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.
Excerpt | Relevance | Reference |
---|---|---|
"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." | 9.34 | 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. ( 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." | 9.24 | Phase 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." | 9.22 | Four-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." | 8.12 | Ixazomib, 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." | 8.12 | Daprodustat 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." | 6.82 | 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. ( 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." | 6.82 | A 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." | 6.82 | Roxadustat (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." | 6.80 | Randomized 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." | 5.41 | Roxadustat 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." | 5.34 | 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. ( 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." | 5.30 | Roxadustat 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)." | 5.24 | Effects 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." | 5.24 | Phase 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." | 5.22 | Four-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." | 4.12 | Ixazomib, 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." | 4.12 | Daprodustat 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)." | 3.64 | Carbon 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." | 3.30 | 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. ( 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." | 3.30 | Open-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." | 3.11 | Efficacy 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." | 3.11 | 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. ( 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)." | 3.11 | An 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." | 3.01 | Factors 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." | 3.01 | Efficacy 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." | 3.01 | Safety 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." | 3.01 | Roxadustat: 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%)." | 3.01 | Efficacy 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." | 3.01 | The 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." | 3.01 | The 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." | 2.94 | Phase 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." | 2.94 | Efficacy 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." | 2.90 | A 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." | 2.90 | Evaluation 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." | 2.82 | A 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." | 2.82 | Efficacy 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." | 2.82 | 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. ( 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." | 2.82 | 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. ( 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." | 2.82 | Roxadustat (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." | 2.80 | Randomized 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." | 2.72 | The 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." | 2.72 | The 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." | 2.61 | Hypoxia-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." | 2.55 | Hypoxia-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 > ." | 1.91 | Correlation 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." | 1.72 | Population 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." | 1.72 | Are 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." | 1.72 | 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. ( 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." | 1.62 | Efficacy 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." | 1.42 | 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. ( Bicakci, Z, 2015) |
Timeframe | Studies, this research(%) | All Research% |
---|---|---|
pre-1990 | 44 (23.78) | 18.7374 |
1990's | 0 (0.00) | 18.2507 |
2000's | 1 (0.54) | 29.6817 |
2010's | 41 (22.16) | 24.3611 |
2020's | 99 (53.51) | 2.80 |
Authors | Studies |
---|---|
Csiky, B | 1 |
Schömig, M | 2 |
Esposito, C | 2 |
Barratt, J | 3 |
Reusch, M | 10 |
Valluri, U | 3 |
Sulowicz, W | 1 |
Sokol, J | 1 |
Guman, T | 1 |
Chudej, J | 1 |
Hlebaskova, M | 1 |
Stecova, N | 1 |
Valekova, L | 1 |
Kucerikova, M | 1 |
Stasko, J | 1 |
Akizawa, T | 12 |
Tanaka-Amino, K | 2 |
Otsuka, T | 5 |
Yamaguchi, Y | 6 |
Bunn, HF | 1 |
Chertow, GM | 7 |
Eckardt, KU | 6 |
Kurata, Y | 1 |
Tanaka, T | 1 |
Nangaku, M | 9 |
Henry, DH | 2 |
Glaspy, J | 2 |
Harrup, R | 1 |
Mittelman, M | 1 |
Zhou, A | 1 |
Carraway, HE | 1 |
Bradley, C | 2 |
Saha, G | 3 |
Modelska, K | 2 |
Bartels, P | 1 |
Leong, R | 8 |
Yu, KP | 6 |
Singh, AK | 3 |
Carroll, K | 3 |
Perkovic, V | 3 |
Solomon, S | 3 |
Jha, V | 3 |
Johansen, KL | 3 |
Lopes, RD | 3 |
Macdougall, IC | 4 |
Obrador, GT | 3 |
Waikar, SS | 3 |
Wanner, C | 3 |
Wheeler, DC | 3 |
Więcek, A | 3 |
Blackorby, A | 3 |
Cizman, B | 3 |
Cobitz, AR | 7 |
Davies, R | 2 |
Dole, J | 1 |
Kler, L | 2 |
Meadowcroft, AM | 4 |
Zhu, X | 1 |
McMurray, JJV | 3 |
DiMino, TL | 1 |
Taft, L | 1 |
Chen, J | 5 |
Li, Z | 3 |
Zhang, H | 2 |
Hu, J | 1 |
Wang, J | 4 |
Zhou, H | 2 |
Liu, Y | 4 |
Liu, J | 3 |
Yi, B | 1 |
Zhang, W | 1 |
Patnaik, MM | 1 |
Santini, V | 1 |
Allison, SJ | 1 |
Li, J | 4 |
Ma, K | 1 |
Wang, L | 1 |
Qi, H | 1 |
Lv, J | 1 |
Rao, Y | 1 |
Peng, W | 1 |
Jatho, A | 1 |
Zieseniss, A | 1 |
Brechtel-Curth, K | 1 |
Guo, J | 1 |
Böker, KO | 1 |
Salinas, G | 1 |
Wenger, RH | 1 |
Katschinski, DM | 1 |
Miki, K | 1 |
Nakamura, Y | 1 |
Yokoyama, T | 1 |
Kamiyama, M | 1 |
Ishii, Y | 1 |
Abdelazeem, B | 1 |
Shehata, J | 1 |
Abbas, KS | 1 |
El-Shahat, NA | 1 |
Malik, B | 1 |
Savarapu, P | 1 |
Eltobgy, M | 1 |
Kunadi, A | 1 |
Stankus, N | 1 |
Strutz, F | 1 |
Paul, G | 1 |
Ranganathan, P | 1 |
Sedani, S | 1 |
Doggrell, SA | 1 |
Dai, S | 1 |
Chen, Y | 1 |
Hao, C | 4 |
Ge, X | 1 |
Xie, Q | 1 |
Shang, D | 1 |
Zhu, T | 1 |
Sullivan, MK | 1 |
Mark, PB | 1 |
Labes, R | 1 |
Brinkmann, L | 1 |
Kulow, VA | 1 |
Roegner, K | 1 |
Mathia, S | 1 |
Balcerek, B | 1 |
Persson, PB | 1 |
Rosenberger, C | 1 |
Fähling, M | 1 |
Koury, MJ | 5 |
Agarwal, R | 5 |
Fishbane, S | 6 |
Ganz, T | 2 |
Haase, VH | 5 |
Hanudel, MR | 2 |
Parfrey, PS | 4 |
Pergola, PE | 6 |
Roy-Chaudhury, P | 2 |
Tumlin, JA | 1 |
Anders, R | 1 |
Farag, YMK | 4 |
Luo, W | 5 |
Minga, T | 1 |
Solinsky, C | 1 |
Vargo, DL | 4 |
Winkelmayer, WC | 7 |
Bao, L | 1 |
Bian, X | 1 |
Zhang, A | 2 |
Huang, J | 1 |
Ren, L | 1 |
Luo, C | 1 |
Hou, YP | 2 |
Wang, C | 6 |
Mao, XY | 2 |
Zhang, MZ | 1 |
Li, B | 2 |
Zheng, F | 1 |
Zhang, P | 1 |
Zhao, M | 1 |
Xu, X | 1 |
Zhang, C | 1 |
Zhang, L | 3 |
Charytan, C | 1 |
Little, DJ | 1 |
Tham, S | 1 |
Szczech, L | 6 |
Yang, F | 1 |
Waheed, Y | 1 |
Li, S | 1 |
Liu, K | 1 |
Zhou, X | 1 |
Cheng, Y | 1 |
Xiang, Q | 1 |
Cao, T | 1 |
Tang, F | 1 |
Qi, D | 1 |
Hu, H | 1 |
Song, H | 1 |
Chang, Z | 1 |
Ku, M | 1 |
Chen, X | 2 |
Chen, C | 2 |
Wan, Q | 1 |
Gabrail, NY | 1 |
Locantore-Ford, P | 1 |
Lee, T | 3 |
Samal, V | 1 |
Li, QY | 1 |
Xiong, QW | 1 |
Yao, X | 1 |
Liu, F | 1 |
Tang, X | 1 |
Fu, H | 1 |
Tong, T | 1 |
Mao, J | 1 |
Peng, WX | 1 |
Dellanna, F | 1 |
Portoles, J | 1 |
Choukroun, G | 1 |
De Nicola, L | 1 |
Young, J | 1 |
Dimković, N | 2 |
Yoshida, S | 1 |
Saito, T | 1 |
Shibagaki, K | 1 |
Hirao, K | 1 |
Yuza, T | 1 |
Tomosugi, N | 2 |
Honda, H | 1 |
You, X | 1 |
Guo, B | 1 |
Wang, Z | 1 |
Ma, H | 1 |
Liu, L | 1 |
Zhou, R | 1 |
Zheng, Y | 1 |
Zhang, X | 5 |
Zhang, Y | 4 |
Jing, Y | 1 |
Zhou, C | 1 |
Berns, JS | 1 |
Vishnepolsky, M | 1 |
Oluwatosin, Y | 1 |
Nolen, J | 1 |
Zhu, L | 1 |
Cooper, K | 1 |
Young, A | 1 |
Zhou, Q | 1 |
Mao, M | 1 |
Deng, F | 2 |
Ge, P | 1 |
Xu, R | 1 |
Ye, Z | 1 |
Song, J | 1 |
Zhou, L | 2 |
Yu, W | 1 |
Liu, H | 1 |
Yuan, F | 1 |
Sanghani, NS | 1 |
Maxwell, PH | 1 |
Bailey, CK | 1 |
Caltabiano, S | 2 |
Huang, C | 1 |
Mahar, KM | 2 |
Patel, VV | 1 |
Voit, RA | 1 |
Sankaran, VG | 1 |
Hayden, JC | 1 |
Bhagavathula, AS | 1 |
Alshehhi, F | 1 |
Rinaldi, G | 1 |
Kontogiannis, V | 1 |
Rahmani, J | 1 |
Wyatt, CM | 1 |
Drueke, TB | 1 |
Hu, Z | 1 |
Tao, H | 1 |
Shi, A | 1 |
Pan, J | 1 |
Yamada, M | 1 |
Osamura, M | 1 |
Ogura, H | 1 |
Onoue, T | 3 |
Wakamatsu, A | 1 |
Numachi, Y | 1 |
Su, K | 1 |
Yu, Y | 1 |
Del Balzo, U | 1 |
Signore, PE | 1 |
Walkinshaw, G | 1 |
Seeley, TW | 1 |
Brenner, MC | 1 |
Wang, Q | 1 |
Guo, G | 1 |
Arend, MP | 1 |
Flippin, LA | 1 |
Chow, FA | 1 |
Gervasi, DC | 1 |
Kjaergaard, CH | 1 |
Langsetmo, I | 1 |
Guenzler, V | 1 |
Liu, DY | 1 |
Klaus, SJ | 2 |
Lin, A | 1 |
Neff, TB | 8 |
Iwasaki, M | 3 |
Majikawa, Y | 4 |
Provenzano, R | 5 |
Tumlin, J | 3 |
Zabaneh, R | 2 |
Chou, J | 1 |
Hemmerich, S | 6 |
Anker, MS | 1 |
Butler, J | 1 |
Anker, SD | 1 |
Zielniok, K | 1 |
Burdzinska, A | 1 |
Paczek, L | 1 |
Mohandas, R | 1 |
Segal, MS | 1 |
Shah, HH | 1 |
Xie, J | 1 |
Chen, N | 4 |
Kaplan, JM | 1 |
Yonekawa, T | 2 |
Okuda, N | 3 |
Kawamatsu, S | 1 |
Endo, Y | 5 |
Hara, K | 2 |
Kile, M | 1 |
Sudchada, P | 1 |
Markham, A | 1 |
Platzbecker, U | 1 |
Dhillon, S | 2 |
Tanaka, M | 1 |
Shinohara, K | 1 |
Ono, A | 1 |
Ikuma, M | 1 |
Ogawa, C | 1 |
Tsuchiya, K | 1 |
Maeda, K | 1 |
Zheng, Q | 1 |
Yang, H | 2 |
Fu, X | 1 |
Huang, Y | 1 |
Wei, R | 1 |
Wang, Y | 1 |
Liu, YN | 1 |
Liu, WJ | 1 |
Block, GA | 5 |
Jardine, AG | 3 |
Khawaja, Z | 5 |
Lewis, EF | 3 |
Matsushita, K | 4 |
McCullough, PA | 5 |
Wittes, J | 3 |
Walters, KA | 3 |
Tseng, C | 2 |
Lin, T | 2 |
Sarnak, MJ | 4 |
Farag, YM | 1 |
Parfrey, P | 1 |
Ross, G | 1 |
Vargo, D | 1 |
Kondo, K | 3 |
Takabe, S | 2 |
Ueta, K | 3 |
Kaneko, G | 2 |
Otsuka, M | 1 |
Kawaguchi, Y | 3 |
Komatsu, Y | 3 |
Qie, S | 1 |
Jiao, N | 1 |
Duan, K | 1 |
Liu, G | 1 |
Yang, Q | 1 |
Wang, X | 2 |
Ren, S | 1 |
Xue, H | 1 |
Wang, AY | 1 |
Zou, Y | 1 |
