21Post-dialysis; Day 15; n= 17, 20, 18, 22, 21Post-dialysis; Day 29; n= 17, 19, 18, 19, 17Post-dialysis; Day 43; n= 16, 20, 19, 21, 21
Dapro 10 mg-2.60.90.1-1.21.50.3
Dapro 15 mg2.33.40.81.1-0.8-0.8
Dapro 25 mg0.70.5-0.60.52.6-0.1
Dapro 30 mg-1.4-3.00.24.46.03.9
Placebo7.02.43.12.24.22.3

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). (NCT02689206)
Timeframe: Up to Day 43

,,,,
InterventionmmHg (Mean)
SBP; pre-dialysis; Day 15; n= 17, 20, 18, 22, 21SBP; pre-dialysis; Day 29; n= 17, 19, 18, 19, 17SBP; pre-dialysis; Day 43; n= 16, 20, 19, 21, 21SBP; post-dialysis; Day 15; n= 17, 20, 18, 22, 21SBP; post-dialysis; Day 29; n= 17, 19, 18, 19, 17SBP; post-dialysis; Day 43; n= 16, 20, 19, 21, 21DBP; pre-dialysis; Day 15; n= 17, 20, 18, 22, 21DBP; pre-dialysis; Day 29; n= 17, 19, 18, 19, 17DBP; pre-dialysis; Day 43; n= 16, 20, 19, 21, 21DBP; post-dialysis; Day 15; n= 17, 20, 18, 22, 21DBP; post-dialysis; Day 29; n= 17, 19, 18, 19, 17DBP; post-dialysis; Day 43; n= 16, 20, 19, 21, 21
Dapro 10 mg1.7-3.91.2-3.6-9.4-3.21.2-4.7-2.02.4-2.5-0.3
Dapro 15 mg-5.6-4.7-6.26.10.8-3.6-1.7-3.0-3.1-2.9-3.2-3.8
Dapro 25 mg2.51.33.35.79.312.01.81.45.23.64.14.5
Dapro 30 mg-1.44.54.3-0.74.04.7-2.1-0.12.1-0.80.24.8
Placebo-2.9-0.6-2.15.42.33.11.1-0.32.22.43.7-0.6

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). (NCT02689206)
Timeframe: Baseline and up to Day 43

,,,,
InterventionMmol/L (Mean)
Sodium; Day 15; n= 17, 20, 18, 22, 20Sodium; Day 29; n= 17, 19, 18, 19, 17Sodium; Day 43; n= 15, 20, 18, 21, 21Potassium; Day 15; n= 17, 20, 18, 22, 20Potassium; Day 29; n= 17, 19, 18, 19, 17Potassium; Day 43; n= 15, 20, 18, 21, 21Glucose; Day 15; n= 17, 20, 18, 22, 20Glucose; Day 29; n= 17, 19, 18, 19, 17Glucose; Day 43; n= 15, 20, 18, 21, 21Calcium; Day 15; n= 17, 20, 18, 22, 20Calcium; Day 29; n= 17, 19, 18, 19, 17Calcium; Day 43; n= 15, 20, 18, 21, 21Phosphate; Day 15; n= 17, 20, 18, 22, 20Phosphate; Day 29; n= 17, 19, 18, 19, 17Phosphate; Day 43; n= 15, 20, 18, 21, 21
Dapro 10 mg-0.6-1.20.10.050.05-0.050.510.700.06-0.051-0.025-0.0350.1830.011-0.068
Dapro 15 mg-0.5-0.9-0.6-0.09-0.14-0.060.450.730.52-0.026-0.0090.0180.1110.069-0.053
Dapro 25 mg-1.4-0.5-0.50.030.02-0.060.210.61-0.81-0.031-0.0120.0010.0300.1290.102
Dapro 30 mg-1.0-1.2-0.6-0.080.11-0.02-0.03-0.36-0.12-0.0100.0010.0330.095-0.026-0.117
Placebo-0.9-1.10.70.040.200.041.141.480.23-0.011-0.054-0.015-0.0910.091-0.067

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). (NCT02689206)
Timeframe: Up to Day 43

,,,,
Interventionkg (Mean)
Day 15; n= 17, 20, 18, 22, 21Day 29; n= 17, 19, 18, 19, 17Day 43; n= 16, 20, 19, 21, 21
Dapro 10 mg0.16-0.050.37
Dapro 15 mg-0.01-1.23-1.39
Dapro 25 mg0.06-0.160.15
Dapro 30 mg-0.31-0.190.33
Placebo-0.16-0.11-0.21

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). (NCT02689206)
Timeframe: Up to Day 43

,,,,
InterventionPercentage of width (Mean)
Day 1; n= 18, 19, 20, 20, 21Day 15; n= 17, 19, 17, 21, 21Day 29; n= 16, 19, 17, 18, 17Day 43; n= 16, 20, 19, 21, 20
Dapro 10 mg16.4015.7715.6915.53
Dapro 15 mg15.4115.2615.3614.95
Dapro 25 mg15.8116.3015.7615.61
Dapro 30 mg15.6816.7416.2315.48
Placebo15.1315.0515.1515.53

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). (NCT02689206)
Timeframe: Up to Day 43

,,,,
Intervention10^12 cells/L (Mean)
Leukocytes; Day 1; n= 18, 19, 19, 20, 21Leukocytes; Day 15; n= 17, 19, 17, 21, 21Leukocytes; Day 29; n= 16, 19, 17, 18, 17Leukocytes; Day 43; n= 16, 20, 19, 20, 19Neutrophils; Day 1; n= 18, 19, 19, 20, 21Neutrophils; Day 15; n= 17, 19, 17, 21, 21Neutrophils; Day 29; n= 16, 18, 17, 17, 15Neutrophils; Day 43; n= 16, 20, 19, 19, 19Basophils; Day 1; n= 18, 19, 19, 20, 21Basophils; Day 15; n= 17, 19, 17, 21, 21Basophils; Day 29; n= 16, 18, 17, 17, 15Basophils; Day 43; n= 16, 20, 19, 19, 19Eosinophils; Day 1; n= 18, 19, 19, 20, 21Eosinophils; Day 15; n= 17, 19, 17, 21, 21Eosinophils; Day 29; n= 16, 18, 17, 17, 15Eosinophils; Day 43; n= 16, 20, 19, 19, 19Lymphocytes; Day 1; n= 18, 19, 19, 20, 21Lymphocytes; Day 15; n= 17, 19, 17, 21, 21Lymphocytes; Day 29; n= 16, 18, 17, 17, 15Lymphocytes; Day 43; n= 16, 20, 19, 19, 19Monocytes; Day 1; n= 18, 19, 20, 20, 21Monocytes; Day 15; n= 17, 19, 17, 21, 21Monocytes; Day 29; n= 16, 18, 17, 17, 15Monocytes; Day 43; n= 16, 20, 19, 19, 19Platelet; Day 1; n= 16, 19, 20, 19, 21Platelet; Day 15; n= 17, 18, 17, 20, 21Platelet; Day 29; n= 16, 19, 17, 17, 17Platelet; Day 43; n= 15, 20, 19, 21, 20
Dapro 10 mg6.075.856.597.254.0973.8874.5915.0490.0160.0260.0210.0180.1740.1660.1490.2101.3931.4161.4271.5090.3960.3520.4570.459189.9175.4174.7195.8
Dapro 15 mg5.886.215.886.003.5223.7073.5223.5450.0250.0220.0210.0200.1840.1920.1450.2321.7391.8421.7751.7360.4350.4360.4030.461198.0198.5187.5188.6
Dapro 25 mg6.446.526.336.773.9544.3463.9784.4770.0280.0250.0240.0250.1960.1870.2370.2431.7471.5261.6121.7210.5180.4460.6000.513196.0194.8198.9194.1
Dapro 30 mg5.905.876.116.423.7854.1294.2244.3430.0170.0240.0270.0240.2400.1860.1850.2171.4421.2061.1811.3990.4210.3840.4260.429192.3181.5194.8170.0
Placebo6.287.016.667.054.0304.6664.1234.6870.0180.0270.0350.0280.1890.1610.1760.2161.6311.7351.8701.6480.4010.4200.4440.461219.0205.4198.1220.8

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). (NCT02689206)
Timeframe: Up to Day 43

,,,,
InterventionPg (Mean)
Day 1; n= 18, 19, 20, 20, 21Day 15; n= 17, 19, 17, 21, 21Day 29; n= 16, 19, 17, 18, 17Day 43; n= 16, 20, 19, 21, 20
Dapro 10 mg30.952.10031.6031.04
Dapro 15 mg30.1930.7430.5630.49
Dapro 25 mg30.7030.8531.1630.67
Dapro 30 mg31.4631.7031.6831.84
Placebo31.1930.8330.9730.86

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). (NCT02689206)
Timeframe: Up to Day 43

,,,,
Interventiong/L (Mean)
Day 1; n= 18, 19, 20, 20, 21Day 15; n= 17, 19, 17, 21, 21Day 29; n= 16, 19, 17, 18, 17Day 43; n= 16, 20, 19, 21, 20
Dapro 10 mg321.7324.0329.6325.2
Dapro 15 mg319.5324.8325.4325.5
Dapro 25 mg321.5318.3323.6321.0
Dapro 30 mg327.6322.7323.9327.0
Placebo322.9321.5323.3321.9

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). (NCT02689206)
Timeframe: Up to Day 43

,,,,
InterventionFemtoliter (fL) (Mean)
Day 1; n= 18, 19, 20, 20, 21Day 15; n= 17, 19, 17, 21, 21Day 29; n= 16, 19, 17, 18, 17Day 43; n= 16, 20, 19, 21, 20
Dapro 10 mg96.495.895.995.4
Dapro 15 mg94.794.894.193.7
Dapro 25 mg95.797.096.395.6
Dapro 30 mg96.198.397.897.5
Placebo96.795.995.896.1

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. (NCT02689206)
Timeframe: Up to Day 43

,,,,
InterventionParticipants (Number)
AEsProtocol deviationParticipant reached stopping criteriaPhysician decisionWithdrawal by subject
Dapro 10 mg00100
Dapro 15 mg10201
Dapro 25 mg01300
Dapro 30 mg12400
Placebo01011

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. (NCT02689206)
Timeframe: Up to Day 29

,,,,
InterventionParticipants (Number)
Baseline(Week -4);Abnormal; NCS;n=19,20,20,22,22Baseline(Week-4);Abnormal;CS;n=19,20,20,22,22Day 29; Abnormal; NCS; n=17,19,18,19,17Day 29; Abnormal; CS; n=17,19,18,19,17
Dapro 10 mg150140
Dapro 15 mg180160
Dapro 25 mg12181
Dapro 30 mg160120
Placebo100120

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. (NCT02689206)
Timeframe: Up to Day 43

,,,,
InterventionParticipants (Number)
Any AEAny SAE
Dapro 10 mg103
Dapro 15 mg62
Dapro 25 mg71
Dapro 30 mg73
Placebo104

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). (NCT02689206)
Timeframe: Up to Day 43

,,,,
InterventionBeats per minute (Mean)
Pre-dialysis; Day 1; n= 19, 20, 20, 22, 22Pre-dialysis; Day 15; n= 17, 20, 18, 22, 21Pre-dialysis; Day 29; n= 17, 19, 18, 19, 17Pre-dialysis; Day 43; n= 16, 20, 19, 21, 21Post-dialysis; Day 1; n= 19, 20, 20, 22, 22Post-dialysis; Day 15; n= 17, 20, 18, 22, 21Post-dialysis; Day 29; n= 17, 19, 18, 19, 17Post-dialysis; Day 43; n= 16, 20, 19, 21, 21
Dapro 10 mg69.967.370.369.968.767.769.969.1
Dapro 15 mg66.768.369.666.966.370.168.868.0
Dapro 25 mg71.472.170.871.373.273.072.271.9
Dapro 30 mg76.575.173.475.878.878.177.477.3
Placebo68.576.170.471.571.072.573.672.0

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). (NCT02689206)
Timeframe: Up to Day 43

,,,,
InterventionMillimoles per liter (mmol/L) (Mean)
Sodium; Day 1; n= 18, 20, 20, 22, 22Sodium; Day 15; n= 17, 20, 18, 22, 20Sodium; Day 29; n= 17, 19, 18, 19, 17Sodium; Day 43; n= 15, 20, 18, 21, 21Potassium; Day 1; n= 18, 20, 20, 22, 22Potassium; Day 15; n= 17, 20, 18, 22, 20Potassium; Day 29; n= 17, 19, 18, 19, 17Potassium; Day 43; n= 15, 20, 18, 21, 21Glucose; Day 1; n= 18, 20, 20, 22, 22Glucose; Day 15; n= 17, 20, 18, 22, 20Glucose; Day 29; n= 17, 19, 18, 19, 17Glucose; Day 43; n= 15, 20, 18, 21, 21Calcium corrected; Day 1; n= 18, 20, 20, 22, 22Calcium corrected; Day 15; n= 17, 20, 18, 22, 20Calcium corrected; Day 29; n= 17, 19, 18, 19, 17Calcium corrected; Day 43; n= 15, 20, 18, 21, 21Phosphate; Day 1; n= 18, 20, 20, 22, 22Phosphate; Day 15; n= 17, 20, 18, 22, 20Phosphate; Day 29; n= 17, 19, 18, 19, 17Phosphate; Day 43; n= 15, 20, 18, 21, 21
Dapro 10 mg138.1137.5136.8138.14.734.774.874.686.667.167.496.722.2702.2192.2482.2351.5281.7101.5921.460
Dapro 15 mg138.7138.1137.9137.94.644.574.574.596.417.037.217.092.2412.2132.2442.2711.4981.6421.6441.472
Dapro 25 mg139.4138.0138.8138.84.794.824.864.767.057.267.776.272.2192.1882.1982.2011.3181.3481.4531.412
Dapro 30 mg138.4137.2137.1137.64.834.804.964.808.958.678.758.932.2152.2032.2252.2561.5661.6451.5501.398
Placebo138.8137.7137.8139.24.684.724.784.696.667.898.216.932.2862.2612.2052.2511.6081.6211.7091.550

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). (NCT02689206)
Timeframe: Up to Day 43

,,,,
InterventionMillimeter of mercury (mmHg) (Mean)
SBP; pre-dialysis; Day 1; n= 19, 20, 20, 22, 22SBP; pre-dialysis; Day 15; n= 17, 20, 18, 22, 21SBP; pre-dialysis; Day 29; n= 17, 19, 18, 19, 17SBP; pre-dialysis; Day 43; n= 16, 20, 19, 21, 21DBP; pre-dialysis; Day 1; n= 19, 20, 20, 22, 22DBP; pre-dialysis; Day 15; n= 17, 20, 18, 22, 21DBP; pre-dialysis; Day 29; n= 17, 19, 18, 19, 17DBP; pre-dialysis; Day 43; n= 16, 20, 19, 21, 21SBP; post-dialysis; Day 1; n= 19, 20, 20, 22, 22SBP; post-dialysis; Day 15; n= 17, 20, 18, 22, 21SBP; post-dialysis; Day 29; n= 17, 19, 18, 19, 17SBP; post-dialysis; Day 43; n= 16, 20, 19, 21, 21DBP; post-dialysis; Day 1; n= 19, 20, 20, 22, 22DBP; post-dialysis; Day 15; n= 17, 20, 18, 22, 21DBP; post-dialysis; Day 29; n= 17, 19, 18, 19, 17DBP; post-dialysis; Day 43; n= 16, 20, 19, 21, 21
Dapro 10 mg136.6138.3133.1137.968.870.063.566.8137.0135.5130.1135.867.970.164.467.4
Dapro 15 mg149.2139.0143.1142.073.370.170.969.9139.9137.7133.7130.468.767.867.967.4
Dapro 25 mg144.1146.6144.2149.071.873.573.377.9136.7137.4142.8145.271.171.372.472.9
Dapro 30 mg144.1142.3148.7147.172.269.772.772.8140.1140.9147.8137.571.571.172.975.3
Placebo142.5138.8143.0140.071.972.570.472.5138.6138.6135.7137.572.172.473.969.5

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)." (NCT02689206)
Timeframe: 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

,,,
InterventionHour (Geometric Mean)
Tmax; n= 19, 15, 16, 14T1/2; n= 12, 9, 8, 11
Dapro 10 mg2.4562.086
Dapro 15 mg2.1061.886
Dapro 25 mg2.2971.418
Dapro 30 mg1.7182.897

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). (NCT02689206)
Timeframe: Up to Day 43

,,,,
InterventionKilograms (kg) (Mean)
Day 1; n= 19, 20, 20, 22, 22Day 15; n= 17, 20, 18, 22, 21Day 29; n= 17, 19, 18, 19, 17Day 43; n= 16, 20, 19, 21, 21
Dapro 10 mg80.0480.0081.0480.21
Dapro 15 mg78.8379.8280.0279.25
Dapro 25 mg79.3879.4482.6680.64
Dapro 30 mg76.0375.5576.0773.66
Placebo82.3884.2483.2283.93

Part 1: Change From Baseline in Hematology Parameter Erythrocyte MCHC

Blood samples were collected to analyze hematology parameter; EMCH. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value. (NCT03493386)
Timeframe: Baseline (Day -1), 24hours post-dose

InterventionPicograms (pg) (Mean)
Part 1: Daprodustat 2mg*20.11
Part 1: Daprodustat 4mg*10.01

Part 1: Change From Baseline in Hematology Parameter Erythrocyte Mean Corpuscular Volume (EMCV)

Blood samples were collected to analyze hematology parameter; EMCV. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value. (NCT03493386)
Timeframe: Baseline (Day -1), 24hours post-dose

InterventionFemtoliters (Mean)
Part 1: Daprodustat 2mg*2-0.2
Part 1: Daprodustat 4mg*1-0.2

Part 1: Change From Baseline in Hematology Parameter: Erythrocytes

Blood samples were collected to analyze hematology parameter; erythrocytes. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value. (NCT03493386)
Timeframe: Baseline (Day -1), 24hours post-dose

InterventionTrillion cells/liter (10^12 cell/L) (Mean)
Part 1: Daprodustat 2mg*20.018
Part 1: Daprodustat 4mg*10.023

Part 1: Change From Baseline in Urinalysis Parameter; Potential of Hydrogen (pH)

Urinary pH measurement is a routine part of urinalysis. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0). Urine samples were collected for the measurement of urine pH by method up to 24 hours in Part 1.Day-1 (one day before the Pre-Dose) was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value. (NCT03493386)
Timeframe: Baseline (Day -1), 24hours post-dose

InterventionpH (Mean)
Part 1: Daprodustat 2mg*2-0.04
Part 1: Daprodustat 4mg*1-0.07

Part 1: Change From Baseline in Urinalysis Parameter; Specific Gravity

Urinary specific gravity measurement is a routine part of urinalysis. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. Urine samples were collected for the measurement of urine specific gravity by dipstick method up to 24 hours in Part 1. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value. (NCT03493386)
Timeframe: Baseline (Day -1), 24hours post-dose

InterventionKilogram per cubic meter (Mean)
Part 1: Daprodustat 2mg*20.0092
Part 1: Daprodustat 4mg*10.0088

Part 1: Elimination Rate Constant (Kel) of Daprodustat

Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3. (NCT03493386)
Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12hours post-dose on Day 1, 24hours post-dose on Day 2

InterventionPer hour (Geometric Mean)
Part 1: Daprodustat 2mg*20.2138
Part 1: Daprodustat 4mg*10.2128

Part 1: Percentage of AUC (0-inf) Obtained by Extrapolation (Percentage AUCex)

Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3. (NCT03493386)
Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2

InterventionPercentage of AUCex (Geometric Mean)
Part 1: Daprodustat 2mg*20.0862
Part 1: Daprodustat 4mg*10.0836

Part 1: Time of Occurrence of Cmax (Tmax) of Daprodustat

Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3. (NCT03493386)
Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2

Interventionhour (Median)
Part 1: Daprodustat 2mg*22.000
Part 1: Daprodustat 4mg*12.000

Part 1:Apparent Clearance (CL/F) of Daprodustat

Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3. (NCT03493386)
Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2

InterventionLiters per hour (Geometric Mean)
Part 1: Daprodustat 2mg*221.8551
Part 1: Daprodustat 4mg*122.2382

Part 1:Apparent Oral Volume of Distribution (Vz/F) of Daprodustat

Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3. (NCT03493386)
Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2

InterventionMilliliters (mL) (Geometric Mean)
Part 1: Daprodustat 2mg*2102244.3
Part 1: Daprodustat 4mg*1104522.8

Part 1:Change From Baseline in Hematology Parameter; Hematocrit

Blood samples were collected to analyze hematology parameters; hematocrit, reticulocytes. Platelets. Day-1 (one day before the Pre-Dose) was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value. (NCT03493386)
Timeframe: Baseline (Day -1), 24hours post-dose

InterventionProportion of red blood cells in blood (Mean)
Part 1: Daprodustat 2mg*20.0005
Part 1: Daprodustat 4mg*10.0014

Part 1:Change From Baseline in Hematology Parameter; Reticulocytes

Blood samples were collected to analyze hematology parameters; reticulocytes. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value. (NCT03493386)
Timeframe: Baseline (Day -1), 24hours post-dose

InterventionPraportion of reticulocytes in blood (Mean)
Part 1: Daprodustat 2mg*2-0.0005
Part 1: Daprodustat 4mg*1-0.0001

Part 1:Maximum Observed Drug Concentration (Cmax) of Daprodustat

Blood samples were collected at indicated timepoints and pharmacokinetic (PK) analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3. (NCT03493386)
Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2

InterventionNanogram/milliliter (Geometric Mean)
Part 1: Daprodustat 2mg*288.8811
Part 1: Daprodustat 4mg*185.1365

Part 2: Change From Baseline in Hematology Parameter EMCV

Blood samples were collected to analyze hematology parameter; EMCV. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value. (NCT03493386)
Timeframe: Baseline (Day -1), 24 hours (post-dose)

InterventionFemtoliters (Mean)
Part 2: Daprodustat 4mg (Fed)0.5
Part 2: Daprodustat 4mg (Fasted)0.3

Part 2: Change From Baseline in Hematology Parameter Erythrocytes

Blood samples were collected to analyze hematology parameter; erythrocytes. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value. (NCT03493386)
Timeframe: Baseline (Day -1), 24 hours (post-dose)

InterventionTrillion cells/liter (10^12 cell/L) (Mean)
Part 2: Daprodustat 4mg (Fed)-0.083
Part 2: Daprodustat 4mg (Fasted)-0.044

Part 2: Change From Baseline in Hematology Parameter: EMCH

Blood samples were collected to analyze hematology parameter; EMCH. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value. (NCT03493386)
Timeframe: Baseline (Day -1), 24 hours (post-dose)

Interventionpicograms (Mean)
Part 2: Daprodustat 4mg (Fed)0.10
Part 2: Daprodustat 4mg (Fasted)0.03

Part 2: Change From Baseline in Hematology Parameters; Hematocrit

Blood samples were collected to analyze hematology parameter; hematocrit. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value. (NCT03493386)
Timeframe: Baseline (Day -1), 24 hours (post-dose)

InterventionPraportion of red blood cells in blood (Mean)
Part 2: Daprodustat 4mg (Fed)-0.0052
Part 2: Daprodustat 4mg (Fasted)-0.0025

Part 2: Change From Baseline in Hematology Parameters; Reticulocytes

Blood samples were collected to analyze hematology parameter; reticulocytes. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value. (NCT03493386)
Timeframe: Baseline (Day -1), 24 hours (post-dose)

InterventionPraportion of reticulocytes in blood (Mean)
Part 2: Daprodustat 4mg (Fed)-0.0002
Part 2: Daprodustat 4mg (Fasted)-0.0010

Part 2: Change From Baseline in Urinalysis Parameter; Potential of Hydrogen (pH)

Urinary pH measurement is a routine part of urinalysis. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0). Urine samples were collected for the measurement of urine pH by method up to 24 hours in Part 2. Day-1 (one day before the Pre-Dose) was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value. (NCT03493386)
Timeframe: Baseline (Day -1), 24 hours (post-dose)

InterventionpH (Mean)
Part 2: Daprodustat 4mg (Fed)0.13
Part 2: Daprodustat 4mg (Fasted)0.13

Part 2: Change From Baseline in Urinalysis Parameter; Specific Gravity

Urinary specific gravity measurement is a routine part of urinalysis. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. Urine samples were collected for the measurement of urine specific gravity by dipstick method up to 24 hours in Part 2. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value. (NCT03493386)
Timeframe: Baseline (Day -1), 24 hours (post-dose)

InterventionKilogram per cubic meter (Mean)
Part 2: Daprodustat 4mg (Fed)0.0054
Part 2: Daprodustat 4mg (Fasted)0.0013

Part 2: CL/F of Daprodustat

Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3. (NCT03493386)
Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2

InterventionLiters per hour (Geometric Mean)
Part 2: Daprodustat 4mg Fed27.9494
Part 2: Daprodustat 4mg Fasted25.5512

Part 2: Cmax of Daprodustat

Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3. (NCT03493386)
Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12hours post-dose on Day 1, 24hours post-dose on Day 2

InterventionNanogram/milliliter (ng/L) (Geometric Mean)
Daprodustat 4mg Fed67.8240
Daprodustat 4mg Fasted76.1944

Part 2: Kel of Daprodustat

Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3. (NCT03493386)
Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2

InterventionPer hour (Geometric Mean)
Part 2: Daprodustat 4mg Fed0.2155
Part 2: Daprodustat 4mg Fasted0.2140

Part 2: Percentage AUCex of Dapordustat

Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3. (NCT03493386)
Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2

InterventionPercentage of AUCex (Geometric Mean)
Part 2: Daprodustat 4mg Fed0.1071
Part 2: Daprodustat 4mg Fasted0.0723

Part 2: Tmax of Daprodustat

Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3. (NCT03493386)
Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2

Interventionhour (Median)
Part 2: Daprodustat 4mg Fed2.750
Part 2: Daprodustat 4mg Fasted1.750

Part 2: Vz/F of Daprodustat

Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3. (NCT03493386)
Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2

InterventionMilliliters (mL) (Geometric Mean)
Part 2: Daprodustat 4mg Fed129676.9
Part 2: Daprodustat 4mg Fasted119394.6

Part 1: Change From Baseline Chemistry Paramters: Glucose, Calcium, Cholesterol, Chloride, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, Potassium, Phosphate, Sodium, Triglycerides, and Urea.

Blood samples were collected to analyze the chemistry parameters; glucose, calcium, cholesterol, chloride, HDL cholesterol, LDL cholesterol, potassium, phosphate, sodium, triglycerides, and urea. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value. (NCT03493386)
Timeframe: Baseline (Day -1), 24hours post-dose

,
InterventionMillimoles per Liter (mmol/L) (Mean)
Glucose 24hoursCalcium 24hoursCholesterol 24hoursChloride 24hoursHDL cholesterol 24hoursLDL cholesterol 24hoursPotassium 24hoursPhosphate 24hoursSodium 24hoursTriglycerides 24hoursUrea 24hours
Part 1: Daprodustat 2mg*2-0.007619-0.016144-0.0436070.9-0.1287930.0228180.04-0.1025680.20.21802-0.14000
Part 1: Daprodustat 4mg*1-0.004270-0.0158340.0467470.5-0.1113970.0994620.03-0.0912810.00.16385-0.29178

Part 1: Change From Baseline in Chemistry Parameters; Albumin, Protein.

Blood samples were collected to analyze the chemistry parameters; albumin, protein. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value. (NCT03493386)
Timeframe: Baseline (Day -1), 24hours post-dose

,
InterventionGrams per liter (g/L) (Mean)
Albumin 24hoursProtein 24hours
Part 1: Daprodustat 2mg*2-2.0-2.3
Part 1: Daprodustat 4mg*1-2.0-2.1

Part 1: Change From Baseline in Chemistry Parameters; Direct Bilirubin, Bilirubin, Creatinine, Urate

Blood samples were collected to analyze the chemistry parameters; direct bilirubin, bilirubin, creatinine, urate. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value. (NCT03493386)
Timeframe: Baseline (Day -1), 24hours post-dose

,
InterventionMicromoles per liter (umol/L) (Mean)
Direct bilirubin 24hoursBilirubin 24hoursCreatinine 24hoursUrate 24hours
Part 1: Daprodustat 2mg*20.2682.6151.716026.1245
Part 1: Daprodustat 4mg*10.1642.9601.411025.6222

Part 1: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase, Lactate Dehydrogenase and Gamma Glutamyl Transferase (GGT).

Blood samples were collected to analyze the chemistry parameters; ALP, ALT, AST, creatine kinase, lactate dehydrogenase and GGT. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value. (NCT03493386)
Timeframe: Baseline (Day -1), 24hours post-dose

,
InterventionInternational unit per liter (IU/L) (Mean)
ALP 24hoursALT 24hoursAST 24hoursCreatine kinase 24hoursGGT 24hoursLactate dehydrogenase 24hours
Part 1: Daprodustat 2mg*2-9.5-2.0-2.1-33.9-1.6-20.5
Part 1: Daprodustat 4mg*1-10.8-1.0-1.8-32.3-1.1-19.2

Part 1: Change From Baseline in ECG Parameter; PR Interval, QRS Interval, QT Interval, QT Duration Corrected for Heart Rate by Friderician Formula (QTcF) Interval

Single 12-lead ECG's were obtained from using an ECG machine that automatically calculated the heart rate and measured PR Interval, QRS Duration, Uncorrected QT interval and Corrected QT (Fridericia's correction) interval at given time point. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. (NCT03493386)
Timeframe: Baseline (Day -1), 3 and 24 hours (post-dose)

,
InterventionMilliseconds (msec) (Mean)
PR Interval, Aggregate 3hoursPR Interval, Aggregate 24hoursQRS Duration, Aggregate 3hoursQRS Duration, Aggregate 24hoursQT interval, Aggregate 3hoursQT interval, Aggregate 24hoursQTcF interval, Aggregate 3hoursQtcF Interval, Aggregate 24hours
Part 1: Daprodustat 2mg*2-3.31.4-2.8-1.60.0-5.21.2-2.4
Part 1: Daprodustat 4mg*1-3.80.0-1.50.20.8-5.31.6-3.1

Part 1: Change From Baseline in Electrocardiogram (ECG) Parameter; Mean Heart Rate (HR)

Single 12-lead ECG's were obtained from using an ECG machine that automatically calculated the heart rate and measured PR Interval, QRS Duration, Uncorrected QT interval and Corrected QT (Fridericia's correction) interval at given time point. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. (NCT03493386)
Timeframe: Baseline (Day -1), 3 and 24 hours (post-dose)

,
InterventionBeats per minute (Mean)
Mean HR 3hoursMean HR 24hours
Part 1: Daprodustat 2mg*20.61.2
Part 1: Daprodustat 4mg*10.20.8

Part 1: Change From Baseline in Hematology Parameters Platelets, Leukocytes

Blood samples were collected to analyze hematology parameter; platelets, leukocytes. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value. (NCT03493386)
Timeframe: Baseline (Day -1), 24hours post-dose

,
InterventionBillion cells per liter (10^9/L) (Mean)
Platelets 24hoursLeukocytes 24hours
Part 1: Daprodustat 2mg*20.7-0.55
Part 1: Daprodustat 4mg*12.0-0.53

Part 1: Change From Baseline in Hematology Parameters; Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils

Blood samples were collected to analyze hematology parameters; basophils, eosinophils, lymphocytes, monocytes, neutrophil. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value. (NCT03493386)
Timeframe: Baseline (Day -1), 24hours post-dose

,
InterventionPercentage of cells (Mean)
Basophils 24hoursEosinophils 24hoursLymphocytes 24hoursMonocytes 24hoursNeutrophils 24hours
Part 1: Daprodustat 2mg*2-0.010.27-1.47-0.431.64
Part 1: Daprodustat 4mg*10.000.25-0.86-0.330.94

Part 1: Change From Baseline in Hematology Parameters; Hemoglobin (Hb), Erythrocyte Mean Corpuscular Hb Concentration (MCHC)

Blood samples were collected to analyze hematology parameters; Hb, EMCH concentration. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value. (NCT03493386)
Timeframe: Baseline (Day -1), 24hours post-dose

,
InterventionGrams per Liter (g/L) (Mean)
Hb 24hoursMCHC 24hours
Part 1: Daprodustat 2mg*21.12.1
Part 1: Daprodustat 4mg*10.80.8

Part 1: Change From Baseline in Pulse Rate

Pulse rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. (NCT03493386)
Timeframe: Baseline (Day -1), 3 and 24 hours (post-dose)

,
InterventionBeats per minute (Mean)
Pulse rate 3hoursPulse rate 24hours
Part 1: Daprodustat 2mg*20.00.1
Part 1: Daprodustat 4mg*10.71.0

Part 1: Change From Baseline in Temperature

Temperature was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. (NCT03493386)
Timeframe: Baseline (Day -1), 3 and 24 hours (post-dose)

,
InterventionCelcius (c) (Mean)
Temperature 3hoursTemperature 24hours
Part 1: Daprodustat 2mg*20.230.10
Part 1: Daprodustat 4mg*10.220.05

Part 1: Change From Baseline in Vital Signs; Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)

DBP and SBP were measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. (NCT03493386)
Timeframe: Baseline (Day -1), 3 and 24 hours (post-dose)

,
InterventionMillimeters of mercury (mmHg) (Mean)
DBP 3hoursDBP 24hoursSBP 3hoursSBP 24hours
Part 1: Daprodustat 2mg*2-2.9-1.8-0.6-0.9
Part 1: Daprodustat 4mg*1-1.50.1-0.40.2

Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant. Safety population comprised of all randomized participants who took at least one dose of study treatment. (NCT03493386)
Timeframe: Up to Day 16

,
InterventionParticipants (Count of Participants)
Any AEAny SAE
Part 1: Daprodustat 2mg*230
Part 1: Daprodustat 4mg*110

Part 1:Area Under Plasma Concentration-time Curve (AUC) From Zero Hours to Last Measurable Concentration (AUC[0-t]) and AUC From Zero Hours Extrapolated to Infinity AUC [0-inf] of Daprodustat

Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3. PK population comprised of all participants in the Safety population (all randomized participants) who received at least one dose of study intervention) who had at least 1 non-missing PK assessment. (NCT03493386)
Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2

,
InterventionHour*nanogram/milliliter (Geometric Mean)
AUC (0-t)AUC (0-inf)
Part 1: Daprodustat 2mg*2182.8420183.0240
Part 1: Daprodustat 4mg*1179.6940179.8710

Part 1:Terminal Phase Half-life (T1/2) of Daprodustat and Mean Residence Time (MRT)

Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3. (NCT03493386)
Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose on Day 1, 24 hours post-dose on Day 2

,
Interventionhour (Geometric Mean)
t1/2MRT
Part 1: Daprodustat 2mg*23.24272.8142
Part 1: Daprodustat 4mg*13.25792.9637

Part 2: Change From Baseline Chemistry Parameters; Glucose, Calcium, Cholesterol, Chloride, HDL Cholesterol, LDL Cholesterol, Potassium, Phosphate, Sodium, Triglycerides, and Urea

Blood samples were collected to analyze the chemistry parameters; glucose, calcium, cholesterol, chloride, HDL cholesterol, LDL cholesterol, potassium, phosphate,sodium, triglycerides, and urea. Day-1 (one day before the Pre-Dose) was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value. (NCT03493386)
Timeframe: Baseline (Day -1), 24 hours (post-dose)

,
InterventionMillimoles per Liter (mmol/L) (Mean)
Glucose, 24hoursCalcium, 24hoursCholesterol, 24hoursChloride, 24hoursHDL cholesterol, 24hoursLDL cholesterol, 24hoursPotassium, 24hoursPhosphate, 24hoursSodium, 24hoursTriglycerides, 24hoursUrea, 24hours
Part 2: Daprodustat 4mg (Fasted)-0.018503-0.058217-0.0948202.1-0.148695-0.0668050.19-0.0807250.90.08475-0.14875
Part 2: Daprodustat 4mg (Fed)-0.425577-0.076929-0.1724001.5-0.165935-0.1702450.06-0.0295990.30.253310.19040

Part 2: Change From Baseline in Chemistry Parameters; Albumin, Protein

Blood samples were collected to analyze the chemistry parameters; albumin, protein. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value. (NCT03493386)
Timeframe: Baseline (Day -1), 24 hours (post-dose)

,
InterventionGrams per liter (g/L) (Mean)
Albumin 24hoursProtein 24hours
Part 2: Daprodustat 4mg (Fasted)-1.9-2.6
Part 2: Daprodustat 4mg (Fed)-3.2-3.4

Part 2: Change From Baseline in Chemistry Parameters; Direct Bilirubin, Bilirubin, Creatinine, Urate

Blood samples were collected to analyze the chemistry parameters; direct bilirubin, bilirubin, creatinine, urate. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value. (NCT03493386)
Timeframe: Baseline (Day -1), 24 hours (post-dose)

,
InterventionMicromoles per liter (umol/L) (Mean)
Direct bilirubin, 24hoursBilirubin, 24hoursCreatinine, 24hoursUrate, 24hours
Part 2: Daprodustat 4mg (Fasted)0.0001.425-1.105021.8093
Part 2: Daprodustat 4mg (Fed)0.0002.280-1.620723.2963

Part 2: Change From Baseline in Chemistry Paremeters; ALP, ALT, AST, Creatine Kinase, Lactate Dehydrogenase, GGT

Blood samples were collected to analyze the chemistry parameters; ALP,ALT, AST, creatine kinase, lactate dehydrogenase and GGT. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value. (NCT03493386)
Timeframe: Baseline (Day -1), 24 hours (post-dose)

,
InterventionInternational unit per liter (IU/L) (Mean)
ALP, 24hoursALT, 24hoursAST, 24hoursCreatine kinase, 24hoursLactate dehydrogenase, 24hoursGGT, 24hours
Part 2: Daprodustat 4mg (Fasted)-13.3-3.5-2.7-15.3-18.4-1.6
Part 2: Daprodustat 4mg (Fed)-18.9-3.1-2.8-28.3-21.0-1.0

Part 2: Change From Baseline in ECG Parameter; Mean Heart Rate (HR)

Single 12-lead ECG's were obtained from using an ECG machine that automatically calculated the heart rate and measured PR Interval, QRS Duration, Uncorrected QT interval and Corrected QT (Fridericia's correction) interval at given time point. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. (NCT03493386)
Timeframe: Baseline (Day -1),3 and 24hours (pre-dose)