Cai, Y | 1 |
He, J | 1 |
Yuan, X | 1 |
Jiang, F | 1 |
Wei, J | 1 |
Yang, D | 1 |
He, D | 1 |
Hu, S | 1 |
Lei, M | 1 |
He, Q | 2 |
Li, G | 1 |
Hong, D | 1 |
Hamano, T | 1 |
Tsubakihara, Y | 3 |
Nagai, R | 2 |
Kurata, K | 2 |
Nagakubo, T | 2 |
Jones, NP | 1 |
Grzeszczak, W | 1 |
Szczyra, D | 1 |
Śnit, M | 1 |
Katagiri, N | 1 |
Hitomi, H | 1 |
Mae, SI | 1 |
Kotaka, M | 1 |
Lei, L | 1 |
Yamamoto, T | 4 |
Nishiyama, A | 1 |
Osafune, K | 1 |
Shutov, E | 3 |
Eremeeva, L | 1 |
Korneyeva, S | 1 |
Poole, L | 3 |
Eyassu, M | 1 |
Besarab, A | 6 |
Liu, CS | 2 |
Sułowicz, W | 1 |
Tataradze, A | 2 |
Andric, B | 2 |
Kokado, Y | 1 |
Matsuda, H | 1 |
Ichii, M | 1 |
Mori, K | 1 |
Miyaoka, D | 1 |
Sonoda, M | 1 |
Tsujimoto, Y | 1 |
Nakatani, S | 1 |
Shoji, T | 1 |
Emoto, M | 1 |
Wong, S | 1 |
Jung, G | 1 |
Qiao, B | 1 |
Gabayan, V | 1 |
Zuk, A | 1 |
Eleftheriadis, T | 1 |
Pissas, G | 1 |
Liakopoulos, V | 1 |
Stefanidis, I | 1 |
Cai, KD | 1 |
Zhu, BX | 1 |
Lin, HX | 1 |
Luo, Q | 1 |
Aswad, A | 1 |
Awad, A | 1 |
Bacci, MR | 1 |
Hubert, H | 1 |
Jardine, A | 1 |
Maroni, BJ | 5 |
Pergola, P | 1 |
Spinowitz, B | 2 |
Zwiech, R | 1 |
Arnold, S | 1 |
Bako, G | 1 |
Burke, S | 1 |
Castillo, FP | 1 |
Sharma, A | 2 |
Levin, A | 1 |
Ugawa, T | 1 |
Ashizaki, M | 1 |
Murata, A | 1 |
Kanai, H | 1 |
Cobitz, A | 3 |
Wang, H | 1 |
Huang, K | 1 |
Fang, H | 1 |
Cao, J | 1 |
Mariat, C | 1 |
Tandai, T | 1 |
Hou, J | 1 |
Su, SS | 1 |
Xue, S | 1 |
Ikeda, Y | 1 |
Xu, ZH | 1 |
Bu, ZH | 1 |
Xu, M | 1 |
Zhou, Y | 1 |
Ren, Q | 1 |
Hu, R | 1 |
Zheng, K | 1 |
Qin, Y | 1 |
Li, X | 3 |
Takada, A | 2 |
Shibata, T | 2 |
Shiga, T | 1 |
Groenendaal-van de Meent, D | 1 |
Komatsu, K | 1 |
Walther, CP | 1 |
Zheng, L | 1 |
Tian, J | 1 |
Liu, D | 1 |
Zhao, Y | 1 |
Fang, X | 1 |
Martin, ER | 1 |
Smith, MT | 1 |
Zuraw, QC | 1 |
deGoma, EM | 2 |
Qian, J | 1 |
Yu, X | 1 |
Mei, C | 1 |
Jiang, G | 2 |
Lin, H | 3 |
Zuo, L | 3 |
Fu, P | 1 |
Ni, D | 1 |
Liu, C | 3 |
Peony Yu, KH | 1 |
Valone, FH | 1 |
Jajosky, RP | 1 |
Cook, LO | 1 |
Manaloor, E | 1 |
Shikle, JF | 1 |
Bollag, RJ | 1 |
Del Vecchio, L | 1 |
Locatelli, F | 2 |
Becker, KA | 1 |
Jones, JJ | 1 |
Wu, Y | 1 |
Jiang, Z | 1 |
Gu, J | 1 |
You, Q | 1 |
Nomura, Y | 1 |
Ueno, M | 2 |
Katashima, M | 1 |
Yazawa, R | 1 |
Furihata, K | 1 |
Xie, D | 1 |
Wu, X | 1 |
Li, M | 1 |
Cygulska, K | 1 |
Wejner-Mik, P | 1 |
Plewka, M | 1 |
Figiel, Ł | 1 |
Chrzanowski, Ł | 1 |
Kasprzak, JD | 1 |
Misumi, T | 1 |
Matsushita, H | 1 |
Kaplan, J | 1 |
Peng, X | 1 |
Yin, A | 1 |
Hao, L | 2 |
Tao, Y | 1 |
Liang, X | 2 |
Liu, Z | 3 |
Xing, C | 2 |
Luo, L | 2 |
Liao, Y | 1 |
Liu, BC | 2 |
Neff, T | 2 |
Zhao, MH | 1 |
Cai, GY | 1 |
Flight, MH | 1 |
Bouchie, A | 1 |
Forristal, CE | 1 |
Levesque, JP | 1 |
Bisbe, E | 1 |
Moltó, L | 1 |
Arroyo, R | 1 |
Muniesa, JM | 1 |
Tejero, M | 1 |
Infante, JR | 1 |
Weiss, GJ | 1 |
Jones, S | 1 |
Tibes, R | 1 |
Bauer, TM | 1 |
Bendell, JC | 1 |
Hinson, JM | 1 |
Von Hoff, DD | 1 |
Burris, HA | 1 |
Orlemans, EO | 1 |
Ramanathan, RK | 1 |
Bicakci, Z | 1 |
Hertel, J | 1 |
Yu, KH | 3 |
Holdstock, L | 1 |
Maier, R | 1 |
Johnson, BM | 1 |
Jones, D | 1 |
Rastogi, A | 1 |
Zeig, S | 2 |
Lepore, JJ | 1 |
Chernyavskaya, E | 1 |
Motylev, I | 1 |
Kumbar, LM | 1 |
Gurevich, K | 1 |
Chan, DT | 1 |
Zhong, M | 1 |
Saikali, KG | 3 |
Franco, M | 1 |
Lenihan, CR | 1 |
Brigandi, RA | 1 |
Johnson, B | 1 |
Oei, C | 1 |
Westerman, M | 1 |
Olbina, G | 1 |
de Zoysa, J | 1 |
Roger, SD | 1 |
Sahay, M | 1 |
Cross, N | 1 |
McMahon, L | 1 |
Guptha, V | 1 |
Smolyarchuk, EA | 1 |
Singh, N | 1 |
Russ, SF | 1 |
Kumar, S | 1 |
Wright, S | 1 |
Dua, S | 1 |
Nguyen, P | 1 |
Sun, CH | 1 |
Diamond, SA | 1 |
Durham, JH | 1 |
Cangiano, JL | 1 |
Aiello, JR | 1 |
Novak, JE | 1 |
Roberts, BK | 1 |
Szczech, LA | 1 |
Gupta, N | 2 |
Hanley, MJ | 1 |
Harvey, RD | 1 |
Badros, A | 1 |
Lipe, B | 1 |
Kukreti, V | 1 |
Berdeja, J | 1 |
Hui, AM | 1 |
Qian, M | 1 |
Venkatakrishnan, K | 1 |
Chari, A | 1 |
Lunetti, P | 1 |
Damiano, F | 1 |
De Benedetto, G | 1 |
Siculella, L | 1 |
Pennetta, A | 1 |
Muto, L | 1 |
Paradies, E | 1 |
Marobbio, CM | 1 |
Dolce, V | 1 |
Capobianco, L | 1 |
Spinowitz, BS | 1 |
Hartman, CS | 1 |
Nakajima, H | 1 |
Kohno, T | 1 |
Imai, Y | 1 |
Kawase, N | 1 |
Lepore, J | 1 |
Wish, JB | 1 |
Becker, K | 1 |
Saad, M | 1 |
Zou, C | 1 |
Ma, N | 1 |
Hui, Y | 1 |
Lv, G | 1 |
Gao, X | 1 |
Beuck, S | 1 |
Schänzer, W | 1 |
Thevis, M | 1 |
JAMES, GW | 2 |
ABBOT, LD | 1 |
BROOKS, JW | 1 |
EVANS, EI | 1 |
THOMAS, RG | 1 |
ALTMAN, KI | 2 |
STANNARD, JN | 1 |
SALOMON, K | 1 |
BERLIN, NI | 2 |
LAWRENCE, JH | 1 |
LEE, HC | 1 |
VON EHRENSTEIN, G | 1 |
KIM, AY | 1 |
BECK, WA | 1 |
KIM, CH | 1 |
PORTOGALLO, HS | 1 |
HERBERT, V | 1 |
SULLIVAN, LW | 1 |
IWASAKI, I | 1 |
ARIMORI, S | 1 |
KAWANISHI, Y | 1 |
TROMBETTI, E | 1 |
MASUYA, T | 1 |
KOZURU, M | 1 |
NAKASHIMA, A | 1 |
HIRATSUKA, S | 1 |
UMEDA, T | 1 |
FUJII, M | 2 |
BERENDSOHN, S | 1 |
LOWMAN, J | 1 |
SUNDBERG, D | 1 |
WATSON, CJ | 1 |
RUSSELL, ES | 1 |
SKANDERBEG, J | 1 |
ZIPURSKY, A | 1 |
ISRAELS, LG | 1 |
BLAUSTEIN, A | 1 |
ABBOTT, LD | 1 |
Del Vecchio, GC | 1 |
Giordani, L | 1 |
De Santis, A | 1 |
De Mattia, D | 1 |
White, P | 1 |
Coburn, RF | 2 |
Williams, WJ | 1 |
Goldwein, MI | 1 |
Rother, ML | 1 |
Shafer, BC | 1 |
Yokota, F | 1 |
Esashi, T | 1 |
Suzue, R | 1 |
Hasegawa, A | 1 |
Urakubo, G | 1 |
Suketa, Y | 1 |
Samson, D | 1 |
Halliday, D | 1 |
Nicholson, DC | 1 |
Chanarin, I | 1 |
Riedel, E | 1 |
Nündel, M | 1 |
Algermissen, B | 1 |
Hampl, H | 1 |
Scigalla, P | 1 |
Stabell, U | 1 |
Krantz, S | 1 |
Krantz, J | 1 |
Hartmann, N | 1 |
Altschule, MD | 1 |
Hegedus, ZL | 1 |
Discombe, G | 1 |
Lund, S | 1 |
Anderson, WF | 1 |
Gulyi, MF | 1 |
Mikhailovskaia, LM | 1 |
Zhurbin, GI | 1 |
Gruzova, LM | 1 |
Stognii, NA | 1 |
Blackwell, RQ | 1 |
Shih, TB | 1 |
Wang, CL | 1 |
Tsuneyama, H | 1 |
Rosa, J | 1 |
Beuzard, Y | 1 |
Brun, B | 1 |
Toulgoat, N | 1 |
Molinari, PF | 1 |
Menninger, FF | 1 |
Rosenkrantz, H | 1 |
Landaw, SA | 1 |
Winchell, HS | 1 |
Lewis, M | 1 |
Ivanov, DP | 1 |
Waltuch, G | 1 |
Lanzerotti, K | 1 |
Schrier, SL | 1 |
Sardesai, VM | 1 |
Park, H | 1 |
Orten, JM | 1 |
Lee, GR | 1 |
Cartwright, GE | 1 |
Wintrobe, MM | 1 |
Björnesjö, KB | 1 |
Jarnulf, B | 1 |
Lausing, E | 1 |
Newman, JW | 1 |
Lichtman, HC | 1 |
Tung, JS | 1 |
Ostwald, R | 1 |
Smith, JE | 1 |
Kaneko, JJ | 1 |
Massaro, AL | 1 |
Mazza, U | 1 |
Bianco, G | 1 |
Accatino, G | 1 |
Prato, V | 1 |
Trial | Phase | Enrollment | Study Type | Start Date | Status | ||
---|---|---|---|---|---|---|---|
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 3 | 334 participants (Actual) | Interventional | 2017-01-12 | Completed | ||
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 4 | 62 participants (Anticipated) | Interventional | 2023-08-31 | Not 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 3 | 140 participants (Actual) | Interventional | 2017-09-07 | Terminated (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 3 | 2,964 participants (Actual) | Interventional | 2016-09-28 | Completed | ||
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 3 | 3,872 participants (Actual) | Interventional | 2016-09-27 | Completed | ||
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 3 | 312 participants (Actual) | Interventional | 2017-05-11 | Completed | ||
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 2 | 103 participants (Actual) | Interventional | 2016-02-17 | Completed | ||
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 1 | 64 participants (Actual) | Interventional | 2018-04-24 | Completed | ||
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 3 | 303 participants (Actual) | Interventional | 2016-11-30 | Completed | ||
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 3 | 271 participants (Actual) | Interventional | 2016-11-21 | Completed | ||
A Phase III, Open-label Study of MT-6548 in Peritoneal Dialysis Subjects With Anemia Associated With Chronic Kidney Disease in Japan[NCT03402386] | Phase 3 | 42 participants (Actual) | Interventional | 2018-01-03 | Completed | ||
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 3 | 355 participants (Actual) | Interventional | 2016-06-06 | Completed | ||
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 3 | 323 participants (Actual) | Interventional | 2018-02-14 | Completed | ||
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 3 | 369 participants (Actual) | Interventional | 2016-07-31 | Completed | ||
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 3 | 3,554 participants (Actual) | Interventional | 2016-08-31 | Completed | ||
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 3 | 1,751 participants (Actual) | Interventional | 2015-12-31 | Completed | ||
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 3 | 1,725 participants (Actual) | Interventional | 2016-02-29 | Completed | ||
A Phase III, Open-label Study of MT-6548 in Hemodialysis Subjects With Anemia Associated With Chronic Kidney Disease in Japan[NCT03461146] | Phase 3 | 24 participants (Actual) | Interventional | 2018-03-05 | Completed | ||
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 2 | 93 participants (Actual) | Interventional | 2011-06-15 | Completed | ||
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 2 | 107 participants (Actual) | Interventional | 2013-09-17 | Completed | ||
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 3 | 28 participants (Actual) | Interventional | 2016-08-08 | Completed | ||
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 3 | 154 participants (Actual) | Interventional | 2015-12-31 | Completed | ||
A Randomized Controlled Trial to Evaluate the Safety and Efficacy of Roxadustat in Patients With Acute ST Elevation Myocardial Infarction[NCT04803864] | Phase 2 | 158 participants (Anticipated) | Interventional | 2021-06-10 | Recruiting | ||
Roxadustat Reduces the Incidence of Acute Kidney Injury After Coronary Artery Bypass Grafting: a Multicenter, Randomized, Double-blind, Placebo-controlled Study[NCT05010460] | Phase 2 | 318 participants (Anticipated) | Interventional | 2021-09-30 | Recruiting | ||
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 3 | 305 participants (Actual) | Interventional | 2015-12-31 | Completed | ||