,
InterventionBeats/minute (Mean)
Mean HR, 3hoursMean HR, 24hours
Part 2: Daprodustat 4mg (Fasted)0.00.6
Part 2: Daprodustat 4mg (Fed)3.73.1

Part 2: Change From Baseline in ECG Parameter; PR Interval, QRS Interval, QT Interval, QTcF Interval

Single 12-lead ECG's were obtained from using an ECG machine that automatically calculated the heart rate and measured PR Interval, QRS Duration, Uncorrected QT interval and Corrected QT (Fridericia's correction) interval at given time point. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. (NCT03493386)
Timeframe: Baseline (Day -1),3 and 24hours (pre-dose)

,
InterventionMilliseconds (msec) (Mean)
PR Interval, Aggregate, 3hoursPR Interval, Aggregate, 24hoursQRS Duration, Aggregate, 3hoursQRS Duration, Aggregate, 24hoursQT interval, Aggregate, 3hoursQT Interval, Aggregate, 24hoursQTcF Interval, Aggregate, 3hoursQTcF Interval, Aggregate, 24hours
Part 2: Daprodustat 4mg (Fasted)-2.7-3.2-0.52.81.0-2.21.2-1.1
Part 2: Daprodustat 4mg (Fed)-6.2-4.0-1.5-0.8-13.0-7.3-5.3-0.6

Part 2: Change From Baseline in Hematology Parameters Platelets, Leukocytes

Blood samples were collected to analyze hematology parameter; platelets, leukocytes. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value. (NCT03493386)
Timeframe: Baseline (Day -1), 24 hours (post-dose)

,
InterventionBillion cells per liter (10^9/L) (Mean)
Platelets, 24hoursLeukocytes, 24hours
Part 2: Daprodustat 4mg (Fasted)-3.2-0.39
Part 2: Daprodustat 4mg (Fed)-10.9-0.27

Part 2: Change From Baseline in Hematology Parameters; Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils

Blood samples were collected to analyze hematology parameters; basophils, eosinophils, lymphocytes, monocytes, neutrophils. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value. (NCT03493386)
Timeframe: Baseline (Day -1), 24 hours (post-dose)

,
InterventionPercentage of cells (Mean)
Basophils, 24hoursEosinophils, 24hoursLymphocytes, 24hoursMonocytes, 24hoursNeutrophils, 24hours
Part 2: Daprodustat 4mg (Fasted)-0.17-0.49-1.14-0.031.83
Part 2: Daprodustat 4mg (Fed)-0.040.62-2.31-0.382.12

Part 2: Change From Baseline in Hematology Parameters; Hb, Erythrocyte MCHC

Blood samples were collected to analyze hematology parameters; Hb, erythrocyte MCHC. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the Post-Dose visit value. (NCT03493386)
Timeframe: Baseline (Day -1), 24 hours (post-dose)

,
InterventionGrams per liter (g/L) (Mean)
Hb 24hoursEMCH concentration 24hours
Part 2: Daprodustat 4mg (Fasted)-1.2-0.6
Part 2: Daprodustat 4mg (Fed)-2.10.4

Part 2: Change From Baseline in Pulse Rate

Pulse rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. (NCT03493386)
Timeframe: Baseline (Day -1),3 and 24hours (pre-dose)

,
InterventionBeats per minute (Mean)
Pulse rate, 3hoursPulse rate, 24hours
Part 2: Daprodustat 4mg (Fasted)-1.52.9
Part 2: Daprodustat 4mg (Fed)6.14.0

Part 2: Change From Baseline in Temperature

Temperature was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. (NCT03493386)
Timeframe: Baseline (Day -1),3 and 24hours (pre-dose)

,
Interventioncelcius (Mean)
Temperature, 3hoursTemperature, 24hours
Part 2: Daprodustat 4mg (Fasted)0.130.03
Part 2: Daprodustat 4mg (Fed)0.280.02

Part 2: Change From Baseline in Vital Signs; Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)

DBP and SBP were measured in semi-supine position after 5 minutes rest for the participants at indicated time point. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. (NCT03493386)
Timeframe: Baseline (Day -1),3 and 24hours (pre-dose)

,
InterventionMillimeters of mercury (mmHg) (Mean)
DBP, 3hoursDBP, 24hoursSBP, 3hoursSBP, 24hours
Part 2: Daprodustat 4mg (Fasted)0.22.8-1.31.3
Part 2: Daprodustat 4mg (Fed)-4.8-0.60.71.4

Part 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant. Safety population comprised of all randomized participants who took at least one dose of study treatment. (NCT03493386)
Timeframe: Up to Day 16

,
InterventionParticipants (Number)
Any AEAny SAE
Part 2: Daprodustat 4mg (Fasted)00
Part 2: Daprodustat 4mg (Fed)00

Part 2: T1/2 and MRT of Daprodustat

Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3. (NCT03493386)
Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12hours post-dose on Day 1, 24hours post-dose on Day 2

,
Interventionhour (Geometric Mean)
t1/2MRT
Daprodustat 4mg Fed3.21603.2420
Part 2: Daprodustat 4mg Fasted3.23892.6695

Part 2:AUC[0-t] andAUC [0-inf] of Daprodustat

Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin version 6.3. (NCT03493386)
Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12hours post-dose on Day 1, 24hours post-dose on Day 2

,
InterventionHour*nanogram/milliliter (Geometric Mean)
AUC (0-t)AUC (0-inf)
Daprodustat 4mg (Fed)142.9556143.1156
Daprodustat 4mg(Fasted)156.4222156.5481

Change From Baseline in Hgb (Hgb Increase Rate) at Week 4

Change from Baseline was calculated as the post-dose Week 4 visit value minus the Baseline value. (NCT02969655)
Timeframe: Baseline and Week 4

Interventiong/dL (Mean)
Daprodustat-0.42
Darbepoetin Alfa0.08

Duration of Treatment Interruption Due to Hgb >13 g/dL

Duration of treatment interruption due to Hgb >13 g/dL for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users has been presented for the daprodustat group. (NCT02969655)
Timeframe: Up to Week 52

InterventionDays (Median)
Daprodustat28.0

Mean Hemoglobin (Hgb) During the Primary Efficacy Evaluation Period (Weeks 40 to 52)

The mean hemoglobin during the Evaluation Period was estimated by a statistical model. (NCT02969655)
Timeframe: Weeks 40 to 52

InterventionGrams per deciliter (g/dL) (Least Squares Mean)
Daprodustat10.89
Darbepoetin Alfa10.83

Number of Dose Adjustments for Daprodustat

Number of dose adjustments has been presented only for daprodustat. (NCT02969655)
Timeframe: Up to Week 52

InterventionDose adjustments (Median)
Daprodustat2.0

Number of Episodes With Hgb Level of More Than 13.0 g/dL

Number of episodes with Hgb level of more than 13.0 g/dL for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users have been presented. (NCT02969655)
Timeframe: Up to Week 52

InterventionEpisodes (Number)
Daprodustat9
Darbepoetin Alfa12

Number of Participants Who Had an Hgb Increase of More Than 2 g/dL Over Any 4 Weeks

Number of participants who had an Hgb increase of more than 2 g/dL over any 4 weeks for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users have been presented. (NCT02969655)
Timeframe: Up to Week 52

InterventionParticipants (Count of Participants)
Daprodustat1
Darbepoetin Alfa2

Number of Participants Who Had an Hgb Level of Less Than 7.5 g/dL

If an initial Hgb value was less than 7.5 g/dL, measurement was repeated at the same study visit (using the same sample) to calculate the average. If the average met the Hgb stopping criteria, study treatment was permanently discontinued. Number of participants who had an Hgb level of less than 7.5 g/dL has been presented. (NCT02969655)
Timeframe: Up to Week 52

InterventionPercentage of participants (Number)
Daprodustat0
Darbepoetin Alfa0

Number of Participants Who Had an Hgb Level of More Than 13.0 g/dL

Number of participants who had an Hgb increase of more than 13 g/dL for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users have been presented. (NCT02969655)
Timeframe: Up to Week 52

InterventionPercentage of participants (Number)
Daprodustat7
Darbepoetin Alfa8

Percentage of Time in Hgb Target Range (10.0 to 12.0 g/dL) During the Primary Efficacy Evaluation Period (Weeks 40 to 52)

Percentage of time in Hgb target range (10.0 to 12.0 g/dL) during the primary efficacy evaluation period (Weeks 40 to 52) for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users has been presented. (NCT02969655)
Timeframe: Weeks 40 to 52

InterventionPercentage of time (Mean)
Daprodustat76.81
Darbepoetin Alfa80.23

Area Under Plasma Concentration Curve From Time Zero to 4 Hours (AUC [0 - 4]) of Plasma Daprodustat

Blood samples for Pharmacokinetic (PK) analysis of daprodustat were collected as the time points provided. PK parameters were calculated by standard non-compartmental analysis according to current working practices and using the currently supported version of WinNonlin (version 6.3 or higher). NA indicates geometric co-efficient of variation could not be calculated as a single participant was analyzed. Data has been provided as a consolidated values for at all time-points (0,1,2,3,and 4 hours post-dose) as provided for a single value at Weeks 12 and 24 respectively. PK population comprised of all daprodustat-treated participants from whom PK samples were collected and analyzed. Data was not calculated for darbepoetin alfa group as the primary interest of analysis was Daprodustat and not comparator drug (darbepoetin alfa). Data is combined from Week 12 and Week 24 data. (NCT02969655)
Timeframe: 0, 1, 2, 3, and 4 hours post-dose at Week 12 and Week 24

InterventionHours*nanograms per milliliter (Geometric Mean)
1 mg, n=82 mg, n=244 mg, n=916 mg, n=618 mg, n=3812 mg, n=1718 mg, n=5
Daprodustat27.5744.5272.68140.58170.41150.53488.93

Change From Baseline in Hgb Values at Each Assessment Visit

Baseline Hgb value was the value from the Day 1 visit. Change from Baseline was calcuated as the post-dose visit value minus the Baseline value. Change from Baseline Hgb values at each assessment visit for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users has been presented. (NCT02969655)
Timeframe: Baseline (Day 1) and Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52

,
Interventiong/dL (Mean)
Week 4, n=133, 134Week 8, n=127, 132Week 12, n=125, 129Week 16, n=124, 129Week 20, n=123, 129Week 24, n=123, 129Week 28, n=123, 129Week 32, n=122, 127Week 36, n=121, 127Week 40, n=120, 125Week 44, n=117, 125Week 48, n=117, 124Week 52,n=115, 120
Daprodustat-0.42-0.45-0.42-0.38-0.090.070.030.160.170.030.03-0.01-0.16
Darbepoetin Alfa0.080.200.270.090.120.100.040.140.090.100.07-0.040.01

Distribution of Daprodustat Dose Level by Visit

Distribution of dose level by visit for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users has been presented for Daprodustat. Median along with the interquartile range (25th and 75th percentile) has been presented. (NCT02969655)
Timeframe: Day 1, Weeks 4,8,12,16,20,24,28,32,36,40,44, and 48)

Interventionmilligrams per day (mg/day) (Median)
Day 1, n=133Week 4, n=133Week 8, n=126Week 12, n=125Week 16, n=123Week 20, n=123Week 24, n=123Week 28, n=123Week 32, n=122Week 36, n=121Week 40, n=119Week 44, n=117Week 48, n=117
Daprodustat4.04.04.06.06.06.06.06.06.06.06.06.06.0

Distribution of Darbepoetin Alfa Dose Level by Visit

Distribution of dose level by visit for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users has been presented for Darbepoetin Alfa. Median along with the interquartile range (25th and 75th percentile) has been presented. (NCT02969655)
Timeframe: Day 1, Weeks 2,4,6,8,10,12,14,16,18,20,22,24,26,28,30,32,34,36,38,40,42,44,46,48, and 50

Interventionmicrograms per week (ug/week) (Median)
Day 1, n=134Week 2. n=134Week 4, n=134Week 6, n=133Week 8, n=131Week 10, n=129Week 12, n=129Week 14, n=129Week 16, n=129Week 18, n=129Week 20, n=129Week 22, n=128Week 24, n=129Week 26, n=129Week 28, n=127Week 30, n=128Week 32, n=127Week 34, n=127Week 36, n=127Week 38, n=127Week 40, n=125Week 42, n=125Week 44, n=125Week 46, n=125Week 48, n=124Week 50, n=122
Darbepoetin Alfa15.015.015.015.015.015.015.015.015.015.015.015.015.015.015.015.015.015.015.015.015.015.015.015.015.015.0

Hgb Values at Each Assessment Visit

Hgb values at each assessment visit for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users has been presented. (NCT02969655)
Timeframe: Baseline (Day 1), Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52

,
Interventiong/dL (Mean)
Baseline (Day 1), n=133, 134Week 4, n=133, 134Week 8, n=127, 132Week 12, n=125, 129Week 16, n=124, 129Week 20, n=123, 129Week 24, n=123, 129Week 28, n=123, 129Week 32, n=122, 127Week 36, n=121, 127Week 40, n=120, 125Week 44, n=117, 125Week 48, n=117, 124Week 52,n=115, 120
Daprodustat10.9410.5210.5010.5310.5710.8511.0110.9711.1011.1210.9710.9810.9410.79
Darbepoetin Alfa10.8210.9011.0111.0910.9210.9510.9210.8610.9610.9110.9010.8710.7610.79

Maximum Concentration (Cmax) of Plasma Daprodustat

Blood samples for PK analysis of daprodustat were collected as the time points provided. PK parameters were calculated by standard non-compartmental analysis according to current working practices and using the currently supported version of WinNonlin (version 6.3 or higher). Data has been provided as a consolidated values for at all time-points (0,1,2,3,and 4 hours post-dose) as provided for a single value at Weeks 12 and 24 respectively. Data was not calculated for darbepoetin alfa group as the primary interest of analysis was Daprodustat and not comparator drug (darbepoetin alfa). Data is combined from Week 12 and Week 24 data. (NCT02969655)
Timeframe: 0, 1, 2, 3, and 4 hours post-dose at Week 12 and Week 24

InterventionNanograms per milliliter (Geometric Mean)
1 mg, n=82 mg, n=244 mg, n=916 mg, n=618 mg, n=3812 mg, n=1718 mg, n=5
Daprodustat16.1125.1642.4583.60105.71108.58306.61

Percentage of Participants by Hgb Change From Baseline Category at Week 4

Percentage of participants within each category were provided only for daprodustat and the categories were classified into 6 (i.e., <=-2, >-2 to -1, >-1 to 0, >0 to 1, >1 to 2, >2 grams per deciliter [g/dL]). In addition, 'within 1.0 g/dL (i.e., <=-1 and >=1) and over 2.0 g/dL (i.e., <-2 and >2) categories were provided. (NCT02969655)
Timeframe: Week 4

InterventionPercentage of participants (Number)
<= -2.0> -2.0 and <= -1.0> -1.0 and <= 0> 0 and <= 1.0> 1.0 and <= 2.0> 2.0within +/- 1.0over +/- 2.0
Daprodustat521442740755

Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit

Percentage of participants with Hgb within the target range was summarized at each assessment visit by treatment group have been presented. (NCT02969655)
Timeframe: Baseline (Day 1) and Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52

,
InterventionPercentage of participants (Number)
Baseline (Day 1), n=133, 134Week 4, n=133,134Week 8, n=127,132Week 12, n=125,129Week 16, n=124,129Week 20, n=123,129Week 24, n=123,129Week 28, n=123,129Week 32, n=122, 127Week 36, n=121,127Week 40, n=120,125Week 44, n=117,125Week 48, n=117,124Week 52, n=115,120
Daprodustat7965656664828585797877747777
Darbepoetin Alfa8780848680818182807880827980

Percentage of Participants With Mean Hgb in the Target Range (10.0-12.0 g/dL) During the Primary Efficacy Evaluation Period (Weeks 40 to 52)

The percentage of participants with observed mean Hgb within the target range during the primary efficacy evaluation period was summarized. Odds ratio was estimated using a logistic regression and provided along with its 95% CI and a one-sided p-value. (NCT02969655)
Timeframe: Weeks 40 to 52

,
InterventionPercentage of participants (Number)
ResponderNon-responder
Daprodustat8813
Darbepoetin Alfa9010

Mean Hb Level of Week 20 and Week 24

(NCT03402386)
Timeframe: Up to Week 24

Interventiong/dL (Least Squares Mean)
MT-654811.35

Hb Level at Each Assessment Time Point

(NCT03402386)
Timeframe: Up to Week 24

Interventiong/dL (Mean)
BaselineWeek 2Week 4Week 6Week 8Week 10Week 12Week 16Week 20Week 24Week 24 (LOCF)
MT-654810.9010.9610.7410.6110.8710.8911.1011.5811.6811.3911.01

Percentage of Subjects With Hb Level at Each Assessment Time Point Within the Target Range During the Treatment Period

(NCT03402386)
Timeframe: Up to Week 24

Interventionpercentage of subjects (Number)
BaselineWeek 2Week 4Week 6Week 8Week 10Week 12Week 16Week 20Week 24
MT-654857.160.041.535.947.444.744.732.466.765.7

Area Under the Concentration-time Curve From Time Zero Extrapolated to 4 Hours (AUC[0-4]) of Daprodustat for All Dose Levels in ND and PD Participants

Blood samples were collected at indicated timepoints. Pharmacokinetic (PK) parameters of Daprodustat were calculated using non-compartmental method. AUC (0-4) is presented for combined Week 12 and 24. Geometric mean and geometric coefficient of variation is presented. NA indicates that the data is not available since geometric coefficient of variation could not be calculated for a single participant. (NCT02791763)
Timeframe: 1, 2, 3 and 4 hours post dose at Weeks 12 and 24

InterventionHour*nanogram per milliliter (Geometric Mean)
Daprodustat 1 mg35.3199
Daprodustat 2 mg63.0175
Daprodustat 4 mg101.9293
Daprodustat 6 mg152.4966
Daprodustat 8 mg167.6515
Daprodustat 12 mg190.0962
Daprodustat 18 mg435.6847
Daprodustat 24 mg404.0567

Change From Baseline in Hgb at Week 4 in ND Participants

Baseline Hgb value was the value from the Day 1 visit. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Data for change from Baseline in Hgb at Week 4 in ND participants is presented. (NCT02791763)
Timeframe: Baseline (Day 1) and Week 4

Interventiong/dL (Mean)
Daprodustat in ND Participants0.47
Epoetin Beta Pegol in ND Participants0.26

Change From Baseline in Hgb at Week 4 in PD Participants

Baseline Hgb value was the value from the Day 1 visit. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Data for change from Baseline in Hgb at week 4 in PD participants is presented. (NCT02791763)
Timeframe: Baseline (Day 1) and Week 4

Interventiong/dL (Mean)
Daprodustat in PD Participants-0.09

Duration of Treatment Interruption Due to Hgb >13 g/dL in ND Participants

The duration (in days) of treatment interruption due to Hgb >13 g/dL per participant was summarized descriptively on participants with a period of treatment interruption due to Hgb >13 g/dL. (NCT02791763)
Timeframe: Up to Week 52

InterventionDays (Median)
Daprodustat in ND Participants28.0
Epoetin Beta Pegol in ND Participants28.0

Duration of Treatment Interruption Due to Hgb >13 g/dL in PD Participants

The duration (in days) of treatment interruption due to Hgb >13 g/dL per participant was summarized descriptively on participants with a period of treatment interruption due to Hgb >13 g/dL. (NCT02791763)
Timeframe: Up to Week 52

InterventionDays (Median)
Daprodustat in PD Participants28.0

Maximum Observed Concentration (Cmax) of Daprodustat for All Dose Levels in ND and PD Participants

Blood samples were collected at indicated timepoints. PK parameters of Daprodustat were calculated using non-compartmental method. Cmax is presented for combined Week 12 and 24. Geometric mean and geometric coefficient of variation is presented. NA indicates that the data is not available since geometric coefficient of variation could not be calculated for a single participant. (NCT02791763)
Timeframe: 1, 2, 3 and 4 hours post dose at Weeks 12 and 24

InterventionNanogram per milliliter (Geometric Mean)
Daprodustat 1 mg17.6522
Daprodustat 2 mg35.0709
Daprodustat 4 mg58.6098
Daprodustat 6 mg81.1851
Daprodustat 8 mg91.0731
Daprodustat 12 mg94.1242
Daprodustat 18 mg197.9290
Daprodustat 24 mg226.0000

Mean Hemoglobin (Hgb) During the Primary Efficacy Evaluation Period (Weeks 40 to 52) in ND Participants

The mean hemoglobin during the primary efficacy evaluation period in ND participants was estimated by a statistical model using Mixed Model Repeated Measures (MMRM). (NCT02791763)
Timeframe: Weeks 40 to 52

InterventionGrams per deciliter (g/dL) (Mean)
Daprodustat in ND Participants11.97
Epoetin Beta Pegol in ND Participants11.86

Monthly Average Dose of Oral Iron During the Primary Efficacy Evaluation Period in ND Participants

Supplemental iron therapy were received by participants if required during treatment period. Participants who used ferric citrate were counted as oral iron use. Monthly average oral iron dose during the primary efficacy evaluation period (Weeks 40 to 52) = Total oral iron dose (mg) during the primary efficacy evaluation period / (duration in the period in days / 30.4375 days). Monthly average dose of oral iron during the primary efficacy evaluation period in ND participants is presented. (NCT02791763)
Timeframe: Weeks 40 to 52

InterventionMilligrams (Mean)
Daprodustat in ND Participants967.41
Epoetin Beta Pegol in ND Participants777.69

Monthly Average Dose of Oral Iron During the Primary Efficacy Evaluation Period in PD Participants

Supplemental iron therapy were received by participants if required during treatment period. Participants who used ferric citrate were counted as oral iron use. Monthly average oral iron dose during the primary efficacy evaluation period (Weeks 40 to 52) = Total oral iron dose (mg) during the primary efficacy evaluation period / (duration in the period in days / 30.4375 days). Monthly average dose of oral iron during the primary efficacy evaluation period in PD participants is presented. (NCT02791763)
Timeframe: Weeks 40 to 52

InterventionMilligrams (Mean)
Daprodustat in PD Participants3038.67

Monthly Average Dose of Oral Iron During the Treatment Period in ND Participants

Supplemental iron therapy were received by participants if required during treatment period. Participants who used ferric citrate were counted as oral iron use. Monthly average oral iron = Total oral iron dose (mg) / (duration in days / 30.4375 days). Monthly average dose of oral iron during the treatment period in ND participants is presented. (NCT02791763)
Timeframe: Up to Week 52

InterventionMilligrams (Mean)
Daprodustat in ND Participants837.37
Epoetin Beta Pegol in ND Participants747.04

Monthly Average Dose of Oral Iron During the Treatment Period in PD Participants

Supplemental iron therapy were received by participants if required during treatment period. Participants who used ferric citrate were counted as oral iron use. Monthly average oral iron = Total oral iron dose (mg) / (duration in days / 30.4375 days). Monthly average dose of oral iron during the treatment period in PD participants is presented. (NCT02791763)
Timeframe: Up to Week 52

InterventionMilligrams (Mean)
Daprodustat in PD Participants2468.68

Number of Dose Adjustments in ND Participants

Number of dose adjustments in ND participants is presented. (NCT02791763)
Timeframe: Up to Week 52

InterventionNumber of dose adjustments (Median)
Daprodustat in ND Participants5.0
Epoetin Beta Pegol in ND Participants6.0

Number of Dose Adjustments in PD Participants

Number of dose adjustments in PD participants is presented. (NCT02791763)
Timeframe: Up to Week 52

InterventionNumber of dose adjustments (Median)
Daprodustat in PD Participants5.0

Number of Episodes With Hgb Level of More Than 13.0 g/dL in ND Participants

Number of episodes with Hgb level of more than 13.0 g/dL in ND participants is presented. (NCT02791763)
Timeframe: Up to week 52

InterventionEpisodes (Number)
Daprodustat in ND Participants76
Epoetin Beta Pegol in ND Participants88

Number of Episodes With Hgb Level of More Than 13.0 g/dL in PD Participants

Number of episodes with Hgb level of more than 13.0 g/dL in PD participants is presented. (NCT02791763)
Timeframe: Up to week 52

InterventionEpisodes (Number)
Daprodustat in PD Participants43

Number of ND Participants Who Had an Hgb Increase of More Than 2 g/dL Over Any 4 Weeks

Number of ND participants who had an Hgb increase of more than 2 g/dL over any 4 weeks is presented. (NCT02791763)
Timeframe: Up to week 52

InterventionParticipants (Count of Participants)
Daprodustat in ND Participants17
Epoetin Beta Pegol in ND Participants11

Number of ND Participants Who Had an Hgb Level of Less Than 7.5 g/dL

Number of ND participants who had an Hgb level of less than 7.5 g/dL is presented. (NCT02791763)
Timeframe: Up to week 52

InterventionParticipants (Count of Participants)
Daprodustat in ND Participants1
Epoetin Beta Pegol in ND Participants0

Number of ND Participants Who Had an Hgb Level of More Than 13.0 g/dL

Number of ND participants who had an Hgb level of more than 13.0 g/dL is presented. (NCT02791763)
Timeframe: Up to week 52

InterventionParticipants (Count of Participants)
Daprodustat in ND Participants49
Epoetin Beta Pegol in ND Participants52

Number of ND Participants Who Used Oral Iron During the Primary Efficacy Evaluation Period

Supplemental iron therapy were received by participants if required during treatment period. Participants who used ferric citrate were counted as oral iron use. The number of ND participants who used oral iron during the primary efficacy evaluation period (Weeks 40 to 52) were summarized. (NCT02791763)
Timeframe: Weeks 40 to 52

InterventionParticipants (Count of Participants)
Daprodustat in ND Participants34
Epoetin Beta Pegol in ND Participants28

Number of ND Participants Who Used Oral Iron During the Treatment Period

Supplemental iron therapy were received by participants if required during treatment period. Participants who used ferric citrate were counted as oral iron use. The number of ND participants who used oral iron during the treatment period were summarized. (NCT02791763)
Timeframe: Up to week 52

InterventionParticipants (Count of Participants)
Daprodustat in ND Participants56
Epoetin Beta Pegol in ND Participants49

Number of PD Participants Who Had an Hgb Increase of More Than 2 g/dL Over Any 4 Weeks

Number of PD participants who had an Hgb increase of more than 2 g/dL over any 4 weeks is presented. (NCT02791763)
Timeframe: Up to week 52

InterventionParticipants (Count of Participants)
Daprodustat in PD Participants11

Number of PD Participants Who Had an Hgb Level of Less Than 7.5 g/dL

Number of PD participants who had an Hgb level of less than 7.5 g/dL is presented. (NCT02791763)
Timeframe: Up to week 52

InterventionParticipants (Count of Participants)
Daprodustat in PD Participants0

Number of PD Participants Who Had an Hgb Level of More Than 13.0 g/dL

Number of PD participants who had an Hgb level of more than 13.0 g/dL is presented. (NCT02791763)
Timeframe: Up to week 52

InterventionParticipants (Count of Participants)
Daprodustat in PD Participants28

Number of PD Participants Who Used Oral Iron During the Primary Efficacy Evaluation Period

Supplemental iron therapy were received by participants if required during treatment period. Participants who used ferric citrate were counted as oral iron use. The number of PD participants who used oral iron during the primary efficacy evaluation period (Weeks 40 to 52) were summarized. (NCT02791763)
Timeframe: Weeks 40 to 52

InterventionParticipants (Count of Participants)
Daprodustat in PD Participants22

Number of PD Participants Who Used Oral Iron During the Treatment Period

Supplemental iron therapy were received by participants if required during treatment period. Participants who used ferric citrate were counted as oral iron use. The number of PD participants who used oral iron during the treatment period were summarized. (NCT02791763)
Timeframe: Up to week 52

InterventionParticipants (Count of Participants)
Daprodustat in PD Participants33

Percentage of ND Participants Who Had an Hgb Increase of More Than 2 g/dL Over Any 4 Weeks

Percentage of ND participants who had an Hgb increase of more than 2 g/dL over any 4 weeks is presented. (NCT02791763)
Timeframe: Up to week 52

InterventionPercentage of participants (Number)
Daprodustat in ND Participants16
Epoetin Beta Pegol in ND Participants10

Percentage of ND Participants Who Had an Hgb Level of Less Than 7.5 g/dL

Percentage of ND participants who had an Hgb level of less than 7.5 g/dL is presented. (NCT02791763)
Timeframe: Up to week 52

InterventionPercentage of participants (Number)
Daprodustat in ND Participants1
Epoetin Beta Pegol in ND Participants0

Percentage of ND Participants Who Had an Hgb Level of More Than 13.0 g/dL

Percentage of ND participants who had an Hgb level of more than 13.0 g/dL is presented. (NCT02791763)
Timeframe: Up to week 52

InterventionPercentage of participants (Number)
Daprodustat in ND Participants45
Epoetin Beta Pegol in ND Participants48

Percentage of ND Participants Who Used Oral Iron During the Primary Efficacy Evaluation Period

Supplemental iron therapy were received by participants if required during treatment period. Participants who used ferric citrate were counted as oral iron use. The percentage of ND participants who used oral iron during the primary efficacy evaluation period (Weeks 40 to 52) were summarized. (NCT02791763)
Timeframe: Weeks 40 to 52

InterventionPercentage of participants (Number)
Daprodustat in ND Participants39
Epoetin Beta Pegol in ND Participants32

Percentage of ND Participants Who Used Oral Iron During the Treatment Period

Supplemental iron therapy were received by participants if required during treatment period. Participants who used ferric citrate were counted as oral iron use. The percentage of ND participants who used oral iron during the treatment period were summarized. (NCT02791763)
Timeframe: Up to week 52

InterventionPercentage of participants (Number)
Daprodustat in ND Participants52
Epoetin Beta Pegol in ND Participants45

Percentage of PD Participants Who Had an Hgb Increase of More Than 2 g/dL Over Any 4 Weeks

Percentage of PD participants who had an Hgb increase of more than 2 g/dL over any 4 weeks is presented. (NCT02791763)
Timeframe: Up to week 52

InterventionPercentage of participants (Number)
Daprodustat in PD Participants20

Percentage of PD Participants Who Had an Hgb Level of Less Than 7.5 g/dL

Percentage of PD participants who had an Hgb level of less than 7.5 g/dL is presented. (NCT02791763)
Timeframe: Up to week 52

InterventionPercentage of participants (Number)
Daprodustat in PD Participants0

Percentage of PD Participants Who Had an Hgb Level of More Than 13.0 g/dL

Percentage of PD participants who had an Hgb level of more than 13.0 g/dL is presented. (NCT02791763)
Timeframe: Up to week 52

InterventionPercentage of participants (Number)
Daprodustat in PD Participants51

Percentage of PD Participants Who Used Oral Iron During the Primary Efficacy Evaluation Period

Supplemental iron therapy were received by participants if required during treatment period. Participants who used ferric citrate were counted as oral iron use. The percentage of PD participants who used oral iron during the primary efficacy evaluation period (Weeks 40 to 52) were summarized. (NCT02791763)
Timeframe: Weeks 40 to 52

InterventionPercentage of participants (Number)
Daprodustat in PD Participants50

Percentage of PD Participants Who Used Oral Iron During the Treatment Period

Supplemental iron therapy were received by participants if required during treatment period. Participants who used ferric citrate were counted as oral iron use. The percentage of PD participants who used oral iron during the treatment period were summarized. (NCT02791763)
Timeframe: Up to week 52

InterventionPercentage of participants (Number)
Daprodustat in PD Participants60

Percentage of Time With Hgb Within the Target Range (11.0 to 13.0 g/dL) During the Primary Efficacy Evaluation Period (Weeks 40 to 52) in ND Participants

Mean percentage of time with Hgb within the target range (11.0 to 13.0 g/dL) is summarized during the primary efficacy evaluation period (Weeks 40 to 52). (NCT02791763)
Timeframe: Weeks 40 to 52

InterventionPercentage of time (Mean)
Daprodustat in ND Participants85.44
Epoetin Beta Pegol in ND Participants80.57

Percentage of Time With Hgb Within the Target Range (11.0 to 13.0 g/dL) During the Primary Efficacy Evaluation Period (Weeks 40 to 52) in PD Participants

Mean percentage of time with Hgb within the target range (11.0 to 13.0 g/dL) is summarized during the primary efficacy evaluation period (Weeks 40 to 52). (NCT02791763)
Timeframe: Weeks 40 to 52

InterventionPercentage of time (Mean)
Daprodustat in PD Participants85.73

Time to Reach the Lower Target Hgb Level (11.0 g/dL) in ND Participants

The time (in days) to reach the lower target Hgb level (11.0 g/dL) was summarized using 25th percentile (P25), median, and 75th percentile (P75) by Kaplan-Meier method. Participants who did not reach the lower Hgb target were considered as censored cases. Participants who were randomized as Hgb >= 11.0 g/dL were excluded in this summary. (NCT02791763)
Timeframe: Up to week 52

InterventionDays (Median)
Daprodustat in ND Participants58.0
Epoetin Beta Pegol in ND Participants57.0

Time to Reach the Lower Target Hgb Level (11.0 g/dL) in PD Participants

The time (in days) to reach the lower target Hgb level (11.0 g/dL) was summarized using 25th percentile (P25), median, and 75th percentile (P75) by Kaplan-Meier method. Participants who did not reach the lower Hgb target were considered as censored cases. Participants who were randomized as Hgb >= 11.0 g/dL were excluded in this summary. (NCT02791763)
Timeframe: Up to week 52

InterventionDays (Median)
Daprodustat in PD Participants84.0

Change From Baseline in Ferritin in ND Participants

Change from Baseline in Ferritin in ND participants was summarized at each assessment visit. The Baseline value was the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Adjusted mean and 95% confidence interval for change from Baseline in Ferritin is presented. For adjusted values, analysis was performed by MMRM with covariates of treatment, Baseline, visit, treatment-by-visit interaction and Baseline-by-visit interaction. (NCT02791763)
Timeframe: Baseline (Day 1 pre-dose) and Weeks 4, 16, 28, 40 and 52

,
InterventionMicrograms per liter (µg/L) (Mean)
Week 4, n=107,109Week 16, n=104,105Week 28, n=96,93Week 40, n=88,87Week 52, n=87,81
Daprodustat in ND Participants-41.4-83.4-80.1-56.3-42.7
Epoetin Beta Pegol in ND Participants-29.0-29.3-16.6-16.0-14.0

Change From Baseline in Ferritin in PD Participants

Change from Baseline in Ferritin in PD participants was summarized at each assessment visit. The Baseline value was the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Adjusted mean and 95% confidence interval for change from Baseline in Ferritin is presented. For adjusted values, analysis was performed by MMRM with covariates of Baseline, visit and Baseline-by-visit interaction. (NCT02791763)
Timeframe: Baseline (Day 1 pre-dose) and Weeks 4, 16, 28, 40 and 52

Interventionµg/L (Mean)
Week 4, n=55Week 16, n=51Week 28, n=48Week 40, n=44Week 52, n=43
Daprodustat in PD Participants-36.4-81.8-89.1-74.6-63.6

Change From Baseline in Hgb Values at Each Assessment Visit in ND Participants

Baseline Hgb value was the value from the Day 1 visit. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Data for change from Baseline in Hgb values at each assessment visit in ND participants is presented. (NCT02791763)
Timeframe: Baseline (Day 1), Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52

,
Interventiong/dL (Mean)
Week 4, n=107,109Week 8, n=107,109Week 12, n=106,107Week 16, n=104,105Week 20, n=102,103Week 24, n=99,99Week 28, n=96,93Week 32, n=92,90Week 36, n=92,88Week 40, n=88,87Week 44, n=88,86Week 48, n=87,83Week 52, n=87,81
Daprodustat in ND Participants0.470.711.041.451.391.411.541.601.491.441.431.611.56
Epoetin Beta Pegol in ND Participants0.260.661.181.401.261.101.081.041.041.261.011.031.21

Change From Baseline in Hgb Values at Each Assessment Visit in PD Participants

Baseline Hgb value was the value from the Day 1 visit. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Data for change from Baseline in Hgb values at each assessment visit in PD participants is presented. (NCT02791763)
Timeframe: Baseline (Day 1), Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52

Interventiong/dL (Mean)
Week 4, n=55Week 8, n=54Week 12, n=52Week 16, n=51Week 20, n=50Week 24, n=49Week 28, n=48Week 32, n=45Week 36, n=45Week 40, n=44Week 44, n=43Week 48, n=43Week 52, n=43
Daprodustat in PD Participants-0.09-0.060.440.520.630.741.001.130.951.130.901.081.10

Change From Baseline in Serum Iron in ND Participants

Change from Baseline in serum iron in ND participants was summarized at each assessment visit. The Baseline value was the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Adjusted mean and 95% confidence interval for change from Baseline in Serum iron is presented. For adjusted values, analysis was performed by MMRM with covariates of treatment, Baseline, visit, treatment-by-visit interaction and Baseline-by-visit interaction. (NCT02791763)
Timeframe: Baseline (Day 1 pre-dose) and Weeks 4, 16, 28, 40 and 52

,
InterventionMicromoles per liter (µmol/L) (Mean)
Week 4, n=107,109Week 16, n=104,105Week 28, n=96,93Week 40, n=88,87Week 52, n=87,81
Daprodustat in ND Participants0.50.30.30.90.7
Epoetin Beta Pegol in ND Participants-0.80.62.01.81.1

Change From Baseline in Serum Iron in PD Participants

Change from Baseline in serum iron in PD participants was summarized at each assessment visit. The Baseline value was the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Adjusted mean and 95% confidence interval for change from Baseline in Serum iron is presented. For adjusted values, analysis was performed by MMRM with covariates of Baseline, visit and Baseline-by-visit interaction. (NCT02791763)
Timeframe: Baseline (Day 1 pre-dose) and Weeks 4, 16, 28, 40 and 52

Interventionµmol/L (Mean)
Week 4, n=55Week 16, n=51Week 28, n=48Week 40, n=44Week 52, n=43
Daprodustat in PD Participants-1.2-2.4-1.0-0.41.0