Efficacy of Intravenous Ferric Carboxymaltose in the Improvement of Anemia in Patients With Postoperative Knee Prosthesis[NCT01913808] | Phase 4 | 122 participants (Actual) | Interventional | 2011-01-31 | Completed | ||
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 2 | 117 participants (Actual) | Interventional | 2006-11-01 | Completed | ||
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 2 | 80 participants (Actual) | Interventional | 2012-05-23 | Completed | ||
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 2 | 72 participants (Actual) | Interventional | 2012-05-17 | Completed | ||
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 2 | 210 participants (Actual) | Interventional | 2013-07-23 | Completed | ||
[information is prepared from clinicaltrials.gov, extracted Sep-2024] |
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)
Intervention | Events per 100 participant years (Number) |
---|---|
Daprodustat | 207.13 |
rhEPO | 206.38 |
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
Intervention | Scores on a scale (Least Squares Mean) |
---|---|
Daprodustat | -1.0 |
rhEPO | 0.8 |
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
Intervention | Scores on a scale (Least Squares Mean) |
---|---|
Daprodustat | -0.0198 |
rhEPO | -0.0201 |
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
Intervention | Grams per deciliter (Least Squares Mean) |
---|---|
Daprodustat | 0.26 |
rhEPO | 0.14 |
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
Intervention | Milligrams (Least Squares Mean) |
---|---|
Daprodustat | 90.8 |
rhEPO | 99.9 |
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)
Intervention | Grams per deciliter (Least Squares Mean) |
---|---|
Daprodustat | 0.28 |
rhEPO | 0.10 |
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
Intervention | Participants (Count of Participants) |
---|---|
Daprodustat | 903 |
rhEPO | 866 |
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)
Intervention | Participants (Count of Participants) |
---|---|
Daprodustat | 1191 |
rhEPO | 1186 |
Percentage of participants permanently stopping randomized treatment due to meeting rescue criteria has been presented. (NCT02879305)
Timeframe: Day 1 to 45.1 months
Intervention | Percentage of participants (Number) |
---|---|
Daprodustat | 3.6 |
rhEPO | 3.6 |
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
Intervention | Percentage of days (Median) |
---|---|
Daprodustat | 60.9 |
rhEPO | 59.4 |
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
Intervention | Percentage of days (Median) |
---|---|
Daprodustat | 60.9 |
rhEPO | 59.4 |
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)
Intervention | Percentage of days (Median) |
---|---|
Daprodustat | 60.9 |
rhEPO | 57.7 |
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)
Intervention | Percentage of days (Median) |
---|---|
Daprodustat | 60.9 |
rhEPO | 57.7 |
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
Intervention | Events per 100 person years (Number) |
---|---|
Daprodustat | 8.32 |
rhEPO | 8.59 |
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
Intervention | Events per 100 person years (Number) |
---|---|
Daprodustat | 3.31 |
rhEPO | 3.46 |
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
Intervention | Events per 100 person years (Number) |
---|---|
Daprodustat | 5.98 |
rhEPO | 6.79 |
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
Intervention | Events per 100 person years (Number) |
---|---|
Daprodustat | 3.30 |
rhEPO | 3.01 |
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
Intervention | Events per 100 person years (Number) |
---|---|
Daprodustat | 11.07 |
rhEPO | 11.86 |
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
Intervention | Events per 100 person years (Number) |
---|---|
Daprodustat | 12.98 |
rhEPO | 13.38 |
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
Intervention | Events per 100 person years (Number) |
---|---|
Daprodustat | 17.74 |
rhEPO | 19.50 |
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
Intervention | Events per 100 person years (Number) |
---|---|
Daprodustat | 15.84 |
rhEPO | 17.85 |
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
Intervention | Events per 100 person years (Number) |
---|---|
Daprodustat | 11.07 |
rhEPO | 11.86 |
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
Intervention | Events per 100 person years (Number) |
---|---|
Daprodustat | 3.34 |
rhEPO | 4.08 |
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
Intervention | Events per 100 person years (Number) |
---|---|
Daprodustat | 1.23 |
rhEPO | 1.48 |
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
Intervention | Events per 100 person years (Number) |
---|---|
Daprodustat | 5.66 |
rhEPO | 6.75 |
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
Intervention | Events per 100 person years (Number) |
---|---|
Daprodustat | 8.86 |
rhEPO | 9.67 |
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
Intervention | Events per 100 person years (Number) |
---|---|
Daprodustat | 43.92 |
rhEPO | 46.03 |
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
Intervention | Scores on a scale (Least Squares Mean) | |||
---|---|---|---|---|
Week 8, n=982,936 | Week 12, n=990,943 | Week 28, n=836,819 | Week 52, n=729,707 | |
Daprodustat | -0.38 | -0.55 | -1.25 | -1.63 |
rhEPO | -0.21 | -0.72 | -1.23 | -1.03 |
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
Intervention | Scores on a scale (Least Squares Mean) | |||
---|---|---|---|---|
Week 8, n=1102,1064 | Week 12, n=1102,1073 | Week 28, n=934,933 | Week 52, n=826,814 | |
Daprodustat | -0.03 | 0.02 | 0.04 | 0.06 |
rhEPO | 0.02 | 0.06 | 0.08 | 0.11 |
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
Intervention | Scores on a scale (Least Squares Mean) | |||
---|---|---|---|---|
Week 8, n=982,936 | Week 12, n=990,943 | Week 28, n=836,819 | Week 52, n=729,707 | |
Daprodustat | 0.30 | 0.33 | -0.23 | -0.52 |
rhEPO | 0.01 | -0.27 | -0.57 | -1.05 |
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
Intervention | Scores on a scale (Least Squares Mean) | |||
---|---|---|---|---|
Week 8, n=982,936 | Week 12, n=990,943 | Week 28, n=836,819 | Week 52, n=729,707 | |
Daprodustat | 0.48 | 0.11 | -0.20 | -0.61 |
rhEPO | -0.16 | -0.45 | -0.97 | -1.19 |
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
Intervention | Scores on a scale (Least Squares Mean) | |||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Bodily pain: Week 8, n=982,936 | Bodily pain: Week 12, n=990,943 | Bodily pain: Week 28, n=836,819 | Bodily pain: Week 52, n=729,707 | General health: Week 8, n=982,936 | General health: Week 12, n=990,943 | General health: Week 28, n=836,819 | General health: Week 52, n=729,707 | Mental health: Week 8, n=982,936 | Mental health: Week 12, n=990,943 | Mental health: Week 28, n=836,819 | Mental health: Week 52, n=729,707 | Role-emotional: Week 8, n=982,936 | Role-emotional: Week 12, n=990,943 | Role-emotional: Week 28, n=836,819 | Role-emotional: Week 52, n=729,707 | Role-physical: Week 8, n=982,936 | Role-physical: Week 12, n=990,943 | Role-physical: Week 28, n=836,819 | Role-physical: Week 52, n=729,707 | Social functioning: Week 8, n=982,936 | Social functioning: Week 12, n=990,943 | Social functioning: Week 28, n=836,819 | Social functioning: Week 52, n=729,707 | |
Daprodustat | -0.13 | 0.20 | -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 | -0.83 | 0.40 | 0.48 | -0.10 | -0.21 | 0.24 | 0.25 | -0.61 | -1.12 |
rhEPO | 0.12 | -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 | -0.92 | 0.32 | 0.08 | -0.39 | -0.60 | 0.38 | -0.44 | -0.94 | -1.14 |
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
Intervention | Scores on a scale (Least Squares Mean) | |||
---|---|---|---|---|
Week 8, n=982,936 | Week 12, n=990,943 | Week 28, n=836,819 | Week 52, n=729,707 | |
Daprodustat | -0.23 | -0.17 | -0.79 | -1.19 |
rhEPO | -0.26 | -0.51 | -1.03 | -1.04 |
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
Intervention | Millimeter of mercury (Least Squares Mean) | ||
---|---|---|---|
SBP | DBP | MAP | |
Daprodustat | -0.43 | -0.92 | -0.75 |
rhEPO | -0.43 | -1.37 | -1.06 |
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
Intervention | Millimeter of mercury (Least Squares Mean) | ||
---|---|---|---|
SBP | DBP | MAP | |
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) 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
Intervention | Participants (Count of Participants) | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Occurrences per participant: 0 | Occurrences per participant: 1 | Occurrences per participant: 2 | Occurrences per participant: 3 | Occurrences per participant: 4 | Occurrences per participant: 5 | Occurrences per participant: 6 | Occurrences per participant: 7 | Occurrences per participant: 8 | Occurrences per participant: 9 | Occurrences per participant: 10 | |
Daprodustat | 1062 | 315 | 72 | 25 | 3 | 4 | 4 | 0 | 0 | 1 | 1 |
rhEPO | 1044 | 300 | 88 | 22 | 11 | 4 | 3 | 2 | 1 | 1 | 1 |
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)
Intervention | Events per 100 participant years (Number) |
---|---|
Daprodustat | 138.50 |
Darbepoetin Alfa | 157.35 |
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
Intervention | Scores on a scale (Least Squares Mean) |
---|---|
Daprodustat | -0.7 |
Darbepoetin Alfa | -1.4 |
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
Intervention | Scores on a scale (Least Squares Mean) |
---|---|
Daprodustat | -0.0253 |
Darbepoetin Alfa | -0.0018 |
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
Intervention | mL per minute per 1.73 square meter (Least Squares Mean) |
---|---|
Daprodustat | -2.88 |
Darbepoetin Alfa | -2.67 |
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
Intervention | Grams per deciliter (Least Squares Mean) |
---|---|
Daprodustat | 0.76 |
Darbepoetin Alfa | 0.73 |
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)
Intervention | Grams per deciliter (Least Squares Mean) |
---|---|
Daprodustat | 0.74 |
Darbepoetin Alfa | 0.66 |
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
Intervention | Participants (Count of Participants) |