Change From Baseline in TIBC in PD Participants

Change from Baseline in TIBC in PD participants was summarized at each assessment visit. The Baseline value was the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Adjusted mean and 95% confidence interval for change from Baseline in TIBC is presented. For adjusted values, analysis was performed by MMRM with covariates of Baseline, visit and Baseline-by-visit interaction. (NCT02791763)
Timeframe: Baseline (Day 1 pre-dose) and Weeks 4, 16, 28, 40 and 52

Interventionµmol/L (Mean)
Week 4, n=55Week 16, n=51Week 28, n=48Week 40, n=44Week 52, n=43
Daprodustat in PD Participants6.99.511.011.09.6

Change From Baseline in Total Iron Binding Capacity (TIBC) in ND Participants

Change from Baseline in TIBC in ND participants was summarized at each assessment visit. The Baseline value was the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Adjusted mean and 95% confidence interval for change from Baseline in TIBC is presented. For adjusted values, analysis was performed by MMRM with covariates of treatment, Baseline, visit, treatment-by-visit interaction and Baseline-by-visit interaction. (NCT02791763)
Timeframe: Baseline (Day 1 pre-dose) and Weeks 4, 16, 28, 40 and 52

,
Interventionµmol/L (Mean)
Week 4, n=107,109Week 16, n=104,105Week 28, n=96,93Week 40, n=88,87Week 52, n=87,81
Daprodustat in ND Participants6.99.99.98.07.8
Epoetin Beta Pegol in ND Participants0.51.91.40.20.1

Daprodustat Dose Level by Visit in ND Participants

Daprodustat dose level at each assessment visit for ND participants is presented using 25th percentile (P25), median, and 75th percentile (P75). (NCT02791763)
Timeframe: Day 1, Weeks 4,8,12,16,20,24,28,32,36,40,44 and 48

InterventionMilligrams per day (mg/day) (Median)
Day 1, n=108Week 4, n=106Week 8, n=106Week 12, n=106Week 16, n=103Week 20, n=100Week 24, n=96Week 28, n=94Week 32, n=92Week 36, n=89Week 40, n=88Week 44, n=88Week 48, n=87
Daprodustat in ND Participants4.04.04.04.04.04.04.04.04.04.04.04.04.0

Daprodustat Dose Level by Visit in PD Participants

Daprodustat dose level at each assessment visit for PD participants is presented using 25th percentile (P25), median, and 75th percentile (P75). (NCT02791763)
Timeframe: Day 1, Weeks 4,8,12,16,20,24,28,32,36,40,44 and 48

Interventionmg/day (Median)
Day 1, n=55Week 4, n=55Week 8, n=52Week 12, n=52Week 16, n=51Week 20, n=50Week 24, n=48Week 28, n=45Week 32, n=45Week 36, n=45Week 40, n=44Week 44, n=43Week 48, n=43
Daprodustat in PD Participants4.06.06.06.06.06.08.08.06.08.06.06.06.0

Epoetin Beta Pegol Dose Level by Visit in ND Participants

Dose of epoetin beta pegol at a scheduled visit was converted to dose per 4 weeks when the dose frequency was every 2 weeks. Epoetin beta pegol dose level at each assessment visit for ND participants is presented using 25th percentile (P25), median, and 75th percentile (P75). (NCT02791763)
Timeframe: Day 1, Weeks 4,8,12,16,20,24,28,32,36,40,44 and 48

InterventionMicrograms per 4 weeks (Median)
Day 1, n=109Week 4, n=109Week 8, n=107Week 12, n=105Week 16, n=104Week 20, n=100Week 24, n=97Week 28, n=92Week 32, n=90Week 36, n=88Week 40, n=87Week 44, n=84Week 48, n=82
Epoetin Beta Pegol in ND Participants50.075.0100.0100.075.075.075.075.075.075.075.0100.0100.0

Hgb Values at Each Assessment Visit in ND Participants

Hgb values at each assessment visit for ND participants is presented. (NCT02791763)
Timeframe: Day 1, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52

,
Interventiong/dL (Mean)
Day 1, n=108,109Week 4, n=107,109Week 8, n=107,109Week 12, n=106,107Week 16, n=104,105Week 20, n=102,103Week 24, n=99,99Week 28, n=96,93Week 32, n=92,90Week 36, n=92,88Week 40, n=88,87Week 44, n=88,86Week 48, n=87,83Week 52, n=87,81
Daprodustat in ND Participants10.4810.9511.1911.5111.9011.8411.8711.9812.0311.9311.8811.8712.0512.01
Epoetin Beta Pegol in ND Participants10.6810.9411.3411.8412.0711.9611.8011.8311.8011.8112.0011.7511.8011.99

Hgb Values at Each Assessment Visit in PD Participants

Hgb values at each assessment visit for PD participants is presented. (NCT02791763)
Timeframe: Day 1, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52

Interventiong/dL (Mean)
Day 1, n=55Week 4, n=55Week 8, n=54Week 12, n=52Week 16, n=51Week 20, n=50Week 24, n=49Week 28, n=48Week 32, n=45Week 36, n=45Week 40, n=44Week 44, n=43Week 48, n=43Week 52, n=43
Daprodustat in PD Participants10.8510.7710.8311.3611.4211.5411.6911.9512.0711.9012.1211.9212.1012.12

Number of ND Participants by Hgb Change From Baseline Category at Week 4

Baseline Hgb value was the value from the Day 1 visit. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Number of participants by Hgb change from Baseline is categorized to <=-2.0, >-2.0 and <=-1.0, >-1.0 and <=0, >0 and <=1.0, >1.0 and <=2.0, >2.0 g/dL, then is additionally categorized to within +/- 1.0 g/dL and over +/- 2.0 g/dL. Number of participants have been included in more than one category at Week 4. (NCT02791763)
Timeframe: Baseline (Day 1) and Week 4

,
InterventionParticipants (Count of Participants)
<=-2.0>-2.0 and <=-1.0>-1.0 and <=0>0 and <=1.0>1.0 and <=2.0>2.0within +/- 1.0over +/- 2.0
Daprodustat in ND Participants142843292723
Epoetin Beta Pegol in ND Participants233356150901

Number of ND Participants Who Had Hgb Level Within the Target Range (11.0-13.0 g/dL) at Each Assessment Visit

Number of ND participants with Hgb level within the target range (11.0 to 13.0 g/dL) are summarized at each assessment visit. (NCT02791763)
Timeframe: Day 1, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52

,
InterventionParticipants (Count of Participants)
Day 1, n=108,109Week 4, n=107,109Week 8, n=107,109Week 12, n=106,107Week 16, n=104,105Week 20, n=102,103Week 24, n=99,99Week 28, n=96,93Week 32, n=92,90Week 36, n=92,88Week 40, n=88,87Week 44, n=88,86Week 48, n=87,83Week 52, n=87,81
Daprodustat in ND Participants2943647884888677797978717567
Epoetin Beta Pegol in ND Participants3648738580858573677072686259

Number of ND Participants With Mean Hgb in the Target Range (11.0-13.0 g/dL) During the Primary Efficacy Evaluation Period (Weeks 40 to 52)

ND participants with observed mean Hgb within the target range during the primary efficacy evaluation period were summarized. Responders were defined as the participants with the mean Hgb within target range during the primary efficacy evaluation period. (NCT02791763)
Timeframe: Weeks 40 to 52

,
InterventionParticipants (Count of Participants)
ResponderNon-Responder
Daprodustat in ND Participants817
Epoetin Beta Pegol in ND Participants807

Number of PD Participants by Hgb Change From Baseline Category at Week 4

Baseline Hgb value was the value from the Day 1 visit. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Number of participants by Hgb change from Baseline is categorized to <=-2.0, >-2.0 and <=-1.0, >-1.0 and <=0, >0 and <=1.0, >1.0 and <=2.0, >2.0 g/dL, then is additionally categorized to within +/- 1.0 g/dL and over +/- 2.0 g/dL. Number of participants have been included in more than one category at Week 4. (NCT02791763)
Timeframe: Baseline (Day 1) and Week 4

InterventionParticipants (Count of Participants)
<=-2.0>-2.0 and <=-1.0>-1.0 and <=0>0 and <=1.0>1.0 and <=2.0>2.0within +/- 1.0over +/- 2.0
Daprodustat in PD Participants010202041411

Number of PD Participants Who Had Hgb Level Within the Target Range (11.0-13.0 g/dL) at Each Assessment Visit

Number of PD participants with Hgb level within the target range (11.0 to 13.0 g/dL) are summarized at each assessment visit. (NCT02791763)
Timeframe: Day 1, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52

InterventionParticipants (Count of Participants)
Day 1, n=55Week 4, n=55Week 8, n=54Week 12, n=52Week 16, n=51Week 20, n=50Week 24, n=49Week 28, n=48Week 32, n=45Week 36, n=45Week 40, n=44Week 44, n=43Week 48, n=43Week 52, n=43
Daprodustat in PD Participants2825263232383639343634333638

Percent Change From Baseline in Hepcidin in ND Participants

Percent change from Baseline in Hepcidin in ND participants was summarized at each assessment visit. The Baseline value was the latest pre-dose assessment (Day 1 pre-dose). Percent change from Baseline was calculated as 100*(exponential [mean change on log scale]-1). Adjusted geometric mean and 95% confidence interval for percent change from Baseline in Hepcidin is presented. For adjusted values, analysis was performed by MMRM with covariates of treatment, Baseline, visit, treatment-by-visit interaction and Baseline-by-visit interaction. (NCT02791763)
Timeframe: Baseline (Day 1 pre-dose) and Weeks 4, 16, 28, 40 and 52

,
InterventionPercent change (Geometric Mean)
Week 4, n=99,100Week 16, n=86,99Week 28, n=81,85Week 40, n=76,80Week 52, n=76,74
Daprodustat in ND Participants-49.13-55.67-56.67-47.77-45.27
Epoetin Beta Pegol in ND Participants-19.20-3.737.619.5410.13

Percent Change From Baseline in Hepcidin in PD Participants

Percent change from Baseline in Hepcidin in PD participants was summarized at each assessment visit. The Baseline value was the latest pre-dose assessment (Day 1 pre-dose). Percent change from Baseline was calculated as 100*(exponential [mean change on log scale]-1). Adjusted geometric mean and 95% confidence interval for percent change from Baseline in Hepcidin is presented. For adjusted values, analysis was performed by MMRM with covariates of Baseline, visit and Baseline-by-visit interaction. (NCT02791763)
Timeframe: Baseline (Day 1 pre-dose) and Weeks 4, 16, 28, 40 and 52

InterventionPercent change (Geometric Mean)
Week 4, n=53Week 16, n=48Week 28, n=39Week 40, n=39Week 52, n=40
Daprodustat in PD Participants-49.79-62.59-65.37-67.91-54.77

Percent Change From Baseline in Transferrin Saturation (TSAT) in ND Participants

Percent change from Baseline in TSAT in ND participants was summarized at each assessment visit. The Baseline value was the latest pre-dose assessment (Day 1 pre-dose). Percent change from Baseline was calculated as 100*(exponential [mean change on log scale]-1). Adjusted geometric mean and 95% confidence interval for percent change from Baseline in TSAT is presented. For adjusted values, analysis was performed by MMRM with covariates of treatment, Baseline, visit, treatment-by-visit interaction and Baseline-by-visit interaction. (NCT02791763)
Timeframe: Baseline (Day 1 pre-dose) and Weeks 4, 16, 28, 40 and 52

,
InterventionPercent change (Geometric Mean)
Week 4, n=107,109Week 16, n=104,105Week 28, n=96,93Week 40, n=88,87Week 52, n=87,81
Daprodustat in ND Participants-12.4-16.3-17.5-11.2-11.7
Epoetin Beta Pegol in ND Participants-5.4-0.310.612.57.0

Percent Change From Baseline in TSAT in PD Participants

Percent change from Baseline in TSAT in PD participants was summarized at each assessment visit. The Baseline value was the latest pre-dose assessment (Day 1 pre-dose). Percent change from Baseline was calculated as 100*(exponential [mean change on log scale]-1). Adjusted geometric mean and 95% confidence interval for percent change from Baseline in TSAT is presented. For adjusted values, analysis was performed by MMRM with covariates of Baseline, visit and Baseline-by-visit interaction. (NCT02791763)
Timeframe: Baseline (Day 1 pre-dose) and Weeks 4, 16, 28, 40 and 52

InterventionPercent change (Geometric Mean)
Week 4, n=55Week 16, n=51Week 28, n=48Week 40, n=44Week 52, n=43
Daprodustat in PD Participants-19.2-29.1-22.6-19.5-14.7

Percentage of ND Participants by Hgb Change From Baseline Category at Week 4

Baseline Hgb value was the value from the Day 1 visit. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Number of participants by Hgb change from Baseline is categorized to <=-2.0, >-2.0 and <=-1.0, >-1.0 and <=0, >0 and <=1.0, >1.0 and <=2.0, >2.0 g/dL, then is additionally categorized to within +/- 1.0 g/dL and over +/- 2.0 g/dL. Number of participants have been included in more than one category at Week 4. (NCT02791763)
Timeframe: Baseline (Day 1) and Week 4

,
InterventionPercentage of participants (Number)
<=-2.0>-2.0 and <=-1.0>-1.0 and <=0>0 and <=1.0>1.0 and <=2.0>2.0within +/- 1.0over +/- 2.0
Daprodustat in ND Participants142640272673
Epoetin Beta Pegol in ND Participants233051140831

Percentage of ND Participants Who Had Hgb Level Within the Target Range (11.0-13.0 g/dL) at Each Assessment Visit

Percentage of ND participants with Hgb level within the target range (11.0 to 13.0 g/dL) are summarized at each assessment visit. (NCT02791763)
Timeframe: Day 1, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52

,
InterventionPercentage of Participants (Number)
Day 1, n=108,109Week 4, n=107,109Week 8, n=107,109Week 12, n=106,107Week 16, n=104,105Week 20, n=102,103Week 24, n=99,99Week 28, n=96,93Week 32, n=92,90Week 36, n=92,88Week 40, n=88,87Week 44, n=88,86Week 48, n=87,83Week 52, n=87,81
Daprodustat in ND Participants2740607481868780868689818677
Epoetin Beta Pegol in ND Participants3344677976838678748083797573

Percentage of ND Participants With Mean Hgb in the Target Range (11.0-13.0 g/dL) During the Primary Efficacy Evaluation Period (Weeks 40 to 52)

The percentage of ND participants with observed mean Hgb within the target range during the primary efficacy evaluation period was summarized. Responders were defined as the participants with the mean Hgb within target range during the primary efficacy evaluation period. (NCT02791763)
Timeframe: Weeks 40 to 52

,
InterventionPercentage of participants (Number)
ResponderNon-Responder
Daprodustat in ND Participants928
Epoetin Beta Pegol in ND Participants928

Percentage of PD Participants by Hgb Change From Baseline Category at Week 4

Baseline Hgb value was the value from the Day 1 visit. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Number of participants by Hgb change from Baseline is categorized to <=-2.0, >-2.0 and <=-1.0, >-1.0 and <=0, >0 and <=1.0, >1.0 and <=2.0, >2.0 g/dL, then is additionally categorized to within +/- 1.0 g/dL and over +/- 2.0 g/dL. Number of participants have been included in more than one category at Week 4. (NCT02791763)
Timeframe: Baseline (Day 1) and Week 4

InterventionPercentage of Participants (Number)
<=-2.0>-2.0 and <=-1.0>-1.0 and <=0>0 and <=1.0>1.0 and <=2.0>2.0within +/- 1.0over +/- 2.0
Daprodustat in PD Participants018363672752

Percentage of PD Participants Who Had Hgb Level Within the Target Range (11.0-13.0 g/dL) at Each Assessment Visit

Percentage of PD participants with Hgb level within the target range (11.0 to 13.0 g/dL) are summarized at each assessment visit. (NCT02791763)
Timeframe: Day 1, Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52

InterventionPercentage of Participants (Number)
Day 1, n=55Week 4, n=55Week 8, n=54Week 12, n=52Week 16, n=51Week 20, n=50Week 24, n=49Week 28, n=48Week 32, n=45Week 36, n=45Week 40, n=44Week 44, n=43Week 48, n=43Week 52, n=43
Daprodustat in PD Participants5145486263767381768077778488

Mean Hb Level of Week 20 and Week 24

(NCT03439137)
Timeframe: Up to Week 24

Interventiong/dL (Least Squares Mean)
MT-654810.61
Darbepoetin Alfa10.65

Mean Hb Level of Week 48 and Week 52

(NCT03439137)
Timeframe: Up to Week 52

Interventiong/dL (Least Squares Mean)
MT-654810.42
Darbepoetin Alfa10.62

Hb Level at Each Assessment Time Point

(NCT03439137)
Timeframe: Up to Week 52

,
Interventiong/dL (Mean)
BaselineWeek 2Week 4Week 6Week 8Week 10Week 12Week 16Week 20Week 24Week 28Week 32Week 36Week 40Week 44Week 48Week 52Week 52 (LOCF)
Darbepoetin Alfa10.7310.8510.8810.8310.8410.8610.9010.8010.6510.6310.6610.7710.7510.6710.6410.6310.6310.61
MT-654810.7310.6110.3810.2410.2410.2410.4310.5710.6910.6510.5810.6010.4910.5310.5410.5010.4710.24

Percentage of Subjects With Hb Level at Each Assessment Time Point Within the Target Range During the Treatment Period

(NCT03439137)
Timeframe: Up to Week 52

,
Interventionpercentage of subjects (Number)
BaselineWeek 2Week 4Week 6Week 8Week 10Week 12Week 16Week 20Week 24Week 28Week 32Week 36Week 40Week 44Week 48Week 52
Darbepoetin Alfa78.981.383.084.385.481.586.684.674.075.777.379.578.981.685.679.786.5
MT-654881.575.063.758.156.056.761.968.873.675.470.573.367.577.074.672.975.7

Change From Baseline in Hb to the Average Over the Secondary Efficacy Period (Weeks 40 to 52)

The Baseline average was calculated as the average of the Hb values obtained at the screening visit closest to the date of randomization and the randomization visit. The average for the Secondary Efficacy Period was calculated as the average Hb value over Weeks 40 to 52. Analysis was conducted using an ANCOVA model with multiple imputation for missing data with Baseline hemoglobin concentration (<9.5 versus ≥9.5 g/dL), geographic region (US versus EU versus ROW), and NYHA CHF class (Class 0 [no CHF] or I versus II or III) as covariates. (NCT02865850)
Timeframe: Baseline; Weeks 40 to 52

Interventiong/dL (Least Squares Mean)
Vadadustat1.42
Darbepoetin Alfa1.50

Change From Baseline in Hemoglobin (Hb) to the Average Over the Primary Efficacy Period (Weeks 24 to 36)

The Baseline average was calculated as the average of the Hb values obtained at the screening visit closest to the date of randomization and the randomization visit. The average for the Primary Efficacy Period was calculated as the average Hb value over Weeks 24 to 36. Analysis was conducted using an analysis of covariance (ANCOVA) model with multiple imputation for missing data with Baseline hemoglobin concentration (<9.5 versus ≥9.5 g/dL), geographic region (United States [US] versus European Union [EU] versus Rest of World [ROW]), and New York Heart Association congestive heart failure (NYHA CHF) class (Class 0 [no CHF] or I versus II or III) as covariates. (NCT02865850)
Timeframe: Baseline; Weeks 24 to 36

InterventionGrams per deciliter (g/dL) (Least Squares Mean)
Vadadustat1.26
Darbepoetin Alfa1.58

Median Time to First All-cause Mortality

"Only events that were positively adjudicated and confirmed by the EAC were included in the MACE analyses. INNOVATE MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0016 (NCT02865850) and AKB-6548-CI-0017 (NCT02892149). Results and statistical analysis from study AKB-6548-CI-0016 has been reported in below table and under section Statistical Analysis 1. Results and statistical analysis of the pooled data from studies AKB-6548-CI-0016 and AKB-6548-CI-0017 has been reported under section Statistical Analysis 2 of this outcome measure." (NCT02865850)
Timeframe: Up to 176 weeks

InterventionWeeks (Median)
Vadadustat31.71
Darbepoetin Alfa45.36

Median Time to First Cardiovascular Death

"Cardiovascular death included EAC adjudicated fatal MI, pump failure, sudden death, presumed sudden death, fatal stroke, fatal pulmonary embolism, cardiovascular procedure-related death, other cardiovascular death, and presumed cardiovascular death. INNOVATE MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0016 (NCT02865850) and AKB-6548-CI-0017 (NCT02892149). Results and statistical analysis from study AKB-6548-CI-0016 has been reported in below table and under section Statistical Analysis 1. Results and statistical analysis of the pooled data from studies AKB-6548-CI-0016 and AKB-6548-CI-0017 has been reported under section Statistical Analysis 2 of this outcome measure." (NCT02865850)
Timeframe: Up to 176 weeks

InterventionWeeks (Median)
Vadadustat22.00
Darbepoetin Alfa58.14

Median Time to First Cardiovascular MACE

"MACE was defined as all-cause mortality, non-fatal MI, or non-fatal stroke. Cardiovascular MACE analysis differed from the primary MACE endpoint as it included only deaths adjudicated by the EAC as cardiovascular deaths (i.e, only EAC-confirmed cardiovascular deaths) in addition to first events of non-fatal MI or non-fatal stroke. INNOVATE MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0016 (NCT02865850) and AKB-6548-CI-0017 (NCT02892149). Results and statistical analysis from study AKB-6548-CI-0016 has been reported in below table and under section Statistical Analysis 1. Results and statistical analysis of the pooled data from studies AKB-6548-CI-0016 and AKB-6548-CI-0017 has been reported under section Statistical Analysis 2 of this outcome measure." (NCT02865850)
Timeframe: Up to 176 weeks

InterventionWeeks (Median)
Vadadustat18.50
Darbepoetin Alfa54.07

Median Time to First MACE Plus Hospitalization for Heart Failure or Thromboembolic Event Excluding Vascular Access Thrombosis

"MACE was defined as all-cause mortality, non-fatal MI, or non-fatal stroke. Hospitalization for EAC adjudicated heart failure included presentation of participants to an acute care facility requiring an overnight hospitalization (change in calendar day) with an exacerbation of heart failure requiring treatment. EAC confirmed thromboembolic events for this secondary outcome measure included arterial thrombosis, deep vein thrombosis, and pulmonary embolism. INNOVATE MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0016 (NCT02865850) and AKB-6548-CI-0017 (NCT02892149). Results and statistical analysis from study AKB-6548-CI-0016 has been reported in below table and under section Statistical Analysis 1. Results and statistical analysis of the pooled data from studies AKB-6548-CI-0016 and AKB-6548-CI-0017 has been reported under section Statistical Analysis 2 of this outcome measure." (NCT02865850)
Timeframe: Up to 176 weeks

InterventionWeeks (Median)
Vadadustat27.14
Darbepoetin Alfa47.00

Median Time to First Major Adverse Cardiovascular Event (MACE)

"MACE was defined as all-cause mortality, non-fatal myocardial infarction (MI), or non-fatal stroke. The primary safety outcome was positively adjudicated first MACE, which was defined as any death, Endpoint Adjudication Committee (EAC)-confirmed non-fatal MI, or EAC-confirmed non-fatal stroke occurring between the first dose date and each participant's last participation date. INNOVATE MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0016 (NCT02865850) and AKB-6548-CI-0017 (NCT02892149). Results and statistical analysis from study AKB-6548-CI-0016 has been reported in below table and under section Statistical Analysis 1. Results and statistical analysis of the pooled data from studies AKB-6548-CI-0016 and AKB-6548-CI-0017 has been reported under section Statistical Analysis 2 of this outcome measure." (NCT02865850)
Timeframe: Up to 176 weeks

InterventionWeeks (Median)
Vadadustat26.21
Darbepoetin Alfa46.64

Change From Baseline in Hb to the Average Over the Secondary Efficacy Period (Weeks 40 to 52)

The Baseline average was calculated as the average of the Hb values obtained at the screening visit closest to the date of randomization and the randomization visit. The average for the Secondary Efficacy Period was calculated as the average Hb value over Weeks 40 to 52. Analysis was conducted using an ANCOVA model with multiple imputation for missing data with Baseline hemoglobin concentration (<10.0 versus ≥10.0 g/dL), geographic region (US versus EU versus ROW), and NYHA CHF class (Class 0 [no CHF] or I versus II or III) as covariates. (NCT02892149)
Timeframe: Baseline; Weeks 40 to 52

Interventiong/dL (Least Squares Mean)
Vadadustat0.23
Darbepoetin Alfa0.41

Change From Baseline in Hemoglobin (Hb) to the Average Over the Primary Efficacy Period (Weeks 24 to 36)

The Baseline average was calculated as the average of the Hb values obtained at the screening visit closest to the date of randomization and the randomization visit. The average for the Primary Efficacy Period was calculated as the average Hb value over Weeks 24 to 36. Analysis was conducted using an analysis of covariance (ANCOVA) model with multiple imputation for missing data with Baseline hemoglobin concentration (<10.0 versus ≥10.0 g/dL), geographic region (United States [US] versus European Union [EU] versus Rest of World [ROW]), and New York Heart Association congestive heart failure (NYHA CHF) class (Class 0 [no CHF] or I versus II or III) as covariates. (NCT02892149)
Timeframe: Baseline; Weeks 24 to 36

InterventionGrams per deciliter (g/dL) (Least Squares Mean)
Vadadustat0.19
Darbepoetin Alfa0.36

Median Time to First All-cause Mortality

"Only events that were positively adjudicated and confirmed by the EAC were included in the MACE analyses. INNOVATE MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0016 (NCT02865850) and AKB-6548-CI-0017 (NCT02892149). Results and statistical analysis from study AKB-6548-CI-0017 has been reported in below table and under section Statistical Analysis 1. Results and statistical analysis of the pooled data from studies AKB-6548-CI-0016 and AKB-6548-CI-0017 has been reported under section Statistical Analysis 2 of this outcome measure." (NCT02892149)
Timeframe: Up to 170 weeks

InterventionWeeks (Median)
Vadadustat50.79
Darbepoetin Alfa50.43

Median Time to First Cardiovascular Death

"Cardiovascular death included EAC adjudicated fatal MI, pump failure, sudden death, presumed sudden death, fatal stroke, fatal pulmonary embolism, cardiovascular procedure-related death, other cardiovascular death, and presumed cardiovascular death. INNOVATE MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0016 (NCT02865850) and AKB-6548-CI-0017 (NCT02892149). Results and statistical analysis from study AKB-6548-CI-0017 has been reported in below table and under section Statistical Analysis 1. Results and statistical analysis of the pooled data from studies AKB-6548-CI-0016 and AKB-6548-CI-0017 has been reported under section Statistical Analysis 2 of this outcome measure." (NCT02892149)
Timeframe: Up to 170 weeks

InterventionWeeks (Median)
Vadadustat46.14
Darbepoetin Alfa47.64

Median Time to First Cardiovascular MACE

"MACE was defined as all-cause mortality, non-fatal MI, or non-fatal stroke. Cardiovascular MACE analysis differed from the primary MACE endpoint as it included only deaths adjudicated by the EAC as cardiovascular deaths (i.e, only EAC-confirmed cardiovascular deaths) in addition to first events of non-fatal MI or non-fatal stroke. INNOVATE MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0016 (NCT02865850) and AKB-6548-CI-0017 (NCT02892149). Results and statistical analysis from study AKB-6548-CI-0017 has been reported in below table and under section Statistical Analysis 1. Results and statistical analysis of the pooled data from studies AKB-6548-CI-0016 and AKB-6548-CI-0017 has been reported under section Statistical Analysis 2 of this outcome measure." (NCT02892149)
Timeframe: Up to 170 weeks

InterventionWeeks (Median)
Vadadustat44.57
Darbepoetin Alfa43.57

Median Time to First MACE Plus Hospitalization for Heart Failure or Thromboembolic Event Excluding Vascular Access Thrombosis

"MACE was defined as all-cause mortality, non-fatal MI, or non-fatal stroke. Hospitalization for EAC adjudicated heart failure included presentation of participants to an acute care facility requiring an overnight hospitalization (change in calendar day) with an exacerbation of heart failure requiring treatment. EAC confirmed thromboembolic events for this secondary outcome measure included arterial thrombosis, deep vein thrombosis, and pulmonary embolism. INNOVATE MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0016 (NCT02865850) and AKB-6548-CI-0017 (NCT02892149). Results and statistical analysis from study AKB-6548-CI-0017 has been reported in below table and under section Statistical Analysis 1. Results and statistical analysis of the pooled data from studies AKB-6548-CI-0016 and AKB-6548-CI-0017 has been reported under section Statistical Analysis 2 of this outcome measure." (NCT02892149)
Timeframe: Up to 170 weeks

InterventionWeeks (Median)
Vadadustat43.29
Darbepoetin Alfa45.21

Median Time to First Major Adverse Cardiovascular Event (MACE)

"MACE was defined as all-cause mortality, non-fatal myocardial infarction (MI), or non-fatal stroke. The primary safety outcome was positively adjudicated first MACE, which was defined as any death, Endpoint Adjudication Committee (EAC)-confirmed non-fatal MI, or EAC-confirmed non-fatal stroke occurring between the first dose date and each participant's last participation date. INNOVATE MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0016 (NCT02865850) and AKB-6548-CI-0017 (NCT02892149). Results and statistical analysis from study AKB-6548-CI-0017 has been reported in below table and under section Statistical Analysis 1. Results and statistical analysis of the pooled data from studies AKB-6548-CI-0016 and AKB-6548-CI-0017 has been reported under section Statistical Analysis 2 of this outcome measure." (NCT02892149)
Timeframe: Up to 170 weeks

InterventionWeeks (Median)
Vadadustat48.86
Darbepoetin Alfa48.00

Change From Baseline in Hb to the Average Over the Secondary Efficacy Period (Weeks 40 to 52)

The Baseline average was calculated as the average of the Hb values obtained at the screening visit closest to the date of randomization and the randomization visit. The average for the Secondary Efficacy Period was calculated as the average Hb value over Weeks 40 to 52. Analysis was conducted using an ANCOVA model with multiple imputation for missing data with Baseline Hb concentration (<9.5 versus ≥9.5 g/dL), geographic region (US versus EU versus ROW), and NYHA CHF class (Class 0 [no CHF] or I versus II or III) as covariates. (NCT02648347)
Timeframe: Baseline; Weeks 40 to 52

Interventiong/dL (Least Squares Mean)
Vadadustat1.52
Darbepoetin Alfa1.48

Change From Baseline in Hemoglobin (Hb) to the Average Over the Primary Efficacy Period (Weeks 24 to 36)

The Baseline average was calculated as the average of the Hb values obtained at the screening visit closest to the date of randomization and the randomization visit. The average for the Primary Efficacy Period was calculated as the average Hb value over Weeks 24 to 36. Analysis was conducted using an analysis of covariance (ANCOVA) model with multiple imputation for missing data with Baseline Hb concentration (<9.5 versus ≥9.5 grams per deciliter [g/dL]), geographic region (United States [US] versus European Union [EU] versus Rest of World [ROW]), and New York Heart Association congestive heart failure (NYHA CHF) class (Class 0 [no CHF] or I versus II or III) as covariates. (NCT02648347)
Timeframe: Baseline; Weeks 24 to 36

Interventiong/dL (Least Squares Mean)
Vadadustat1.43
Darbepoetin Alfa1.38

Median Time to First All-cause Mortality

"Only events that were positively adjudicated and confirmed by the EAC were included in the MACE analyses. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0014 has been reported in below table and under section Statistical Analysis 1. Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section Statistical Analysis 2 of this outcome measure." (NCT02648347)
Timeframe: Up to Week 208

InterventionWeeks (Median)
Vadadustat46.57
Darbepoetin Alfa47.79

Median Time to First Cardiovascular Death

"Cardiovascular death included EAC adjudicated fatal MI, pump failure, sudden death, presumed sudden death, fatal stroke, fatal pulmonary embolism, cardiovascular procedure-related death, other cardiovascular death, and presumed cardiovascular death. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0014 has been reported in below table and under section Statistical Analysis 1. Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section Statistical Analysis 2 of this outcome measure." (NCT02648347)
Timeframe: Up to Week 208

InterventionWeeks (Median)
Vadadustat48.29
Darbepoetin Alfa41.86

Median Time to First Cardiovascular MACE

"MACE was defined as all-cause mortality, non-fatal MI, or non-fatal stroke. Cardiovascular MACE analysis differed from the primary MACE endpoint as it included only deaths adjudicated by the EAC as cardiovascular deaths (i.e, only EAC-confirmed cardiovascular deaths) in addition to first events of non-fatal MI or non-fatal stroke. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0014 has been reported in below table and under section Statistical Analysis 1. Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section Statistical Analysis 2 of this outcome measure." (NCT02648347)
Timeframe: Up to Week 208

InterventionWeeks (Median)
Vadadustat45.86
Darbepoetin Alfa41.86

Median Time to First MACE Plus Hospitalization for Heart Failure or Thromboembolic Event Excluding Vascular Access Thrombosis

"MACE was defined as all-cause mortality, non-fatal MI, or non-fatal stroke. Hospitalization for EAC adjudicated heart failure included presentation of participants to an acute care facility requiring an overnight hospitalization (change in calendar day) with an exacerbation of heart failure requiring treatment. EAC confirmed thromboembolic events for this secondary outcome measure included arterial thrombosis, deep vein thrombosis, and pulmonary embolism. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0014 has been reported in below table and under section Statistical Analysis 1. Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section Statistical Analysis 2 of this outcome measure." (NCT02648347)
Timeframe: Up to Week 208

InterventionWeeks (Median)
Vadadustat37.64
Darbepoetin Alfa41.43

Median Time to First Major Adverse Cardiovascular Event (MACE)

"MACE was defined as all-cause mortality, non-fatal myocardial infarction (MI), or non-fatal stroke. The primary safety outcome was positively adjudicated first MACE, which was defined as any death, Endpoint Adjudication Committee (EAC)-confirmed non-fatal MI, or EAC-confirmed non-fatal stroke occurring between the first dose date and each participant's last participation date. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0014 has been reported in below table and under section Statistical Analysis 1. Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section Statistical Analysis 2 of this outcome measure." (NCT02648347)
Timeframe: Up to Week 208

InterventionWeeks (Median)
Vadadustat45.71
Darbepoetin Alfa46.71

Change From Baseline in Hb to the Average Over the Secondary Efficacy Period (Weeks 40 to 52)

The Baseline average was calculated as the average of the Hb values obtained at the screening visit closest to the date of randomization and the randomization visit. The average for the Secondary Efficacy Period was calculated as the average Hb value over Weeks 40 to 52. Analysis was conducted using an ANCOVA model with multiple imputation for missing data with Baseline hemoglobin concentration (<10.0 versus ≥10.0 g/dL), geographic region (US versus EU versus ROW), and NYHA CHF class (Class 0 [no CHF] or I versus II or III) as covariates. (NCT02680574)
Timeframe: Baseline; Weeks 40 to 52

Interventiong/dL (Least Squares Mean)
Vadadustat0.43
Darbepoetin Alfa0.44

Change From Baseline in Hemoglobin (Hb) to the Average Over the Primary Efficacy Period (Weeks 24 to 36)

The Baseline average was calculated as the average of the Hb values obtained at the screening visit closest to the date of randomization and the randomization visit. The average for the Primary Efficacy Period was calculated as the average Hb value over Weeks 24 to 36. Analysis was conducted using an analysis of covariance (ANCOVA) model with multiple imputation for missing data with Baseline hemoglobin concentration (<10.0 versus ≥10.0 g/dL), geographic region (United States [US] versus European Union [EU] versus Rest of World [ROW]), and New York Heart Association congestive heart failure (NYHA CHF) class (Class 0 [no CHF] or I versus II or III) as covariates. (NCT02680574)
Timeframe: Baseline; Weeks 24 to 36

InterventionGrams per deciliter (g/dL) (Least Squares Mean)
Vadadustat0.41
Darbepoetin Alfa0.42

Median Time to First All-cause Mortality

"Only events that were positively adjudicated and confirmed by the EAC were included in the MACE analyses. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0015 has been reported in below table and under section Statistical Analysis 1. Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section Statistical Analysis 2 of this outcome measure." (NCT02680574)
Timeframe: Up to Week 208

InterventionWeeks (Median)
Vadadustat57.71
Darbepoetin Alfa62.14

Median Time to First Cardiovascular Death

"Cardiovascular death included EAC adjudicated fatal MI, pump failure, sudden death, presumed sudden death, fatal stroke, fatal pulmonary embolism, cardiovascular procedure-related death, other cardiovascular death, and presumed cardiovascular death. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0015 has been reported in below table and under section Statistical Analysis 1. Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section Statistical Analysis 2 of this outcome measure." (NCT02680574)
Timeframe: Up to Week 208

InterventionWeeks (Median)
Vadadustat48.29
Darbepoetin Alfa54.21

Median Time to First Cardiovascular MACE

"MACE was defined as all-cause mortality, non-fatal MI, or non-fatal stroke. Cardiovascular MACE analysis differed from the primary MACE endpoint as it included only deaths adjudicated by the EAC as cardiovascular deaths (i.e, only EAC-confirmed cardiovascular deaths) in addition to first events of non-fatal MI or non-fatal stroke. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0015 has been reported in below table and under section Statistical Analysis 1. Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section Statistical Analysis 2 of this outcome measure." (NCT02680574)
Timeframe: Up to Week 208

InterventionWeeks (Median)
Vadadustat45.57
Darbepoetin Alfa50.29

Median Time to First MACE Plus Hospitalization for Heart Failure or Thromboembolic Event Excluding Vascular Access Thrombosis

"MACE was defined as all-cause mortality, non-fatal MI, or non-fatal stroke. Hospitalization for EAC adjudicated heart failure included presentation of participants to an acute care facility requiring an overnight hospitalization (change in calendar day) with an exacerbation of heart failure requiring treatment. EAC confirmed thromboembolic events for this secondary outcome measure included arterial thrombosis, deep vein thrombosis, and pulmonary embolism. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0015 has been reported in below table and under section Statistical Analysis 1. Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section Statistical Analysis 2 of this outcome measure." (NCT02680574)
Timeframe: Up to Week 208

InterventionWeeks (Median)
Vadadustat48.29
Darbepoetin Alfa49.29

Median Time to First Major Adverse Cardiovascular Event (MACE)

"MACE was defined as all-cause mortality, non-fatal myocardial infarction (MI), or non-fatal stroke. The primary safety outcome was positively adjudicated first MACE, which was defined as any death, Endpoint Adjudication Committee (EAC)-confirmed non-fatal MI, or EAC-confirmed non-fatal stroke occurring between the first dose date and each participant's last participation date. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0015 has been reported in below table and under section Statistical Analysis 1. Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section Statistical Analysis 2 of this outcome measure." (NCT02680574)
Timeframe: Up to Week 208

InterventionWeeks (Median)
Vadadustat53.21
Darbepoetin Alfa58.00

Mean Hb Level of Week 20 and Week 24

(NCT03461146)
Timeframe: Up to Week 24

Interventiong/dL (Least Squares Mean)
MT-654810.75

Time to Reach the Target Hb Range

(NCT03461146)
Timeframe: Up to Week 24

Interventiondays (Mean)
MT-654867.2

Hb Level at Each Assessment Time Point

(NCT03461146)
Timeframe: Up to Week 24

Interventiong/dL (Mean)
BaselineWeek 2Week 4Week 6Week 8Week 10Week 12Week 16Week 20Week 24Week 24 (LOCF)
MT-65489.159.259.539.9010.3310.5610.6811.1711.0811.0310.56

Percentage of Subjects With Hb Level at Each Assessment Time Point Within the Target Range During the Treatment Period

(NCT03461146)
Timeframe: Up to Week 24

Interventionpercentage of subjects (Number)
BaselineWeek 2Week 4Week 6Week 8Week 10Week 12Week 16Week 20Week 24
MT-654816.721.736.447.655.063.268.463.278.973.7

Rate of Increase in Hb Level

(NCT03461146)
Timeframe: Up to Week 6

Interventiong/dL/week (Mean)
Calculated based on Hb at baseline and Week 4Calculated based on Hb up to Week6
MT-65480.050.09

Number of Participants With Clinically Significant Abnormal 12-Electrocardiogram (ECG) Findings

A standard 12-lead ECG was performed following dosing in a supine position for approximately 10 minutes. ECGs were taken prior to blood draws when possible. Clinical significance is determined by the investigator. The investigator was responsible for reviewing laboratory results for clinical significance. (NCT01381094)
Timeframe: Up to Week 8 (Follow-up Visit 2 weeks after last dose)

InterventionParticipants (Count of Participants)
AKB-6548 240 mg0
AKB-6548 370 mg0
AKB-6548 500 mg0
AKB-6548 630 mg0
Placebo0

Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values

Parameters assessed for laboratory values included hematology, serum chemistry, C-reactive protein, DHEA-S, VEGF, and cystatin C. The investigator was responsible for reviewing laboratory results for clinically significant changes. (NCT01381094)
Timeframe: Up to Week 8 (Follow-up Visit 2 weeks after last dose)

InterventionParticipants (Count of Participants)
AKB-6548 240 mg0
AKB-6548 370 mg0
AKB-6548 500 mg0
AKB-6548 630 mg0
Placebo0

Number of Participants With Clinically Significant Changes From Baseline in Vital Signs Parameter

Parameters assessed for vital signs included sitting blood pressure, pulse, respiratory rate, and body temperature. The investigator was responsible for reviewing laboratory results for clinically significant changes. (NCT01381094)
Timeframe: Up to Week 8 (Follow-up Visit 2 weeks after last dose)

InterventionParticipants (Count of Participants)
AKB-6548 240 mg0
AKB-6548 370 mg0
AKB-6548 500 mg0
AKB-6548 630 mg0
Placebo0

Absolute Change From Baseline in Hemoglobin (Hgb) to End of Treatment (Week 6)

Absolute change from Baseline was calculated as the Week 6 (end of treatment) value minus the Baseline value. Baseline Hgb was defined as the average of the last two measurements obtained prior to dosing. If there was only one measurement prior to dosing, this measurement served as Baseline. A positive change from Baseline indicated that hemoglobin concentration increased. (NCT01381094)
Timeframe: Baseline, Week 6

,,,,
InterventionGrams per deciliter (g/dL) (Mean)
BaselineChange from Baseline at Week 6
AKB-6548 240 mg9.460.77
AKB-6548 370 mg9.930.73
AKB-6548 500 mg9.861.25
AKB-6548 630 mg9.671.43
Placebo9.83-0.03

Change From Baseline in Absolute Reticulocyte Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)

Change from Baseline was calculated as the visit value minus the Baseline value. Baseline Reticulocyte count was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated reticulocyte count increased. (NCT01381094)
Timeframe: Baseline, Week 1, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)

,,,,
Intervention10^6 cells/μL (Mean)
BaselineChange from Baseline to Week 1Change from Baseline to Week 2Change from Baseline to Week 4Change from Baseline to Week 6Change from Baseline to Follow-up Visit (up to Week 8)
AKB-6548 240 mg0.07660.00220.00120.0029-0.0020-0.0042
AKB-6548 370 mg0.05690.01340.01960.01280.01160.0015
AKB-6548 500 mg0.08110.02590.03460.02340.0061-0.0152
AKB-6548 630 mg0.06740.02890.02920.02060.0047-0.0119
Placebo0.07000.0010-0.0015-0.0023-0.0004-0.0035

Change From Baseline in Erythropoietin at Week 2, Week 6, and Follow-up Visit (up to Week 8)

Change from Baseline was calculated as the visit value minus the Baseline value. Baseline erythropoietin was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. (NCT01381094)
Timeframe: Baseline, Week 2, Week 6, Follow-up Visit (up to Week 8)

,,,,
Interventionng/mL (Mean)
BaselineChange from Baseline to Week 2Change from Baseline to Week 6Change from Baseline to Follow-up Visit (up to Week 8)
AKB-6548 240 mg18.011-3.538-3.050-3.853
AKB-6548 370 mg4.3390.606-1.013-0.563
AKB-6548 500 mg7.2871.142-3.329-2.061
AKB-6548 630 mg8.826-2.483-0.372-4.844
Placebo6.963-0.850-1.492-2.650

Change From Baseline in Ferritin at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)

Change from Baseline was calculated as the visit value minus the Baseline value. Baseline ferritin was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. (NCT01381094)
Timeframe: Baseline, Week 2, Week 4, Week 6, Follow-up (up to Week 8)

,,,,
InterventionNanograms per milliliter (ng/mL) (Mean)
BaselineChange from Baseline to Week 2Change from Baseline to Week 4Change from Baseline to Week 6Change from Baseline to Follow-up Visit (up to Week 8)
AKB-6548 240 mg349.5-66.0-69.8-65.5-50.4
AKB-6548 370 mg245.8-41.7-48.7-59.4-37.7
AKB-6548 500 mg332.3-72.0-89.6-88.9-86.1
AKB-6548 630 mg240.2-58.9-80.6-86.6-27.4
Placebo200.8-12.9-20.5-19.6-20.2

Change From Baseline in Hematocrit (HCT) at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)

Change from Baseline was calculated as the visit value minus the Baseline value. Baseline HCT was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated HCT concentration increased. (NCT01381094)
Timeframe: Baseline, Week 1, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)

,,,,
InterventionPercentage of red blood cells in blood (Mean)
BaselineChange from Baseline to Week 1Change from Baseline to Week 2Change from Baseline to Week 4Change from Baseline to Week 6Change from Baseline to Follow-up Visit (up to Week 8)
AKB-6548 240 mg29.00.50.21.71.81.9
AKB-6548 370 mg29.60.20.10.62.10.7
AKB-6548 500 mg30.41.21.63.13.42.4
AKB-6548 630 mg29.61.61.53.44.32.8
Placebo29.80.20.30.1-0.40.0

Change From Baseline in Hepcidin at Week 6

Change from Baseline was calculated as the Week 6 value minus the Baseline value. Baseline hepcidin was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. (NCT01381094)
Timeframe: Baseline, Week 6

,,,,
Interventionng/mL (Mean)
BaselineChange from Baseline at Week 6
AKB-6548 240 mg326.35-28.64
AKB-6548 370 mg241.03-90.91
AKB-6548 500 mg242.51-85.01
AKB-6548 630 mg282.75-144.90
Placebo258.29-32.54

Change From Baseline in Hgb at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)

Change from Baseline was calculated as the visit value minus the Baseline value. Baseline Hgb was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated that hemoglobin concentration increased. (NCT01381094)
Timeframe: Baseline, Week 1, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)

,,,,
Interventiong/dL (Mean)
BaselineChange from Baseline to Week 1Change from Baseline to Week 2Change from Baseline to Week 4Change from Baseline to Week 6Change from Baseline to Follow-up Visit (up to Week 8)
AKB-6548 240 mg9.460.060.160.540.770.78
AKB-6548 370 mg9.93-0.120.000.360.730.40
AKB-6548 500 mg9.860.280.540.851.251.04
AKB-6548 630 mg9.670.290.531.061.431.01
Placebo9.830.040.140.08-0.030.06

Change From Baseline in Iron Saturation at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)

Change from Baseline was calculated as the visit value minus the Baseline value. Baseline iron saturation was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. (NCT01381094)
Timeframe: Baseline, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)

,,,,
InterventionPercentage of saturation (Mean)
BaselineChange from Baseline to Week 2Change from Baseline to Week 4Change from Baseline to Week 6Change from Baseline to Follow-up Visit (up to Week 8)
AKB-6548 240 mg30.4-1.5-1.9-0.3-4.1
AKB-6548 370 mg32.4-3.8-2.3-3.8-3.9
AKB-6548 500 mg31.41.4-3.7-2.30.5
AKB-6548 630 mg26.50.6-0.2-4.61.6
Placebo27.7-0.9-0.2-2.11.2

Change From Baseline in Red Blood Cell (RBC) Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)

Change from Baseline was calculated as the visit value minus the Baseline value. Baseline RBC count was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated RBC count increased. (NCT01381094)
Timeframe: Baseline, Week 1, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)

,,,,
Intervention10^6 cells/microliter (10^6 cells/μL) (Mean)
BaselineChange from Baseline to Week 1Change from Baseline to Week 2Change from Baseline to Week 4Change from Baseline to Week 6Change from Baseline to Follow-up Visit (up to Week 8)
AKB-6548 240 mg3.21-0.010.020.160.170.24
AKB-6548 370 mg3.38-0.07-0.050.010.180.06
AKB-6548 500 mg3.370.090.140.260.390.30
AKB-6548 630 mg3.250.040.110.270.410.26
Placebo3.34-0.020.030.02-0.020.01

Change From Baseline in Reticulocyte Hgb Content at Week 6

Change from Baseline was calculated as the Week 6 value minus the Baseline value. Baseline Reticulocyte count was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated reticulocyte Hgb content increased. (NCT01381094)
Timeframe: Baseline, Week 6

,,,,
InterventionPicogram (Mean)
BaselineChange From Baseline at Week 6
AKB-6548 240 mg31.020.37
AKB-6548 370 mg31.440.29
AKB-6548 500 mg30.260.06
AKB-6548 630 mg31.540.15
Placebo30.730.03

Change From Baseline in Total Iron at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)

Change from Baseline was calculated as the visit value minus the Baseline value. Baseline total iron was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. (NCT01381094)
Timeframe: Baseline, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)

,,,,
InterventionMicrograms per deciliter (µg/dL) (Mean)
BaselineChange from Baseline to Week 2Change from Baseline to Week 4Change from Baseline to Week 6Change from Baseline to Follow-up Visit (up to Week 8)
AKB-6548 240 mg66.0-1.8-1.53.6-7.4
AKB-6548 370 mg77.8-3.74.02.8-7.5
AKB-6548 500 mg76.110.9-1.63.70.9
AKB-6548 630 mg60.710.413.20.76.2
Placebo67.6-4.1-2.2-8.63.4

Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)

Change from Baseline was calculated as the visit value minus the Baseline value. Baseline TIBC was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. (NCT01381094)
Timeframe: Baseline, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)

,,,,
Interventionµg/dL (Mean)
BaselineChange from Baseline to Week 2Change from Baseline to Week 4Change from Baseline to Week 6Change from Baseline to Follow-up Visit (up to Week 8)
AKB-6548 240 mg219.49.212.918.87.8
AKB-6548 370 mg245.818.730.136.88.7
AKB-6548 500 mg249.228.129.933.00.2
AKB-6548 630 mg231.831.750.550.310.2
Placebo243.1-5.5-5.9-9.94.1

Change From Baseline in Unsaturated Iron Binding Capacity at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)

Change from Baseline was calculated as the visit value minus the Baseline value. Baseline Unsaturated Iron Binding Capacity was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. (NCT01381094)
Timeframe: Baseline, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)

,,,,
Interventionµg/dL (Mean)
BaselineChange from Baseline to Week 2Change from Baseline to Week 4Change from Baseline to Week 6Change from Baseline to Follow-up Visit (up to Week 8)
AKB-6548 240 mg153.410.914.415.315.1
AKB-6548 370 mg168.022.426.134.016.2
AKB-6548 500 mg173.117.231.529.3-0.7
AKB-6548 630 mg171.221.337.449.63.9
Placebo175.5-1.5-3.7-1.30.7

Maximum Change From Baseline in HCT

Change from Baseline was calculated as the maximum value minus the Baseline value. Baseline HCT was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated that HCT concentration increased. (NCT01381094)
Timeframe: Baseline; up to Week 8

,,,,
InterventionPercentage of red blood cells (Mean)
BaselineMaximum change from Baseline (up to Week 8)
AKB-6548 240 mg29.02.94
AKB-6548 370 mg29.62.56
AKB-6548 500 mg30.44.43
AKB-6548 630 mg29.64.84
Placebo29.81.89

Maximum Change From Baseline in Hgb

Change from Baseline was calculated as the maximum value minus the Baseline value. Baseline Hgb was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated that hemoglobin concentration increased. (NCT01381094)
Timeframe: Baseline; up to Week 8

,,,,
Interventiong/dL (Mean)
BaselineMaximum change from Baseline (up to Week 8)
AKB-6548 240 mg9.461.04
AKB-6548 370 mg9.930.82
AKB-6548 500 mg9.861.44
AKB-6548 630 mg9.671.54
Placebo9.830.59

Maximum Change From Baseline in RBC Count

Change from Baseline was calculated as the maximum value minus the Baseline value. Baseline RBC Count was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated that RBC count increased. (NCT01381094)
Timeframe: Baseline; up to Week 8

,,,,
Intervention10^6 cells/μL (Mean)
BaselineMaximum change from Baseline (up to Week 8)
AKB-6548 240 mg3.210.31
AKB-6548 370 mg3.380.22
AKB-6548 500 mg3.370.44
AKB-6548 630 mg3.250.44
Placebo3.340.18

Maximum Change in Absolute Reticulocyte Count From Baseline

Change from Baseline was calculated as the maximum value minus the Baseline value. Baseline absolute reticulocyte count was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. A positive change from Baseline indicated that reticulocyte count increased. (NCT01381094)
Timeframe: Baseline; up to Week 8

,,,,
Intervention10^6 cells/μL (Mean)
BaselineMaximum Change from Baseline (up to Week 8)
AKB-6548 240 mg0.07660.013
AKB-6548 370 mg0.05690.028
AKB-6548 500 mg0.08110.040
AKB-6548 630 mg0.06740.042
Placebo0.07000.011

Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval

A standard 12-lead ECG was performed following dosing in a supine position for approximately 10 minutes. ECGs were taken prior to blood draws when possible. The parameters evaluated from the participant ECG trace included PR interval, QT interval, QRS interval, and QTc (corrected). (NCT01381094)
Timeframe: Baseline, Week 6

,,,,
InterventionMilliseconds (Mean)
Baseline PR IntervalChange from Baseline PR IntervalBaseline QRS DurationChange from Baseline QRS DurationBaseline QT IntervalChange from Baseline QT IntervalBaseline QTC IntervalChange from Baseline QTC Interval
AKB-6548 240 mg156.7-0.894.94.1412.03.8424.95.1
AKB-6548 370 mg174.62.2113.82.0421.47.8436.33.6
AKB-6548 500 mg172.811.497.1-1.3419.0-1.6445.1-5.8
AKB-6548 630 mg187.8-11.794.51.4406.94.5427.6-1.6
Placebo175.8-0.494.6-1.6419.111.0435.63.3

Mean Plasma Vadadustat Acyl-Glucuronide Concentrations on Week 2 and Week 4

Plasma samples were collected for the analysis. (NCT01381094)
Timeframe: Week 2: Pre-dose; Week 4: Pre-dose

,,,
Interventionμg/mL (Mean)
Week 2 Pre-DoseWeek 4 Pre-Dose
AKB-6548 240 mg1848.41999.3
AKB-6548 370 mg2708.52687.5
AKB-6548 500 mg5900.16866.9
AKB-6548 630 mg6425.07960.8

Mean Plasma Vadadustat Concentrations on Week 2 and Week 4

Plasma samples were collected for the analysis. (NCT01381094)
Timeframe: Week 2: Pre-dose and post-dose; Week 4: Pre-dose

,,,
Interventionμg/mL (Mean)
Week 2 Pre-DoseWeek 2 Post-DoseWeek 4 Pre-Dose
AKB-6548 240 mg4358.2817036.824698.21
AKB-6548 370 mg6640.0421371.637884.56
AKB-6548 500 mg10791.7939892.0014274.80
AKB-6548 630 mg12443.1741656.1117700.17

Number of Participants Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

An adverse event (AE) was defined as any untoward medical occurrence (including a clinically significant abnormal laboratory finding) that occurred in the protocol-specified AE reporting period. A TEAE included medical conditions, signs, and symptoms not previously observed in the participant that emerged during the protocol-specified AE reporting period, including signs or symptoms associated with pre-existing underlying conditions that were not present prior to the AE reporting period. A SAE included AEs that met one or more of the following criteria/outcomes: death, life-threatening, in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, and congenital anomaly/birth defect. (NCT01381094)
Timeframe: Up to Week 8 (Follow-up Visit 2 weeks after last dose)

,,,,
InterventionParticipants (Count of Participants)
TEAEsSAEs
AKB-6548 240 mg92
AKB-6548 370 mg63
AKB-6548 500 mg81
AKB-6548 630 mg111
Placebo111

Number of Participants With Absolute Change From Baseline in Hgb ≥ 0.4, 0.6, 0.8, and 1.0 g/dL at the End of Dosing Period

Change from Baseline was calculated as the maximum value minus the Baseline value. Baseline Hgb was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. (NCT01381094)
Timeframe: Up to Week 6 (End of the Dosing Period)

,,,,
InterventionParticipants (Count of Participants)
Change from Baseline in Hgb ≥0.4 g/dLChange from Baseline in Hgb ≥0.6 g/dLChange from Baseline in Hgb ≥0.8 g/dLChange from Baseline in Hgb ≥1.0 g/dL
AKB-6548 240 mg3335
AKB-6548 370 mg2226
AKB-6548 500 mg20311
AKB-6548 630 mg11114
Placebo2002

Number of Participants With Change From Baseline in HCT ≥5.0, 7.5, and 10.0% by the End of Dosing Period

Change from Baseline was calculated as the maximum value minus the Baseline value. Baseline HCT was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. (NCT01381094)
Timeframe: Up to Week 6 (End of The Dosing Period)

,,,,
InterventionParticipants (Count of Participants)
% Change from Baseline in HCT ≥5%% Change from Baseline in HCT ≥7.5%% Change from Baseline in HCT ≥10.0%
AKB-6548 240 mg414
AKB-6548 370 mg306
AKB-6548 500 mg209
AKB-6548 630 mg0411
Placebo111

Number of Participants With Change From Baseline in Hgb ≥5.0, 7.5, and 10.0% by the End of Dosing Period

Change from Baseline was calculated as the maximum value minus the Baseline value. Baseline Hgb was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. (NCT01381094)
Timeframe: Up to Week 6 (End of The Dosing Period)

,,,,
InterventionParticipants (Count of Participants)
% Change from Baseline in Hgb ≥5%% Change from Baseline in Hgb ≥7.5%% Change from Baseline in Hgb ≥10.0%
AKB-6548 240 mg445
AKB-6548 370 mg335
AKB-6548 500 mg1311
AKB-6548 630 mg1114
Placebo202

Number of Participants With Change From Baseline in RBC Count ≥5.0, 7.5, and 10.0% by the End of Dosing Period

Change from Baseline was calculated as the maximum value minus the Baseline value. Baseline RBC Count was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. (NCT01381094)
Timeframe: Up to Week 6 (End of The Dosing Period)

,,,,
InterventionParticipants (Count of Participants)
% Change from Baseline in RBCs ≥5%% Change from Baseline in RBCs ≥7.5%% Change from Baseline in RBCs ≥10.0%
AKB-6548 240 mg422
AKB-6548 370 mg324
AKB-6548 500 mg238
AKB-6548 630 mg3111
Placebo101

Number of Participants With Change From Baseline in Reticulocyte Count ≥6000, 12000, and 18000 Cells/uL by the End of Dosing Period

Change from Baseline was calculated as the maximum value minus the Baseline value. Baseline reticulocytes count was defined as the average of the last two measurements obtained prior to dosing; if there was only one value prior to dosing, this value served as Baseline. (NCT01381094)
Timeframe: Up to Week 6 (End of The Dosing Period)

,,,,
InterventionParticipants (Count of Participants)
Change from Baseline in Reticulocytes ≥6000 cells/uLChange from Baseline in Reticulocytes ≥12000 cells/uLChange from Baseline in Reticulocytes ≥18000 cells/uL
AKB-6548 240 mg112
AKB-6548 370 mg135
AKB-6548 500 mg404
AKB-6548 630 mg235
Placebo312

Change From Baseline in Hgb at Week 4

Blood samples were collected from participants for measurement of Hgb values. The Baseline value was the latest pre-dose assessment. Change from Baseline at Week 4 was calculated by subtracting Baseline value from the post-dose visit value. The analysis was performed on All Treated Subjects Population which comprised of all participants who received at least one dose of GSK1278863. (NCT02829320)
Timeframe: Baseline and Week 4

InterventionG/dL (Mean)
All Participants0.79

Duration of Treatment Interruption Due to Hgb >13 g/dL

Hgb values were used for making decision of treatment interruption. On-therapy Hgb values observed in both scheduled and unscheduled visits were counted. Participants who have no treatment interruption due to Hgb >13.0 g/dL are not included (NCT02829320)
Timeframe: Up to Week 24

InterventionDays (Median)
All Participants84

Number of Episodes of Achieving Hgb Level of More Than 13.0 g/dL

Blood samples were collected from participants for measurement of Hgb values at indicated time points. Hgb was evaluated using Hgb analyzer. The number of episodes in participants who had Hgb level of more than 13.0 g/dL were summarized. On-therapy Hgb values observed in both scheduled and unscheduled visits were included. (NCT02829320)
Timeframe: Up to Week 24

InterventionEpisodes (Number)
All Participants7

Number of Participants Who Had Hgb Increase of More Than 2 g/dL Over Any 4 Weeks

Blood samples were collected from participants for measurement of Hgb values at indicated time points. Hgb was evaluated using Hgb analyzer. The number of participants who had Hgb increase of more than 2.0 g/dL over any 4 weeks were summarized. On-therapy Hgb values observed in both scheduled and unscheduled visits were included. (NCT02829320)
Timeframe: Up to Week 24

InterventionParticipants (Count of Participants)
All Participants1

Number of Participants Who Had Hgb Level of Less Than 7.5 g/dL

Blood samples were collected from participants for measurement of Hgb values at indicated time points. Hgb was evaluated using Hgb analyzer. The number of participants who had Hgb level of less than 7.5 g/dL were summarized. On-therapy Hgb values observed in both scheduled and unscheduled visits were included. (NCT02829320)
Timeframe: Up to Week 24

InterventionParticipants (Count of Participants)
All Participants0

Number of Participants Who Had Hgb Level of More Than 13.0 g/dL

Blood samples were collected from participants for measurement of Hgb values at indicated time points. Hgb was evaluated using Hgb analyzer. The number of participants who had Hgb level of more than 13.0 g/dL were summarized. On-therapy Hgb values observed in both scheduled and unscheduled visits were included. (NCT02829320)
Timeframe: Up to Week 24

InterventionParticipants (Count of Participants)
All Participants3

Time to Reach the Lower Target Hgb Level (10.0 g/dL)

Blood samples were collected from participants for measurement of Hgb values at indicated time points. Hgb was evaluated using Hgb analyzer. Participants who could not reach lower target were regarded as censored. The time (in days) to reach the lower target Hgb level (10.0 g/dL) was summarized using 25th percentile (P25), median, and 75th percentile (P75) by Kaplan-Meier method. (NCT02829320)
Timeframe: Up to Week 24

InterventionDays (Median)
All Participants57.0

Area Under the Concentration-time Curve (AUC) From Time Zero to 4 Hours (AUC [0-4]) of GSK1278863

Blood samples were collected to evaluate AUC (0-4) at 1, 2, 3 and 4 hours post dose at Weeks 12 and 24. Pharmacokinetic (PK) parameters were calculated by standard non-compartmental analysis. PK Population consisted of all participants who received GSK1278863 with the PK samples collected and analyzed. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). NA indiates data was not available. Geometric coefficient of variation could not be calculated when number of participant was equal to 1. (NCT02829320)
Timeframe: 1, 2, 3 and 4 hours post dose at Weeks 12 and 24

,,
InterventionHour*nanogram per milliliter (h*ng/mL) (Geometric Mean)
AUC (0-4), Week 24, n=1,8,8,5,2,1,1AUC (0-4), All, n=1,12,22,13,3,1,1
GSK1278863 1 mg43.310043.3100
GSK1278863 12 mg749.4583749.4583
GSK1278863 18 mg126.2883126.2883

Area Under the Concentration-time Curve (AUC) From Time Zero to 4 Hours (AUC [0-4]) of GSK1278863

Blood samples were collected to evaluate AUC (0-4) at 1, 2, 3 and 4 hours post dose at Weeks 12 and 24. Pharmacokinetic (PK) parameters were calculated by standard non-compartmental analysis. PK Population consisted of all participants who received GSK1278863 with the PK samples collected and analyzed. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). NA indiates data was not available. Geometric coefficient of variation could not be calculated when number of participant was equal to 1. (NCT02829320)
Timeframe: 1, 2, 3 and 4 hours post dose at Weeks 12 and 24

,,,
InterventionHour*nanogram per milliliter (h*ng/mL) (Geometric Mean)
AUC (0-4), Week 12, n=0,4,14,8,1,0,0AUC (0-4), Week 24, n=1,8,8,5,2,1,1AUC (0-4), All, n=1,12,22,13,3,1,1
GSK1278863 2 mg25.722833.894130.9164
GSK1278863 4 mg95.131986.370291.8474
GSK1278863 6 mg200.6036133.3020171.4229
GSK1278863 8 mg233.3933437.0983354.6083

Change From Baseline in Ferritin

Blood samples were collected from participants for measurement of serum ferritin at indicated time points. The Baseline value was the latest pre-dose assessment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. (NCT02829320)
Timeframe: Baseline and up to Week 24

InterventionMicrogram per liter (µg/L) (Mean)
Week 4Week 12Week 24
All Participants-80.11-126.29-107.03

Change From Baseline in Hgb at the Indicated Time Points

Blood samples were collected from participants for measurement of Hgb values at indicated time points. Hgb was evaluated using Hgb analyzer. The Baseline value was the latest pre-dose assessment. Change from Baseline at indicated time-points was calculated by subtracting Baseline value from the post-dose visit value. (NCT02829320)
Timeframe: Baseline and up to Week 24

InterventionG/dL (Mean)
Week 4Week 8Week 12Week 16Week 20Week 24
All Participants0.791.661.982.282.242.01

Change From Baseline in Serum Iron

Blood samples were collected from participants for measurement of serum iron at indicated time points. The Baseline value was the latest pre-dose assessment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. (NCT02829320)
Timeframe: Baseline and up to Week 24

InterventionMicromoles per liter (µmol/L) (Mean)
Week 4Week 12Week 24
All Participants-0.81232.09161.4584

Change From Baseline in Total Iron Binding Capacity (TIBC)

Blood samples were collected from participants for measurement of TIBC at indicated time points. The Baseline value was the latest pre-dose assessment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. (NCT02829320)
Timeframe: Baseline and up to Week 24

Interventionumol/L (Mean)
Week 4Week 12Week 24
All Participants8.590410.86119.3388

Dose Level of GSK1278863 at Indicated Time Points

Dose adjustment algorithm was used which was based on Hgb values at scheduled visits. Hgb values measured at unscheduled visits were not included. Mean dose during Week 12 to 24 is the average of dose at Weeks 12, 16, and 20. (NCT02829320)
Timeframe: Up to Week 24

Interventionmg (Median)
Day 1Week 4Week 8Week 12Week 16Week 20Week 12 to 24
All Participants4.04.04.04.04.04.04.00

Hgb Values at the Indicated Time Points

Blood samples were collected from participants for measurement of Hgb values at indicated time points. Hgb was evaluated using Hgb analyzer. (NCT02829320)
Timeframe: Up to Week 24

InterventionG/dL (Mean)
Day 1Week 4Week 8Week 12Week 16Week 20Week 24
All Participants9.109.9010.7611.0911.3811.3411.12

Maximum Observed Concentration (Cmax) of GSK1278863

Blood samples were collected to evaluate Cmax at 1, 2, 3 and 4 hours post dose at Weeks 12 and 24. PK parameters were calculated by standard non-compartmental analysis. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). NA indiates data was not available. Geometric coefficient of variation could not be calculated when number of participant was equal to 1. (NCT02829320)
Timeframe: 1, 2, 3 and 4 hours post dose at Weeks 12 and 24

,,
Interventionng/mL (Geometric Mean)
Cmax, Week 24, n=1,8,8,5,2,1,1Cmax, All, n=1,12,22,13,3,1,1
GSK1278863 1 mg27.500027.5000
GSK1278863 12 mg311.0000311.0000
GSK1278863 18 mg93.400093.4000

Maximum Observed Concentration (Cmax) of GSK1278863

Blood samples were collected to evaluate Cmax at 1, 2, 3 and 4 hours post dose at Weeks 12 and 24. PK parameters were calculated by standard non-compartmental analysis. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). NA indiates data was not available. Geometric coefficient of variation could not be calculated when number of participant was equal to 1. (NCT02829320)
Timeframe: 1, 2, 3 and 4 hours post dose at Weeks 12 and 24

,,,
Interventionng/mL (Geometric Mean)
Cmax, Week 12, n=0,4,14,8,1,0,0Cmax, Week 24, n=1,8,8,5,2,1,1Cmax, All, n=1,12,22,13,3,1,1
GSK1278863 2 mg13.957818.344816.7474
GSK1278863 4 mg57.657244.885352.6391
GSK1278863 6 mg122.9883100.2261113.6784
GSK1278863 8 mg179.0000202.9384194.6229

Monthly Average Dose of Intravenous (IV) Iron During the Treatment Period

Records of on-therapy iron medication were used to calculate average quarterly IV iron dose. Quarter 1 = (Randomization Date - Treatment Start Date at Week 12 - 1 [day]). Quarter 2 = (Treatment Start Date at Week 12 - Study Treatment Stop Date). Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). (NCT02829320)
Timeframe: Up to Week 24

InterventionMg (Mean)
Quarter 1; n= 3Quarter 2; n= 4
All Participants231.61217.19

Number of Participants by Hgb Change From Baseline Category at Week 4

Blood samples were collected from participants for measurement of Hgb values. The Baseline value was the latest pre-dose assessment. Change from Baseline at Week 4 was calculated by subtracting Baseline value from the post-dose visit value. The change in Hgb at Week 4 was classified into different categories (i.e., <=-2.0, >-2.0 to -1.0, >-1.0 to 0, >0 to 1.0, >1.0 to 2.0, and >2 g/dL), and the number of participants in each category were summarized. (NCT02829320)
Timeframe: Baseline and Week 4

InterventionParticipants (Count of Participants)
<= -2.0> -2.0 to -1.0> -1.0 to 0> 0 to 1.0> 1.0 to 2.0> 2.0
All Participants00413110

Number of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL)

Blood samples were collected from participants for measurement of Hgb values at indicated time points. Hgb was evaluated using Hgb analyzer. The number of participants with Hgb withinthe target range (10.0 to 12.0 g/dL) at each assessment visit was summarized. (NCT02829320)
Timeframe: Up to Week 24

InterventionParticipants (Count of Participants)
Day 1, within rangeWeek 4, within rangeWeek 8, within rangeWeek 12, within rangeWeek 16, within rangeWeek 20, within rangeWeek 24, within range
All Participants3132018172023

Number of Participants Who Used Iron During the Treatment Period

The number of participants who used iron (both IV and oral iron) during the treatment period were summarized. (NCT02829320)
Timeframe: Up to Week 24

InterventionParticipants (Count of Participants)
Oral ironIntravenous ironAny iron medication
All Participants9412

Number of Participants With Frequency of Dose Adjustments

Dose adjustment algorithm was used which was based on Hgb values at scheduled visits. Hgb values measured at unscheduled visits were not included. For dose adjustments frequency, the number of participants were provided by the number of dose adjustments (i.e. zero, one, two, three, four, and five or more). (NCT02829320)
Timeframe: Up to Week 24

InterventionParticipants (Count of Participants)
Any dose adjustmentsNumber of dose adjustments=0Number of dose adjustments=1Number of dose adjustments=2Number of dose adjustments=3Number of dose adjustments=4Number of dose adjustments=5 or more
All Participants21797410

Percent Change From Baseline in Hepcidin

Blood samples were collected from participants for measurement of hepcidin at indicated time points. The Baseline value was the latest pre-dose assessment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Percent change from Baseline was calculated as 100*(exponential [mean change on log scale]-1). If a laboratory value had a non-detectable level reported in the database, where the numeric value was missing, the value was not included in a summary. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). (NCT02829320)
Timeframe: Baseline and up to Week 24

InterventionPercentage of hepcidin (Geometric Mean)
Week 4, n=26Week 12, n=22Week 24, n=21
All Participants-64.78-61.74-55.67

Percent Change From Baseline in TSAT

Blood samples were collected from participants for measurement of TSAT at indicated time points. The Baseline value was the latest pre-dose assessment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Percent change from Baseline was calculated as 100*(exponential [mean change on log scale]-1). (NCT02829320)
Timeframe: Baseline and up to Week 24

InterventionPercentage of transferrin (Geometric Mean)
Week 4Week 12Week 24
All Participants-23.06-15.31-10.07

Change From Baseline in Plasma Erythropoietin in Part 1 Participants at Day 26 or Day 29

Baseline is defined as the last value obtained prior to the first dose. (NCT00761657)
Timeframe: Baseline (Day 1), 1, 2, 3, 4, 6, 8, 12, 18, 24, 48, and 72 hours on Day 26 (TIW Dosing) or Day 29 (BIW Dosing)

Interventionmilli-international units (mIU)/mL (Mean)
Day 1, Baseline
Roxadustat 2.0 mg/kg BIW9.00

Change From Baseline in Plasma Erythropoietin in Part 1 Participants at Day 26 or Day 29

Baseline is defined as the last value obtained prior to the first dose. (NCT00761657)
Timeframe: Baseline (Day 1), 1, 2, 3, 4, 6, 8, 12, 18, 24, 48, and 72 hours on Day 26 (TIW Dosing) or Day 29 (BIW Dosing)

,
Interventionmilli-international units (mIU)/mL (Mean)
Day 1, BaselineChange at Day 26, 1 HourChange at Day 26, 2 HourChange at Day 26, 3 HourChange at Day 26, 4 HourChange at Day 26, 6 HourChange at Day 26, 8 HourChange at Day 26, 12 HourChange at Day 26, 18 HourChange at Day 26, 24 HourChange at Day 26, 48 HourChange at Day 26, 72 Hour
Roxadustat 1.0 mg/kg TIW13.30-1.50-0.85-0.95-0.458.0557.9581.8037.3022.350.55-2.85
Roxadustat 2.0 mg/kg TIW8.500.00-0.602.3029.70132.80462.00492.00176.9033.90-0.50-1.50

Change From Baseline in Plasma Erythropoietin in Part 1 Participants at Day 26 or Day 29

Baseline is defined as the last value obtained prior to the first dose. (NCT00761657)
Timeframe: Baseline (Day 1), 1, 2, 3, 4, 6, 8, 12, 18, 24, 48, and 72 hours on Day 26 (TIW Dosing) or Day 29 (BIW Dosing)

Interventionmilli-international units (mIU)/mL (Mean)
Day 1, BaselineChange at Day 29, 1 HourChange at Day 29, 2 HourChange at Day 29, 3 HourChange at Day 29, 4 HourChange at Day 29, 6 HourChange at Day 29, 8 HourChange at Day 29, 12 HourChange at Day 29, 18 HourChange at Day 29, 24 HourChange at Day 29, 48 HourChange at Day 29, 72 Hour
Roxadustat 1.0 mg/kg BIW13.46-1.08-1.27-0.5512.0366.85135.0877.3543.8010.18-5.17-2.93

Change From Baseline in Plasma Erythropoietin in Part 1 Participants at Day 26 or Day 29

Baseline is defined as the last value obtained prior to the first dose. (NCT00761657)
Timeframe: Baseline (Day 1), 1, 2, 3, 4, 6, 8, 12, 18, 24, 48, and 72 hours on Day 26 (TIW Dosing) or Day 29 (BIW Dosing)

Interventionmilli-international units (mIU)/mL (Mean)
Day 1, BaselineChange at Day 26, 1 HourChange at Day 26, 2 HourChange at Day 26, 3 HourChange at Day 26, 4 HourChange at Day 26, 6 HourChange at Day 26, 8 HourChange at Day 26, 12 HourChange at Day 26, 18 HourChange at Day 26, 24 HourChange at Day 26, 48 HourChange at Day 26, 72 HourChange at Day 29, 1 HourChange at Day 29, 2 HourChange at Day 29, 3 HourChange at Day 29, 4 HourChange at Day 29, 6 HourChange at Day 29, 8 HourChange at Day 29, 12 HourChange at Day 29, 18 HourChange at Day 29, 24 HourChange at Day 29, 48 HourChange at Day 29, 72 Hour
Placebo13.750.170.67-1.270.500.330.20-1.300.872.60-7.50-0.60-1.57-2.73-3.70-4.90-4.17-2.97-2.07-0.20-3.07-4.87-1.63