---|---|
Daprodustat | 1167 |
Darbepoetin Alfa | 1063 |
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)
Intervention | Participants (Count of Participants) |
---|---|
Daprodustat | 939 |
Darbepoetin Alfa | 1012 |
Percentage of participants permanently stopping randomized treatment due to meeting rescue criteria has been presented. (NCT02876835)
Timeframe: Day 1 to 51.1 months
Intervention | Percentage of participants (Number) |
---|---|
Daprodustat | 2.0 |
Darbepoetin Alfa | 3.3 |
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)
Intervention | Percentage of days (Median) |
---|---|
Daprodustat | 66.1 |
Darbepoetin Alfa | 62.1 |
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
Intervention | Percentage of days (Median) |
---|---|
Daprodustat | 70.5 |
Darbepoetin Alfa | 63.2 |
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
Intervention | Percentage of days (Median) |
---|---|
Daprodustat | 70.5 |
Darbepoetin Alfa | 63.2 |
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)
Intervention | Percentage of days (Median) |
---|---|
Daprodustat | 66.1 |
Darbepoetin Alfa | 62.1 |
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
Intervention | Events per 100 person years (Number) |
---|---|
Daprodustat | 8.35 |
Darbepoetin Alfa | 8.27 |
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
Intervention | Events per 100 person years (Number) |
---|---|
Daprodustat | 3.02 |
Darbepoetin Alfa | 2.55 |
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
Intervention | Events per 100 person years (Number) |
---|---|
Daprodustat | 5.36 |
Darbepoetin Alfa | 4.98 |
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
Intervention | Events per 100 person years (Number) |
---|---|
Daprodustat | 4.05 |
Darbepoetin Alfa | 3.30 |
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
Intervention | Events per 100 person years (Number) |
---|---|
Daprodustat | 10.86 |
Darbepoetin Alfa | 10.63 |
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
Intervention | Events per 100 person years (Number) |
---|---|
Daprodustat | 13.16 |
Darbepoetin Alfa | 12.22 |
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
Intervention | Events per 100 person years (Number) |
---|---|
Daprodustat | 14.60 |
Darbepoetin Alfa | 13.32 |
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
Intervention | Events per 100 person years (Number) |
---|---|
Daprodustat | 12.34 |
Darbepoetin Alfa | 11.77 |
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
Intervention | Events per 100 person years (Number) |
---|---|
Daprodustat | 10.86 |
Darbepoetin Alfa | 10.63 |
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
Intervention | Events per 100 person years (Number) |
---|---|
Daprodustat | 2.94 |
Darbepoetin Alfa | 2.76 |
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
Intervention | Events per 100 person years (Number) |
---|---|
Daprodustat | 1.26 |
Darbepoetin Alfa | 0.95 |
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
Intervention | Events per 100 person years (Number) |
---|---|
Daprodustat | 1.81 |
Darbepoetin Alfa | 1.43 |
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
Intervention | Events per 100 person years (Number) |
---|---|
Daprodustat | 7.78 |
Darbepoetin Alfa | 7.55 |
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
Intervention | Events per 100 person years (Number) |
---|---|
Daprodustat | 41.13 |
Darbepoetin Alfa | 38.99 |
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
Intervention | Events per 100 person years (Number) |
---|---|
Daprodustat | 12.20 |
Darbepoetin Alfa | 12.06 |
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
Intervention | Events per 100 person years (Number) |
---|---|
Daprodustat | 17.55 |
Darbepoetin Alfa | 17.76 |
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
Intervention | Events per 100 person years (Number) |
---|---|
Daprodustat | 8.21 |
Darbepoetin Alfa | 8.90 |
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
Intervention | Events per 100 person years (Number) |
---|---|
Daprodustat | 1.00 |
Darbepoetin Alfa | 1.14 |
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
Intervention | Scores on a scale (Least Squares Mean) | |||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Tired/Low energy/Weak domain: Week 8,n=1340,1294 | Tired/Low energy/Weak domain: Week 12,n=1341,1360 | Tired/Low energy/Weak domain: Week 28,n=1053,1047 | Tired/Low energy/Weak domain: Week 52,n=870,865 | Chest pain/SOB domain: Week 8,n=1340,1294 | Chest pain/ SOB domain: Week 12,n=1341,1360 | Chest pain/ SOB domain: Week 28,n=1053,1047 | Chest pain/ SOB domain: Week 52,n=870,865 | Cognitive domain: Week 8,n=1340,1294 | Cognitive domain: Week 12,n=1341,1360 | Cognitive domain: Week 28,n=1053,1047 | Cognitive domain: Week 52,n=870,865 | SOB, no activity: Week 8,n=1340,1294 | SOB, no activity: Week 12,n=1341,1360 | SOB, no activity: Week 28,n=1053,1047 | SOB, no activity: Week 52,n=870,865 | Severity-short breath, Resting: Week 8,n=1340,1294 | Severity-short breath, Resting:Week 12,n=1341,1360 | Severity-short breath, Resting:Week 28,n=1053,1047 | Severity-short breath, Resting:Week 52,n=870,865 | Diff std for long time: Week 8,n=1340,1294 | Diff std for long time: Week 12,n=1341,1360 | Diff std for long time: Week 28,n=1053,1047 | Diff std for long time: Week 52,n=870,865 | Difficulty sleeping: Week 8,n=1340,1294 | Difficulty sleeping: Week 12,n=1341,1360 | Difficulty sleeping: Week 28,n=1053,1047 | Difficulty sleeping: Week 52,n=870,865 | |
Daprodustat | 1.72 | 2.11 | 1.27 | 0.20 | 0.63 | 0.88 | 0.01 | -0.71 | 0.13 | -0.17 | -0.40 | -2.00 | -0.1 | 0.1 | -1.1 | -1.7 | -0.3 | -0.3 | -1.1 | -2.0 | 1.0 | 0.7 | 0.4 | -2.1 | 1.6 | 0.5 | -0.7 | -2.6 |
Darbepoetin Alfa | 2.94 | 3.08 | 1.87 | 1.77 | 1.83 | 1.53 | 0.53 | 0.47 | 0.89 | 1.01 | 0.37 | -0.35 | 1.0 | 0.4 | -0.2 | -1.6 | 0.8 | 0.0 | -0.7 | -0.5 | 2.5 | 1.6 | 1.7 | 1.2 | 1.1 | 2.0 | -0.3 | -0.3 |
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
Intervention | Scores on a scale (Least Squares Mean) | |||
---|---|---|---|---|
Week 8, n=1238,1187 | Week 12, n=1237,1227 | Week 28, n=968,956 | Week 52, n=804,780 | |
Daprodustat | 0.08 | 0.02 | -0.35 | -0.71 |
Darbepoetin Alfa | 0.37 | 0.18 | -0.02 | -0.35 |
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
Intervention | Scores on a scale (Least Squares Mean) | |||
---|---|---|---|---|
Week 8, n=1341,1295 | Week 12, n=1341,1362 | Week 28, n=1054,1051 | Week 52, n=871,865 | |
Daprodustat | 0.00 | 0.03 | 0.05 | 0.11 |
Darbepoetin Alfa | -0.02 | -0.02 | 0.09 | 0.06 |
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
Intervention | Scores on a scale (Least Squares Mean) | |||
---|---|---|---|---|
Week 8, n=1238,1187 | Week 12, n=1237,1227 | Week 28, n=968,956 | Week 52, n=804,780 | |
Daprodustat | 0.42 | 0.60 | 0.16 | -0.32 |
Darbepoetin Alfa | 0.78 | 0.71 | 0.04 | -0.12 |
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
Intervention | Scores on a scale (Least Squares Mean) | |||
---|---|---|---|---|
Week 8, n=1238,1187 | Week 12, n=1237,1227 | Week 28, n=968,956 | Week 52, n=804,780 | |
Daprodustat | 0.51 | 0.65 | 0.05 | -0.69 |
Darbepoetin Alfa | 0.83 | 0.52 | -0.10 | -0.37 |
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
Intervention | Scores on a scale (Least Squares Mean) | |||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Bodily pain: Week 8, n=1238,1187 | Bodily pain: Week 12, n=1237,1227 | Bodily pain: Week 28, n=968,956 | Bodily pain: Week 52, n=804,780 | General health: Week 8, n=1238,1187 | General health: Week 12, n=1237,1227 | General health: Week 28, n=968,956 | General health: Week 52, n=804,780 | Mental health: Week 8, n=1238,1187 | Mental health: Week 12, n=1237,1227 | Mental health: Week 28, n=968,956 | Mental health: Week 52, n=804,780 | Role-emotional: Week 8, n=1238,1187 | Role-emotional: Week 12, n=1237,1227 | Role-emotional: Week 28, n=968,956 | Role-emotional: Week 52, n=804,780 | Role-physical: Week 8, n=1238,1187 | Role-physical: Week 12, n=1237,1227 | Role-physical: Week 28, n=968,956 | Role-physical: Week 52, n=804,780 | Social functioning: Week 8, n=1238,1187 | Social functioning: Week 12, n=1237,1227 | Social functioning: Week 28, n=968,956 | Social functioning: Week 52, n=804,780 | |
Daprodustat | 0.11 | 0.35 | -0.48 | -0.34 | 0.36 | 0.28 | 0.14 | -0.27 | -0.19 | -0.07 | -0.67 | -0.85 | 0.45 | 0.17 | -0.30 | -0.90 | 0.33 | 0.40 | 0.06 | -0.63 | 0.19 | 0.21 | 0.04 | -0.58 |
Darbepoetin Alfa | 0.45 | 0.50 | 0.02 | 0.13 | 0.43 | 0.48 | 0.04 | -0.19 | 0.12 | -0.09 | -0.37 | -0.61 | 0.54 | 0.43 | 0.07 | -0.38 | 0.83 | 0.73 | 0.00 | -0.44 | 0.82 | 0.53 | 0.17 | -0.20 |
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
Intervention | Scores on a scale (Least Squares Mean) | |||
---|---|---|---|---|
Week 8, n=1238,1187 | Week 12, n=1237,1227 | Week 28, n=968,956 | Week 52, n=804,780 | |
Daprodustat | 0.35 | 0.62 | 0.22 | -0.14 |
Darbepoetin Alfa | 0.90 | 0.74 | 0.32 | 0.35 |
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
Intervention | Millimeter of mercury (Least Squares Mean) | ||
---|---|---|---|
SBP, n=1919, 1884 | DBP, n=1918, 1884 | MAP, n=1918, 1884 | |
Daprodustat | -1.19 | -0.26 | -0.57 |
Darbepoetin Alfa | -1.10 | -0.38 | -0.62 |
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
Intervention | Millimeter of mercury (Least Squares Mean) | ||
---|---|---|---|
SBP, n=1913, 1884 | DBP, n=1912, 1884 | MAP, n=1912, 1884 | |
Daprodustat | -0.62 | 0.06 | -0.17 |
Darbepoetin Alfa | -1.17 | -0.59 | -0.77 |
Number of participants with adjudicated MACE or hospitalization for heart failure (recurrent events analysis) 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
Intervention | Participants (Count of Participants) | ||||||||
---|---|---|---|---|---|---|---|---|---|
Occurrences per participant: 0 | Occurrences per participant: 1 | Occurrences per participant: 2 | Occurrences per participant: 3 | Occurrences per participant: 4 | Occurrences per participant: 5 | Occurrences per participant: 6 | Occurrences per participant: 7 | Occurrences per participant: 8 | |
Daprodustat | 1493 | 318 | 76 | 26 | 14 | 5 | 1 | 4 | 0 |