Change From Baseline in Plasma Erythropoietin in Part 2 Participants at 4, 8, 12, and 24 Hours on Day 1

Baseline is defined as the last value obtained prior to the first dose. (NCT00761657)
Timeframe: Baseline, 4, 8, 12, and 24 hours on Day 1

,,
InterventionmIU/mL (Mean)
BaselineChange at 4 HourChange at 8 HourChange at 12 HourChange at 24 Hour
Roxadustat 0.7 mg/kg TIW8.302.8066.7066.2510.05
Roxadustat 1.5 mg/kg BIW9.552.10100.40147.15107.65
Roxadustat 2.0 mg/kg BIW10.451.0042.05201.10461.05

Co-Primary Efficacy Outcome Measure: Change From Baseline in Hb at Day 26-29 (End of Treatment)

Mean Hb change from baseline was analyzed by treatment group and study visit. Baseline was defined as the mean of last 3 available values prior to the first dose. (NCT00761657)
Timeframe: Baseline, End of Treatment (EoT) (Day 26 for TIW Dosing or Day 29 for BIW Dosing)

,,,,,,,,
Interventiong/dL (Mean)
BaselineChange at Day 26-29
Placebo10.10-0.05
Roxadustat 0.7 mg/kg BIW10.320.25
Roxadustat 0.7 mg/kg TIW10.030.60
Roxadustat 1.0 mg/kg BIW9.180.44
Roxadustat 1.0 mg/kg TIW10.350.21
Roxadustat 1.5 mg/kg BIW10.281.22
Roxadustat 1.5 mg/kg TIW10.081.65
Roxadustat 2.0 mg/kg BIW9.971.35
Roxadustat 2.0 mg/kg TIW9.931.75

Co-Primary Efficacy Outcome Measure: Change From Baseline in Hb at Week 8 (2 Weeks of Follow Up)

Mean Hb change from baseline was analyzed by treatment group and study visit. Baseline is defined as the mean of last 3 available values prior to the first dose. (NCT00761657)
Timeframe: Baseline, Week 8 (2 Weeks of Follow Up)

,,,,,,,,
Interventiong/dL (Mean)
BaselineChange at Week 8
Placebo10.100.04
Roxadustat 0.7 mg/kg BIW10.320.59
Roxadustat 0.7 mg/kg TIW10.030.24
Roxadustat 1.0 mg/kg BIW9.180.50
Roxadustat 1.0 mg/kg TIW10.350.05
Roxadustat 1.5 mg/kg BIW10.280.79
Roxadustat 1.5 mg/kg TIW10.081.31
Roxadustat 2.0 mg/kg BIW9.971.21
Roxadustat 2.0 mg/kg TIW9.931.52

Number of Participants With a Hemoglobin Response (Not Due to a RBC Transfusion or IV Iron Supplementation During Treatment)

Hb response defined as an increase in Hb from baseline by ≥1.0 g/dL (not due to red blood cell transfusion or IV iron supplementation during treatment). The baseline for Hb was defined as the mean of the last 3 available Hb values obtained prior to the first dose. (NCT00761657)
Timeframe: Baseline up to Day 26-29 (EoT), up to Week 8 (2 weeks of follow up), and up to Week 16 (EoS, 4 weeks of follow up)

,,,,,,,,
InterventionParticipants (Count of Participants)
Day 26-29Week 8Week 16
Placebo368
Roxadustat 0.7 mg/kg BIW157
Roxadustat 0.7 mg/kg TIW677
Roxadustat 1.0 mg/kg BIW133
Roxadustat 1.0 mg/kg TIW122
Roxadustat 1.5 mg/kg BIW889
Roxadustat 1.5 mg/kg TIW101010
Roxadustat 2.0 mg/kg BIW799
Roxadustat 2.0 mg/kg TIW91111

Plasma Roxadustat Concentration (Part 2)

(NCT00761657)
Timeframe: Predose on Days 3 (TIW dose groups) or 4 (BIW dose groups), 8, 15, 22, and 26 (TIW dose groups) or 29 (BIW dose groups)

,,
Interventionnanograms (ng)/milliliter (mL) (Mean)
Day 3Day 8Day 15Day 22Day 26
Roxadustat 0.7 mg/kg TIW394.800203.535195.483153.903331.640
Roxadustat 1.5 mg/kg TIW260.027168.955247.945163.100223.140
Roxadustat 2.0 mg/kg TIW422.700297.500175.570239.600508.889

Plasma Roxadustat Concentration (Part 2)

(NCT00761657)
Timeframe: Predose on Days 3 (TIW dose groups) or 4 (BIW dose groups), 8, 15, 22, and 26 (TIW dose groups) or 29 (BIW dose groups)

,,
Interventionnanograms (ng)/milliliter (mL) (Mean)
Day 4Day 8Day 15Day 22Day 29
Roxadustat 0.7 mg/kg BIW28.59619.88422.99736.43214.332
Roxadustat 2.0 mg/kg BIW283.067291.856358.400171.833193.622
Roxadustat 1.5 mg/kg BIW168.310125.185134.116147.323150.599

Primary Safety Outcome Measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Severe TEAEs, Drug-Related TEAEs, and TEAEs Leading to Treatment Discontinuation (Parts 1 and 2 Combined)

An adverse event (AE) was any untoward medical event in a participant who received study drug whether or not the event is considered drug related. TEAEs defined as an AE beginning after first dose of study drug until 28 days after last dose of study drug or existing AEs that worsened after first dose of study drug until the participant's last study visit. Severe AEs defined as incapacitating, inability to perform usual activities. Drug-related TEAEs defined as TEAEs with possible, probable, or definite relationship to study drug. Serious AE criteria included death, life-threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed here. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. (NCT00761657)
Timeframe: Baseline up to Week 16 (End of Study (EoS])

,,,,,,,,
InterventionParticipants (Count of Participants)
Any TEAEsSerious TEAEsSevere TEAEsDrug-Related TEAEsTEAEs Leading to Treatment Discontinuation
Placebo131131
Roxadustat 0.7 mg/kg BIW30010
Roxadustat 0.7 mg/kg TIW94320
Roxadustat 1.0 mg/kg BIW70120
Roxadustat 1.0 mg/kg TIW50011
Roxadustat 1.5 mg/kg BIW90030
Roxadustat 1.5 mg/kg TIW70130
Roxadustat 2.0 mg/kg BIW70131
Roxadustat 2.0 mg/kg TIW50010

Change From Baseline (Pre-dose on Day 1) for Total Iron Over 4 Weeks

Evaluation of change from Baseline for total iron was performed over 4 weeks. Change from Baseline is the value at indicated time point minus the Baseline value. Baseline was recorded pre-dose on Day 1. Adjusted mean was presented as LS mean. (NCT01587924)
Timeframe: Baseline (pre-dose on Day 1) and at Week 4

InterventionMicromoles per Liter (Least Squares Mean)
0.5 mg GSK12788634.3
2 mg GSK12788636.2
5 mg GSK12788632.5
rhEPO0.3

Change From Baseline (Pre-dose on Day 1) for Transferrin Saturation Over 4 Weeks

Transferrin saturation is a medical laboratory test and is the ratio of serum iron and total iron-binding capacity, multiplied by 100 and expressed as a ratio. Evaluation of change from baseline for transferrin saturation was performed up to 4 weeks. Change from Baseline is the value at indicated time point minus the Baseline value. Baseline value was recorded pre-dose on Day 1. Model adjusted mean values are presented as LS mean values. (NCT01587924)
Timeframe: Baseline (pre-dose on Day 1) and Week 4

InterventionRatio (Least Squares Mean)
0.5 mg GSK12788636.4
2 mg GSK127886311.7
5 mg GSK12788631.3
rhEPO-0.1

Change From Baseline (Pre-dose on Day 1) in Total Iron Binding Capacity Over 4 Weeks

Evaluation of change from Baseline in total iron binding capacity was performed over 4 weeks. Baseline was recorded pre-dose on Day 1. Change from Baseline is the value at indicated time point minus the Baseline value. Adjusted means are presented as LS means. (NCT01587924)
Timeframe: Baseline (pre-dose on Day 1) and Week 4

InterventionMicromoles per Liter (Least Squares Mean)
0.5 mg GSK12788633.2
2 mg GSK12788633.7
5 mg GSK12788635.2
rhEPO1.3

Change From Baseline for Erythropoeitin (EPO) Over Period

Evaluation of change from Baseline (pre-dose on Day 1) for EPO was analyzed over 4 weeks. Change from Baseline is the value at indicated time point minus the Baseline value. Baseline was the pre-dose Day 1 value. Adjusted means are presented as LS means. (NCT01587924)
Timeframe: Baseline (pre-dose on Day 1) and up to 4 weeks

InterventionUnits per liter (U/L) (Least Squares Mean)
0.5 mg GSK12788634.368
2 mg GSK12788633.263
5 mg GSK1278863181.948
rhEPO393.159

Evaluation of Change From Baseline (Pre-dose on Day 1) for Peak Vascular Endothelial Growth Factor (VEGF) Over 4 Weeks

Evaluation of change from Baseline for peak VEGF was analyzed up to 4 weeks. Baseline assessment was performed pre-dose on Day 1. Change from Baseline is the value at indicated time point minus the Baseline value. Absolute mean change and peak change from Baseline in peak VGEF were also calculated; however, only model adjusted peak change in peak VGEF from Baseline has been presented as LS means. (NCT01587924)
Timeframe: Baseline (pre-dose on Day 1) and up to 4 weeks

InterventionNanograms per liter (ng/L) (Least Squares Mean)
0.5 mg GSK127886323.21
2 mg GSK127886321.52
5 mg GSK127886353.85
rhEPO20.59

Evaluation of Change From Baseline (Pre-dose on Day 1) for Transferrin Over 4 Weeks

Evaluation of change from Baseline for ferritin was performed over 4 weeks. Change from Baseline is the value at indicated time point minus the Baseline value. Model adjusted mean has been presented as LS mean. (NCT01587924)
Timeframe: Baseline (pre-dose on Day 1) and Week 4

InterventionGrams per liter (Least Squares Mean)
0.5 mg GSK12788630.105
2 mg GSK12788630.155
5 mg GSK12788630.221
rhEPO0.059

Evaluation of Change From Baseline (Pre-dose on Day 1) in Ferritin Over 4 Weeks

Change from Baseline (pre-dose on Day 1) in ferritin over 4 weeks was analyzed. Change from Baseline is the value at indicated time point minus the Baseline value. Model adjusted mean has been presented as LS mean. (NCT01587924)
Timeframe: Baseline (pre-dose on Day 1) and Week 4

InterventionMicrograms per liter (Least Squares Mean)
0.5 mg GSK127886376.7
2 mg GSK1278863-1.6
5 mg GSK1278863-76.7
rhEPO-38.0

Evaluation of Change From Baseline (Pre-dose on Day 1) in High Sensitivity C-Reactive Protein (hsCRP) Over 4 Weeks

Evaluation of change from Baseline for hsCRP was analyzed over 4 weeks. Change from Baseline is the value at indicated time point minus the Baseline value. Baseline was the last pre-dose value. Peak change from Baseline also was calculated; however adjusted mean change from Baseline has been presented here as LS means. (NCT01587924)
Timeframe: Baseline (pre-dose on Day 1) and up to 4 weeks

InterventionMilligrams per liter (mg/L) (Least Squares Mean)
0.5 mg GSK1278863-0.40
2 mg GSK1278863-4.76
5 mg GSK1278863-1.48
rhEPO-2.92

Evaluation of Change From Baseline in Hepcidin Over Period

Evaluation of change from baseline for hepcidin was performed over 4 weeks. Change from Baseline is the value at indicated time point minus the Baseline value. Baseline was the last pre-dose value. Adjusted mean change from Baseline is presented as Least square (LS) mean. (NCT01587924)
Timeframe: Baseline (pre-dose on Day 1) and up to 4 weeks

InterventionMicrograms per liter (mcg/L) (Least Squares Mean)
0.5 mg GSK1278863204.88
2 mg GSK1278863150.29
5 mg GSK127886316.42
rhEPO-45.47

Hgb Variability Over 4 Weeks

Within participant standard deviation for Hgb acts as a measure of Hgb variability. Hgb of participants was recorded over 4 weeks. (NCT01587924)
Timeframe: Up to 4 weeks

Interventiong/dL (Mean)
0.5 mg GSK12788630.53
2 mg GSK12788630.55
5 mg GSK12788630.40
rhEPO0.35

Modeled Hemoglobin (Hgb) Change From Baseline (Pre-dose on Day 1) at 4 Weeks of Treatment

Modeled Hgb change from Baseline over 4 weeks of treatment. Change from Baseline is the actual value of Hgb at Week 4 minus the Baseline value. For modeled change at Week 4 participants required a Baseline and two or more non missing post-baseline values. Baseline is the average of Week -2, -1 and Day 1 values. The model included fixed effects for Baseline Hgb, treatment, and treatment by day interaction. Covariate analysis for modeled Hgb change was performed. Random effects were fitted in the intercept and the slope over time. (NCT01587924)
Timeframe: Baseline (pre-dose on Day 1) and up to week 4

InterventionGrams per deciliter (g/dL) (Mean)
0.5 mg GSK1278863-1.130
2 mg GSK1278863-1.070
5 mg GSK12788630.212
rhEPO-0.273

Number of Participants Discontinuing the Study Treatment Due to AEs

Discontinuation of the study drug could be due to safety-related reasons AE. The AEs responsible included anemia, gastrointestinal hemorrhage, and nausea. (NCT01587924)
Timeframe: Up to 4 weeks

InterventionParticipants (Count of Participants)
0.5 mg GSK12788631
2 mg GSK12788632
5 mg GSK12788630
rhEPO0

Number of Participants With Abnormal Hematology and Clinical Chemistry Parameters of Potential Clinical Concern (PCI)

Participants were analyzed up to 6 weeks for hematological and clinical chemistry parameters of PCI whether they had any higher or lower values than the reference range post screening. Normal alkaline phosphatase (ALP) was 0-46 U/L, aspartate amino transferase (AST) 0-42 U/L, ALP 20-125 U/L, total bilirubin 0-1.3 mg/dL, troponin 0-0.1ng/mL, Hgb 12 - 16 g/dL, platelets 140-450 G/L, creatine phosphokinase 29-168 U/L, creatinine 0.57 - 1.25 mg/dL, Potassium 3.6-5.0 mmol/L, hematocrit 38-45%; however, no participants with abnormal hematology and clinical chemistry parameters were recorded. (NCT01587924)
Timeframe: Up to 6 weeks (including follow-up)

InterventionParticipants (Count of Participants)
0.5 mg GSK12788630
2 mg GSK12788630
5 mg GSK12788630
rhEPO0

Residual Standard Deviation in Hgb (From the Linear Regression)

Residual standard deviation was derived by linear regression. Hgb of participants was recorded over 4 weeks (NCT01587924)
Timeframe: Up to 4 weeks

Interventiong/L (Mean)
0.5 mg GSK12788630.24
2 mg GSK12788630.26
5 mg GSK12788630.26
rhEPO0.20

Change From Baseline (Pre-dose on Day 1) for Red Blood Cells (RBCs) Over 4 Weeks

Change from Baseline in RBCs was a pharmacodynamic (PD) biomarker. Change from Baseline is the value at indicated time point minus the Baseline value. Baseline was recorded pre-dose on Day 1. Change from Baseline (pre-dose on Day 1) in RBCs was calculated over 4 weeks. (NCT01587924)
Timeframe: Baseline (pre-dose on Day 1) and up to 4 weeks

,,,
Intervention10^12 cells per Liter (Giga cells per L) (Mean)
Week 1Week 2Week 3Week 4
0.5 mg GSK1278863-0.04-0.13-0.22-0.29
2 mg GSK1278863-0.03-0.14-0.19-0.25
5 mg GSK1278863-0.06-0.05-0.05-0.03
rhEPO0.020.180.01-0.03

Change From Baseline (Pre-dose on Day 1) for Reticulocytes Over 4 Weeks

Evaluation of change from Baseline for reticulocytes was a PD parameter. Change from Baseline is the value at indicated time point minus the Baseline value. Baseline value was recorded pre-dose on Day 1. (NCT01587924)
Timeframe: Baseline (pre-dose on Day 1) and up to 4 weeks

,,,
InterventionPercentage change (Mean)
Week 1Week 2Week 3Week 4
0.5 mg GSK1278863-0.42-0.45-0.34-0.36
2 mg GSK1278863-0.56-0.49-0.27-0.26
5 mg GSK12788630.03-0.08-0.06-0.03
rhEPO-0.08-0.14-0.35-0.29

Evaluation of Change From Baseline (Pre-dose on Day 1) for Hematocrit Over 4 Weeks

Evaluation of change from Baseline for hematocrit over 4 weeks was performed. Change from Baseline is the value at indicated time point minus the Baseline value. (NCT01587924)
Timeframe: Baseline (pre-dose on Day 1) and up to 4 weeks

,,,
InterventionPercentage (Mean)
Week 1Week 2Week 3Week 4
0.5 mg GSK1278863-0.59-1.33-2.32-3.22
2 mg GSK1278863-0.16-1.56-2.22-2.63
5 mg GSK1278863-0.75-0.75-0.65-0.33
rhEPO0.202.020.24-0.22

Mean Plasma Concentration of GSK1278863 and GSK1278863 Metabolites Over 4 Weeks

Each of the plasma concentration-time plot contained one plot on the untransformed scale (i.e. a linear plot) and one plot on the log transformed scale (i.e. log-linear plot). Plasma concentrations were analyzed for the study drug (GSK1278863), and its metabolites namely GSK2391220 (M2), GSK2531403 (M3), GSK2487818A (M4), GSK2506102A (M5), GSK2531398 (M6), and GSK2531401A (M13). Pharmacokinetic analysis was done on Weeks (W) 2 and 4 at a fixed timely interval of 5 hours (h) on W2 and every hour on W4. Only the data for last visit for W2 and last visit of W4 has been presented. (NCT01587924)
Timeframe: Up to 4 weeks

,,
InterventionNanograms per milliliter (ng/mL) (Mean)
GSK1278863, Week 2, 7-11hGSK1278863, Week 4, 3hM2, Week 2, 7-11hM2, Week 4, 3hM3, Week 2, 7-11hM3, Week 4, 3hM4, Week 2, 7-11hM4, Week 4, 3hM5, Week 2, 7-11hM5, Week 4, 3hM6, Week 2, 7-11hM6, Week 4, 3hM13, Week 2, 7-11hM13, Week 4, 3h
0.5 mg GSK12788630.22923.31130.45820.67800.63860.79210.21560.60160.15460.19950.17760.32350.48750.4651
2 mg GSK12788633.314817.90091.54682.03822.11882.28570.81211.83550.55110.71320.69561.06261.40141.3623
5 mg GSK12788635.617034.72534.31657.42885.69358.45822.32166.18561.45811.99721.89573.45693.96475.3494

Number of Days Spent Within Hgb Range ( ±0.5 g/dL and ±1 g/dL ) From Baseline Hgb

Time spent with Hgb within range (where range was defined as +-0.5 g/dL and +-1 g/dL from baseline Hgb ) was analyzed. Baseline value of Hgb was recorded pre-dose on Day 1. (NCT01587924)
Timeframe: Baseline (pre-dose on Day 1) and up to 4 weeks

,,,
InterventionDays (Median)
Within +/- 0.5 g/dLWithin +/- 1 g/dL
0.5 mg GSK127886312.8227.71
2 mg GSK127886314.3420.79
5 mg GSK127886324.4128.00
rhEPO21.1528.00

Number of Participants Reaching Hgb Stopping Criteria

Participants were analyzed whether they had any increase or decrease from the Baseline Hgb. Hgb increase based stopping criteria included analysis of Increase or decrease of more than or equal to (>=) 2 g/dL from the Baseline (pre-dose on Day 1) was recorded and also the participants with hemoglobin >=13 g/dL were recorded. (NCT01587924)
Timeframe: Up to 4 weeks

,,,
InterventionParticipants (Count of Participants)
Post Baseline Hgb <8.0>=2g/dL Hgb increase post BaselinePost Baseline Hgb >=13.0
0.5 mg GSK1278863100
2 mg GSK1278863110
5 mg GSK1278863011
rhEPO000

Number of Participants With Abnormal Vital Signs of PCI

Vital signs include systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR). Three measurements of SBP, DBP and HR were recorded from the participant in a supine position for at least 5 minutes (allowing enough time between measurement to completely deflate and loosen the inflatable cuff). Data has been presented for vital signs with values high and low from the reference range. (NCT01587924)
Timeframe: Up to 6 weeks

,,,
InterventionParticipants (Count of Participants)
DBP, lowDBP, highSBP, lowSBP, highHR, lowHR, high
0.5 mg GSK12788631201000
2 mg GSK1278863221900
5 mg GSK1278863200603
rhEPO3211002

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

An AE is an unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain time period after the study has ended. This change may or may not be caused by the intervention being studied. An SAE is an adverse event that results in death, is life-threatening, requires inpatient hospitalization or extends a current hospital stay, results in an ongoing or significant incapacity or interferes substantially with normal life functions, or causes a congenital anomaly or birth defect. Medical events that do not result in death, are not life-threatening, or do not require hospitalization may be considered serious adverse events if they put the participant in danger or require medical or surgical intervention to prevent one of the results listed above. Only on-treatment data has been presented. (NCT01587924)
Timeframe: Up to 4 weeks

,,,
InterventionParticipants (Count of Participants)
Any AEAny SAE
0.5 mg GSK127886390
2 mg GSK127886372
5 mg GSK127886310
rhEPO62

Number of Participants With Electrocardiogram (ECG) Findings Over Period

Participants were analyzed for any abnormality in ECG and was categorized as abnormal clinically significant and abnormal and clinically insignificant. The parameters that were analyzed for ECG were atrial fibrillation, Atrial premature complex, Bigeminy, First degree AV block (PR interval > 200 msec), Incomplete right bundle branch block, Junctional rhythm, Junctional tachycardia (heart rate >100 beats/min), Left anterior hemi block (synonymous to left anterior fascicular block), Left atrial abnormality, Left axis deviation (QRS axis more negative than -30 degrees), Left bundle branch block, Left ventricular hypertrophy, Myocardial infarction, anterior, Myocardial infarction, inferior, Non-specific ST-T changes, Normal sinus rhythm, Poor R wave progression, Right atrial abnormality, Right QRS axis deviation, bundle block, ventricular hypertrophy, ST depression or abnormality, AV block, arrhythmia, short PR interval, bradycardia, tachycardia, and T-wave abnormality. (NCT01587924)
Timeframe: Up to 6 weeks

,,,
InterventionParticipants (Count of Participants)
Abnormal, clinically significantAbnormal, not clinically significant
0.5 mg GSK1278863105
2 mg GSK1278863126
5 mg GSK127886389
rhEPO126

Model-Adjusted Maximum Hgb Changes Over 4 Weeks

Maximum Hgb change over 4 weeks was analyzed using an ANCOVA model with terms included for treatment and baseline Hgb value. Least square mean estimates and 95% CI for each treatment group were reported. Baseline was the average of Week -2 , Week -1 and Day 1 visits. The change from Baseline was calculated by subtracting the baseline value from the individual post-dose visit values. (NCT01587898)
Timeframe: Baseline (average of Week -2 , -1 and Day 1 visits) and 4 weeks

Interventiong/dL (Least Squares Mean)
Placebo0.153
GSK1278863, 0.5 mg0.137
GSK1278863, 2 mg0.474
GSK1278863, 5 mg1.069

Modeled Hgb Change From Baseline Over 4 Weeks of Treatment

Modeled Hgb change from baseline over 4 weeks was derived using a random coefficient mixed effects linear regression model. The model included fixed effects for baseline Hgb, treatment and a treatment by day interaction. Random effects was fitted in the intercept and the slope over time. All data up until investigational product discontinuation was included for Hgb efficacy evaluable participants; where efficacy evaluable was defined as having a baseline and at least 2 on-treatment Hgb assessments. Baseline was the average of Week -2 , Week -1 and Day 1 visits. The change from Baseline was calculated by subtracting the Baseline value from the individual post-dose visit values. (NCT01587898)
Timeframe: Baseline (average of Week -2, -1 and Day 1) and Week 4

Interventiongram per decilitre (g/dL) (Mean)
Placebo-0.148
GSK1278863, 0.5 mg0.132
GSK1278863, 2 mg0.463
GSK1278863, 5 mg1.010

Number of Participants Discontinuing the Study Treatment Due to AEs

AE was defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE include AEs those result in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. number of participants discontinuing the study treatment due to AEs. (NCT01587898)
Timeframe: Up to 6 weeks

InterventionParticipants (Count of Participants)
Placebo1
GSK1278863, 0.5 mg1
GSK1278863, 2 mg0
GSK1278863, 5 mg0

Absolute Electrocardiogram (ECG) Parameter Values at Baseline (Screening), Week 2, 4, and 6

Full 12-lead ECGs were recorded in participants who were rested supine or seated for at least 10 minutes before each reading. All ECGs were transmitted to a central reviewer for blinded assessment. Full 12-lead ECGs were recorded on the provided ECG machine that automatically calculates heart rate, PR, QRS, QT and QTc intervals. Absolute ECG parameters including PR interval, QT interval and QRS duration values at Baseline (Screening), Week 2, 4, and 6 were reported. (NCT01587898)
Timeframe: Baseline (Screening), Week 2, 4, and 6

,,,
InterventionMilliseconds (msec) (Mean)
PR Interval, Day 1PR Interval, Week 2PR Interval, Week 4PR Interval, Week 6QRS Duration, Day 1QRS Duration, Week 2QRS Duration, Week 4QRS Duration, Week 6Uncorrected QT Interval, Day 1Uncorrected QT Interval, Week 2Uncorrected QT Interval, Week 4Uncorrected QT Interval, Week 6QTc Interval (Bazett's), Day 1QTc Interval (Bazett's), Week 2QTc Interval (Bazett's), Week 4QTc Interval (Bazett's), Week 6QTc Interval (Fridericias's), Day 1QTc Interval (Fridericias's), Week 2QTc Interval (Fridericias's), Week 4QTc Interval (Fridericias's), Week 6
GSK1278863, 0.5 mg164.727187.002180.000183.314101.227101.111104.205104.729432.455422.837413.333428.077446.712440.390434.590441.622441.424434.178427.103436.666
GSK1278863, 2 mg165.313172.909174.875175.32199.532102.328103.965101.811405.541408.936411.859396.778435.351428.144429.480429.983424.970421.124422.943418.161
GSK1278863, 5 mg177.630176.875176.000179.307106.444106.556104.392105.617426.074419.444423.255417.686437.593431.500426.549431.700433.815426.944424.961426.591
Placebo160.750165.961161.689153.91499.750107.647101.46796.186412.000411.804413.111404.500430.833440.843435.556444.771424.417430.549427.711430.357

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

Clinical chemistry parameters including ALT, ALP, AST, CK were assessed at Baseline (Day 1 pre-dose), Week 2, 4, and at follow-up visit (Week 6). (NCT01587898)
Timeframe: Baseline (Day 1 pre-dose), Week 2, 4, and 6

,,,
InterventionInternational Units per litre (IU/L) (Mean)
ALT, Day 1ALT, Week 2ALT, Week 4ALT, Week 6ALP, Day 1ALP, Week 2ALP, Week 4ALP, Week 6AST, Day 1AST, Week 2AST, Week 4AST, Week 6CK, Day 1CK, Week 2CK, Week 4CK, Week 6
GSK1278863, 0.5 mg13.812.414.614.995.691.590.489.219.117.518.220.1132.4130.8114.2132.2
GSK1278863, 2 mg18.820.122.216.997.792.292.687.122.926.126.721.4159.4150.2136.4137.4
GSK1278863, 5 mg16.214.113.216.585.987.290.192.418.719.017.419.894.4100.083.1130.9
Placebo11.810.811.410.186.684.384.183.916.716.115.615.2101.686.794.490.6

Absolute Values of Albumin, Apolipoprotein A1, Apolipoprotein Total, Total Protein at Baseline (Day 1), Week 2, 4, and 6

Clinical chemistry parameters including albumin, apolipoprotein A1, apolipoprotein total, total protein were assessed at Baseline (Day 1 pre-dose), Week 2, 4, and at follow-up visit (Week 6). (NCT01587898)
Timeframe: Baseline (Day 1 pre-dose), Week 2, 4, and 6

,,,
InterventionG/L (Mean)
Albumin, Day 1Albumin, Week 2Albumin, Week 4Albumin, Week 6Apolipoprotein A1, Day 1Apolipoprotein A1, Week 2Apolipoprotein A1, Week 4Apolipoprotein A1, Week 6Apolipoprotein Total, Day 1Apolipoprotein Total, Week 2Apolipoprotein Total, Week 4Apolipoprotein Total, Week 6Total Protein, Day 1Total Protein, Week 2Total Protein, Week 4Total Protein, Week 6
GSK1278863, 0.5 mg40.940.341.339.91.5151.4721.4521.5010.9360.9010.8880.87271.170.171.869.7
GSK1278863, 2 mg39.738.839.140.61.4611.4691.4361.4680.7880.7330.7240.75768.566.466.968.3
GSK1278863, 5 mg39.840.139.238.91.5721.3701.4051.4920.7920.7510.7430.77667.768.367.666.9
Placebo39.840.840.640.01.4811.4181.4821.4720.7940.7540.7200.73269.470.870.769.8

Absolute Values of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count (Absolute) at Baseline, Week 1, 2, 3, 4, and 6

Hematology parameters including Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet count, WBC count (absolute) were assessed at Baseline (Day 1 pre-dose), Week 2, 3, 4, and at follow-up visit (Week 6). (NCT01587898)
Timeframe: Baseline (Day 1 pre-dose), Week 1, 2, 3, 4, and 6

,,,
Intervention10^9 cells/L (Mean)
Basophils, Day 1Basophils, Week 1Basophils, Week 2Basophils, Week 3Basophils, Week 4Basophils, Week 6Eosinophils, Day 1Eosinophils, Week 1Eosinophils, Week 2Eosinophils, Week 3Eosinophils, Week 4Eosinophils, Week 6Lymphocytes, Day 1Lymphocytes, Week 1Lymphocytes, Week 2Lymphocytes, Week 3Lymphocytes, Week 4Lymphocytes, Week 6Monocytes, Day 1Monocytes, Week 1Monocytes, Week 2Monocytes, Week 3Monocytes, Week 4Monocytes, Week 6Total Neutrophils, Day 1Total Neutrophils, Week 1Total Neutrophils, Week 2Total Neutrophils, Week 3Total Neutrophils, Week 4Total Neutrophils, Week 6Platelet Count, Day 1Platelet Count, Week 1Platelet Count, Week 2Platelet Count, Week 3Platelet Count, Week 4Platelet Count, Week 6WBC count (absolute), Day 1WBC count (absolute), Week 1WBC count (absolute), Week 2WBC count (absolute), Week 3WBC count (absolute), Week 4WBC count (absolute), Week 6
GSK1278863, 0.5 mg0.0350.0230.0220.0310.0330.0290.2050.1890.2230.2120.1900.2291.6621.6731.7411.7651.7361.4910.3450.3750.3390.3880.3880.3364.8084.6704.5234.7895.2384.061229.9219.8230.1237.3255.8207.97.066.926.847.187.576.14
GSK1278863, 2 mg0.0250.0340.0240.0240.0230.0230.1650.1260.1220.1050.1240.1341.4731.6771.3561.4751.4281.4270.3190.3710.3050.3620.3650.3504.5334.2034.1214.1814.3154.126219.2225.8209.7208.5215.3217.96.516.425.936.146.266.06
GSK1278863, 5 mg0.0250.0300.0290.0260.0240.0240.1410.1690.1120.1220.1460.1501.6021.6761.5331.4611.3301.4660.3730.4520.3830.4180.3670.4304.6145.3374.7465.0114.5394.891223.5238.8229.9224.6240.5227.16.767.676.807.046.426.97
Placebo0.0230.0230.0260.0270.0270.0240.2260.2120.2040.2160.1910.2021.8441.8421.6291.8131.7951.7390.3840.4180.4000.4520.3050.3694.6545.0764.3054.5883.8344.163199.9204.8211.3211.5184.6195.17.147.566.577.116.166.50

Absolute Values of Calcium, Chloride, Cholesterol, Glucose, Inorganic Phosphorus, Potassium, Sodium at Baseline (Day 1), Week 2, 4, and 6

Clinical chemistry parameters including calcium, chloride, cholesterol, glucose, inorganic phosphorus, potassium, sodium were assessed at Baseline (Day 1 pre-dose), Week 2, 4, and at follow-up visit (Week 6). (NCT01587898)
Timeframe: Baseline (Day 1 pre-dose), Week 2, 4, and 6

,,,
InterventionMillimol per Litre (MMOL/L) (Mean)
Calcium, Day 1Calcium, Week 2Calcium, Week 4Calcium, Week 6Chloride, Day 1Chloride, Week 2Chloride, Week 4Chloride, Week 6Cholesterol, Day 1Cholesterol, Week 2Cholesterol, Week 4Cholesterol, Week 6Glucose, Day 1Glucose, Week 2Glucose, Week 4Glucose, Week 6Phosphorus, inorganic, Day 1Phosphorus, inorganic, Week 2Phosphorus, inorganic, Week 4Phosphorus, inorganic, Week 6Potassium, Day 1Potassium, Week 2Potassium, Week 4Potassium, Week 6Sodium, Day 1Sodium, Week 2Sodium, Week 4Sodium, Week 6
GSK1278863, 0.5 mg2.2962.2982.3022.331103.1104.2105.0105.34.6324.6234.4484.5209.118.489.038.341.3641.4211.3881.3454.654.614.614.58137.8137.9139.2139.4
GSK1278863, 2 mg2.2592.3312.3012.309103.9103.6104.0103.84.0883.8003.7763.9289.469.648.639.141.4031.4351.4031.3664.654.714.564.70137.5138.2138.5137.9
GSK1278863, 5 mg2.3352.3472.3482.322104.7103.1106.4104.24.4114.2824.0914.4067.759.426.717.811.3131.2851.2441.2034.634.624.424.65138.6137.5140.2138.8
Placebo2.2582.2992.2742.255105.4105.6106.6106.74.1473.9973.8933.9446.976.786.498.881.3251.3091.2931.3194.574.674.544.56140.1139.8140.6140.3

Absolute Values of Creatinine, Direct Bilirubin, Indirect Bilirubin, Total Bilirubin at Baseline (Day 1), Week 2, 4, and 6

Clinical chemistry parameters including creatinine, direct bilirubin, indirect bilirubin, total bilirubin were assessed at Baseline (Day 1 pre-dose), Week 2, 4, and at follow-up visit (Week 6). (NCT01587898)
Timeframe: Baseline (Day 1 pre-dose), Week 2, 4, and 6

,,,
InterventionMicromol/L (Mean)
Creatinine, Day 1Creatinine, Week 2Creatinine, Week 4Creatinine, Week 6Direct bilirubin, Day 1Direct bilirubin, Week 2Direct bilirubin, Week 4Direct bilirubin, Week 6Indirect bilirubin, Day 1Indirect bilirubin, Week 2Indirect bilirubin, Week 4Indirect bilirubin, Week 6Total bilirubin, Day 1Total bilirubin, Week 2Total bilirubin, Week 4Total bilirubin, Week 6
GSK1278863, 0.5 mg237.05245.16250.10238.072.11.71.81.84.44.54.25.06.56.16.06.8
GSK1278863, 2 mg274.34267.07254.86254.862.11.81.91.84.44.84.84.86.56.66.76.5
GSK1278863, 5 mg237.43217.84209.76219.501.62.11.92.14.64.64.93.86.26.76.85.9
Placebo250.67235.92242.21244.431.91.51.61.84.05.14.34.45.96.65.96.1

Absolute Values of Heart Rate at Baseline (Day 1), Week 1, 2, 3, 4, and 6

Absolute values of heart rate at Baseline (Day 1), Week 1, 2, 3, 4, and 6 were reported as vital parameter. Three measurements of heart rate were recorded from the participant in a supine position for at least 5 minutes (allowed enough time between measurement to completely deflate and loosen the inflatable cuff). (NCT01587898)
Timeframe: Baseline (Day 1 pre-dose), Week 1, 2, 3, 4, and 6

,,,
InterventionBeats per minute (Mean)
Heart rate, Day 1Heart rate, Week 1Heart rate, Week 2Heart rate, Week 3Heart rate, Week 4Heart rate, Week 6
GSK1278863, 0.5 mg68.469.567.569.868.567.6
GSK1278863, 2 mg69.169.466.968.767.968.0
GSK1278863, 5 mg67.869.467.666.965.468.9
Placebo68.468.768.971.967.971.0

Absolute Values of Mean Corpuscle Hgb Concentration at Baseline (Day 1), Week 1, 2, 3, 4, and 6

Hematology parameter Mean Corpuscle Hgb Concentration was assessed at Baseline (Day 1 pre-dose), Week 2, 3, 4, and at follow-up visit (Week 6). (NCT01587898)
Timeframe: Baseline (Day 1 pre-dose), Week 1, 2, 3, 4, and 6

,,,
InterventionG/L (Mean)
Mean Corpuscle Hgb, Day 1Mean Corpuscle Hgb, Week 1Mean Corpuscle Hgb, Week 2Mean Corpuscle Hgb, Week 3Mean Corpuscle Hgb, Week 4Mean Corpuscle Hgb, Week 6
GSK1278863, 0.5 mg330.9330.1329.9329.5328.8330.7
GSK1278863, 2 mg330.2330.8331.3331.2329.6331.4
GSK1278863, 5 mg328.4328.0326.5326.0326.1328.2
Placebo328.6329.3327.3328.4329.6326.4

Absolute Values of Mean Corpuscle Volume at Baseline, Week 1, 2, 3, 4 and 6

Hematology parameter mean corpuscle volume was assessed at Baseline (Day 1 pre-dose), Week 2, 3, 4, and at follow-up visit (Week 6). (NCT01587898)
Timeframe: Baseline (Day 1 pre-dose), Week 1, 2, 3, 4, and 6

,,,
InterventionFemtolitre (FL) (Mean)
Mean Corpuscle Volume, Day 1Mean Corpuscle Volume, Week 1Mean Corpuscle Volume, Week 2Mean Corpuscle Volume, Week 3Mean Corpuscle Volume, Week 4Mean Corpuscle Volume, Week 6
GSK1278863, 0.5 mg92.492.792.893.193.494.1
GSK1278863, 2 mg94.894.695.595.696.195.8
GSK1278863, 5 mg94.295.395.495.995.795.1
Placebo93.893.693.993.693.994.1

Absolute Values of Reticulocyte Count at Baseline (Day 1), Week 1, 2, 3, 4, and 6

Hematology parameter reticulocyte were assessed at Baseline (Day 1 pre-dose), Week 2, 3, 4, and at follow-up visit (Week 6). (NCT01587898)
Timeframe: Baseline (Day 1 pre-dose), Week 1, 2, 3, 4, and 6

,,,
InterventionRatio (Mean)
Reticulocytes, Day 1Reticulocytes, Week 1Reticulocytes, Week 2Reticulocytes, Week 3Reticulocytes, Week 4Reticulocytes, Week 6
GSK1278863, 0.5 mg0.01790.01980.02010.01890.01870.0196
GSK1278863, 2 mg0.02080.02560.02240.02290.02030.0161
GSK1278863, 5 mg0.01880.02840.02680.02320.02360.0142
Placebo0.01830.01850.01780.01910.01740.0154

Absolute Values of Systolic Blood Pressure and Diastolic Blood Pressure Baseline, Week 1, Week 2, Week 3, Week 4 and Week 6

Absolute values of systolic blood pressure and diastolic blood pressure Baseline (Day 1), Week 1, 2, 3, 4, and 6 as vital parameters were reported. Three measurements of systolic blood pressure and diastolic blood pressure were recorded from the participant in a supine position for at least 5 minutes (allowed enough time between measurement to completely deflate and loosen the inflatable cuff). (NCT01587898)
Timeframe: Baseline (Day 1 pre-dose), Week 1, 2, 3, 4, and 6

,,,
InterventionMillimeter mercury (mmHg) (Mean)
Systolic blood pressure, Day 1Systolic blood pressure, Week 1Systolic blood pressure, Week 2Systolic blood pressure, Week 3Systolic blood pressure, Week 4Systolic blood pressure, Week 6Diastolic blood pressure, Day 1Diastolic blood pressure, Week 1Diastolic blood pressure, Week 2Diastolic blood pressure, Week 3Diastolic blood pressure, Week 4Diastolic blood pressure, Week 6
GSK1278863, 0.5 mg135.5136.0129.4133.5133.1131.769.068.868.669.568.267.2
GSK1278863, 2 mg134.0134.6129.9133.0134.2135.068.267.466.066.566.266.6
GSK1278863, 5 mg140.1137.8139.1131.7135.4130.471.771.572.766.968.970.1
Placebo132.9132.3128.4130.2132.6134.369.966.967.767.768.970.3

Absolute Values of Urine Total Protein/Creatinine Ratio at Baseline (Day 1), Week 2, 4, and 6

Absolute values of urine total protein/creatinine ratio at Baseline (Day 1), Week 2, 4, and follow-up (week 6) were reported. (NCT01587898)
Timeframe: Baseline (Day 1), Week 2, 4, and 6

,,,
Interventionmg/MMOL (Mean)
Urine Total Protein/Creatinine ratio, Day 1Urine Total Protein/Creatinine ratio, Week 2Urine Total Protein/Creatinine ratio, Week 4Urine Total Protein/Creatinine ratio, Week 6
GSK1278863, 0.5 mg205.73207.82169.31162.81
GSK1278863, 2 mg342.39194.14196.37175.16
GSK1278863, 5 mg211.58149.08219.47160.01
Placebo226.00170.41114.71232.80

Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count, WBC Count (Absolute) at Week 1, 2, 3, 4, and 6

Baseline values were recorded on Day 1. If the Day 1 value was missing, the last non-missing value from week -1 or week-2 was represented as the baseline value. The change from baseline was calculated by subtracting the baseline value from the individual post-dose visit values. Change from Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet count, WBC count (absolute) at Week 1, 2, 3, 4, and 6 were reported. (NCT01587898)
Timeframe: Baseline (Day 1), Week 1, 2, 3, 4, and 6

,,,
Intervention10^9 cells/L (Mean)
Basophils, Week 1Basophils, Week 2Basophils, Week 3Basophils, Week 4Basophils, Week 6Eosinophils, Week 1Eosinophils, Week 2Eosinophils, Week 3Eosinophils, Week 4Eosinophils, Week 6Lymphocytes, Week 1Lymphocytes, Week 2Lymphocytes, Week 3Lymphocytes, Week 4Lymphocytes, Week 6Monocytes, Week 1Monocytes, Week 2Monocytes, Week 3Monocytes, Week 4Monocytes, Week 6Total Neutrophils, Week 1Total Neutrophils, Week 2Total Neutrophils, Week 3Total Neutrophils, Week 4Total Neutrophils, Week 6Platelet count, Week 1Platelet count, Week 2Platelet count, Week 3Platelet count, Week 4Platelet count, Week 6WBC count (absolute), Week 1WBC count (absolute), Week 2WBC count (absolute), Week 3WBC count (absolute), Week 4WBC count (absolute), Week 6
GSK1278863, 0.5 mg-0.011-0.013-0.005-0.000-0.003-0.0140.0210.012-0.0040.0340.0240.0620.0720.030-0.0860.0420.0290.0750.0700.0060.027-0.217-0.1010.493-0.278-7.375-10.500-3.33312.417-14.0710.050-0.1360.0460.567-0.336
GSK1278863, 2 mg0.008-0.001-0.001-0.003-0.003-0.029-0.013-0.040-0.028-0.0180.126-0.176-0.028-0.082-0.0830.032-0.0440.0150.005-0.010-0.362-0.400-0.373-0.239-0.4286.0560.200-7.412-0.5632.063-0.211-0.625-0.435-0.344-0.538
GSK1278863, 5 mg0.0030.0040.002-0.001-0.0010.023-0.031-0.0180.0110.0090.048-0.0360.021-0.0810.0250.0960.0250.054-0.0070.0660.4570.0860.335-0.1480.21514.50012.9418.17622.50010.6470.6390.0500.394-0.2060.329
Placebo-0.0000.0040.0040.005-0.000-0.014-0.033-0.014-0.020-0.012-0.002-0.234-0.050-0.137-0.1860.0340.0090.060-0.039-0.0120.4220.1550.014-0.394-0.2294.83316.37514.118-1.3578.9330.422-0.1000.018-0.579-0.443

Change From Baseline in ECG Parameters at Week 2, 4 and 6

Full 12-lead ECGs were recorded in participants who were rested supine or seated for at least 10 minutes before each reading. All ECGs were transmitted to a central reviewer for blinded assessment. Full 12-lead ECGs were recorded on the provided ECG machine that automatically calculates heart rate, PR, QRS, QT and QTc intervals. Baseline ECG values were defined as measurements taken at screening. The change from baseline was calculated by subtracting the baseline value from the individual post-dose visit values. (NCT01587898)
Timeframe: Baseline (Screening), Week 2, 4, and 6

,,,
Interventionmsec (Mean)
PR Interval, Week 2PR Interval, Week 4PR Interval, Week 6QRS Duration, Week 2QRS Duration, Week 4QRS Duration, Week 6Uncorrected QT Interval, Week 2Uncorrected QT Interval, Week 4Uncorrected QT Interval, Week 6QTc Interval (Bazett's), Week 2QTc Interval (Bazett's), Week 4QTc Interval (Bazett's), Week 6QTc Interval (Fridericias's), Week 2QTc Interval (Fridericias's), Week 4QTc Interval (Fridericias's), Week 6
GSK1278863, 0.5 mg3.61.80.5-0.01.80.2-1.9-10.9-2.43.4-0.82.91.7-4.21.0
GSK1278863, 2 mg2.53.1-0.20.41.3-1.93.15.4-6.7-4.0-1.80.0-1.70.5-2.4
GSK1278863, 5 mg-0.6-2.01.34.62.33.55.88.83.21.7-1.93.33.01.63.2
Placebo-1.2-2.6-5.82.5-0.4-0.3-10.8-2.9-7.97.92.511.41.61.04.6

Change From Baseline in Erythropoietin at Week 2 and Week 4

Blood samples for erythropoietin were collected at Day 1 (pre-dose), Week 2 (first samples was collected approximately between 4 to 8 h and then 1 and 3 h after this fist sample) and Week 4 (Pre-dose and 3 h post-dose). The change from Baseline was calculated by subtracting the Baseline value from the individual post-dose visit values. (NCT01587898)
Timeframe: Baseline (Day 1 Pre-dose), Week 2 and 4

,,,
InterventionUnits per litre (U/L) (Mean)
Week 2, 4-8 Hours Post-DoseWeek 2, 5-9 Hours, Post DoseWeek 2, 7-11 Hours, Post DoseWeek 4, Pre-doseWeek 4, 3 Hour Post-Dose
GSK1278863, 0.5 mg1.0221.0270.5380.0141.039
GSK1278863, 2 mg3.6224.6126.6300.814-0.075
GSK1278863, 5 mg13.26715.80020.1002.9752.102
Placebo0.7211.5410.4376.6446.346

Change From Baseline in Ferritin at Week 2 and Week 4

Baseline was the Day 1 pre-dose value. The change from Baseline was calculated by subtracting the Baseline value from the individual post-dose visit values. (NCT01587898)
Timeframe: Baseline (Day 1 Pre-dose), Week 2 and 4

,,,
Interventionmcg/L (Mean)
Week 2Week 4
GSK1278863, 0.5 mg-20.0-35.8
GSK1278863, 2 mg-38.6-8.2
GSK1278863, 5 mg-58.8-101.8
Placebo2.6-24.3

Change From Baseline in Heart Rate at Week 1, 2, 3, 4, and 6

Three measurements of heart rate were recorded from the participant in a supine position for at least 5 minutes (allowed enough time between measurement to completely deflate and loosen the inflatable cuff). Baseline values were recorded on Day 1. If the Day 1 value was missing, the last non-missing value from week -1 or week-2 was represented as the baseline value. The change from baseline was calculated by subtracting the baseline value from the individual post-dose visit values. change from baseline in heart rate at Week 1, 2, 3, 4, and 6 were reported. (NCT01587898)
Timeframe: Baseline (Day 1 pre-dose), Week 1, 2, 3, 4, and 6

,,,
InterventionBeats per minute (Mean)
Heart rate, Week 1Heart rate, Week 2Heart rate, Week 3Heart rate, Week 4Heart rate, Week 6
GSK1278863, 0.5 mg1.375-1.3100.9761.111-0.167
GSK1278863, 2 mg0.315-1.3330.412-0.500-0.458
GSK1278863, 5 mg1.632-0.500-0.510-2.0200.917
Placebo0.2960.4123.392-1.1671.854

Change From Baseline in Hematocrit and Reticulocytes Over 4 Weeks

Baseline was the Day 1 pre-dose value. The change from Baseline was calculated by subtracting the Baseline value from the individual post-dose visit values. (NCT01587898)
Timeframe: Baseline (Day 1 pre-dose), Week 1, 2, 3, and 4

,,,
InterventionRatio (Mean)
Hematocrit, Week 1Hematocrit, Week 2Hematocrit, Week 3Hematocrit, Week 4Reticulocyte, Week 1Reticulocyte, Week 2Reticulocyte, Week 3Reticulocyte, Week 4
GSK1278863, 0.5 mg-0.290.11-0.56-0.140.240.320.230.11
GSK1278863, 2 mg-0.350.240.081.160.460.120.15-0.07
GSK1278863, 5 mg0.391.642.113.380.950.850.450.49
Placebo-0.150.35-0.24-0.500.050.010.13-0.07

Change From Baseline in Hepcidin at Week 2 and Week 4

Blood samples for hepcidin were collected at Day 1 (pre-dose), Week 2 (approximately between 4 to 8 h) and Week 4 (pre-dose). Hepcidin is a regulator of iron metabolism. Baseline was the last pre-dose value on Day 1. The change from Baseline was calculated by subtracting the Baseline value from the individual post-dose visit values. Where hepcidin values were missing because the value was below the quantification limit (BQL), the BQL value was imputed. (NCT01587898)
Timeframe: Baseline (Pre-dose on Day 1), Week 2 and 4

,,,
InterventionMicrogram per Litre (mcg/L) (Mean)
Week 2Week 4
GSK1278863, 0.5 mg-23.46-22.16
GSK1278863, 2 mg-75.24-77.34
GSK1278863, 5 mg-120.31-143.09
Placebo10.19-2.62

Change From Baseline in High Sensitivity C-reactive Protein (hsCRP) at Week 2 and Week 4

Baseline was the Day 1 pre-dose value. The change from Baseline was calculated by subtracting the Baseline value from the individual post-dose visit values. (NCT01587898)
Timeframe: Baseline (Day 1 Pre-dose), Week 2 and 4

,,,
Interventionmiligram per litre (mg/L) (Mean)
Week 2Week 4
GSK1278863, 0.5 mg2.350.65
GSK1278863, 2 mg-1.00-2.09
GSK1278863, 5 mg4.321.76
Placebo6.130.21

Change From Baseline in Mean Corpuscle Hgb Concentration at Week 1, 2, 3, 4, and 6

Baseline values were recorded on Day 1. If the Day 1 value was missing, the last non-missing value from week -1 or week-2 was represented as the baseline value. The change from baseline was calculated by subtracting the baseline value from the individual post-dose visit values. Change from Baseline in Mean Corpuscle Hgb Concentration at Week 1, 2, 3, 4, and 6 were reported. (NCT01587898)
Timeframe: Baseline (Day 1), Week 1, 2, 3, 4, and 6

,,,
InterventionG/L (Mean)
Mean Corpuscle Hgb Concentration, Week 1Mean Corpuscle Hgb Concentration, Week 2Mean Corpuscle Hgb Concentration, Week 3Mean Corpuscle Hgb Concentration, Week 4Mean Corpuscle Hgb Concentration, Week 6
GSK1278863, 0.5 mg-0.688-0.214-0.462-1.417-1.714
GSK1278863, 2 mg0.2220.7500.294-1.3750.438
GSK1278863, 5 mg-0.389-2.111-2.588-2.625-0.353
Placebo0.667-0.8750.6472.429-1.200

Change From Baseline in Mean Corpuscle Volume at Week 1, 2, 3, 4, and 6

Baseline values were recorded on Day 1. If the Day 1 value was missing, the last non-missing value from week -1 or week-2 was represented as the baseline value. The change from baseline was calculated by subtracting the baseline value from the individual post-dose visit values. Change from Baseline in Mean Corpuscle Volume at Week 1, 2, 3, 4, and 6 were reported. (NCT01587898)
Timeframe: Baseline (Day 1), Week 1, 2, 3, 4, and 6

,,,
InterventionFL (Mean)
Mean Corpuscle Volume, Week 1Mean Corpuscle Volume, Week 2Mean Corpuscle Volume, Week 3Mean Corpuscle Volume, Week 4Mean Corpuscle Volume, Week 6
GSK1278863, 0.5 mg0.125-0.214-0.2310.083-0.071
GSK1278863, 2 mg-0.2220.1250.1180.188-0.125
GSK1278863, 5 mg0.2780.9441.1761.1880.353
Placebo-0.2220.188-0.235-0.143-0.133

Change From Baseline in Red Blood Cells Count Over 4 Weeks

Baseline was the Day 1 pre-dose value. The change from Baseline was calculated by subtracting the Baseline value from the individual post-dose visit values. (NCT01587898)
Timeframe: Baseline (Day 1 pre-dose), week 1, 2, 3, 4

,,,
Intervention10^12 cells /L (Mean)
Week 1Week 2Week 3Week 4
GSK1278863, 0.5 mg-0.030.03-0.020.01
GSK1278863, 2 mg-0.030.01-0.020.09
GSK1278863, 5 mg0.040.140.160.33
Placebo-0.010.02-0.03-0.05

Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at Week 1, 2, 3, 4, and 6

Three measurements of SBP and DBP were recorded from the participant in a supine position for at least 5 minutes (allowed enough time between measurement to completely deflate and loosen the inflatable cuff). Baseline values were recorded on Day 1. If the Day 1 value was missing, the last non-missing value from week -1 or week-2 was represented as the baseline value. The change from baseline was calculated by subtracting the baseline value from the individual post-dose visit values. Change from Baseline in systolic blood pressure and diastolic blood pressure at Week 1, 2, 3, 4, and 6 were reported. (NCT01587898)
Timeframe: Baseline (Day 1 pre-dose), Week 1, 2, 3, 4, and 6

,,,
InterventionmmHg (Mean)
Systolic blood pressure, Week 1Systolic blood pressure, Week 2Systolic blood pressure, Week 3Systolic blood pressure, Week 4Systolic blood pressure, Week 6Diastolic blood pressure, Week 1Diastolic blood pressure, Week 2Diastolic blood pressure, Week 3Diastolic blood pressure, Week 4Diastolic blood pressure, Week 6
GSK1278863, 0.5 mg1.167-5.786-1.643-0.944-2.4580.521-0.0240.857-0.111-1.312
GSK1278863, 2 mg0.565-5.284-2.2060.8441.656-0.750-2.206-1.755-1.615-1.281
GSK1278863, 5 mg-2.3681.241-5.216-1.510-6.451-0.1931.963-2.627-0.6670.529
Placebo-0.519-3.373-1.5290.8540.125-3.037-1.608-1.647-0.6251.396

Change From Baseline in Total Iron at Week 2 and Week 4

Baseline was the Day 1 pre-dose value. The change from Baseline was calculated by subtracting the Baseline value from the individual post-dose visit values. (NCT01587898)
Timeframe: Baseline (Day 1 Pre-dose), Week 2 and 4

,,,
Interventionmicromol/L (Mean)
Week 2Week 4
GSK1278863, 0.5 mg-1.1-1.7
GSK1278863, 2 mg-1.3-0.4
GSK1278863, 5 mg0.4-0.4
Placebo0.40.6

Change From Baseline in Total Iron Binding Capacity at Week 2 and Week 4

Total iron-binding capacity is a medical laboratory test that measures the blood's capacity to bind iron with transferrin. Baseline was the Day 1 pre-dose value. The change from Baseline was calculated by subtracting the Baseline value from the individual post-dose visit values. (NCT01587898)
Timeframe: Baseline (Day 1 Pre-dose), Week 2 and 4

,,,
InterventionMicromol per litre (micromol/L) (Mean)
Week 2Week 4
GSK1278863, 0.5 mg-1.60.3
GSK1278863, 2 mg2.95.1
GSK1278863, 5 mg5.98.3
Placebo0.6-0.5

Change From Baseline in Transferrin at Week 2 and Week 4

Baseline was the Day 1 pre-dose value. The change from Baseline was calculated by subtracting the Baseline value from the individual post-dose visit values. (NCT01587898)
Timeframe: Baseline (Day 1 Pre-dose), Week 2 and 4

,,,
InterventionGrams per litre (G/L) (Mean)
Week 2Week 4
GSK1278863, 0.5 mg-0.1000.028
GSK1278863, 2 mg0.1530.294
GSK1278863, 5 mg0.1410.388
Placebo-0.0170.011

Change From Baseline in Transferrin Saturation at Week 2 and Week 4

Transferrin saturation was measured as a percentage, and is the ratio of serum iron and total iron-binding capacity, multiplied by 100. Baseline value for transferrin saturation was the pre-dose value on Day 1. The change from Baseline was calculated by subtracting the Baseline value from the individual post-dose visit values. (NCT01587898)
Timeframe: Baseline (Day 1 Pre-dose), Week 2 and 4

,,,
InterventionPercentage of transferrin saturation (Mean)
Week 2Week 4
GSK1278863, 0.5 mg-1.5-3.1
GSK1278863, 2 mg-3.7-2.6
GSK1278863, 5 mg-2.1-3.4
Placebo0.71.5

Change From Baseline in Vascular Endothelial Growth Factor (VEGF) at Week 2 and Week 4

Blood samples for VEGF were collected at Day 1 (pre-dose), Week 2 (first samples was collected approximately between 4 to 8 h and then 1 and 3 h after this fist sample) and Week 4 (Pre-dose and 3 h post-dose). Baseline was the Day 1 pre-dose value. The change from baseline was calculated by subtracting the baseline value from the individual post-dose visit values. (NCT01587898)
Timeframe: Baseline (Pre-dose), week 2 and 4

,,,
InterventionNanogram per litre (ng/L) (Mean)
WEEK 2, 4-8 HOURS POST-DOSEWEEK 2, 5-9 HOURS, POST DOSEWEEK 2, 7-11 HOURS, POST DOSEWEEK 4, PRE-DOSEWEEK 4, 3 HOUR POST-DOSE
GSK1278863, 0.5 mg-17.23-18.21-30.5665.890.77
GSK1278863, 2 mg-19.55-11.80-17.88-7.47-3.87
GSK1278863, 5 mg20.388.3814.40-1.485.56
Placebo-12.09-23.04-41.40-39.69-43.33

Change From Baseline Values of Albumin, Apolipoprotein A1, Apolipoprotein Total, Total Protein at Week 2, 4, and 6

Baseline values were recorded on Day 1 (Pre dose). If the Day 1 value was missing, the last non-missing value from week -1 or week-2 was represented as the baseline value. The change from baseline was calculated by subtracting the baseline value from the individual post-dose visit values. Change from Baseline values of albumin, apolipoprotein A1, apolipoprotein total, total protein at Week 2, 4, and 6 were reported. (NCT01587898)
Timeframe: Baseline (Day 1), Week 2, 4, and 6

,,,
InterventionG/L (Mean)
Albumin, Week 2Albumin, Week 4Albumin, Week 6Apolipoprotein A1, Week 2Apolipoprotein A1, Week 4Apolipoprotein A1, Week 6Apolipoprotein total, Week 2Apolipoprotein total, Week 4Apolipoprotein total, Week 6Total protein, Week 2Total protein, Week 4Total protein, Week 6
GSK1278863, 0.5 mg-0.5-0.2-1.2-0.063-0.061-0.026-0.067-0.051-0.077-0.7-0.1-1.5
GSK1278863, 2 mg-0.9-0.60.1-0.023-0.025-0.011-0.051-0.0550.014-1.3-0.8-0.3
GSK1278863, 5 mg-0.4-0.6-1.0-0.197-0.163-0.076-0.048-0.0240.009-0.20.2-0.6
Placebo0.70.40.2-0.045-0.011-0.009-0.016-0.036-0.0071.10.50.4

Change From Baseline Values of ALT, ALP, AST, CK at Week 2, 4, and 6

Baseline values were recorded on Day 1. If the Day 1 value was missing, the last non-missing value from week -1 or week-2 was represented as the Baseline value. The change from Baseline was calculated by subtracting the Baseline value from the individual post-dose visit values. Change from Baseline values of ALT, AST, ALP and CK at Week 2, 4, and 6 (NCT01587898)
Timeframe: Baseline (Day 1), Week 2, 4, and 6

,,,
InterventionIU/L (Mean)
ALT, Week 2ALT, Week 4ALT, Week 6ALP, Week 2ALP, Week 4ALP, Week 6AST, Week 2AST, Week 4AST, Week 6CK, Week 2CK, Week 4CK, Week 6
GSK1278863, 0.5 mg-1.20.70.7-2.8-4.8-6.4-1.7-0.5-0.17.9-8.5-9.4
GSK1278863, 2 mg3.96.00.4-1.2-0.8-5.74.75.1-0.31.2-12.6-5.1
GSK1278863, 5 mg-1.9-2.80.52.72.64.90.1-1.11.44.4-7.540.4
Placebo-1.10.1-1.30.81.1-1.9-0.9-1.3-1.6-18.7-21.4-19.1

Change From Baseline Values of Calcium, Chloride, Cholesterol, Glucose, Inorganic Phosphorus, Potassium, Sodium at Week 2, 4, and 6

Baseline values were recorded on Day 1. If the Day 1 value was missing, the last non-missing value from week -1 or week-2 was represented as the baseline value. The change from baseline was calculated by subtracting the baseline value from the individual post-dose visit values. Change from Baseline values of calcium, chloride, cholesterol, glucose, inorganic phosphorus, potassium, sodium at Week 2, 4, and 6 were reported. (NCT01587898)
Timeframe: Baseline (Day 1), Week 2, 4, and 6

,,
InterventionMMOL/L (Mean)
Calcium, Week 2Calcium, Week 4Calcium, Week 6Chloride, Week 2Chloride, Week 4Chloride, Week 6Cholesterol, Week 2Cholesterol, Week 4Cholesterol, Week 6Glucose, Week 2Glucose, Week 4Glucose, Week 6Inorganic phosphorus, Week 2Inorganic phosphorus, Week 4Inorganic phosphorus, Week 6Potassium, Week 2Potassium, Week 4Potassium, Week 6Sodium, Week 2Sodium, Week 4Sodium, Week 6
GSK1278863, 0.5 mg0.0170.0080.0190.91.81.9-0.150-0.195-0.223-0.59-0.210.530.0650.015-0.0310.01-0.02-0.050.11.61.3
GSK1278863, 2 mg0.032-0.000-0.001-0.5-0.1-0.1-0.256-0.288-0.0400.13-0.88-0.570.0320.000-0.0090.08-0.040.060.30.60.1
GSK1278863, 5 mg0.0140.010-0.014-1.50.9-1.3-0.244-0.2850.0291.67-0.510.590.026-0.032-0.074-0.02-0.230.01-0.91.3-0.1

Change From Baseline Values of Calcium, Chloride, Cholesterol, Glucose, Inorganic Phosphorus, Potassium, Sodium at Week 2, 4, and 6

Baseline values were recorded on Day 1. If the Day 1 value was missing, the last non-missing value from week -1 or week-2 was represented as the baseline value. The change from baseline was calculated by subtracting the baseline value from the individual post-dose visit values. Change from Baseline values of calcium, chloride, cholesterol, glucose, inorganic phosphorus, potassium, sodium at Week 2, 4, and 6 were reported. (NCT01587898)
Timeframe: Baseline (Day 1), Week 2, 4, and 6

InterventionMMOL/L (Mean)
Calcium, Week 2Calcium, Week 4Calcium, Week 6Chloride, Week 2Chloride, Week 4Chloride, Week 6Cholesterol, Week 1Cholesterol, Week 2Cholesterol, Week 4Cholesterol, Week 6Glucose, Week 2Glucose, Week 4Glucose, Week 6Inorganic phosphorus, Week 2Inorganic phosphorus, Week 4Inorganic phosphorus, Week 6Potassium, Week 2Potassium, Week 4Potassium, Week 6Sodium, Week 2Sodium, Week 4Sodium, Week 6
Placebo0.0440.0210.0000.01.41.10.050-0.029-0.136-0.1340.350.011.890.0120.0250.0030.100.050.05-0.30.5-0.2

Change From Baseline Values of Creatinine, Direct Bilirubin, Indirect Bilirubin, Total Bilirubin at Week 2, 4, and 6

Baseline values were recorded on Day 1. If the Day 1 value was missing, the last non-missing value from week -1 or week-2 was represented as the baseline value. The change from baseline was calculated by subtracting the baseline value from the individual post-dose visit values. Change from Baseline values of creatinine, direct bilirubin, indirect bilirubin, total bilirubin at Week 2, 4, and 6 were reported. (NCT01587898)
Timeframe: Baseline (Day 1), Week 2, 4, and 6

,,,
InterventionMicromol/L (Mean)
Creatinine, Week 2Creatinine, Week 4Creatinine, Week 6Direct bilirubin, Week 2Direct bilirubin, Week 4Direct bilirubin, Week 6Indirect bilirubin, Week 2Indirect bilirubin, Week 4Indirect bilirubin, Week 6Total bilirubin, Week 2Total bilirubin, Week 4Total bilirubin, Week 6
GSK1278863, 0.5 mg-0.991.65-5.01-0.3-0.2-0.50.1-0.20.9-0.3-0.50.4
GSK1278863, 2 mg10.78-1.447.24-0.4-0.2-0.40.50.50.30.10.2-0.1
GSK1278863, 5 mg-2.60-16.96-7.230.40.20.5-0.10.5-0.70.20.7-0.2
Placebo-1.4111.790.71-0.5-0.6-0.41.20.40.40.7-0.10.0

Change From Baseline Values of Urine Total Protein/Creatinine Ratio at Week 2, 4, and 6

Baseline values were recorded on Day 1. If the Day 1 value was missing, the last non-missing value from week -1 or week-2 was represented as the baseline value. The change from baseline was calculated by subtracting the baseline value from the individual post-dose visit values. Change from Baseline values of urine total protein/creatinine ratio at Week 2, 4, and 6 were reported. (NCT01587898)
Timeframe: Baseline (Day 1), Week 2, 4, and 6

,,,
InterventionMG/MMOL (Mean)
Urine Total Protein/Creatinine ratio, Week 2Urine Total Protein/Creatinine ratio, Week 4Urine Total Protein/Creatinine ratio, Week 6
GSK1278863, 0.5 mg-38.8317.43-26.73
GSK1278863, 2 mg-115.28-99.40-72.19
GSK1278863, 5 mg-77.9839.90-41.40
Placebo3.44-20.5647.22

Mean Maximum Plasma Concentration (Cmax) of GSK1278863 and GSK1278863 Metabolites

Cmax of GSK1278863 and GSK1278863 metabolites (M1, M2, M3, M4, M5 and M6) were reported. For assessment of Pharmacokinetics parameters blood samples were collected at 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). (NCT01587898)
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).

,,
Interventionnanogram per millilitre (ng/mL) (Geometric Mean)
GSK1278863M2M3M4M5M6
GSK1278863, 0.5 mg2.681.031.230.7210.2960.455
GSK1278863, 2 mg12.83.834.452.741.081.74
GSK1278863, 5 mg35.710.311.87.292.814.43

Mean Steady State Area Under the Curve (AUC) of GSK1278863 and GSK1278863 Metabolites

Mean Steady state AUC of GSK1278863 and GSK1278863 metabolites (M1, M2, M3, M4, M5 and M6) were reported. For pharmacokinetic parameter assessment blood samples were collected at 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 fist sample) and Week 4 (Pre-dose 1, 2 and 3 h post-dose). (NCT01587898)
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)

,,
Interventionng*hour/mL (Geometric Mean)
GSK1278863M2M3M4M5M6
GSK1278863, 0.5 mg10.313.017.85.544.645.34
GSK1278863, 2 mg51.151.967.122.017.321.5
GSK1278863, 5 mg14814017563.443.556.3

Number of Participants Achieving an Increase of 0.5, 1.0, 1.5 and 2.0 g/dL in Hgb

Number of participants achieving an increase of 0.5, 1.0, 1.5 and 2.0 g/dL in Hgb from baseline were reported. Entry into the study required a target stable Hgb of 8.5-11.0 g/dL. A stable Hgb value was confirmed from three Hgb values taken during the screening period at Week -2, Week -1 and Day 1 (randomization). The average of these three values was used for Baseline Hgb. (NCT01587898)
Timeframe: Up to 4 weeks

,,,
InterventionParticipants (Count of Participants)
Decrease/increase of < 0.5 g/dLIncrease of >=0.5 g/dLIncrease of >=1 g/dLIncrease of >=1.5 g/dLIncrease of >=2 g/dL
GSK1278863, 0.5 mg124100
GSK1278863, 2 mg126200
GSK1278863, 5 mg414951
Placebo163100

Number of Participants Who Reached Hgb Stopping Criteria

The Hgb stopping criteria was defined as reaching to value <8.0 g/dL, >=8.0 - <13.0 (>= 2g/dL absolute Hgb change over 1 week ) or >=13.0 g/dL. The number of participants who reached the Hgb stopping criteria of Hgb concentration were presented. (NCT01587898)
Timeframe: Up to Week 4

,,,
InterventionParticipants (Count of Participants)
<8.0>=8.0-<13.0 and >=2.0 decrease>=8.0-<13.0 and >=2.0 increase
GSK1278863, 0.5 mg001
GSK1278863, 2 mg101
GSK1278863, 5 mg000
Placebo010

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

AE was defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE include AEs those result in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. (NCT01587898)
Timeframe: Up to 6 weeks

,,,
InterventionParticipants (Count of Participants)
Any AEsAny SAEs
GSK1278863, 0.5 mg100
GSK1278863, 2 mg52
GSK1278863, 5 mg61
Placebo91

Percentage of Participants Achieving an Increase of 0.5, 1.0, 1.5 and 2.0 g/dL in Hgb

Percentage of participants achieving an increase of 0.5, 1.0, 1.5 and 2.0 g/dL in Hgb from baseline were reported. Entry into the study requires a target stable Hgb of 8.5-11.0 g/dL. A stable Hgb value was confirmed from three Hgb values taken during the screening period at Week -2, Week -1 and Day 1 (randomization). The average of these three values was used for Baseline Hgb. (NCT01587898)
Timeframe: Up to 4 weeks

,,,
InterventionPercentage of participants (Number)
Decrease/increase of < 0.5 g/dLIncrease of >=0.5 g/dLIncrease of >=1 g/dLIncrease of >=1.5 g/dLIncrease of >=2 g/dL
GSK1278863, 0.5 mg7525600
GSK1278863, 2 mg67331100
GSK1278863, 5 mg227850286
Placebo8416500

Number of Packed Red Blood Cell Transfusion Administered Per Participant

Participants were administered packed red blood cells as a rescue medication who have met the Hgb rescue criteria in addition to having experienced a clinically significant worsening of their anemia or the symptoms of anemia. (NCT01906489)
Timeframe: Up to 20 Weeks

InterventionUnits of blood per participant (Median)
Placebo1.0

Number of Participants With Clinically Abnormal 12-Lead Electrocardiogram (ECG) Findings

A standard 12-lead ECG was performed following dosing in a supine position for approximately 10 minutes. ECGs were taken prior to blood draws when possible. The investigator was responsible for reviewing laboratory results for clinical significance. (NCT01906489)
Timeframe: Up to 20 Weeks

InterventionParticipants (Count of Participants)
Vadadustat1
Placebo0

Number of Participants With Clinically Significant Changes From Baseline in Physical Examination Findings

A Baseline physical examination was performed at screening. Otherwise, abbreviated physical examinations were conducted and were to include heart, lung, and abdomen. The investigator was responsible for reviewing laboratory results for clinically significant changes. (NCT01906489)
Timeframe: Up to 20 Weeks

InterventionParticipants (Count of Participants)
Vadadustat0
Placebo0

Number of Participants With Clinically Significant Changes From Baseline in Vital Signs

Parameters assessed for vital signs included sitting (at rest for a minimum of 5 minutes) heart rate, respiratory rate, body temperature, and blood pressure. The investigator was responsible for reviewing laboratory results for clinically significant changes. (NCT01906489)
Timeframe: Up to 20 Weeks

InterventionParticipants (Count of Participants)
Vadadustat0
Placebo0

Percentage of Participants Achieving a Successful Hemoglobin Response

Hemoglobin (Hgb) response was defined as participants with mean Hgb ≥11.0 grams per deciliter (g/dL) (average of Weeks 19 and 20) or increase in Hgb by ≥ 1.2 g/dL (average of Weeks 19 and 20) over pre-dose average (average of the two Hgb values obtained prior to dosing) without receiving Erythropoiesis-Stimulating Agents (ESA) or transfusion. (NCT01906489)
Timeframe: Weeks 19 and 20

InterventionPercentage of participants (Number)
Vadadustat54.9
Placebo10.3

Percentage of Participants Achieving a Successful Hemoglobin Response in ESA Actively Treated Group

Hgb response was defined as participants with mean Hgb ≥11.0 g/dL (average of Weeks 19 and 20) or increase in Hgb by ≥ 1.2 g/dL (average of Weeks 19 and 20) over pre-dose average (average of the two Hgb values obtained prior to dosing) without receiving ESA or transfusion. Participants were assigned to 1 of 3 study groups based on their ESA status at the screening visit: Naïve, Previously Treated and Actively Treated. Analysis of this secondary outcome measure was performed in the ESA Actively Treated group, defined as participants who had been actively treated with an ESA for a minimum of 4 months before screening, had received at least 2 doses within the last 4 months, had received their last dose within 6 weeks before screening, and had a screening Hgb level ≥9.5 g/dL and ≤12.0 g/dL. (NCT01906489)
Timeframe: Weeks 19 and 20

InterventionPercentage of participants (Number)
Vadadustat33.3
Placebo7.7

Percentage of Participants Achieving a Successful Hemoglobin Response in ESA Previously Treated Group

Hgb response was defined as participants with mean Hgb ≥11.0 g/dL (average of Weeks 19 and 20) or increase in Hgb by ≥ 1.2 g/dL (average of Weeks 19 and 20) over pre-dose average (average of the two Hgb values obtained prior to dosing) without receiving ESA or transfusion. Participants were assigned to 1 of 3 study groups based on their ESA status at the screening visit: Naïve, Previously Treated and Actively Treated. Analysis of this secondary outcome measure was performed in the ESA Previously Treated group, defined as participants who had previously received ≥1 dose of an ESA, had been off of ESA therapy for ≥11 weeks at the time of screening, and had a screening Hgb level of ≤10.5 g/dL. (NCT01906489)
Timeframe: Weeks 19 and 20

InterventionPercentage of participants (Number)
Vadadustat41.5
Placebo19

Percentage of Participants Achieving a Successful Hemoglobin Response in ESA Treatment naïve Group

Hgb response was defined as participants with mean Hgb ≥11.0 g/dL (average of Weeks 19 and 20) or increase in Hgb by ≥ 1.2 g/dL (average of Weeks 19 and 20) over pre-dose average (average of the two Hgb values obtained prior to dosing) without receiving ESA or transfusion. Participants were assigned to 1 of 3 study groups based on their ESA status at the screening visit: Naïve, Previously Treated and Actively Treated. Analysis of this secondary outcome measure was performed in the ESA Treatment Naïve group, defined as participants who had never received treatment with an ESA and who had a screening Hgb level of ≤10.5 g/dL. (NCT01906489)
Timeframe: Weeks 19 and 20

InterventionPercentage of participants (Number)
Vadadustat50
Placebo7.9

Percentage of Participants Achieving a Successful Hemoglobin Response, Analyzed in mITT Population