Darbepoetin Alfa | 1518 | 317 | 64 | 22 | 9 | 3 | 0 | 1 | 1 |
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
Intervention | Milligram (Least Squares Mean) |
---|---|
Daprodustat | 144.7 |
Darbepoetin Alfa | 125.3 |
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
Intervention | Events per 100 participant year (Number) |
---|---|
Daprodustat | 352.50 |
Darbepoetin Alfa | 350.00 |
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
Intervention | Scores on a scale (Least Squares Mean) |
---|---|
Daprodustat | 3.4 |
Darbepoetin Alfa | 6.8 |
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
Intervention | Scores on a scale (Least Squares Mean) |
---|---|
Daprodustat | 0.00 |
Darbepoetin Alfa | -0.03 |
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
Intervention | Grams per deciliter (Least Squares Mean) |
---|---|
Daprodustat | 1.17 |
Darbepoetin Alfa | 1.13 |
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)
Intervention | Grams per deciliter (Least Squares Mean) |
---|---|
Daprodustat | 1.02 |
Darbepoetin Alfa | 1.12 |
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
Intervention | Participants (Count of Participants) |
---|---|
Daprodustat | 86 |
Darbepoetin Alfa | 87 |
Number of participants permanently stopping randomized treatment due to meeting rescue criteria has been presented. (NCT03029208)
Timeframe: Up to Week 52
Intervention | Participants (Count of Participants) |
---|---|
Daprodustat | 5 |
Darbepoetin Alfa | 5 |
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
Intervention | Participants (Count of Participants) |
---|---|
Daprodustat | 91 |
Darbepoetin Alfa | 100 |
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
Intervention | Percentage of days (Median) |
---|---|
Daprodustat | 57.0 |
Darbepoetin Alfa | 54.7 |
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
Intervention | Percentage of days (Median) |
---|---|
Daprodustat | 57.0 |
Darbepoetin Alfa | 54.7 |
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
Intervention | Scores on a scale (Least Squares Mean) | ||||||
---|---|---|---|---|---|---|---|
Tired/Low energy/Weak domain | Chest pain/Shortness of breath domain | Cognitive domain | Shortness of breath, no activity | Severity-short breath, Resting | Difficulty standing for long time | Difficulty sleeping | |
Daprodustat | -2.36 | -1.83 | -4.17 | -1.90 | -4.16 | -2.00 | -5.27 |
Darbepoetin Alfa | 4.07 | 2.28 | 2.43 | 1.14 | 0.12 | 3.30 | 1.26 |
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
Intervention | Scores on a scale (Least Squares Mean) | |||
---|---|---|---|---|
Week 8, n=88,86 | Week 12, n=88,88 | Week 28, n=80,74 | Week 52, n=67,65 | |
Daprodustat | 0.10 | 0.08 | -0.02 | -0.95 |
Darbepoetin Alfa | 0.76 | 1.60 | 0.30 | -0.72 |
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
Intervention | Scores on a scale (Least Squares Mean) | |||
---|---|---|---|---|
Week 8, n=100,100 | Week 12, n=100,103 | Week 28, n=92,85 | Week 52, n=75,77 | |
Daprodustat | 0.16 | 0.02 | 0.09 | 0.22 |
Darbepoetin Alfa | -0.11 | -0.03 | -0.07 | 0.04 |
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
Intervention | Scores on a scale (Least Squares Mean) | |||
---|---|---|---|---|
Week 8, n=88,86 | Week 12, n=88,88 | Week 28, n=80,74 | Week 52, n=67,65 | |
Daprodustat | 0.79 | 1.67 | 0.94 | 0.61 |
Darbepoetin Alfa | 1.18 | 0.54 | 0.45 | 1.93 |
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
Intervention | Scores on a scale (Least Squares Mean) | |
---|---|---|
Week 28, n=80,74 | Week 52, n=67,65 | |
Daprodustat | 0.55 | 0.14 |
Darbepoetin Alfa | 0.83 | 1.58 |
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)
Intervention | Millimeter of mercury (Least Squares Mean) | ||
---|---|---|---|
SBP | DBP | MAP | |
Daprodustat | -3.23 | 0.60 | -0.68 |
Darbepoetin Alfa | -3.14 | -1.39 | -1.97 |
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
Intervention | Scores on a scale (Least Squares Mean) | |||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Bodily pain: Week 8, n=88,86 | Bodily pain: Week 12, n=88,88 | Bodily pain: Week 28, n=80,74 | Bodily pain: Week 52, n=67,65 | General health: Week 8, n=88,86 | General health: Week 12, n=88,88 | General health: Week 28, n=80,74 | General health: Week 52, n=67,65 | Mental health: Week 8, n=88,86 | Mental health: Week 12, n=88,88 | Mental health: Week 28, n=80,74 | Mental health: Week 52, n=67,65 | Role-emotional: Week 8, n=88,86 | Role-emotional: Week 12, n=88,88 | Role-emotional: Week 28, n=80,74 | Role-emotional: Week 52, n=67,65 | Role-physical: Week 8, n=88,86 | Role-physical: Week 12, n=88,88 | Role-physical: Week 28, n=80,74 | Role-physical: Week 52, n=67,65 | Social functioning: Week 8, n=88,86 | Social functioning: Week 12, n=88,88 | Social functioning: Week 28, n=80,74 | Social functioning: Week 52, n=67,65 | |
Daprodustat | -0.41 | -0.13 | 1.08 | -2.00 | 0.80 | 0.87 | 0.63 | 0.40 | -0.90 | 0.01 | -0.69 | -0.53 | 0.83 | 0.55 | 0.91 | -1.60 | 1.34 | 2.39 | 0.62 | 1.49 | 0.52 | 0.98 | 1.03 | 0.39 |
Darbepoetin Alfa | -0.55 | -0.06 | -1.26 | 0.61 | 0.75 | 0.59 | 0.37 | 0.58 | 0.25 | 1.42 | -0.21 | -0.27 | 0.50 | -0.07 | 0.39 | -0.11 | 2.64 | 1.69 | 1.49 | 2.22 | 1.55 | 2.15 | 0.95 | -0.33 |
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
Intervention | Millimeter of mercury (Least Squares Mean) | ||
---|---|---|---|
SBP | DBP | MAP | |
Daprodustat | -3.57 | 0.21 | -0.95 |
Darbepoetin Alfa | -6.80 | -4.01 | -5.05 |
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
Intervention | Scores on a scale (Least Squares Mean) | |
---|---|---|
Week 28, n=80,74 | Week 52, n=67,65 | |
Daprodustat | -0.08 | 0.16 |
Darbepoetin Alfa | 0.95 | 1.61 |
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
Intervention | Nanogram per milliliter (Mean) | |||
---|---|---|---|---|
Daprodustat | GSK2391220 | GSK2506104 | GSK2531401 | |
Daprodustat 1 mg | 21.74 | 2.160 | 2.477 | 2.283 |
Daprodustat 10 mg | 145.0 | 16.60 | 22.00 | 10.20 |
Daprodustat 2 mg | 32.29 | 4.139 | 5.212 | 3.565 |
Daprodustat 4 mg | 76.92 | 5.780 | 7.075 | 5.328 |
Daprodustat 6 mg | 100.2 | 10.36 | 11.60 | 7.836 |
Daprodustat 8 mg | 32.00 | 6.090 | 10.10 | 5.760 |
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
Intervention | Nanogram per milliliter (Mean) | |||
---|---|---|---|---|
Daprodustat | GSK2391220 | GSK2506104 | GSK2531401 | |
Daprodustat 1 mg | 2.118 | 0.7106 | 1.270 | 1.642 |
Daprodustat 10 mg | 0.1090 | 6.560 | 9.500 | 7.760 |
Daprodustat 2 mg | 1.015 | 2.124 | 3.508 | 2.729 |
Daprodustat 4 mg | 0.5787 | 2.087 | 3.879 | 3.750 |
Daprodustat 6 mg | 2.867 | 3.560 | 5.921 | 5.111 |
Daprodustat 8 mg | 0.1030 | 4.450 | 8.710 | 5.660 |
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
Intervention | Nanogram per milliliter (Mean) | ||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Daprodustat: Pre-Dose, n=19,26,20,18,1,1,0,0,0 | Daprodustat: 1 hour, n=19,26,20,18,1,1,0,0,0 | Daprodustat: 2 hours, n=19,26,20,18,1,1,0,0,0 | Daprodustat: 3 hours, n=19,26,19,18,1,1,0,0,0 | GSK2391220: Pre-Dose, n=19,26,20,18,1,1,0,0,0 | GSK2391220: 0.5 hour, n=19,25,20,18,1,1,0,0,0 | GSK2391220: 1 hour, n=18,26,20,18,1,1,0,0,0 | GSK2391220: 2 hours, n=19,26,20,18,1,1,0,0,0 | GSK2391220: 3 hours, n=19,26,19,18,1,1,0,0,0 | GSK2506104: Pre-Dose, n=19,26,20,18,1,1,0,0,0 | GSK2506104: 0.5 hour, n=19,26,20,18,1,1,0,0,0 | GSK2506104: 1 hour, n=19,26,20,18,1,1,0,0,0 | GSK2506104: 2 hours, n=19,26,20,18,1,1,0,0,0 | GSK2506104: 3 hours, n=19,26,19,18,1,1,0,0,0 | GSK2531401: Pre-Dose, n=19,26,20,18,1,1,0,0,0 | GSK2531401: 0.5 hour, n=19,26,20,18,1,1,0,0,0 | GSK2531401: 1 hour, n=19,26,20,18,1,1,0,0,0 | GSK2531401: 2 hours, n=19,26,20,18,1,1,0,0,0 | GSK2531401: 3 hours, n=19,26,19,18,1,1,0,0,0 | |
Daprodustat 8 mg | 0.1030 | 0.9120 | 32.00 | 25.30 | 4.450 | 3.950 | 3.900 | 4.700 | 6.090 | 8.710 | 7.740 | 7.460 | 8.930 | 10.10 | 5.660 | 4.960 | 4.810 | 5.190 | 5.760 |
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
Intervention | Nanogram per milliliter (Mean) | |||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Daprodustat: Pre-Dose, n=19,26,20,18,1,1,0,0,0 | Daprodustat: 0.5 hour, n=19,26,20,18,0,1,0,0,0 | Daprodustat: 1 hour, n=19,26,20,18,1,1,0,0,0 | Daprodustat: 2 hours, n=19,26,20,18,1,1,0,0,0 | Daprodustat: 3 hours, n=19,26,19,18,1,1,0,0,0 | GSK2391220: Pre-Dose, n=19,26,20,18,1,1,0,0,0 | GSK2391220: 0.5 hour, n=19,25,20,18,1,1,0,0,0 | GSK2391220: 1 hour, n=18,26,20,18,1,1,0,0,0 | GSK2391220: 2 hours, n=19,26,20,18,1,1,0,0,0 | GSK2391220: 3 hours, n=19,26,19,18,1,1,0,0,0 | GSK2506104: Pre-Dose, n=19,26,20,18,1,1,0,0,0 | GSK2506104: 0.5 hour, n=19,26,20,18,1,1,0,0,0 | GSK2506104: 1 hour, n=19,26,20,18,1,1,0,0,0 | GSK2506104: 2 hours, n=19,26,20,18,1,1,0,0,0 | GSK2506104: 3 hours, n=19,26,19,18,1,1,0,0,0 | GSK2531401: Pre-Dose, n=19,26,20,18,1,1,0,0,0 | GSK2531401: 0.5 hour, n=19,26,20,18,1,1,0,0,0 | GSK2531401: 1 hour, n=19,26,20,18,1,1,0,0,0 | GSK2531401: 2 hours, n=19,26,20,18,1,1,0,0,0 | GSK2531401: 3 hours, n=19,26,19,18,1,1,0,0,0 | |
Daprodustat 10 mg | 0.1090 | 145.0 | 79.60 | 27.60 | 11.00 | 6.560 | 6.740 | 10.00 | 16.20 | 16.60 | 9.500 | 8.110 | 12.40 | 19.60 | 22.00 | 7.760 | 6.460 | 6.630 | 8.290 | 10.20 |
Daprodustat 2 mg | 1.015 | 4.664 | 21.45 | 20.36 | 15.58 | 2.124 | 1.807 | 1.752 | 2.969 | 3.535 | 3.508 | 2.788 | 2.610 | 3.583 | 4.145 | 2.729 | 2.170 | 1.979 | 2.338 | 2.734 |
Daprodustat 4 mg | 0.5787 | 10.27 | 36.78 | 54.68 | 43.34 | 2.087 | 1.822 | 1.965 | 4.008 | 5.553 | 3.879 | 3.315 | 3.268 | 4.989 | 6.503 | 3.750 | 3.263 | 3.146 | 3.711 | 4.715 |
Daprodustat 6 mg | 2.867 | 12.58 | 45.48 | 55.62 | 56.49 | 3.560 | 2.410 | 3.140 | 6.336 | 9.372 | 5.921 | 4.015 | 4.333 | 7.130 | 9.942 | 5.111 | 3.800 | 3.776 | 4.892 | 6.631 |
Daprodustat 1 mg | 2.118 | 5.675 | 12.34 | 12.74 | 7.719 | 0.7106 | 0.7602 | 1.123 | 1.745 | 1.911 | 1.270 | 1.197 | 1.364 | 1.966 | 2.190 | 1.642 | 1.427 | 1.399 | 1.690 | 1.847 |
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
Intervention | Beats per minute (Mean) |
---|---|
Placebo | -2.0 |
Dapro 10 mg | 0.5 |
Dapro 15 mg | 1.1 |
Dapro 25 mg | 2.2 |
Dapro 30 mg | 0.9 |
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