Hgb response was defined as participants with mean Hgb ≥11.0 g/dL (average of Weeks 19 and 20) or increase in Hgb by ≥ 1.2 g/dL (average of Weeks 19 and 20) over pre-dose average (average of the two Hgb values obtained prior to dosing) without receiving ESA or transfusion. Analysis of this secondary outcome measure was performed in the mITT population. (NCT01906489)
Timeframe: Weeks 19 and 20

InterventionPercentage of participants (Number)
Vadadustat44.1
Placebo11.1

Percentage of Participants Achieving a Successful Hemoglobin Response, Determined Solely Based on the Hemoglobin Value

Hgb response was defined as participants with mean Hgb ≥11.0 g/dL (average of Weeks 19 and 20) or increase in Hgb by ≥ 1.2 g/dL (average of Weeks 19 and 20) over pre-dose average (average of the two Hgb values obtained prior to dosing). Analysis of this secondary outcome measure is a reanalysis of the primary outcome measure whereby the response was determined solely by the Hgb value and receiving rescue therapy did not make the participant a failure. (NCT01906489)
Timeframe: Weeks 19 and 20

InterventionPercentage of participants (Number)
Vadadustat44.9
Placebo13.9

Percentage of Participants Who Received Packed Red Blood Cell Transfusion Rescue

Participants were administered packed red blood cell transfusion as a rescue medication who have met the Hgb rescue criteria in addition to having experienced a clinically significant worsening of their anemia or the symptoms of anemia (NCT01906489)
Timeframe: Up to 20 Weeks

InterventionPercentage of participants (Number)
Vadadustat0
Placebo1.4

Percentage of Participants With Hemoglobin Value ≥13.0 g/dL at Any Time During the Study

"Participants who have experienced an excursion in Hgb to ≥13.0 g/dL at any time during the study were considered as failures. Data was presented for failures." (NCT01906489)
Timeframe: Up to 20 Weeks

InterventionPercentage of participants (Number)
Vadadustat59.6
Placebo88.9

Time to First Transfusion or ESA Rescue Medication Intake

Rescue therapy was defined as red blood cell transfusion or ESA administration in participants meeting Hgb rescue criteria in addition to having experienced a clinically significant worsening of their anemia or the symptoms of anemia. (NCT01906489)
Timeframe: Up to 20 Weeks

InterventionWeeks (Mean)
Vadadustat21.6
Placebo21.2

Absolute Values of Hematocrit

Blood samples were collected at indicated time points for analysis of Hematocrit. (NCT01906489)
Timeframe: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20

,
InterventionPercentage of red blood cells in blood (Mean)
BaselineWeek 2Week 4Week 6Week 8Week 12Week 16Week 19Week 20
Placebo30.329.729.729.429.330.230.330.730.4
Vadadustat30.431.232.433.133.233.53433.733.6

Absolute Values of Hemoglobin

Blood samples were collected at indicated time points for analysis of hemoglobin (NCT01906489)
Timeframe: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20

,
Interventiong/dL (Mean)
BaselineWeek 2Week 4Week 6Week 8Week 12Week 16Week 19Week 20
Placebo9.969.749.79.69.69.829.839.939.93
Vadadustat9.9410.0210.3510.6110.6610.8710.7910.7410.88

Absolute Values of Red Blood Cell Count

Blood samples were collected at indicated time points for analysis of red blood cell count. (NCT01906489)
Timeframe: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20

,
Intervention10^6 cells per microliter (Mean)
BaselineWeek 2Week 4Week 6Week 8Week 12Week 16Week 19Week 20
Placebo3.343.253.243.23.213.273.293.323.33
Vadadustat3.383.393.513.573.613.683.693.673.7

Absolute Values of Reticulocyte Count

Blood samples were collected at indicated time points for analysis of reticulocyte count. (NCT01906489)
Timeframe: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20

,
Intervention10^6 cells per microliter (Mean)
BaselineWeek 2Week 4Week 6Week 8Week 12Week 16Week 19Week 20
Placebo1.971.912.062.072.0921.961.922.1
Vadadustat2.122.742.442.322.052.022.132.212.17

Change From Baseline in Hematocrit

Blood samples were collected to assess Hematocrit. Baseline was defined as the mean of two samples obtained prior to dosing (Screening and Baseline). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. A positive change from Baseline indicated Hematocrit concentration increased. (NCT01906489)
Timeframe: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20

,
InterventionPercentage of red blood cells in blood (Mean)
BaselineWeek 2Week 4Week 6Week 8Week 12Week 16Week 19Week 20
Placebo30.3-0.6-0.5-1-1-0.3-0.100.1
Vadadustat30.40.822.52.733.33.13

Change From Baseline in Hemoglobin

Blood samples were collected to assess Hgb. Baseline was defined as the mean of two samples obtained prior to dosing (Screening and Baseline). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. A positive change from Baseline indicated Hgb concentration increased. (NCT01906489)
Timeframe: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20

,
Interventiong/dL (Mean)
BaselineWeek 2Week 4Week 6Week 8Week 12Week 16Week 19Week 20
Placebo9.96-0.22-0.25-0.41-0.4-0.2-0.18-0.16-0.08
Vadadustat9.940.10.390.630.690.90.760.730.88

Change From Baseline in Red Blood Cell Count

Blood samples were collected to assess red blood cell count. Baseline was defined as the mean of two samples obtained prior to dosing (Screening and Baseline). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. A positive change from Baseline indicated red blood cell count increased. (NCT01906489)
Timeframe: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20

,
Intervention10^6 cells per microliter (Mean)
BaselineWeek 2Week 4Week 6Week 8Week 12Week 16Week 19Week 20
Placebo3.34-0.08-0.08-0.14-0.14-0.08-0.06-0.04-0.01
Vadadustat3.380.020.120.180.230.30.280.260.3

Change From Baseline in Reticulocyte Count

Blood samples were collected to assess reticulocyte count. Baseline was defined as mean of two samples obtained prior to dosing (Screening and Baseline). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. A positive change from Baseline indicated reticulocyte count increased. (NCT01906489)
Timeframe: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20

,
Intervention10^6 cells per microliter (Mean)
BaselineWeek 2Week 4Week 6Week 8Week 12Week 16Week 19Week 20
Placebo1.97-0.070.060.080.060.02-0.03-0.050.12
Vadadustat2.120.610.290.19-0.08-0.120.030.070.03

Mean Number of ESA Rescue Doses Administered Per Participant

Participants were administered epoetin alfa or darbepoetin alfa as a rescue medication who have met the Hgb rescue criteria in addition to having experienced a clinically significant worsening of their anemia or the symptoms of anemia. (NCT01906489)
Timeframe: Up to 20 Weeks

InterventionDoses/participants (Mean)
Epoetin Alfa
Vadadustat1.7

Mean Number of ESA Rescue Doses Administered Per Participant

Participants were administered epoetin alfa or darbepoetin alfa as a rescue medication who have met the Hgb rescue criteria in addition to having experienced a clinically significant worsening of their anemia or the symptoms of anemia. (NCT01906489)
Timeframe: Up to 20 Weeks

InterventionDoses/participants (Mean)
Epoetin AlfaDarbepoetin Alfa
Placebo2.84.3

Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values

Parameters assessed for laboratory values included hematology, serum chemistry, and urinalysis. The investigator was responsible for reviewing laboratory results for clinically significant changes. (NCT01906489)
Timeframe: Up to 20 Weeks

,
InterventionParticipants (Count of Participants)
HematologySerum chemistryUrinalysis
Placebo000
Vadadustat010

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (SAEs)

An Adverse Event (AE) was defined as any untoward medical occurrence, signs, symptoms, disease, or laboratory or physiological observations occurring in a participant administered with drug, regardless of a causal relationship with that treatment or usage. This also included all suspected adverse medication reactions, reactions from medication overdose, abuse, withdrawal, sensitivity, toxicity, unrelated illnesses, including worsening a pre-existing condition, injury, or accidents. Serious Adverse Events (SAEs) was defined as any life-threatening condition; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or death. (NCT01906489)
Timeframe: Up to 20 Weeks

,
InterventionParticipants (Count of Participants)
TEAEsTreatment-emergent SAEs
Placebo2911
Vadadustat5833

Percentage of Participants Who Received ESA Rescue

Participants were administered epoetin alfa or darbepoetin alfa as a rescue medication who met the Hgb rescue criteria in addition to having experienced a clinically significant worsening of their anemia or the symptoms of anemia. (NCT01906489)
Timeframe: Up to 20 Weeks

,
InterventionPercentage of participants (Number)
Epoetin AlfaDarbepoetin Alfa
Placebo12.54.2
Vadadustat4.40

Reviews

30 reviews available for glycine and Anemia

ArticleYear
The efficacy and safety of roxadustat for the treatment of anemia in non-dialysis dependent chronic kidney disease patients: An updated systematic review and meta-analysis of randomized clinical trials.
    PloS one, 2022, Volume: 17, Issue:4

    Topics: Anemia; Ferritins; Glycine; Hepcidins; Humans; Iron; Isoquinolines; Randomized Controlled Trials as

2022
Roxadustat regulates iron metabolism in dialysis-dependent and non-dialysis-dependent chronic kidney disease patients: A meta-analysis.
    Journal of the Formosan Medical Association = Taiwan yi zhi, 2022, Volume: 121, Issue:11

    Topics: Anemia; Ferritins; Glycine; Hemoglobins; Hepcidins; Humans; Iron; Isoquinolines; Renal Insufficiency

2022
The role of roxadustat in chronic kidney disease patients complicated with anemia.
    The Korean journal of internal medicine, 2023, Volume: 38, Issue:2

    Topics: Anemia; Glycine; Humans; Iron; Isoquinolines; Renal Insufficiency, Chronic

2023
Roxadustat: Do we know all the answers?
    Biomolecules & biomedicine, 2023, May-01, Volume: 23, Issue:3

    Topics: Anemia; Glycine; Humans; Hypoxia-Inducible Factor-Proline Dioxygenases; Iron; Isoquinolines; Renal I

2023
The efficacy and safety of roxadustat for anemia in patients with dialysis-dependent chronic kidney disease: a systematic review and meta-analysis.
    Renal failure, 2023, Volume: 45, Issue:1

    Topics: Anemia; Cardiovascular Diseases; Cholesterol, LDL; Glycine; Hematinics; Hemoglobins; Humans; Iron; R

2023
Hypoxia-Inducible Factor Activators in Renal Anemia: Current Clinical Experience.
    Advances in chronic kidney disease, 2019, Volume: 26, Issue:4

    Topics: Anemia; Barbiturates; Glycine; Humans; Isoquinolines; Picolinic Acids; Prolyl-Hydroxylase Inhibitors

2019
Roxadustat (FG-4592) treatment for anemia in dialysis-dependent (DD) and not dialysis-dependent (NDD) chronic kidney disease patients: A systematic review and meta-analysis.
    Pharmacological research, 2020, Volume: 155

    Topics: Anemia; Glycine; Humans; Isoquinolines; Randomized Controlled Trials as Topic; Renal Dialysis; Renal

2020
The efficacy and economic evaluation of roxadustat treatment for anemia in patients with kidney disease not receiving dialysis.
    Expert review of pharmacoeconomics & outcomes research, 2020, Volume: 20, Issue:4

    Topics: Anemia; Cost-Benefit Analysis; Glycine; Humans; Isoquinolines; Markov Chains; Quality-Adjusted Life

2020
The prolyl hydroxylase inhibitor roxadustat: Paradigm in drug discovery and prospects for clinical application beyond anemia.
    Drug discovery today, 2020, Volume: 25, Issue:7

    Topics: Anemia; Animals; Drug Discovery; Erythropoietin; Glycine; Humans; Isoquinolines; Prolyl-Hydroxylase

2020
Current treatment practices for anemia in patients with chronic kidney disease and future opportunities with hypoxia-inducible factor prolyl hydroxylase inhibitors: a narrative review.
    International urology and nephrology, 2021, Volume: 53, Issue:2

    Topics: Anemia; Barbiturates; Forecasting; Glycine; Humans; Hypoxia-Inducible Factor-Proline Dioxygenases; I

2021
Vadadustat: First Approval.
    Drugs, 2020, Volume: 80, Issue:13

    Topics: Adult; Anemia; Clinical Trials as Topic; Drug Approval; Drug Development; Glycine; History, 21st Cen

2020
Daprodustat: First Approval.
    Drugs, 2020, Volume: 80, Issue:14

    Topics: Anemia; Animals; Barbiturates; Drug Approval; Glycine; Humans; Japan; Molecular Structure; Prolyl Hy

2020
The efficacy and safety of roxadustat for anemia in patients with chronic kidney disease: a meta-analysis.
    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2021, 08-27, Volume: 36, Issue:9

    Topics: Anemia; Glycine; Humans; Isoquinolines; Randomized Controlled Trials as Topic; Renal Dialysis; Renal

2021
The efficacy and safety of roxadustat treatment for anemia in patients with kidney disease: a meta-analysis and systematic review.
    International urology and nephrology, 2021, Volume: 53, Issue:5

    Topics: Anemia; Glycine; Humans; Isoquinolines; Renal Insufficiency, Chronic; Treatment Outcome

2021
Whether Prolyl Hydroxylase Blocker-Roxadustat-In the Treatment of Anemia in Patients with Chronic Kidney Disease Is the Future?
    International journal of environmental research and public health, 2021, 02-08, Volume: 18, Issue:4

    Topics: Anemia; Glycine; Humans; Isoquinolines; Prolyl Hydroxylases; Renal Insufficiency, Chronic

2021
Successful application of roxadustat in the treatment of patients with anti-erythropoietin antibody-mediated renal anaemia: a case report and literature review.
    The Journal of international medical research, 2021, Volume: 49, Issue:4

    Topics: Anemia; Erythropoietin; Female; Glycine; Humans; Isoquinolines; Middle Aged; Recombinant Proteins

2021
Effectiveness and safety of roxadustat in the treatment of anemia of kidney disease: a systematic review and meta-analysis.
    Annals of palliative medicine, 2021, Volume: 10, Issue:4

    Topics: Anemia; China; Glycine; Humans; Isoquinolines

2021
Roxadustat for the treatment of anemia in patients with chronic kidney diseases: a meta-analysis.
    Aging, 2021, 06-11, Volume: 13, Issue:13

    Topics: Anemia; Animals; Glycine; Hematinics; Hemoglobins; Humans; Isoquinolines; Renal Insufficiency, Chron

2021
Efficacy and safety of roxadustat for anaemia in dialysis-dependent and non-dialysis-dependent chronic kidney disease patients: A systematic review and meta-analysis.
    British journal of clinical pharmacology, 2022, Volume: 88, Issue:3

    Topics: Anemia; Female; Glycine; Hematinics; Humans; Iron; Isoquinolines; Male; Renal Dialysis; Renal Insuff

2022
HIF-prolyl hydroxylases as therapeutic targets in erythropoiesis and iron metabolism.
    Hemodialysis international. International Symposium on Home Hemodialysis, 2017, Volume: 21 Suppl 1

    Topics: Anemia; Barbiturates; Clinical Trials as Topic; Erythropoiesis; Erythropoietin; Glycine; Humans; Hyp

2017
An Emerging Treatment Alternative for Anemia in Chronic Kidney Disease Patients: A Review of Daprodustat.
    Advances in therapy, 2018, Volume: 35, Issue:1

    Topics: Anemia; Barbiturates; Clinical Trials, Phase III as Topic; Erythropoietin; Glycine; Humans; Renal Di

2018
Effect of daprodustat on anemia in patients with chronic kidney disease: a meta-analysis.
    International urology and nephrology, 2018, Volume: 50, Issue:12

    Topics: Anemia; Barbiturates; Glycine; Hemoglobins; Hepcidins; Humans; Hypoxia-Inducible Factor-Proline Diox

2018
Roxadustat: First Global Approval.
    Drugs, 2019, Volume: 79, Issue:5

    Topics: Anemia; China; Drug Approval; Erythropoiesis; Erythropoietin; Glycine; Hepcidins; Humans; Isoquinoli

2019
Targeting Hypoxia-Inducible Factors for the Treatment of Anemia in Chronic Kidney Disease Patients.
    American journal of nephrology, 2017, Volume: 45, Issue:3

    Topics: Anemia; Animals; Barbiturates; Blood Pressure; Disease Models, Animal; Drug Design; Drug Interaction

2017
Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors: A Potential New Treatment for Anemia in Patients With CKD.
    American journal of kidney diseases : the official journal of the National Kidney Foundation, 2017, Volume: 69, Issue:6

    Topics: Anemia; Barbiturates; Clinical Trials as Topic; Enzyme Inhibitors; Erythropoietin; Glycine; Humans;

2017
A New Approach to the Management of Anemia in CKD Patients: A Review on Roxadustat.
    Advances in therapy, 2017, Volume: 34, Issue:4

    Topics: Anemia; Glycine; Hematinics; Humans; Isoquinolines; Renal Insufficiency, Chronic

2017
Hypoxia-inducible factor stabilizers and other small-molecule erythropoiesis-stimulating agents in current and preventive doping analysis.
    Drug testing and analysis, 2012, Volume: 4, Issue:11

    Topics: Anemia; Animals; Cobalt; Doping in Sports; Erythropoiesis; GATA Transcription Factors; Glycine; Hema

2012
DETERMINATION OF RED BLOOD CELL LIFE SPAN.
    JAMA, 1964, Apr-27, Volume: 188

    Topics: Anemia; Carbon Isotopes; Chromium Isotopes; Erythrocytes; Glycine; Hemoglobins; Hemoglobins, Abnorma

1964
[ON THE SHUNT HYPERBILIRUBINEMIA].
    Naika hokan. Japanese archives of internal medicine, 1964, Volume: 11

    Topics: Anemia; Anemia, Hypochromic; Anemia, Pernicious; Anemia, Sickle Cell; Bilirubin; Blood Chemical Anal

1964
Endogenous carbon monoxide production.
    The New England journal of medicine, 1970, Jan-22, Volume: 282, Issue:4

    Topics: Anemia; Animals; Bilirubin; Carbon Isotopes; Carbon Monoxide; Dogs; Erythrocytes; Glycine; Heme; Hem

1970

Trials

52 trials available for glycine and Anemia

ArticleYear
Roxadustat for the Maintenance Treatment of Anemia in Patients with End-Stage Kidney Disease on Stable Dialysis: A European Phase 3, Randomized, Open-Label, Active-Controlled Study (PYRENEES).
    Advances in therapy, 2021, Volume: 38, Issue:10

    Topics: Anemia; Glycine; Hematinics; Hemoglobins; Humans; Isoquinolines; Kidney Failure, Chronic; Renal Dial

2021
Factors Affecting Doses of Roxadustat Versus Darbepoetin Alfa for Anemia in Nondialysis Patients.
    American journal of nephrology, 2021, Volume: 52, Issue:9

    Topics: Aged; Aged, 80 and over; Anemia; Darbepoetin alfa; Female; Glycine; Hematinics; Humans; Isoquinoline

2021
An evaluation of roxadustat for the treatment of anemia associated with chronic kidney disease.
    Expert opinion on pharmacotherapy, 2022, Volume: 23, Issue:1

    Topics: Anemia; Glycine; Humans; Isoquinolines; Renal Insufficiency, Chronic

2022
Roxadustat for the treatment of anemia in patients with lower-risk myelodysplastic syndrome: Open-label, dose-selection, lead-in stage of a phase 3 study.
    American journal of hematology, 2022, 02-01, Volume: 97, Issue:2

    Topics: Aged; Anemia; Double-Blind Method; Female; Glycine; Humans; Isoquinolines; Male; Middle Aged; Myelod

2022
Roxadustat for the treatment of anemia in patients with lower-risk myelodysplastic syndrome: Open-label, dose-selection, lead-in stage of a phase 3 study.
    American journal of hematology, 2022, 02-01, Volume: 97, Issue:2

    Topics: Aged; Anemia; Double-Blind Method; Female; Glycine; Humans; Isoquinolines; Male; Middle Aged; Myelod

2022
Roxadustat for the treatment of anemia in patients with lower-risk myelodysplastic syndrome: Open-label, dose-selection, lead-in stage of a phase 3 study.
    American journal of hematology, 2022, 02-01, Volume: 97, Issue:2

    Topics: Aged; Anemia; Double-Blind Method; Female; Glycine; Humans; Isoquinolines; Male; Middle Aged; Myelod

2022
Roxadustat for the treatment of anemia in patients with lower-risk myelodysplastic syndrome: Open-label, dose-selection, lead-in stage of a phase 3 study.
    American journal of hematology, 2022, 02-01, Volume: 97, Issue:2

    Topics: Aged; Anemia; Double-Blind Method; Female; Glycine; Humans; Isoquinolines; Male; Middle Aged; Myelod

2022
Daprodustat for the Treatment of Anemia in Patients Undergoing Dialysis.
    The New England journal of medicine, 2021, 12-16, Volume: 385, Issue:25

    Topics: Aged; Anemia; Barbiturates; Cardiovascular Diseases; Darbepoetin alfa; Epoetin Alfa; Female; Glycine

2021
Daprodustat for the Treatment of Anemia in Patients Not Undergoing Dialysis.
    The New England journal of medicine, 2021, 12-16, Volume: 385, Issue:25

    Topics: Aged; Anemia; Barbiturates; Cardiovascular Diseases; Darbepoetin alfa; Female; Glycine; Hematinics;

2021
A Prospective, Self-Controlled Pilot Study of the Efficacy of Roxadustat for Erythropoietin Hyporesponsiveness in Patients Requiring Chronic Ambulatory Peritoneal Dialysis.
    Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation, 2022, Volume: 32, Issue:5

    Topics: Anemia; C-Reactive Protein; Erythropoietin; Glycine; Hemoglobins; Humans; Inflammation; Interleukin-

2022
Efficacy and Safety of Daprodustat for Treatment of Anemia of Chronic Kidney Disease in Incident Dialysis Patients: A Randomized Clinical Trial.
    JAMA internal medicine, 2022, 06-01, Volume: 182, Issue:6

    Topics: Anemia; Barbiturates; Darbepoetin alfa; Erythropoietin; Female; Glycine; Hematinics; Hemoglobins; Hu

2022
Clinical parameters among patients in Japan with anemia and non-dialysis-dependent chronic kidney disease with and without diabetes mellitus who received roxadustat.
    Clinical and experimental nephrology, 2022, Volume: 26, Issue:9

    Topics: Anemia; Cholesterol; Diabetes Mellitus; Glycated Hemoglobin; Glycine; Hemoglobins; Humans; Iron; Iso

2022
Open-label, Phase 2 study of roxadustat for the treatment of anemia in patients receiving chemotherapy for non-myeloid malignancies.
    American journal of hematology, 2023, Volume: 98, Issue:5

    Topics: Anemia; Antineoplastic Agents; Erythropoietin; Glycine; Hematinics; Hemoglobins; Humans; Isoquinolin

2023
Safety of Roxadustat Versus Erythropoiesis-Stimulating Agents in Patients with Anemia of Non-dialysis-Dependent or Incident-to-Dialysis Chronic Kidney Disease: Pooled Analysis of Four Phase 3 Studies.
    Advances in therapy, 2023, Volume: 40, Issue:4

    Topics: Anemia; Erythropoiesis; Female; Glycine; Hematinics; Hemoglobins; Humans; Isoquinolines; Male; Renal

2023
A phase 3b, multicenter, open-label, single-arm study of roxadustat (ASPEN): Operational learnings within United States dialysis organizations.
    Hemodialysis international. International Symposium on Home Hemodialysis, 2023, Volume: 27, Issue:4

    Topics: Adolescent; Adult; Anemia; COVID-19; Glycine; Hematinics; Hemoglobins; Humans; Isoquinolines; Renal

2023
A randomized, 29-day, dose-ranging, efficacy and safety study of daprodustat, administered three times weekly in patients with anemia on hemodialysis.
    BMC nephrology, 2019, 10-16, Volume: 20, Issue:1

    Topics: Aged; Aged, 80 and over; Anemia; Barbiturates; Dose-Response Relationship, Drug; Double-Blind Method

2019
A Single-Dose, Open-Label, Randomized, Two-Way Crossover Study in Healthy Japanese Participants to Evaluate the Bioequivalence and the Food Effect on the Pharmacokinetics of Daprodustat.
    Clinical pharmacology in drug development, 2020, Volume: 9, Issue:8

    Topics: Administration, Oral; Adult; Anemia; Area Under Curve; Asian People; Barbiturates; Cross-Over Studie

2020
Phase 3, Randomized, Double-Blind, Active-Comparator (Darbepoetin Alfa) Study of Oral Roxadustat in CKD Patients with Anemia on Hemodialysis in Japan.
    Journal of the American Society of Nephrology : JASN, 2020, Volume: 31, Issue:7

    Topics: Adult; Aged; Aged, 80 and over; Anemia; Contusions; Darbepoetin alfa; Diarrhea; Double-Blind Method;

2020
A Phase 3, Multicenter, Randomized, Two-Arm, Open-Label Study of Intermittent Oral Dosing of Roxadustat for the Treatment of Anemia in Japanese Erythropoiesis-Stimulating Agent-Naïve Chronic Kidney Disease Patients Not on Dialysis.
    Nephron, 2020, Volume: 144, Issue:8

    Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anemia; Dialysis; Female; Glycine; Hematinics;

2020
Oral Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor Roxadustat (FG-4592) for Treatment of Anemia in Chronic Kidney Disease: A Placebo-Controlled Study of Pharmacokinetic and Pharmacodynamic Profiles in Hemodialysis Patients.
    Journal of clinical pharmacology, 2020, Volume: 60, Issue:11

    Topics: Administration, Oral; Adult; Aged; Anemia; Area Under Curve; Dose-Response Relationship, Drug; Doubl

2020
Efficacy and Safety of Daprodustat Compared with Darbepoetin Alfa in Japanese Hemodialysis Patients with Anemia: A Randomized, Double-Blind, Phase 3 Trial.
    Clinical journal of the American Society of Nephrology : CJASN, 2020, 08-07, Volume: 15, Issue:8

    Topics: Aged; Anemia; Barbiturates; Biomarkers; Darbepoetin alfa; Double-Blind Method; Female; Glycine; Hema

2020
Cardiovascular safety and efficacy of vadadustat for the treatment of anemia in non-dialysis-dependent CKD: Design and baseline characteristics.
    American heart journal, 2021, Volume: 235

    Topics: Administration, Oral; Aged; Anemia; Female; Follow-Up Studies; Glycine; Humans; Male; Middle Aged; P

2021
Global Phase 3 programme of vadadustat for treatment of anaemia of chronic kidney disease: rationale, study design and baseline characteristics of dialysis-dependent patients in the INNO2VATE trials.
    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2021, 11-09, Volume: 36, Issue:11

    Topics: Adult; Anemia; Erythropoietin; Glycine; Hematinics; Hemoglobins; Humans; Picolinic Acids; Renal Dial

2021
Factors affecting the doses of roxadustat vs darbepoetin alfa for anemia treatment in hemodialysis patients.
    Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy, 2021, Volume: 25, Issue:5

    Topics: Adult; Aged; Aged, 80 and over; Anemia; Darbepoetin alfa; Dose-Response Relationship, Drug; Double-B

2021
Vadadustat for anemia in chronic kidney disease patients on peritoneal dialysis: A phase 3 open-label study in Japan.
    Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy, 2021, Volume: 25, Issue:5

    Topics: Anemia; Female; Glycine; Humans; Japan; Male; Middle Aged; Peritoneal Dialysis; Picolinic Acids; Ren

2021
Daprodustat Compared with Epoetin Beta Pegol for Anemia in Japanese Patients Not on Dialysis: A 52-Week Randomized Open-Label Phase 3 Trial.
    American journal of nephrology, 2021, Volume: 52, Issue:1

    Topics: Adolescent; Adult; Aged; Anemia; Barbiturates; Erythropoietin; Female; Glycine; Humans; Japan; Male;

2021
Roxadustat for anemia in patients with end-stage renal disease incident to dialysis.
    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2021, 08-27, Volume: 36, Issue:9

    Topics: Anemia; Epoetin Alfa; Erythropoietin; Glycine; Hematinics; Hemoglobins; Humans; Isoquinolines; Kidne

2021
Roxadustat for the treatment of anemia in chronic kidney disease patients not on dialysis: a Phase 3, randomized, double-blind, placebo-controlled study (ALPS).
    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2021, 08-27, Volume: 36, Issue:9

    Topics: Anemia; Double-Blind Method; Glycine; Hemoglobins; Humans; Isoquinolines; Renal Dialysis; Renal Insu

2021
Efficacy and safety of vadadustat compared with darbepoetin alfa in Japanese anemic patients on hemodialysis: a Phase 3, multicenter, randomized, double-blind study.
    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2021, 08-27, Volume: 36, Issue:9

    Topics: Anemia; Darbepoetin alfa; Double-Blind Method; Erythropoietin; Glycine; Hematinics; Hemoglobins; Hum

2021
Safety and Efficacy of Vadadustat for Anemia in Patients Undergoing Dialysis.
    The New England journal of medicine, 2021, 04-29, Volume: 384, Issue:17

    Topics: Aged; Anemia; Cardiovascular Diseases; Darbepoetin alfa; Female; Glycine; Hematinics; Hemoglobins; H

2021
Safety and Efficacy of Vadadustat for Anemia in Patients Undergoing Dialysis.
    The New England journal of medicine, 2021, 04-29, Volume: 384, Issue:17

    Topics: Aged; Anemia; Cardiovascular Diseases; Darbepoetin alfa; Female; Glycine; Hematinics; Hemoglobins; H

2021
Safety and Efficacy of Vadadustat for Anemia in Patients Undergoing Dialysis.
    The New England journal of medicine, 2021, 04-29, Volume: 384, Issue:17

    Topics: Aged; Anemia; Cardiovascular Diseases; Darbepoetin alfa; Female; Glycine; Hematinics; Hemoglobins; H

2021
Safety and Efficacy of Vadadustat for Anemia in Patients Undergoing Dialysis.
    The New England journal of medicine, 2021, 04-29, Volume: 384, Issue:17

    Topics: Aged; Anemia; Cardiovascular Diseases; Darbepoetin alfa; Female; Glycine; Hematinics; Hemoglobins; H

2021
Vadadustat in Patients with Anemia and Non-Dialysis-Dependent CKD.
    The New England journal of medicine, 2021, 04-29, Volume: 384, Issue:17

    Topics: Administration, Oral; Aged; Anemia; Cardiovascular Diseases; Darbepoetin alfa; Female; Glycine; Hema

2021
Vadadustat in Patients with Anemia and Non-Dialysis-Dependent CKD.
    The New England journal of medicine, 2021, 04-29, Volume: 384, Issue:17

    Topics: Administration, Oral; Aged; Anemia; Cardiovascular Diseases; Darbepoetin alfa; Female; Glycine; Hema

2021
Vadadustat in Patients with Anemia and Non-Dialysis-Dependent CKD.
    The New England journal of medicine, 2021, 04-29, Volume: 384, Issue:17

    Topics: Administration, Oral; Aged; Anemia; Cardiovascular Diseases; Darbepoetin alfa; Female; Glycine; Hema

2021
Vadadustat in Patients with Anemia and Non-Dialysis-Dependent CKD.
    The New England journal of medicine, 2021, 04-29, Volume: 384, Issue:17

    Topics: Administration, Oral; Aged; Anemia; Cardiovascular Diseases; Darbepoetin alfa; Female; Glycine; Hema

2021
Efficacy and safety of daprodustat in Japanese peritoneal dialysis patients.
    Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy, 2021, Volume: 25, Issue:6

    Topics: Anemia; Barbiturates; Cohort Studies; Female; Glycine; Humans; Japan; Male; Middle Aged; Peritoneal

2021
Roxadustat for the treatment of anaemia in chronic kidney disease patients not on dialysis: a Phase 3, randomized, open-label, active-controlled study (DOLOMITES).
    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2021, 08-27, Volume: 36, Issue:9

    Topics: Anemia; Calcium Carbonate; Glycine; Hematinics; Hemoglobins; Humans; Isoquinolines; Magnesium; Renal

2021
A phase 3, open-label, single-arm study of vadadustat for anemia in chronic kidney disease for Japanese patients on hemodialysis not receiving erythropoiesis-stimulating agents.
    Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy, 2022, Volume: 26, Issue:1

    Topics: Anemia; Female; Glycine; Hematinics; Humans; Japan; Male; Middle Aged; Picolinic Acids; Renal Dialys

2022
Roxadustat treatment for anemia in peritoneal dialysis patients: A randomized controlled trial.
    Journal of the Formosan Medical Association = Taiwan yi zhi, 2022, Volume: 121, Issue:2

    Topics: Anemia; Glycine; Hemoglobins; Humans; Isoquinolines; Peritoneal Dialysis; Renal Insufficiency, Chron

2022
Clinical Trial of Vadadustat in Patients with Anemia Secondary to Stage 3 or 4 Chronic Kidney Disease.
    American journal of nephrology, 2017, Volume: 45, Issue:5

    Topics: Adult; Aged; Anemia; Biomarkers; C-Reactive Protein; Cholesterol; Dose-Response Relationship, Drug;

2017
Phase 2 studies of oral hypoxia-inducible factor prolyl hydroxylase inhibitor FG-4592 for treatment of anemia in China.
    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2017, Aug-01, Volume: 32, Issue:8

    Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Cohort Studies; Double-Blind Method; Female; Gly

2017
Effects of vadadustat on hemoglobin concentrations in patients receiving hemodialysis previously treated with erythropoiesis-stimulating agents.
    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2019, 01-01, Volume: 34, Issue:1

    Topics: Adolescent; Adult; Aged; Anemia; Erythropoiesis; Female; Glycine; Hematinics; Hemoglobins; Humans; M

2019
Evaluation of Food and Spherical Carbon Adsorbent Effects on the Pharmacokinetics of Roxadustat in Healthy Nonelderly Adult Male Japanese Subjects.
    Clinical pharmacology in drug development, 2019, Volume: 8, Issue:3

    Topics: Administration, Oral; Adsorption; Adult; Anemia; Area Under Curve; Charcoal; Cross-Over Studies; Dru

2019
Roxadustat Treatment of Chronic Kidney Disease-Associated Anemia in Japanese Patients Not on Dialysis: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Trial.
    Advances in therapy, 2019, Volume: 36, Issue:6

    Topics: Adult; Aged; Anemia; Chronic Disease; Double-Blind Method; Female; Glycine; Humans; Isoquinolines; J

2019
Intermittent Oral Dosing of Roxadustat in Peritoneal Dialysis Chronic Kidney Disease Patients with Anemia: A Randomized, Phase 3, Multicenter, Open-Label Study.
    Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy, 2020, Volume: 24, Issue:2

    Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anemia; Dose-Response Relationship, Drug; Fema

2020
A 24-Week Anemia Correction Study of Daprodustat in Japanese Dialysis Patients.
    Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy, 2020, Volume: 24, Issue:2

    Topics: Aged; Anemia; Barbiturates; Female; Glycine; Hemoglobins; Humans; Hypoxia-Inducible Factor-Proline D

2020
Roxadustat for Anemia in Patients with Kidney Disease Not Receiving Dialysis.
    The New England journal of medicine, 2019, 09-12, Volume: 381, Issue:11

    Topics: Acidosis; Adult; Aged; Anemia; Cholesterol; Double-Blind Method; Female; Glycine; Hematinics; Hemogl

2019
Roxadustat for Anemia in Patients with Kidney Disease Not Receiving Dialysis.
    The New England journal of medicine, 2019, 09-12, Volume: 381, Issue:11

    Topics: Acidosis; Adult; Aged; Anemia; Cholesterol; Double-Blind Method; Female; Glycine; Hematinics; Hemogl

2019
Roxadustat for Anemia in Patients with Kidney Disease Not Receiving Dialysis.
    The New England journal of medicine, 2019, 09-12, Volume: 381, Issue:11

    Topics: Acidosis; Adult; Aged; Anemia; Cholesterol; Double-Blind Method; Female; Glycine; Hematinics; Hemogl

2019
Roxadustat for Anemia in Patients with Kidney Disease Not Receiving Dialysis.
    The New England journal of medicine, 2019, 09-12, Volume: 381, Issue:11

    Topics: Acidosis; Adult; Aged; Anemia; Cholesterol; Double-Blind Method; Female; Glycine; Hematinics; Hemogl

2019
Roxadustat for Anemia in Patients with Kidney Disease Not Receiving Dialysis.
    The New England journal of medicine, 2019, 09-12, Volume: 381, Issue:11

    Topics: Acidosis; Adult; Aged; Anemia; Cholesterol; Double-Blind Method; Female; Glycine; Hematinics; Hemogl

2019
Roxadustat for Anemia in Patients with Kidney Disease Not Receiving Dialysis.
    The New England journal of medicine, 2019, 09-12, Volume: 381, Issue:11

    Topics: Acidosis; Adult; Aged; Anemia; Cholesterol; Double-Blind Method; Female; Glycine; Hematinics; Hemogl

2019
Roxadustat for Anemia in Patients with Kidney Disease Not Receiving Dialysis.
    The New England journal of medicine, 2019, 09-12, Volume: 381, Issue:11

    Topics: Acidosis; Adult; Aged; Anemia; Cholesterol; Double-Blind Method; Female; Glycine; Hematinics; Hemogl

2019
Roxadustat for Anemia in Patients with Kidney Disease Not Receiving Dialysis.
    The New England journal of medicine, 2019, 09-12, Volume: 381, Issue:11

    Topics: Acidosis; Adult; Aged; Anemia; Cholesterol; Double-Blind Method; Female; Glycine; Hematinics; Hemogl

2019
Roxadustat for Anemia in Patients with Kidney Disease Not Receiving Dialysis.
    The New England journal of medicine, 2019, 09-12, Volume: 381, Issue:11

    Topics: Acidosis; Adult; Aged; Anemia; Cholesterol; Double-Blind Method; Female; Glycine; Hematinics; Hemogl

2019
Roxadustat Treatment for Anemia in Patients Undergoing Long-Term Dialysis.
    The New England journal of medicine, 2019, 09-12, Volume: 381, Issue:11

    Topics: Adult; Aged; Analysis of Variance; Anemia; Cholesterol; Double-Blind Method; Epoetin Alfa; Female; G

2019
Roxadustat Treatment for Anemia in Patients Undergoing Long-Term Dialysis.
    The New England journal of medicine, 2019, 09-12, Volume: 381, Issue:11