Intervention | Proportion of red blood cells in blood (Mean) |
---|---|
Placebo | -0.0218 |
Dapro 10 mg | -0.0127 |
Dapro 15 mg | -0.0149 |
Dapro 25 mg | 0.0150 |
Dapro 30 mg | 0.0215 |
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
Intervention | g/dL (Mean) |
---|---|
Placebo | -0.61 |
Dapro 10 mg | -0.19 |
Dapro 15 mg | -0.13 |
Dapro 25 mg | 0.64 |
Dapro 30 mg | 0.55 |
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
Intervention | 10^12 cells/L (Mean) |
---|---|
Placebo | -0.19 |
Dapro 10 mg | -0.12 |
Dapro 15 mg | -0.13 |
Dapro 25 mg | 0.12 |
Dapro 30 mg | 0.15 |
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
Intervention | Percentage of reticulocyte (Mean) |
---|---|
Placebo | -0.08 |
Dapro 10 mg | -0.11 |
Dapro 15 mg | -0.04 |
Dapro 25 mg | 0.43 |
Dapro 30 mg | 0.09 |
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
Intervention | Picograms (pg) (Mean) |
---|---|
Placebo | -0.15 |
Dapro 10 mg | 0.23 |
Dapro 15 mg | 0.26 |
Dapro 25 mg | 0.23 |
Dapro 30 mg | 0.59 |
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
Intervention | International unit per liter (IU/L) (Mean) |
---|---|
Placebo | 53.761 |
Dapro 10 mg | 2.255 |
Dapro 15 mg | 73.369 |
Dapro 25 mg | 302.529 |
Dapro 30 mg | 477.644 |
"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
Intervention | ng/mL (Geometric Mean) |
---|---|
Dapro 10 mg | 140.0 |
Dapro 15 mg | 141.4 |
Dapro 25 mg | 246.9 |
Dapro 30 mg | 387.3 |
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
Intervention | Nanograms per liter (ng/L) (Geometric Mean) |
---|---|
Placebo | 20.35 |
Dapro 10 mg | 43.75 |
Dapro 15 mg | 32.16 |
Dapro 25 mg | 53.34 |
Dapro 30 mg | 76.09 |
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
Intervention | Micrograms per liter (µg/L) (Geometric Mean) |
---|---|
Placebo | 27.81 |
Dapro 10 mg | 35.37 |
Dapro 15 mg | 3.83 |
Dapro 25 mg | -36.74 |
Dapro 30 mg | -36.09 |
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
Intervention | IU/L (Mean) | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
ALT; Day 1; n= 18, 20, 20, 22, 22 | ALT; Day 15; n= 17, 20, 18, 22, 20 | ALT; Day 29; n= 17, 19, 18, 19, 17 | ALT; Day 43; n= 15, 20, 18, 21, 21 | AST; Day 1; n= 18, 20, 20, 22, 22 | AST; Day 15; n= 17, 20, 18, 22, 20 | AST; Day 29; n= 17, 19, 18, 19, 17 | AST; Day 43; n= 15, 20, 18, 21, 21 | Alk. phosph; Day 1; n= 18, 20, 20, 22, 22 | Alk. phosph; Day 15; n= 17, 20, 18, 22,20 | Alk. phosph.; Day 29; n= 17, 19, 18, 19,17 | Alk. phosph.; Day 43; n= 15, 20, 18, 21,21 | |
Dapro 10 mg | 13.4 | 13.9 | 12.8 | 13.8 | 14.2 | 14.3 | 13.8 | 14.9 | 112.3 | 115.4 | 120.2 | 117.6 |
Dapro 15 mg | 14.6 | 12.4 | 12.2 | 12.8 | 17.2 | 15.0 | 16.0 | 17.2 | 106.8 | 114.5 | 109.2 | 113.8 |
Dapro 25 mg | 10.7 | 11.9 | 10.9 | 13.1 | 14.4 | 15.4 | 15.0 | 15.7 | 99.4 | 101.5 | 93.5 | 116.2 |
Dapro 30 mg | 11.5 | 8.4 | 8.6 | 11.2 | 13.6 | 12.4 | 13.5 | 14.3 | 115.4 | 110.0 | 120.4 | 108.6 |
Placebo | 12.6 | 16.5 | 24.4 | 14.3 | 14.9 | 17.1 | 26.8 | 15.9 | 97.0 | 102.4 | 94.1 | 96.5 |
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
Intervention | grams per liter (g/L) (Mean) | |||||||
---|---|---|---|---|---|---|---|---|
Albumin; Day 1; n= 18, 20, 20, 22, 22 | Albumin; Day 15; n= 17, 20, 18, 22, 20 | Albumin; Day 29; n= 17, 19, 18, 19, 17 | Albumin; Day 43; n= 15, 20, 18, 21, 21 | Protein; Day 1; n= 18, 20 ,20, 22, 22 | Protein; Day 15; n= 17, 20, 18, 22, 20 | Protein; Day 29; n= 17, 19, 18, 19, 17 | Protein; Day 43; n= 15, 20, 18, 21, 21 | |
Dapro 10 mg | 38.6 | 38.1 | 37.2 | 38.1 | 66.9 | 66.5 | 65.7 | 67.4 |
Dapro 15 mg | 38.7 | 38.4 | 37.6 | 37.9 | 67.4 | 67.3 | 66.0 | 66.8 |
Dapro 25 mg | 38.8 | 38.4 | 37.4 | 39.0 | 66.4 | 65.6 | 65.5 | 66.7 |
Dapro 30 mg | 38.1 | 37.2 | 36.9 | 37.5 | 65.7 | 64.3 | 65.3 | 66.6 |
Placebo | 37.6 | 38.1 | 36.5 | 37.1 | 67.3 | 68.1 | 66.1 | 67.2 |
"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
Intervention | hour into nanograms/milliliter (h*ng/mL) (Geometric Mean) | |
---|---|---|
AUC (0-t); n= 19, 15, 16, 14 | AUC (0-inf); n= 12, 9, 8, 11 | |
Dapro 10 mg | 311.7 | 348.2 |
Dapro 15 mg | 416.7 | 383.5 |
Dapro 25 mg | 513.9 | 1214 |
Dapro 30 mg | 1010 | 1369 |
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
Intervention | Micromoles per liter (µmol/L) (Mean) | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Bilirubin; Day 1; n= 18, 20, 20, 22, 22 | Bilirubin; Day 15; n= 17, 20, 18, 22, 20 | Bilirubin; Day 29; n= 17, 19, 18, 19, 17 | Bilirubin; Day 43; n= 15, 20 ,18, 21, 21 | Direct bilirubin; Day 1; n= 18, 20, 20, 22, 22 | Direct bilirubin; Day 15; n= 17, 20, 18, 22, 20 | Direct bilirubin; Day 29; n= 17, 19, 18, 19,17 | Direct bilirubin; Day 43; n= 15, 20, 18, 21,21 | Indirect bilirubin; Day 1; n= 18, 20, 20, 22, 22 | Indirect bilirubin; Day 15; n= 17, 20, 18, 22, 20 | Indirect bilirubin; Day 29; n= 17, 19, 18, 19, 17 | Indirect bilirubin; Day 43; n= 15, 20, 18, 21, 21 | |
Dapro 10 mg | 7.8 | 7.1 | 6.9 | 7.0 | 1.9 | 2.2 | 1.6 | 1.9 | 5.9 | 4.9 | 5.4 | 5.1 |
Dapro 15 mg | 6.6 | 7.2 | 7.6 | 7.2 | 2.0 | 2.4 | 2.7 | 2.3 | 4.6 | 4.8 | 4.9 | 4.9 |
Dapro 25 mg | 6.5 | 6.5 | 6.5 | 6.5 | 1.9 | 1.8 | 1.8 | 1.7 | 4.6 | 4.7 | 4.7 | 4.8 |
Dapro 30 mg | 7.2 | 7.8 | 7.8 | 7.5 | 2.4 | 2.6 | 2.4 | 2.3 | 4.8 | 5.2 | 5.4 | 5.2 |
Placebo | 6.6 | 6.7 | 6.8 | 6.0 | 1.8 | 1.5 | 2.5 | 1.3 | 4.8 | 5.2 | 4.4 | 4.7 |
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
Intervention | g/L (Mean) | |||||
---|---|---|---|---|---|---|
Albumin; Day 15; n= 17, 20, 18, 22, 20 | Albumin; Day 29; n= 17, 19, 18, 19, 17 | Albumin; Day 43; n= 15, 20, 18, 21, 21 | Protein; Day 15; n= 17, 20, 18, 22, 20 | Protein; Day 29; n= 17, 19, 18, 19, 17 | Protein; Day 43; n= 15, 20, 18, 21, 21 | |
Dapro 10 mg | -0.5 | -1.3 | -0.6 | -0.4 | -0.8 | 0.6 |
Dapro 15 mg | 0.2 | -0.7 | -0.7 | 0.3 | -1.2 | -0.9 |
Dapro 25 mg | -0.5 | -1.3 | 0.1 | -0.7 | -1.0 | 0.3 |
Dapro 30 mg | -1.0 | -0.9 | -0.3 | -1.5 | 0.1 | 1.2 |
Placebo | 0.8 | -0.5 | 0.1 | 0.8 | -1.1 | -0.1 |
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
Intervention | IU/L (Mean) | ||||||||
---|---|---|---|---|---|---|---|---|---|
ALT; Day 15; n= 17, 20, 18, 22, 20 | ALT; Day 29; n= 17, 19, 18, 19, 17 | ALT; Day 43; n= 15, 20, 18, 21, 21 | AST; Day 15; n= 17, 20, 18, 22, 20 | AST; Day 29; n= 17, 19, 18, 19, 17 | AST; Day 43; n= 15, 20, 18, 21, 21 | Alk.phosph.; Day 15; n= 17, 20, 18, 22, 20 | Alk.phosph.; Day 29; n= 17, 19, 18, 19, 17 | Alk.phosph.; Day 43; n= 15, 20, 18, 21, 21 | |
Dapro 10 mg | 0.5 | -0.9 | 0.4 | 0.1 | -0.3 | 0.7 | 3.2 | 5.1 | 5.4 |
Dapro 15 mg | -3.1 | -3.4 | -2.5 | -2.7 | -1.8 | -0.6 | 2.7 | -0.9 | 2.7 |
Dapro 25 mg | 1.1 | -0.2 | 2.2 | 1.0 | 0.9 | 1.5 | 2.1 | 0.9 | 18.0 |
Dapro 30 mg | -3.4 | -3.6 | -0.4 | -1.6 | -0.3 | 0.7 | -4.7 | -1.2 | -8.4 |
Placebo | 3.6 | 11.8 | 0.9 | 2.3 | 11.5 | 0.6 | 3.2 | -0.4 | -1.5 |
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
Intervention | µmol/L (Mean) | ||||||||
---|---|---|---|---|---|---|---|---|---|
Bilirubin; Day 15; n= 17, 20, 18, 22, 20 | Bilirubin; Day 29; n= 17, 19, 18, 19, 17 | Bilirubin; Day 43; n= 15, 20, 18, 21, 21 | Direct bilirubin; Day 15; n= 17, 20, 18, 22, 20 | Direct bilirubin; Day 29; n= 17, 19, 18, 19, 17 | Direct bilirubin; Day 43; n= 15, 20, 18, 21, 21 | Indirect bilirubin; Day 15; n= 17, 20, 18, 22, 20 | Indirect bilirubin; Day 29; n= 17, 19, 18, 19, 17 | Indirect bilirubin; Day 43; n= 15, 20, 18, 21, 21 | |
Dapro 10 mg | -0.7 | -0.3 | -0.8 | 0.3 | -0.3 | 0.0 | -1.0 | 0.0 | -0.8 |
Dapro 15 mg | 0.8 | 1.0 | 0.6 | 0.6 | 0.7 | 0.3 | 0.2 | 0.3 | 0.2 |
Dapro 25 mg | 0.0 | 0.1 | 0.1 | -0.1 | -0.1 | -0.2 | 0.1 | 0.2 | 0.3 |
Dapro 30 mg | 0.5 | 0.2 | 0.4 | 0.2 | -0.1 | -0.1 | 0.3 | 0.4 | 0.5 |
Placebo | 0.2 | 0.2 | -0.1 | -0.1 | 0.7 | -0.1 | 0.4 | -0.5 | 0.0 |
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
Intervention | Milliseconds (msec) (Mean) | |||
---|---|---|---|---|
PR interval; n= 17, 18, 18, 17, 16 | QRS duration; n= 17, 19, 18, 19, 17 | QT interval; n= 17, 19, 18, 19, 17 | QTcB; n= 17, 19, 18, 19, 17 | |
Dapro 10 mg | 7.3 | -5.7 | 0.7 | 5.6 |
Dapro 15 mg | -3.3 | -4.7 | -19.2 | -3.7 |
Dapro 25 mg | 2.1 | 1.7 | -1.4 | 1.1 |
Dapro 30 mg | -11.5 | 2.5 | -8.2 | -5.7 |
Placebo | 7.8 | -1.4 | 10.5 | 0.0 |
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
Intervention | Percentage of width (Mean) | ||
---|---|---|---|
Day 15; n= 17, 19, 17, 21, 21 | Day 29; n= 16, 19, 17, 18, 17 | Day 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 mg | 0.54 | 0.58 | 0.23 |
Dapro 30 mg | 1.06 | 0.40 | -0.22 |
Placebo | -0.18 | -0.31 | 0.18 |
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
Intervention | 10^12 cells/L (Mean) | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Leukocytes; Day 15; n= 17, 19, 17, 21, 21 | Leukocytes; Day 29; n= 16, 19, 17, 18, 17 | Leukocytes; Day 43; n= 16, 20, 19, 20, 19 | Neutrophils; Day 15; n= 17, 19, 17, 21, 21 | Neutrophils; Day 29; n= 16, 18, 17, 17, 15 | Neutrophils; Day 43; n= 16, 20, 19, 19, 19 | Basophils; Day 15; n= 17, 19, 17, 21, 21 | Basophils; Day 29; n= 16, 18, 17, 17, 15 | Basophils; Day 43; n= 16, 20, 19, 19, 19 | Eosinophils; Day 15; n= 17, 19, 17, 21, 21 | Eosinophils; Day 29; n= 16, 18, 17, 17, 15 | Eosinophils; Day 43; n= 16, 20, 19, 19, 19 | Lymphocytes; Day 15; n= 17, 19, 17, 21, 21 | Lymphocytes; Day 29; n= 16, 18, 17, 17, 15 | Lymphocytes; Day 43; n= 16, 20, 19, 19, 19 | Monocytes; Day 15; n= 17, 19, 17, 21, 21 | Monocytes; Day 29; n= 16, 18, 17, 17, 15 | Monocytes; Day 43; n= 16, 20, 19, 19, 19 | Platelet; Day 15; n= 17, 18, 17, 20, 21 | Platelet; Day 29; n= 16, 18, 17, 17, 17 | Platelet; Day 43; n= 15, 19, 19, 21, 20 | |
Dapro 10 mg | -0.21 | 0.40 | 1.08 | -0.146 | 0.469 | 0.904 | 0.009 | 0.006 | 0.001 | -0.017 | -0.002 | 0.030 | -0.019 | 0.026 | 0.061 | -0.042 | 0.053 | 0.065 | -16.2 | -12.8 | 4.4 |
Dapro 15 mg | 0.40 | 0.00 | 0.23 | 0.280 | -0.021 | 0.112 | -0.002 | -0.004 | -0.004 | -0.006 | -0.006 | 0.051 | 0.106 | 0.019 | 0.007 | -0.016 | -0.031 | 0.026 | -3.2 | -18.1 | -10.4 |
Dapro 25 mg | -0.03 | -0.14 | 0.21 | 0.259 | -0.009 | 0.504 | -0.002 | 0.000 | -0.001 | -0.006 | 0.025 | 0.021 | -0.208 | -0.074 | -0.064 | -0.068 | 0.077 | -0.021 | -3.3 | 1.3 | -1.6 |
Dapro 30 mg | -0.03 | 0.20 | 0.67 | 0.344 | 0.273 | 0.691 | 0.007 | 0.012 | 0.007 | -0.053 | 0.007 | -0.024 | -0.236 | -0.154 | -0.041 | -0.037 | 0.015 | 0.023 | -10.8 | -2.4 | -7.1 |
Placebo | 0.47 | 0.49 | 0.54 | 0.391 | 0.237 | 0.423 | 0.005 | 0.013 | 0.006 | 0.009 | 0.020 | 0.061 | 0.082 | 0.194 | 0.018 | -0.005 | 0.027 | 0.033 | -14.2 | -17.1 | -4.9 |
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
Intervention | Pg (Mean) | ||
---|---|---|---|
Day 15; n= 17, 19, 17, 21, 21 | Day 29; n= 16, 19, 17, 18, 17 | Day 43; n= 16, 20, 19, 21, 20 | |
Dapro 10 mg | 0.19 | 0.58 | 0.13 |
Dapro 15 mg | 0.27 | 0.42 | 0.34 |
Dapro 25 mg | 0.16 | 0.41 | 0.11 |
Dapro 30 mg | 0.25 | 0.15 | 0.29 |
Placebo | 0.16 | 0.16 | 0.11 |
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
Intervention | g/L (Mean) | ||
---|---|---|---|
Day 15; n= 17, 19, 17, 21, 21 | Day 29; n= 16, 19, 17, 18, 17 | Day 43; n= 16, 20, 19, 21, 20 | |
Dapro 10 mg | 3.0 | 7.3 | 3.0 |
Dapro 15 mg | 3.5 | 7.6 | 6.0 |
Dapro 25 mg | -3.2 | 0.8 | -1.0 |
Dapro 30 mg | -5.0 | -4.4 | -0.3 |
Placebo | 2.6 | 5.6 | 3.9 |
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
Intervention | fL (Mean) | ||
---|---|---|---|
Day 15; n= 17, 19, 17, 21, 21 | Day 29; n= 16, 19, 17, 18, 17 | Day 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 mg | 1.3 | 0.9 | 0.6 |
Dapro 30 mg | 2.2 | 1.6 | 0.9 |
Placebo | -0.4 | -1.4 | -0.8 |
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
Intervention | Beats per minute (Mean) | |||||
---|---|---|---|---|---|---|
Pre-dialysis; Day 15; n= 17, 20, 18, 22, 21 | Pre-dialysis; Day 29; n= 17, 19, 18, 19, 17 | Pre-dialysis; Day 43; n= 16, 20, 19, 21, 21 | Post-dialysis; Day 15; n= 17, 20, 18, 22, 21 | Post-dialysis; Day 29; n= 17, 19, 18, 19, 17 | Post-dialysis; Day 43; n= 16, 20, 19, 21, 21 | |
Dapro 10 mg | -2.6 | 0.9 | 0.1 | -1.2 | 1.5 | 0.3 |
Dapro 15 mg | 2.3 | 3.4 | 0.8 | 1.1 | -0.8 | -0.8 |
Dapro 25 mg | 0.7 | 0.5 | -0.6 | 0.5 | 2.6 | -0.1 |
Dapro 30 mg | -1.4 | -3.0 | 0.2 | 4.4 | 6.0 | 3.9 |
Placebo | 7.0 | 2.4 | 3.1 | 2.2 | 4.2 | 2.3 |
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
Intervention | mmHg (Mean) | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
SBP; pre-dialysis; Day 15; n= 17, 20, 18, 22, 21 | SBP; pre-dialysis; Day 29; n= 17, 19, 18, 19, 17 | SBP; pre-dialysis; Day 43; n= 16, 20, 19, 21, 21 | SBP; post-dialysis; Day 15; n= 17, 20, 18, 22, 21 | SBP; post-dialysis; Day 29; n= 17, 19, 18, 19, 17 | SBP; post-dialysis; Day 43; n= 16, 20, 19, 21, 21 | DBP; pre-dialysis; Day 15; n= 17, 20, 18, 22, 21 | DBP; pre-dialysis; Day 29; n= 17, 19, 18, 19, 17 | DBP; pre-dialysis; Day 43; n= 16, 20, 19, 21, 21 | DBP; post-dialysis; Day 15; n= 17, 20, 18, 22, 21 | DBP; post-dialysis; Day 29; n= 17, 19, 18, 19, 17 | DBP; post-dialysis; Day 43; n= 16, 20, 19, 21, 21 | |
Dapro 10 mg | 1.7 | -3.9 | 1.2 | -3.6 | -9.4 | -3.2 | 1.2 | -4.7 | -2.0 | 2.4 | -2.5 | -0.3 |
Dapro 15 mg | -5.6 | -4.7 | -6.2 | 6.1 | 0.8 | -3.6 | -1.7 | -3.0 | -3.1 | -2.9 | -3.2 | -3.8 |
Dapro 25 mg | 2.5 | 1.3 | 3.3 | 5.7 | 9.3 | 12.0 | 1.8 | 1.4 | 5.2 | 3.6 | 4.1 | 4.5 |
Dapro 30 mg | -1.4 | 4.5 | 4.3 | -0.7 | 4.0 | 4.7 | -2.1 | -0.1 | 2.1 | -0.8 | 0.2 | 4.8 |
Placebo | -2.9 | -0.6 | -2.1 | 5.4 | 2.3 | 3.1 | 1.1 | -0.3 | 2.2 | 2.4 | 3.7 | -0.6 |
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
Intervention | Mmol/L (Mean) | ||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Sodium; Day 15; n= 17, 20, 18, 22, 20 | Sodium; Day 29; n= 17, 19, 18, 19, 17 | Sodium; Day 43; n= 15, 20, 18, 21, 21 | Potassium; Day 15; n= 17, 20, 18, 22, 20 | Potassium; Day 29; n= 17, 19, 18, 19, 17 | Potassium; Day 43; n= 15, 20, 18, 21, 21 | Glucose; Day 15; n= 17, 20, 18, 22, 20 | Glucose; Day 29; n= 17, 19, 18, 19, 17 | Glucose; Day 43; n= 15, 20, 18, 21, 21 | Calcium; Day 15; n= 17, 20, 18, 22, 20 | Calcium; Day 29; n= 17, 19, 18, 19, 17 | Calcium; Day 43; n= 15, 20, 18, 21, 21 | Phosphate; Day 15; n= 17, 20, 18, 22, 20 | Phosphate; Day 29; n= 17, 19, 18, 19, 17 | Phosphate; Day 43; n= 15, 20, 18, 21, 21 | |
Dapro 10 mg | -0.6 | -1.2 | 0.1 | 0.05 | 0.05 | -0.05 | 0.51 | 0.70 | 0.06 | -0.051 | -0.025 | -0.035 | 0.183 | 0.011 | -0.068 |
Dapro 15 mg | -0.5 | -0.9 | -0.6 | -0.09 | -0.14 | -0.06 | 0.45 | 0.73 | 0.52 | -0.026 | -0.009 | 0.018 | 0.111 | 0.069 | -0.053 |
Dapro 25 mg | -1.4 | -0.5 | -0.5 | 0.03 | 0.02 | -0.06 | 0.21 | 0.61 | -0.81 | -0.031 | -0.012 | 0.001 | 0.030 | 0.129 | 0.102 |
Dapro 30 mg | -1.0 | -1.2 | -0.6 | -0.08 | 0.11 | -0.02 | -0.03 | -0.36 | -0.12 | -0.010 | 0.001 | 0.033 | 0.095 | -0.026 | -0.117 |
Placebo | -0.9 | -1.1 | 0.7 | 0.04 | 0.20 | 0.04 | 1.14 | 1.48 | 0.23 | -0.011 | -0.054 | -0.015 | -0.091 | 0.091 | -0.067 |
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
Intervention | kg (Mean) | ||
---|---|---|---|
Day 15; n= 17, 20, 18, 22, 21 | Day 29; n= 17, 19, 18, 19, 17 | Day 43; n= 16, 20, 19, 21, 21 | |
Dapro 10 mg | 0.16 | -0.05 | 0.37 |
Dapro 15 mg | -0.01 | -1.23 | -1.39 |
Dapro 25 mg | 0.06 | -0.16 | 0.15 |
Dapro 30 mg | -0.31 | -0.19 | 0.33 |
Placebo | -0.16 | -0.11 | -0.21 |
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
Intervention | Percentage of width (Mean) | |||
---|---|---|---|---|
Day 1; n= 18, 19, 20, 20, 21 | Day 15; n= 17, 19, 17, 21, 21 | Day 29; n= 16, 19, 17, 18, 17 | Day 43; n= 16, 20, 19, 21, 20 | |
Dapro 10 mg | 16.40 | 15.77 | 15.69 | 15.53 |
Dapro 15 mg | 15.41 | 15.26 | 15.36 | 14.95 |
Dapro 25 mg | 15.81 | 16.30 | 15.76 | 15.61 |
Dapro 30 mg | 15.68 | 16.74 | 16.23 | 15.48 |
Placebo | 15.13 | 15.05 | 15.15 | 15.53 |
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
Intervention | 10^12 cells/L (Mean) | |||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Leukocytes; Day 1; n= 18, 19, 19, 20, 21 | Leukocytes; Day 15; n= 17, 19, 17, 21, 21 | Leukocytes; Day 29; n= 16, 19, 17, 18, 17 | Leukocytes; Day 43; n= 16, 20, 19, 20, 19 | Neutrophils; Day 1; n= 18, 19, 19, 20, 21 | Neutrophils; Day 15; n= 17, 19, 17, 21, 21 | Neutrophils; Day 29; n= 16, 18, 17, 17, 15 | Neutrophils; Day 43; n= 16, 20, 19, 19, 19 | Basophils; Day 1; n= 18, 19, 19, 20, 21 | Basophils; Day 15; n= 17, 19, 17, 21, 21 | Basophils; Day 29; n= 16, 18, 17, 17, 15 | Basophils; Day 43; n= 16, 20, 19, 19, 19 | Eosinophils; Day 1; n= 18, 19, 19, 20, 21 | Eosinophils; Day 15; n= 17, 19, 17, 21, 21 | Eosinophils; Day 29; n= 16, 18, 17, 17, 15 | Eosinophils; Day 43; n= 16, 20, 19, 19, 19 | Lymphocytes; Day 1; n= 18, 19, 19, 20, 21 | Lymphocytes; Day 15; n= 17, 19, 17, 21, 21 | Lymphocytes; Day 29; n= 16, 18, 17, 17, 15 | Lymphocytes; Day 43; n= 16, 20, 19, 19, 19 | Monocytes; Day 1; n= 18, 19, 20, 20, 21 | Monocytes; Day 15; n= 17, 19, 17, 21, 21 | Monocytes; Day 29; n= 16, 18, 17, 17, 15 | Monocytes; Day 43; n= 16, 20, 19, 19, 19 | Platelet; Day 1; n= 16, 19, 20, 19, 21 | Platelet; Day 15; n= 17, 18, 17, 20, 21 | Platelet; Day 29; n= 16, 19, 17, 17, 17 | Platelet; Day 43; n= 15, 20, 19, 21, 20 | |
Dapro 10 mg | 6.07 | 5.85 | 6.59 | 7.25 | 4.097 | 3.887 | 4.591 | 5.049 | 0.016 | 0.026 | 0.021 | 0.018 | 0.174 | 0.166 | 0.149 | 0.210 | 1.393 | 1.416 | 1.427 | 1.509 | 0.396 | 0.352 | 0.457 | 0.459 | 189.9 | 175.4 | 174.7 | 195.8 |
Dapro 15 mg | 5.88 | 6.21 | 5.88 | 6.00 | 3.522 | 3.707 | 3.522 | 3.545 | 0.025 | 0.022 | 0.021 | 0.020 | 0.184 | 0.192 | 0.145 | 0.232 | 1.739 | 1.842 | 1.775 | 1.736 | 0.435 | 0.436 | 0.403 | 0.461 | 198.0 | 198.5 | 187.5 | 188.6 |
Dapro 25 mg | 6.44 | 6.52 | 6.33 | 6.77 | 3.954 | 4.346 | 3.978 | 4.477 | 0.028 | 0.025 | 0.024 | 0.025 | 0.196 | 0.187 | 0.237 | 0.243 | 1.747 | 1.526 | 1.612 | 1.721 | 0.518 | 0.446 | 0.600 | 0.513 | 196.0 | 194.8 | 198.9 | 194.1 |
Dapro 30 mg | 5.90 | 5.87 | 6.11 | 6.42 | 3.785 | 4.129 | 4.224 | 4.343 | 0.017 | 0.024 | 0.027 | 0.024 | 0.240 | 0.186 | 0.185 | 0.217 | 1.442 | 1.206 | 1.181 | 1.399 | 0.421 | 0.384 | 0.426 | 0.429 | 192.3 | 181.5 | 194.8 | 170.0 |
Placebo | 6.28 | 7.01 | 6.66 | 7.05 | 4.030 | 4.666 | 4.123 | 4.687 | 0.018 | 0.027 | 0.035 | 0.028 | 0.189 | 0.161 | 0.176 | 0.216 | 1.631 | 1.735 | 1.870 | 1.648 | 0.401 | 0.420 | 0.444 | 0.461 | 219.0 | 205.4 | 198.1 | 220.8 |
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
Intervention | Pg (Mean) | |||
---|---|---|---|---|
Day 1; n= 18, 19, 20, 20, 21 | Day 15; n= 17, 19, 17, 21, 21 | Day 29; n= 16, 19, 17, 18, 17 | Day 43; n= 16, 20, 19, 21, 20 | |
Dapro 10 mg | 30.95 | 2.100 | 31.60 | 31.04 |
Dapro 15 mg | 30.19 | 30.74 | 30.56 | 30.49 |
Dapro 25 mg | 30.70 | 30.85 | 31.16 | 30.67 |
Dapro 30 mg | 31.46 | 31.70 | 31.68 | 31.84 |
Placebo | 31.19 | 30.83 | 30.97 | 30.86 |
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
Intervention | g/L (Mean) | |||
---|---|---|---|---|
Day 1; n= 18, 19, 20, 20, 21 | Day 15; n= 17, 19, 17, 21, 21 | Day 29; n= 16, 19, 17, 18, 17 | Day 43; n= 16, 20, 19, 21, 20 | |
Dapro 10 mg | 321.7 | 324.0 | 329.6 | 325.2 |
Dapro 15 mg | 319.5 | 324.8 | 325.4 | 325.5 |
Dapro 25 mg | 321.5 | 318.3 | 323.6 | 321.0 |
Dapro 30 mg | 327.6 | 322.7 | 323.9 | 327.0 |
Placebo | 322.9 | 321.5 | 323.3 | 321.9 |
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
Intervention | Femtoliter (fL) (Mean) | |||
---|---|---|---|---|
Day 1; n= 18, 19, 20, 20, 21 | Day 15; n= 17, 19, 17, 21, 21 | Day 29; n= 16, 19, 17, 18, 17 | Day 43; n= 16, 20, 19, 21, 20 | |
Dapro 10 mg | 96.4 | 95.8 | 95.9 | 95.4 |
Dapro 15 mg | 94.7 | 94.8 | 94.1 | 93.7 |
Dapro 25 mg | 95.7 | 97.0 | 96.3 | 95.6 |
Dapro 30 mg | 96.1 | 98.3 | 97.8 | 97.5 |
Placebo | 96.7 | 95.9 | 95.8 | 96.1 |
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
Intervention | Participants (Number) | ||||
---|---|---|---|---|---|
AEs | Protocol deviation | Participant reached stopping criteria | Physician decision | Withdrawal by subject | |
Dapro 10 mg | 0 | 0 | 1 | 0 | 0 |
Dapro 15 mg | 1 | 0 | 2 | 0 | 1 |
Dapro 25 mg | 0 | 1 | 3 | 0 | 0 |
Dapro 30 mg | 1 | 2 | 4 | 0 | 0 |
Placebo | 0 | 1 | 0 | 1 | 1 |
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
Intervention | Participants (Number) | |||
---|---|---|---|---|
Baseline(Week -4);Abnormal; NCS;n=19,20,20,22,22 | Baseline(Week-4);Abnormal;CS;n=19,20,20,22,22 | Day 29; Abnormal; NCS; n=17,19,18,19,17 | Day 29; Abnormal; CS; n=17,19,18,19,17 | |