    Topics: Adult; Aged; Analysis of Variance; Anemia; Cholesterol; Double-Blind Method; Epoetin Alfa; Female; G

2019
Roxadustat Treatment for Anemia in Patients Undergoing Long-Term Dialysis.
    The New England journal of medicine, 2019, 09-12, Volume: 381, Issue:11

    Topics: Adult; Aged; Analysis of Variance; Anemia; Cholesterol; Double-Blind Method; Epoetin Alfa; Female; G

2019
Roxadustat Treatment for Anemia in Patients Undergoing Long-Term Dialysis.
    The New England journal of medicine, 2019, 09-12, Volume: 381, Issue:11

    Topics: Adult; Aged; Analysis of Variance; Anemia; Cholesterol; Double-Blind Method; Epoetin Alfa; Female; G

2019
Randomized trial comparing ferric carboxymaltose vs oral ferrous glycine sulphate for postoperative anaemia after total knee arthroplasty.
    British journal of anaesthesia, 2014, Volume: 113, Issue:3

    Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anemia; Arthroplasty, Replacement, Knee; Femal

2014
Phase I dose-escalation studies of SNX-5422, an orally bioavailable heat shock protein 90 inhibitor, in patients with refractory solid tumours.
    European journal of cancer (Oxford, England : 1990), 2014, Volume: 50, Issue:17

    Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Benzamides; Bio

2014
Randomized placebo-controlled dose-ranging and pharmacodynamics study of roxadustat (FG-4592) to treat anemia in nondialysis-dependent chronic kidney disease (NDD-CKD) patients.
    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2015, Volume: 30, Issue:10

    Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Cohort Studies; Dose-Response Relationship, Drug

2015
Four-Week Studies of Oral Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor GSK1278863 for Treatment of Anemia.
    Journal of the American Society of Nephrology : JASN, 2016, Volume: 27, Issue:4

    Topics: Aged; Anemia; Barbiturates; Erythropoietin; Female; Glycine; Hemoglobins; Humans; Hypoxia-Inducible

2016
Four-Week Studies of Oral Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor GSK1278863 for Treatment of Anemia.
    Journal of the American Society of Nephrology : JASN, 2016, Volume: 27, Issue:4

    Topics: Aged; Anemia; Barbiturates; Erythropoietin; Female; Glycine; Hemoglobins; Humans; Hypoxia-Inducible

2016
Four-Week Studies of Oral Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor GSK1278863 for Treatment of Anemia.
    Journal of the American Society of Nephrology : JASN, 2016, Volume: 27, Issue:4

    Topics: Aged; Anemia; Barbiturates; Erythropoietin; Female; Glycine; Hemoglobins; Humans; Hypoxia-Inducible

2016
Four-Week Studies of Oral Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor GSK1278863 for Treatment of Anemia.
    Journal of the American Society of Nephrology : JASN, 2016, Volume: 27, Issue:4

    Topics: Aged; Anemia; Barbiturates; Erythropoietin; Female; Glycine; Hemoglobins; Humans; Hypoxia-Inducible

2016
Roxadustat (FG-4592): Correction of Anemia in Incident Dialysis Patients.
    Journal of the American Society of Nephrology : JASN, 2016, Volume: 27, Issue:4

    Topics: Anemia; Female; Glycine; Hepcidins; Humans; Isoquinolines; Male; Middle Aged; Peritoneal Dialysis; R

2016
A Novel Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor (GSK1278863) for Anemia in CKD: A 28-Day, Phase 2A Randomized Trial.
    American journal of kidney diseases : the official journal of the National Kidney Foundation, 2016, Volume: 67, Issue:6

    Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Barbiturates; Female; Glycine; Humans; Hypoxia-I

2016
Roxadustat (FG-4592) Versus Epoetin Alfa for Anemia in Patients Receiving Maintenance Hemodialysis: A Phase 2, Randomized, 6- to 19-Week, Open-Label, Active-Comparator, Dose-Ranging, Safety and Exploratory Efficacy Study.
    American journal of kidney diseases : the official journal of the National Kidney Foundation, 2016, Volume: 67, Issue:6

    Topics: Adult; Aged; Aged, 80 and over; Anemia; Epoetin Alfa; Female; Glycine; Hematinics; Humans; Isoquinol

2016
Oral Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor Roxadustat (FG-4592) for the Treatment of Anemia in Patients with CKD.
    Clinical journal of the American Society of Nephrology : CJASN, 2016, 06-06, Volume: 11, Issue:6

    Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anemia; C-Reactive Protein; Cholesterol; Enzym

2016
A pharmacokinetics and safety phase 1/1b study of oral ixazomib in patients with multiple myeloma and severe renal impairment or end-stage renal disease requiring haemodialysis.
    British journal of haematology, 2016, Volume: 174, Issue:5

    Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anemia; Blood Proteins; Boron Compounds; Drug

2016
Vadadustat, a novel oral HIF stabilizer, provides effective anemia treatment in nondialysis-dependent chronic kidney disease.
    Kidney international, 2016, Volume: 90, Issue:5

    Topics: Aged; Anemia; Double-Blind Method; Female; Glycine; Humans; Hypoxia-Inducible Factor-Proline Dioxyge

2016
Effects of Daprodustat, a Novel Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor on Anemia Management in Japanese Hemodialysis Subjects.
    American journal of nephrology, 2017, Volume: 45, Issue:2

    Topics: Aged; Anemia; Barbiturates; Dose-Response Relationship, Drug; Double-Blind Method; Erythropoietin; F

2017

Other Studies

103 other studies available for glycine and Anemia

ArticleYear
Ixazomib, lenalidomide, and dexamethasone combination in "real-world" clinical practice in patients with relapsed/refractory multiple myeloma.
    Annals of hematology, 2022, Volume: 101, Issue:1

    Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Boron Compounds; Cohort Studies

2022
Vadadustat for Anemia in Patients with Dialysis-Dependent or Non-Dialysis-Dependent Chronic Kidney Disease.
    The New England journal of medicine, 2021, 10-14, Volume: 385, Issue:16

    Topics: Anemia; Glycine; Humans; Picolinic Acids; Renal Dialysis; Renal Insufficiency, Chronic

2021
Vadadustat for Anemia in Patients with Dialysis-Dependent or Non-Dialysis-Dependent Chronic Kidney Disease. Reply.
    The New England journal of medicine, 2021, 10-14, Volume: 385, Issue:16

    Topics: Anemia; Glycine; Humans; Picolinic Acids; Renal Dialysis; Renal Insufficiency, Chronic

2021
Targeting ineffective hematopoiesis in myelodysplastic syndromes.
    American journal of hematology, 2022, 02-01, Volume: 97, Issue:2

    Topics: Aged; Anemia; Blood Transfusion; Disease Management; Female; Glycine; Hematinics; Hematopoiesis; Hum

2022
Daprodustat for anaemia in CKD.
    Nature reviews. Nephrology, 2022, Volume: 18, Issue:1

    Topics: Anemia; Barbiturates; Glycine; Humans; Renal Insufficiency, Chronic

2022
Efficacy and safety of roxadustat in the treatment of renal allograft anemia patients: a case series.
    Annals of palliative medicine, 2021, Volume: 10, Issue:11

    Topics: Allografts; Anemia; Glycine; Humans; Hypoxia-Inducible Factor-Proline Dioxygenases; Isoquinolines; K

2021
The HIFα-Stabilizing Drug Roxadustat Increases the Number of Renal Epo-Producing Sca-1
    Cells, 2022, 02-21, Volume: 11, Issue:4

    Topics: Anemia; Animals; Erythropoietin; Glycine; Hypoxia; Isoquinolines; Kidney; Mice; Procollagen-Proline

2022
Therapeutic Effect of Roxadustat on Patients With Posttransplant Anemia.
    Transplantation proceedings, 2022, Volume: 54, Issue:3

    Topics: Anemia; Cholesterol, LDL; Ferritins; Glycine; Hemoglobins; Humans; Hypoxia-Inducible Factor-Proline

2022
Are there advantages of daprodustat over erythropoiesis-stimulating agents (ESAs) in treating anemia associated with chronic kidney disease (CKD)?
    Expert opinion on pharmacotherapy, 2022, Volume: 23, Issue:7

    Topics: Anemia; Barbiturates; Erythropoiesis; Glycine; Hematinics; Humans; Hypoxia-Inducible Factor-Proline

2022
Addition of roxadustat to erythropoiesis-stimulating agent (ESA) effectively corrects ESA-hyporesponsive anaemia in patients on peritoneal dialysis.
    Journal of clinical pharmacy and therapeutics, 2022, Volume: 47, Issue:10

    Topics: Anemia; Erythropoiesis; Glycine; Hematinics; Hemoglobins; Humans; Isoquinolines; Peritoneal Dialysis

2022
Daprodustat in renal anaemia: changing the response to cellular hypoxia, but is it a game changer?
    Cardiovascular research, 2022, 06-29, Volume: 118, Issue:8

    Topics: Anemia; Barbiturates; Cell Hypoxia; Glycine; Humans; Hypoxia; Renal Insufficiency, Chronic

2022
Daprodustat prevents cyclosporine-A-mediated anemia and peritubular capillary loss.
    Kidney international, 2022, Volume: 102, Issue:4

    Topics: Anemia; Animals; Barbiturates; Calcineurin; Cyclosporine; Glycine; Hemoglobins; Hypoxia; Mice; Prote

2022
Erythropoietic effects of vadadustat in patients with anemia associated with chronic kidney disease.
    American journal of hematology, 2022, Volume: 97, Issue:9

    Topics: Anemia; Clinical Trials, Phase III as Topic; Darbepoetin alfa; Erythropoiesis; Erythropoietin; Ferri

2022
Long-term efficacy, safety, and medication compliance of roxadustat on peritoneal dialysis patients with renal anemia affected by the COVID-19 pandemic: a retrospective study.
    Annals of palliative medicine, 2022, Volume: 11, Issue:6

    Topics: Anemia; Chronic Disease; COVID-19; Glycine; Humans; Iron; Isoquinolines; Medication Adherence; Pande

2022
Effect of Roxadustat on Factors Associated with Renal Fibrosis and Efficacy.
    Computational and mathematical methods in medicine, 2022, Volume: 2022

    Topics: Anemia; Fibrosis; Glycine; Hemoglobins; Hepcidins; Humans; Isoquinolines; Kidney Diseases; Transform

2022
Changes in Iron Availability with Roxadustat in Nondialysis- and Dialysis-Dependent Patients with Anemia of CKD.
    Kidney360, 2022, 09-29, Volume: 3, Issue:9

    Topics: Anemia; Clinical Trials, Phase III as Topic; Epoetin Alfa; Erythropoietin; Ferritins; Glycine; Hemog

2022
Suppression of thyroid profile during roxadustat treatment in chronic kidney disease patients.
    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2023, 05-31, Volume: 38, Issue:6

    Topics: Anemia; Glycine; Humans; Isoquinolines; Renal Insufficiency, Chronic; Thyroid Gland

2023
Changes of biomarkers for erythropoiesis, iron metabolism, and FGF23 by supplementation with roxadustat in patients on hemodialysis.
    Scientific reports, 2023, 02-23, Volume: 13, Issue:1

    Topics: Anemia; Biomarkers; Darbepoetin alfa; Dietary Supplements; Erythropoiesis; Erythropoietin; Ferritins

2023
Integrated proteomic and metabolomic profiling of urine of renal anemia patients uncovers the molecular mechanisms of roxadustat.
    Molecular omics, 2023, 07-10, Volume: 19, Issue:6

    Topics: Anemia; Glycine; Humans; Isoquinolines; Metabolomics; Proteomics; Renal Insufficiency, Chronic

2023
Correlation between blood concentration of roxadustat and clinical efficacy in patients with anemia of chronic kidney disease.
    Medicine, 2023, Apr-14, Volume: 102, Issue:15

    Topics: Anemia; Chronic Disease; Glycine; Humans; Hypoxia-Inducible Factor-Proline Dioxygenases; Isoquinolin

2023
What Is the Role of Daprodustat in Treatment of Anemia in People on Maintenance Dialysis?
    Clinical journal of the American Society of Nephrology : CJASN, 2023, 11-01, Volume: 18, Issue:11

    Topics: Anemia; Barbiturates; Glycine; Hemoglobins; Humans; Renal Dialysis; Renal Insufficiency, Chronic

2023
Evaluating the effect of Roxadustat on ventricular repolarization in patients undergoing peritoneal dialysis.
    European journal of medical research, 2023, Oct-11, Volume: 28, Issue:1

    Topics: Anemia; Glycine; Humans; Isoquinolines; Peritoneal Dialysis; Prospective Studies; Renal Insufficienc

2023
Roxadustat treatment for erythropoiesis-stimulating agent-hyporesponsive anemia in maintenance hemodialysis patients.
    The Journal of international medical research, 2023, Volume: 51, Issue:10

    Topics: Anemia; Erythropoiesis; Glycine; Hematinics; Hemoglobins; Humans; Interleukin-6; Iron; Isoquinolines

2023
A new approach to treating renal anaemia.
    Nature reviews. Nephrology, 2019, Volume: 15, Issue:12

    Topics: Anemia; Glycine; Humans; Isoquinolines; Renal Dialysis

2019
Stabilizing HIF to Ameliorate Anemia.
    Cell, 2020, 01-09, Volume: 180, Issue:1

    Topics: Anemia; Glycine; Humans; Hypoxia-Inducible Factor 1; Isoquinolines; Kidney; Prolyl Hydroxylases; Ren

2020
Inhibition of HIF prolyl-hydroxylase domain to correct anemia in patients with chronic kidney disease.
    Kidney international, 2020, Volume: 97, Issue:4

    Topics: Anemia; Glycine; Humans; Isoquinolines; Prolyl Hydroxylases; Renal Dialysis; Renal Insufficiency, Ch

2020
Nonclinical Characterization of the Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor Roxadustat, a Novel Treatment of Anemia of Chronic Kidney Disease.
    The Journal of pharmacology and experimental therapeutics, 2020, Volume: 374, Issue:2

    Topics: Anemia; Animals; Basic Helix-Loop-Helix Transcription Factors; Cell Line; Erythropoiesis; Erythropoi

2020
Roxadustat for Anemia in Patients with Chronic Kidney Disease.
    The New England journal of medicine, 2020, 07-02, Volume: 383, Issue:1

    Topics: Anemia; Glycine; Humans; Isoquinolines; Renal Dialysis; Renal Insufficiency, Chronic

2020
Roxadustat for Anemia in Patients with Chronic Kidney Disease.
    The New England journal of medicine, 2020, 07-02, Volume: 383, Issue:1

    Topics: Anemia; Glycine; Humans; Isoquinolines; Renal Dialysis; Renal Insufficiency, Chronic

2020
Roxadustat for Anemia in Patients with Chronic Kidney Disease.
    The New England journal of medicine, 2020, 07-02, Volume: 383, Issue:1

    Topics: Anemia; Glycine; Humans; Isoquinolines; Renal Dialysis; Renal Insufficiency, Chronic

2020
Roxadustat for Anemia in Patients with Chronic Kidney Disease.
    The New England journal of medicine, 2020, 07-02, Volume: 383, Issue:1

    Topics: Anemia; Glycine; Humans; Isoquinolines; Renal Dialysis; Renal Insufficiency, Chronic

2020
Roxadustat for Anemia in Patients with Chronic Kidney Disease. Reply.
    The New England journal of medicine, 2020, 07-02, Volume: 383, Issue:1

    Topics: Anemia; Glycine; Humans; Isoquinolines; Renal Insufficiency, Chronic

2020
Roxadustat for Anemia in Patients with Chronic Kidney Disease. Reply.
    The New England journal of medicine, 2020, 07-02, Volume: 383, Issue:1

    Topics: Anemia; Glycine; Humans; Isoquinolines; Renal Insufficiency, Chronic

2020
New Approaches for Anemia in MDS.
    Clinical lymphoma, myeloma & leukemia, 2020, Volume: 20 Suppl 1

    Topics: Activin Receptors, Type II; Anemia; Female; Glycine; Humans; Immunoglobulin Fc Fragments; Isoquinoli

2020
Role of Roxadustat for ESA-Resistant Renal Anemia? -Read with Caution.
    Journal of the American Society of Nephrology : JASN, 2020, Volume: 31, Issue:11

    Topics: Anemia; Darbepoetin alfa; Double-Blind Method; Glycine; Humans; Isoquinolines; Japan; Renal Dialysis

2020
Authors' Reply.
    Journal of the American Society of Nephrology : JASN, 2020, Volume: 31, Issue:11

    Topics: Anemia; Darbepoetin alfa; Double-Blind Method; Glycine; Humans; Isoquinolines; Japan; Renal Dialysis

2020
A Hypoxia-Inducible Factor Stabilizer Improves Hematopoiesis and Iron Metabolism Early after Administration to Treat Anemia in Hemodialysis Patients.
    International journal of molecular sciences, 2020, Sep-28, Volume: 21, Issue:19

    Topics: Aged; Aged, 80 and over; Anemia; Cell Count; Darbepoetin alfa; Drug Substitution; Erythrocytes; Eryt

2020
A case report of rhabdomyolysis caused by the use of roxadustat in the treatment caused by renal anaemia.
    International journal of clinical practice, 2021, Volume: 75, Issue:6

    Topics: Anemia; Glycine; Humans; Isoquinolines; Male; Renal Insufficiency, Chronic; Rhabdomyolysis

2021
Roxadustat in treating anemia in dialysis patients (ROAD): protocol and rationale of a multicenter prospective observational cohort study.
    BMC nephrology, 2021, 01-13, Volume: 22, Issue:1

    Topics: Anemia; Clinical Protocols; Cohort Studies; Glycine; Humans; Isoquinolines; Multicenter Studies as T

2021
Retinoic acid regulates erythropoietin production cooperatively with hypoxia-inducible factors in human iPSC-derived erythropoietin-producing cells.
    Scientific reports, 2021, 02-16, Volume: 11, Issue:1

    Topics: Anemia; Animals; Basic Helix-Loop-Helix Transcription Factors; Drug Evaluation, Preclinical; Drug Th

2021
Suppression of thyrotropin secretion during roxadustat treatment for renal anemia in a patient undergoing hemodialysis.
    BMC nephrology, 2021, 03-20, Volume: 22, Issue:1

    Topics: Aged; Anemia; Glycine; Humans; Isoquinolines; Male; Renal Dialysis; Renal Insufficiency; Thyrotropin

2021
Amelioration of chronic kidney disease-associated anemia by vadadustat in mice is not dependent on erythroferrone.
    Kidney international, 2021, Volume: 100, Issue:1

    Topics: Anemia; Animals; Erythropoietin; Fibroblast Growth Factor-23; Glycine; Hepcidins; Humans; Kidney; Mi

2021
On the Increased Event Rate of Urinary Tract Infection and Pneumonia in CKD Patients Treated with Roxadustat for Anemia.
    Journal of the American Society of Nephrology : JASN, 2021, 06-01, Volume: 32, Issue:6

    Topics: Anemia; Glycine; Humans; Isoquinolines; Pneumonia; Renal Insufficiency, Chronic; Urinary Tract Infec

2021
Therapy for Anemia in Chronic Kidney Disease - New Interventions and New Questions.
    The New England journal of medicine, 2021, 04-29, Volume: 384, Issue:17

    Topics: Anemia; Glycine; Humans; Picolinic Acids; Renal Insufficiency, Chronic

2021
[Roxadustat (Evrenzo
    Nihon yakurigaku zasshi. Folia pharmacologica Japonica, 2021, Volume: 156, Issue:3

    Topics: Anemia; Animals; Glycine; Humans; Isoquinolines; Japan; Rats; Renal Insufficiency, Chronic; Tablets

2021
Novel roles of HIF-PHIs in chronic kidney disease: the link between iron metabolism, kidney function, and FGF23.
    Kidney international, 2021, Volume: 100, Issue:1

    Topics: Anemia; Animals; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Glycine; Hypoxia-Inducible

2021
Does HIF-PHI increased risk of gastrointestinal hemorrhage in patients with renal anemia: a review of cases reported to the U.S. Food and drug administration adverse event reporting system.
    Renal failure, 2021, Volume: 43, Issue:1

    Topics: Adverse Drug Reaction Reporting Systems; Anemia; Barbiturates; Female; Gastrointestinal Hemorrhage;

2021
Population pharmacokinetics of roxadustat in Japanese dialysis-dependent chronic kidney disease patients with anaemia.
    British journal of clinical pharmacology, 2022, Volume: 88, Issue:2

    Topics: Anemia; Female; Glycine; Humans; Isoquinolines; Japan; Male; Renal Dialysis; Renal Insufficiency, Ch

2022
Cardiovascular Safety of Roxadustat in CKD Anemia: A Fig Leaf Named Noninferiority.
    Clinical journal of the American Society of Nephrology : CJASN, 2021, Volume: 16, Issue:8

    Topics: Anemia; Ficus; Glycine; Humans; Isoquinolines; Renal Insufficiency, Chronic

2021
Hematologic complications in a patient with Glycine soja polyagglutination following fresh frozen plasma transfusion.
    Immunohematology, 2017, Volume: 33, Issue:2

    Topics: Anemia; Blood Transfusion; Glycine; Hemolysis; Humans; Male; Methicillin-Resistant Staphylococcus au

2017
Roxadustat in the treatment of anaemia in chronic kidney disease.
    Expert opinion on investigational drugs, 2018, Volume: 27, Issue:1

    Topics: Anemia; Animals; Cardiovascular Diseases; Erythropoietin; Glycine; Hematinics; Humans; Isoquinolines

2018
Click Chemistry-Based Discovery of [3-Hydroxy-5-(1 H-1,2,3-triazol-4-yl)picolinoyl]glycines as Orally Active Hypoxia-Inducing Factor Prolyl Hydroxylase Inhibitors with Favorable Safety Profiles for the Treatment of Anemia.
    Journal of medicinal chemistry, 2018, 06-28, Volume: 61, Issue:12

    Topics: Administration, Oral; Anemia; Animals; Cisplatin; Click Chemistry; Erythropoietin; Female; Fluoresce

2018
Roxadustat: another drug that causes pulmonary hypertension? Report of first human case.
    Polish archives of internal medicine, 2019, 05-31, Volume: 129, Issue:5

    Topics: Aged; Anemia; Dose-Response Relationship, Drug; Echocardiography, Doppler; Female; Glycine; Humans;

2019
Roxadustat and Anemia of Chronic Kidney Disease.
    The New England journal of medicine, 2019, 09-12, Volume: 381, Issue:11

    Topics: Anemia; Glycine; Humans; Isoquinolines; Renal Dialysis; Renal Insufficiency, Chronic

2019
Deal watch: AstraZeneca bets on FibroGen's anaemia drug.
    Nature reviews. Drug discovery, 2013, Volume: 12, Issue:10

    Topics: Anemia; Clinical Trials, Phase III as Topic; Cooperative Behavior; Drug Design; Drug Industry; Enzym

2013
First-in-class anemia drug takes aim at Amgen's dominion.
    Nature biotechnology, 2013, Volume: 31, Issue:11

    Topics: Anemia; Drug Industry; Glycine; Humans; Hypoxia-Inducible Factor-Proline Dioxygenases; Isoquinolines

2013
Targeting the hypoxia-sensing pathway in clinical hematology.
    Stem cells translational medicine, 2014, Volume: 3, Issue:2

    Topics: Amino Acids, Dicarboxylic; Anemia; Apoptosis Regulatory Proteins; Aryl Hydrocarbon Receptor Nuclear

2014
Growth retardation, general hypotonia, and loss of acquired neuromotor skills in the infants of mothers with cobalamin deficiency and the possible role of succinyl-CoA and glycine in the pathogenesis.
    Medicine, 2015, Volume: 94, Issue:9

    Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Acyl Coenzyme A; Amino Acid Metabolism, I

2015
The Dawning of a New Day in CKD Anemia Care?
    Journal of the American Society of Nephrology : JASN, 2016, Volume: 27, Issue:4

    Topics: Anemia; Barbiturates; Female; Glycine; Humans; Isoquinolines; Male; Renal Dialysis

2016
Characterization of Human and Yeast Mitochondrial Glycine Carriers with Implications for Heme Biosynthesis and Anemia.
    The Journal of biological chemistry, 2016, 09-16, Volume: 291, Issue:38

    Topics: Anemia; Genetic Complementation Test; Glycine; Heme; Humans; Mitochondria; Mitochondrial Membrane Tr

2016
The effect of the Gly139His, Gly143His, and Ser142His mouse heme oxygenase-1 mutants on the HO reaction in vivo and in vitro.
    Anatomical record (Hoboken, N.J. : 2007), 2011, Volume: 294, Issue:1

    Topics: Amino Acid Substitution; Anemia; Animals; Animals, Newborn; Chlorocebus aethiops; COS Cells; Female;

2011
The anemia of thermal injury. III. Erythropoiesis and hemoglobin metabolism studied with N15-glycine in dog and man.
    The Journal of clinical investigation, 1954, Volume: 33, Issue:2

    Topics: Anemia; Animals; Burns; Dogs; Erythrocytes; Erythropoiesis; Glycine; Hemoglobins; Humans

1954
The effect of various pathological conditions on in vivo hemoglobin synthesis. II. Polonium-induced anemia as studied with alpha-C14-glycine.
    Radiation research, 1954, Volume: 1, Issue:2

    Topics: Anemia; Glycine; Hemoglobins; Polonium; Research

1954
The pathogenesis of the anemia of chronic leukemia; measurement of the life span of the red blood cell with glycine-2-C14.
    The Journal of laboratory and clinical medicine, 1954, Volume: 44, Issue:6

    Topics: Anemia; Chronic Disease; Erythrocytes; Glycine; Humans; Leukemia

1954
The life span of the erythrocytes of normal and tumourbearing mice as determined by glycine-2-14C.
    Acta physiologica Scandinavica, 1958, Oct-28, Volume: 44, Issue:1

    Topics: Anemia; Animals; Erythrocytes; Glycine; Mice; Neoplasms, Experimental

1958
Glycine in hypochromic microcytic anemia.
    Northwest medicine, 1959, Volume: 58, Issue:3

    Topics: Anemia; Anemia, Hypochromic; Glycine; Humans

1959
Formiminoglutamicaciduria in humans with megaloblastic anemia: diminution by methionine or glycine.
    Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.), 1963, Volume: 112

    Topics: Amino Acids; Anemia; Anemia, Macrocytic; Anemia, Megaloblastic; Glutamates; Glycine; Methionine; Ser

1963
[On amino acid metabolism in blood diseases with special reference to aplastic anemia].
    Rinsho byori. The Japanese journal of clinical pathology, 1962, Volume: 10

    Topics: Alanine; Amino Acids; Anemia; Anemia, Aplastic; Glutamates; Glycine; Humans; Hydroxyproline; Serine;

1962
[Ferroglycine sulfate in the therapy of hypochromic anemia in infants].
    Il Lattante, 1963, Volume: 34

    Topics: Anemia; Anemia, Hypochromic; Ferrous Compounds; Glycine; Humans; Iron

1963
CLINICAL AND EXPERIMENTAL STUDIES ON THE METABOLISM OF TRANSFERRIN. III. THE INCORPORATION OF GLYCINE-2-C14 INTO TRANSFERRIN FRACTION OF RAT LIVER SUPERNATANT IN VITRO.
    Kyushu journal of medical science, 1963, Volume: 14

    Topics: Anemia; Anemia, Hypochromic; Blood Protein Disorders; Carbon Isotopes; Chromatography; Erythrocyte C

1963
STUDIES ON THE HEME SYNTHESIS BY BONE MARROW CELLS IN VITRO AND IN VIVO WITH 2-14C-GLYCINE. I. IN VITRO HEME SYNTHESIS AS AN ASSAY METHOD OF ERYTHROPOIETIC FACTOR IN SERUM.
    Naika hokan. Japanese archives of internal medicine, 1964, Volume: 11

    Topics: Anemia; Animals; Bone Marrow; Bone Marrow Cells; Carbon Isotopes; Epoetin Alfa; Erythropoietin; Glyc

1964
IDIOPATHIC DYSERYTHROPOIETIC JAUNDICE.
    Blood, 1964, Volume: 24

    Topics: Anemia; Bile Pigments; Bilirubin; Blood Cell Count; Bone Marrow Examination; Clinical Enzyme Tests;

1964
HEME SYNTHESIS IN NORMAL AND GENETICALLY ANEMIC MICE.
    Journal of cellular and comparative physiology, 1964, Volume: 64

    Topics: Anemia; Carbon Isotopes; Erythropoiesis; Genetics; Glycine; Heme; Hemoglobins; Levulinic Acids; Meta

1964
THE EARLY APPEARING BILIRUBIN: EVIDENCE FOR TWO COMPONENTS.
    The Journal of clinical investigation, 1965, Volume: 44

    Topics: Amino Acids; Anemia; Anemia, Pernicious; Animals; Bile; Biliary Fistula; Bilirubin; Blood; Bone Marr

1965
BIOSYNTHESIS OF HEME AND STERCOBILIN IN CHRONIC MYELOID LEUKEMIA AND IRON DEFICIENCY ANEMIA. STUDY WITH 2-14C-GLYCINE.
    Nihon Ketsueki Gakkai zasshi : journal of Japan Haematological Society, 1964, Volume: 27

    Topics: Anemia; Anemia, Hypochromic; Anemia, Iron-Deficiency; Bile Pigments; Glycine; Heme; Humans; Leukemia

1964
Clinical trials with a new antianemic agent, acidiron.
    Journal of the American Geriatrics Society, 1955, Volume: 3, Issue:2

    Topics: Aged; Anemia; Disease; Glycine; Humans; Iron

1955
Erythrocyte destruction in sickle-cell anemia: simultaneous N15-hemin and N15-stercobilin studies.
    Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.), 1955, Volume: 88, Issue:3

    Topics: Anemia; Anemia, Sickle Cell; Bile Pigments; Erythrocytes; Glycine; Hemin; Humans

1955
Dyserythropoietic anemia and thrombocytopenia due to a novel mutation in GATA-1.
    Acta haematologica, 2005, Volume: 114, Issue:2

    Topics: Amino Acid Substitution; Anemia; Arginine; Child, Preschool; DNA-Binding Proteins; Erythroid-Specifi

2005
Carbon monoxide production associated with ineffective erythropoiesis.
    The Journal of clinical investigation, 1967, Volume: 46, Issue:12

    Topics: Adolescent; Adult; Aged; Anemia; Anemia, Sideroblastic; Bile Pigments; Bilirubin; Carbon Isotopes; C

1967
Nutritional anemia induced by excess methionine in rat and the alleviative effects of glycine on it.
    Journal of nutritional science and vitaminology, 1978, Volume: 24, Issue:5

    Topics: 5-Aminolevulinate Synthetase; Amino Acids; Anemia; Animals; Blood Cells; Bone Marrow; Glycine; Heme;

1978
[Mechanism of anemia in selenium poisoning rats. (I). State of anemia caused by selenium dosing and behavior of iron (author's transl)].
    Nihon eiseigaku zasshi. Japanese journal of hygiene, 1977, Volume: 32, Issue:2

    Topics: Anemia; Animals; Female; Glycine; Heme; Iron; Porphyrins; Rats; Selenium

1977
Quantitation of ineffective erythropoiesis from the incorporation of [15N] delta-aminolaevulinic acid and [15N] glycin into early labelled bilirubin. II. Anaemic patients.
    British journal of haematology, 1976, Volume: 34, Issue:1

    Topics: Adolescent; Aged; Aminolevulinic Acid; Anemia; Anemia, Aplastic; Anemia, Hypochromic; Anemia, Sidero

1976
Changes in the concentrations of hydroxyproline, glycine and serine in the plasma of haemodialysis patients undergoing erythropoietin therapy.
    Journal of clinical chemistry and clinical biochemistry. Zeitschrift fur klinische Chemie und klinische Biochemie, 1989, Volume: 27, Issue:11

    Topics: Adult; Aged; Anemia; Erythropoietin; Female; Follow-Up Studies; Glycine; Hemoglobins; Humans; Hydrox

1989
[On the influence of zinc compounds on the serum proteins of normal and anemic rabbits].
    Acta biologica et medica Germanica, 1967, Volume: 18, Issue:6

    Topics: Acetates; Amino Acids; Anemia; Animals; Asparagine; Blood Protein Electrophoresis; gamma-Globulins;

1967
Orthohydroxyhippuric (salicyluric) acid--its physiologic and clinical significance.
    Clinical pharmacology and therapeutics, 1974, Volume: 15, Issue:2

    Topics: Anemia; Animals; Cattle; Dihydroxyphenylalanine; Dogs; Down Syndrome; Fever; Glycine; Humans; Hypert

1974
Urea inhibition of lactate dehydrogenase. A convenient routine procedure.
    Acta medica Academiae Scientiarum Hungaricae, 1970, Volume: 27, Issue:1

    Topics: Anemia; Buffers; Clinical Enzyme Tests; Glycine; Humans; Ischemia; L-Lactate Dehydrogenase; Liver; L

1970
Isolation and translation of messenger RNA from beta-thalassemia red cells.
    Annals of the New York Academy of Sciences, 1974, Volume: 232, Issue:0

    Topics: Anemia; Anemia, Sickle Cell; Animals; Bone Marrow; Bone Marrow Cells; Carbon Radioisotopes; Cell-Fre

1974
[CO2 fixation (carboxylation) and blood regeneration in rabbits with experimental posthemorrhagic anemia].
    Voprosy meditsinskoi khimii, 1973, Volume: 19, Issue:6

    Topics: Acid-Base Equilibrium; Anemia; Animals; Bicarbonates; Blood Proteins; Bone Marrow; Carbon Dioxide; E

1973
Hemoglobin G Hsi-Tsou: 79 Asp to Gly.
    Biochimica et biophysica acta, 1972, Jan-26, Volume: 257, Issue:1

    Topics: Amino Acid Sequence; Amino Acids; Anemia; Aspartic Acid; Chromatography, Ion Exchange; Female; Glyci

1972
[Clinical studies on porphyrin metabolism. 1. Studies on -aminolevulinic acid synthetase].
    Nihon Ketsueki Gakkai zasshi : journal of Japan Haematological Society, 1971, Volume: 34, Issue:5

    Topics: 5-Aminolevulinate Synthetase; Acyltransferases; Adult; Anemia; Animals; Bone Marrow; Bone Marrow Cel

1971
Evidence of various types of synthesis of human gamma chains of haemoglobin in acquired haematological disorders.
    Nature: New biology, 1971, Sep-22, Volume: 233, Issue:38

    Topics: Alanine; Anemia; Anemia, Sideroblastic; Blood Cell Count; Child, Preschool; Chromatography; Chromato

1971
Detection of an inhibitor of hemoglobin synthesis in rat plasma.
    The Journal of laboratory and clinical medicine, 1970, Volume: 76, Issue:3

    Topics: Anemia; Animals; Antimetabolites; Carbon Isotopes; Chemical Precipitation; Dialysis; Glycine; Hemogl

1970
Endogenous production of 14CO: A method for calculation of RBC life-span in vivo.
    Blood, 1970, Volume: 36, Issue:5

    Topics: Anemia; Anemia, Hypochromic; Animals; Carbon Isotopes; Carbon Monoxide; Erythrocyte Aging; Erythrocy

1970
Glycine decarboxylation as an assay for erythrocyte aminolevulinic acid synthesis.
    Journal of applied physiology, 1971, Volume: 31, Issue:1

    Topics: Anemia; Anemia, Hypochromic; Anemia, Pernicious; Aspartate Aminotransferases; Biological Assay; Carb

1971
[The use of ferroglycine-75 for prevention of anemia in pigs and calves].
    Veterinariia, 1967, Volume: 44, Issue:6

    Topics: Anemia; Animals; Animals, Newborn; Cattle; Cattle Diseases; Glycine; Iron; Swine; Swine Diseases

1967
Marrow defect in idiopathic ineffective erythropoiesis.
    Annals of internal medicine, 1968, Volume: 68, Issue:5

    Topics: Adult; Aged; Anemia; Bone Marrow; Bone Marrow Cells; Carbon Isotopes; Erythropoiesis; Female; Glycin

1968
A comparison of porphyrin synthesis in certain tissues from normal and anemic dogs: some observations on the in vivo control of porphyrinogenesis.
    Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.), 1968, Volume: 127, Issue:4

    Topics: Acetates; Amino Acids; Anemia; Animals; Dogs; Erythropoietin; Glycine; Hemorrhage; Iron; Kidney; Lev

1968
Heme biosynthesis in copper deficient swine.
    Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.), 1968, Volume: 127, Issue:4

    Topics: Amino Acids; Anemia; Animals; Carbon Isotopes; Copper; Deficiency Diseases; Erythrocytes; Globins; G

1968
Uptake of labelled amino acids into human erythrocytes in disease.
    Clinica chimica acta; international journal of clinical chemistry, 1968, Volume: 20, Issue:1

    Topics: Acute Disease; Alanine; Amino Acids; Anemia; Bronchitis; Bronchopneumonia; Carbon Isotopes; Erythroc

1968
Liquid-scintillation radioassay of 14C-labeled hemoglobin in a thixotropic gel.
    Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 1969, Volume: 10, Issue:6

    Topics: Anemia; Carbon Isotopes; Erythrocytes; Gels; Glycine; Hemoglobins; Humans; Injections, Intravenous;

1969
Effect of dietary cholesterol on bile-acid composition of gall bladder bile from guinea pigs.
    Lipids, 1969, Volume: 4, Issue:3

    Topics: Anemia; Animals; Bile; Bile Acids and Salts; Cholesterol; Chromatography, Thin Layer; Colorimetry; D

1969
Heme and porphyrin synthesis by porphyric bovine erythrocytes.
    Life sciences, 1965, Volume: 4, Issue:18

    Topics: Anemia; Animals; Cattle; Chromatography; Erythrocytes; Glycine; Heme; In Vitro Techniques; Levulinic

1965
[Changes in porphyrin metabolism after double overloads of glycine. 3. In patients with porphyria cutanea tarda and of anemias of various origins].
    Bollettino della Societa italiana di biologia sperimentale, 1965, Sep-30, Volume: 41, Issue:18

    Topics: Anemia; Anemia, Macrocytic; Glycine; Humans; Lead Poisoning; Methemoglobinemia; Porphyrias; Porphyri

1965