Dapro 10 mg | 15 | 0 | 14 | 0 |
Dapro 15 mg | 18 | 0 | 16 | 0 |
Dapro 25 mg | 12 | 1 | 8 | 1 |
Dapro 30 mg | 16 | 0 | 12 | 0 |
Placebo | 10 | 0 | 12 | 0 |
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
Intervention | Participants (Number) | |
---|---|---|
Any AE | Any SAE | |
Dapro 10 mg | 10 | 3 |
Dapro 15 mg | 6 | 2 |
Dapro 25 mg | 7 | 1 |
Dapro 30 mg | 7 | 3 |
Placebo | 10 | 4 |
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
Intervention | Beats per minute (Mean) | |||||||
---|---|---|---|---|---|---|---|---|
Pre-dialysis; Day 1; n= 19, 20, 20, 22, 22 | Pre-dialysis; Day 15; n= 17, 20, 18, 22, 21 | Pre-dialysis; Day 29; n= 17, 19, 18, 19, 17 | Pre-dialysis; Day 43; n= 16, 20, 19, 21, 21 | Post-dialysis; Day 1; n= 19, 20, 20, 22, 22 | Post-dialysis; Day 15; n= 17, 20, 18, 22, 21 | Post-dialysis; Day 29; n= 17, 19, 18, 19, 17 | Post-dialysis; Day 43; n= 16, 20, 19, 21, 21 | |
Dapro 10 mg | 69.9 | 67.3 | 70.3 | 69.9 | 68.7 | 67.7 | 69.9 | 69.1 |
Dapro 15 mg | 66.7 | 68.3 | 69.6 | 66.9 | 66.3 | 70.1 | 68.8 | 68.0 |
Dapro 25 mg | 71.4 | 72.1 | 70.8 | 71.3 | 73.2 | 73.0 | 72.2 | 71.9 |
Dapro 30 mg | 76.5 | 75.1 | 73.4 | 75.8 | 78.8 | 78.1 | 77.4 | 77.3 |
Placebo | 68.5 | 76.1 | 70.4 | 71.5 | 71.0 | 72.5 | 73.6 | 72.0 |
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
Intervention | Millimoles per liter (mmol/L) (Mean) | |||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Sodium; Day 1; n= 18, 20, 20, 22, 22 | Sodium; Day 15; n= 17, 20, 18, 22, 20 | Sodium; Day 29; n= 17, 19, 18, 19, 17 | Sodium; Day 43; n= 15, 20, 18, 21, 21 | Potassium; Day 1; n= 18, 20, 20, 22, 22 | Potassium; Day 15; n= 17, 20, 18, 22, 20 | Potassium; Day 29; n= 17, 19, 18, 19, 17 | Potassium; Day 43; n= 15, 20, 18, 21, 21 | Glucose; Day 1; n= 18, 20, 20, 22, 22 | Glucose; Day 15; n= 17, 20, 18, 22, 20 | Glucose; Day 29; n= 17, 19, 18, 19, 17 | Glucose; Day 43; n= 15, 20, 18, 21, 21 | Calcium corrected; Day 1; n= 18, 20, 20, 22, 22 | Calcium corrected; Day 15; n= 17, 20, 18, 22, 20 | Calcium corrected; Day 29; n= 17, 19, 18, 19, 17 | Calcium corrected; Day 43; n= 15, 20, 18, 21, 21 | Phosphate; Day 1; n= 18, 20, 20, 22, 22 | Phosphate; Day 15; n= 17, 20, 18, 22, 20 | Phosphate; Day 29; n= 17, 19, 18, 19, 17 | Phosphate; Day 43; n= 15, 20, 18, 21, 21 | |
Dapro 10 mg | 138.1 | 137.5 | 136.8 | 138.1 | 4.73 | 4.77 | 4.87 | 4.68 | 6.66 | 7.16 | 7.49 | 6.72 | 2.270 | 2.219 | 2.248 | 2.235 | 1.528 | 1.710 | 1.592 | 1.460 |
Dapro 15 mg | 138.7 | 138.1 | 137.9 | 137.9 | 4.64 | 4.57 | 4.57 | 4.59 | 6.41 | 7.03 | 7.21 | 7.09 | 2.241 | 2.213 | 2.244 | 2.271 | 1.498 | 1.642 | 1.644 | 1.472 |
Dapro 25 mg | 139.4 | 138.0 | 138.8 | 138.8 | 4.79 | 4.82 | 4.86 | 4.76 | 7.05 | 7.26 | 7.77 | 6.27 | 2.219 | 2.188 | 2.198 | 2.201 | 1.318 | 1.348 | 1.453 | 1.412 |
Dapro 30 mg | 138.4 | 137.2 | 137.1 | 137.6 | 4.83 | 4.80 | 4.96 | 4.80 | 8.95 | 8.67 | 8.75 | 8.93 | 2.215 | 2.203 | 2.225 | 2.256 | 1.566 | 1.645 | 1.550 | 1.398 |
Placebo | 138.8 | 137.7 | 137.8 | 139.2 | 4.68 | 4.72 | 4.78 | 4.69 | 6.66 | 7.89 | 8.21 | 6.93 | 2.286 | 2.261 | 2.205 | 2.251 | 1.608 | 1.621 | 1.709 | 1.550 |
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
Intervention | Millimeter of mercury (mmHg) (Mean) | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SBP; pre-dialysis; Day 1; n= 19, 20, 20, 22, 22 | SBP; pre-dialysis; Day 15; n= 17, 20, 18, 22, 21 | SBP; pre-dialysis; Day 29; n= 17, 19, 18, 19, 17 | SBP; pre-dialysis; Day 43; n= 16, 20, 19, 21, 21 | DBP; pre-dialysis; Day 1; n= 19, 20, 20, 22, 22 | DBP; pre-dialysis; Day 15; n= 17, 20, 18, 22, 21 | DBP; pre-dialysis; Day 29; n= 17, 19, 18, 19, 17 | DBP; pre-dialysis; Day 43; n= 16, 20, 19, 21, 21 | SBP; post-dialysis; Day 1; n= 19, 20, 20, 22, 22 | SBP; post-dialysis; Day 15; n= 17, 20, 18, 22, 21 | SBP; post-dialysis; Day 29; n= 17, 19, 18, 19, 17 | SBP; post-dialysis; Day 43; n= 16, 20, 19, 21, 21 | DBP; post-dialysis; Day 1; n= 19, 20, 20, 22, 22 | DBP; post-dialysis; Day 15; n= 17, 20, 18, 22, 21 | DBP; post-dialysis; Day 29; n= 17, 19, 18, 19, 17 | DBP; post-dialysis; Day 43; n= 16, 20, 19, 21, 21 | |
Dapro 10 mg | 136.6 | 138.3 | 133.1 | 137.9 | 68.8 | 70.0 | 63.5 | 66.8 | 137.0 | 135.5 | 130.1 | 135.8 | 67.9 | 70.1 | 64.4 | 67.4 |
Dapro 15 mg | 149.2 | 139.0 | 143.1 | 142.0 | 73.3 | 70.1 | 70.9 | 69.9 | 139.9 | 137.7 | 133.7 | 130.4 | 68.7 | 67.8 | 67.9 | 67.4 |
Dapro 25 mg | 144.1 | 146.6 | 144.2 | 149.0 | 71.8 | 73.5 | 73.3 | 77.9 | 136.7 | 137.4 | 142.8 | 145.2 | 71.1 | 71.3 | 72.4 | 72.9 |
Dapro 30 mg | 144.1 | 142.3 | 148.7 | 147.1 | 72.2 | 69.7 | 72.7 | 72.8 | 140.1 | 140.9 | 147.8 | 137.5 | 71.5 | 71.1 | 72.9 | 75.3 |
Placebo | 142.5 | 138.8 | 143.0 | 140.0 | 71.9 | 72.5 | 70.4 | 72.5 | 138.6 | 138.6 | 135.7 | 137.5 | 72.1 | 72.4 | 73.9 | 69.5 |
"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
Intervention | Hour (Geometric Mean) | |
---|---|---|
Tmax; n= 19, 15, 16, 14 | T1/2; n= 12, 9, 8, 11 | |
Dapro 10 mg | 2.456 | 2.086 |
Dapro 15 mg | 2.106 | 1.886 |
Dapro 25 mg | 2.297 | 1.418 |
Dapro 30 mg | 1.718 | 2.897 |
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
Intervention | Kilograms (kg) (Mean) | |||
---|---|---|---|---|
Day 1; n= 19, 20, 20, 22, 22 | Day 15; n= 17, 20, 18, 22, 21 | Day 29; n= 17, 19, 18, 19, 17 | Day 43; n= 16, 20, 19, 21, 21 | |
Dapro 10 mg | 80.04 | 80.00 | 81.04 | 80.21 |
Dapro 15 mg | 78.83 | 79.82 | 80.02 | 79.25 |
Dapro 25 mg | 79.38 | 79.44 | 82.66 | 80.64 |
Dapro 30 mg | 76.03 | 75.55 | 76.07 | 73.66 |
Placebo | 82.38 | 84.24 | 83.22 | 83.93 |
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
Intervention | Picograms (pg) (Mean) |
---|---|
Part 1: Daprodustat 2mg*2 | 0.11 |
Part 1: Daprodustat 4mg*1 | 0.01 |
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
Intervention | Femtoliters (Mean) |
---|---|
Part 1: Daprodustat 2mg*2 | -0.2 |
Part 1: Daprodustat 4mg*1 | -0.2 |
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
Intervention | Trillion cells/liter (10^12 cell/L) (Mean) |
---|---|
Part 1: Daprodustat 2mg*2 | 0.018 |
Part 1: Daprodustat 4mg*1 | 0.023 |
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
Intervention | pH (Mean) |
---|---|
Part 1: Daprodustat 2mg*2 | -0.04 |
Part 1: Daprodustat 4mg*1 | -0.07 |
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
Intervention | Kilogram per cubic meter (Mean) |
---|---|
Part 1: Daprodustat 2mg*2 | 0.0092 |
Part 1: Daprodustat 4mg*1 | 0.0088 |
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
Intervention | Per hour (Geometric Mean) |
---|---|
Part 1: Daprodustat 2mg*2 | 0.2138 |
Part 1: Daprodustat 4mg*1 | 0.2128 |
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
Intervention | Percentage of AUCex (Geometric Mean) |
---|---|
Part 1: Daprodustat 2mg*2 | 0.0862 |
Part 1: Daprodustat 4mg*1 | 0.0836 |
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
Intervention | hour (Median) |
---|---|
Part 1: Daprodustat 2mg*2 | 2.000 |
Part 1: Daprodustat 4mg*1 | 2.000 |
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
Intervention | Liters per hour (Geometric Mean) |
---|---|
Part 1: Daprodustat 2mg*2 | 21.8551 |
Part 1: Daprodustat 4mg*1 | 22.2382 |
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
Intervention | Milliliters (mL) (Geometric Mean) |
---|---|
Part 1: Daprodustat 2mg*2 | 102244.3 |
Part 1: Daprodustat 4mg*1 | 104522.8 |
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
Intervention | Proportion of red blood cells in blood (Mean) |
---|---|
Part 1: Daprodustat 2mg*2 | 0.0005 |
Part 1: Daprodustat 4mg*1 | 0.0014 |
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
Intervention | Praportion of reticulocytes in blood (Mean) |
---|---|
Part 1: Daprodustat 2mg*2 | -0.0005 |
Part 1: Daprodustat 4mg*1 | -0.0001 |
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
Intervention | Nanogram/milliliter (Geometric Mean) |
---|---|
Part 1: Daprodustat 2mg*2 | 88.8811 |
Part 1: Daprodustat 4mg*1 | 85.1365 |
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)
Intervention | Femtoliters (Mean) |
---|---|
Part 2: Daprodustat 4mg (Fed) | 0.5 |
Part 2: Daprodustat 4mg (Fasted) | 0.3 |
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)
Intervention | Trillion cells/liter (10^12 cell/L) (Mean) |
---|---|
Part 2: Daprodustat 4mg (Fed) | -0.083 |
Part 2: Daprodustat 4mg (Fasted) | -0.044 |
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)
Intervention | picograms (Mean) |
---|---|
Part 2: Daprodustat 4mg (Fed) | 0.10 |
Part 2: Daprodustat 4mg (Fasted) | 0.03 |
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)
Intervention | Praportion of red blood cells in blood (Mean) |
---|---|
Part 2: Daprodustat 4mg (Fed) | -0.0052 |
Part 2: Daprodustat 4mg (Fasted) | -0.0025 |
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)
Intervention | Praportion of reticulocytes in blood (Mean) |
---|---|
Part 2: Daprodustat 4mg (Fed) | -0.0002 |
Part 2: Daprodustat 4mg (Fasted) | -0.0010 |
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)
Intervention | pH (Mean) |
---|---|
Part 2: Daprodustat 4mg (Fed) | 0.13 |
Part 2: Daprodustat 4mg (Fasted) | 0.13 |
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)
Intervention | Kilogram per cubic meter (Mean) |
---|---|
Part 2: Daprodustat 4mg (Fed) | 0.0054 |
Part 2: Daprodustat 4mg (Fasted) | 0.0013 |
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
Intervention | Liters per hour (Geometric Mean) |
---|---|
Part 2: Daprodustat 4mg Fed | 27.9494 |
Part 2: Daprodustat 4mg Fasted | 25.5512 |
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
Intervention | Nanogram/milliliter (ng/L) (Geometric Mean) |
---|---|
Daprodustat 4mg Fed | 67.8240 |
Daprodustat 4mg Fasted | 76.1944 |
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
Intervention | Per hour (Geometric Mean) |
---|---|
Part 2: Daprodustat 4mg Fed | 0.2155 |
Part 2: Daprodustat 4mg Fasted | 0.2140 |
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
Intervention | Percentage of AUCex (Geometric Mean) |
---|---|
Part 2: Daprodustat 4mg Fed | 0.1071 |
Part 2: Daprodustat 4mg Fasted | 0.0723 |
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
Intervention | hour (Median) |
---|---|
Part 2: Daprodustat 4mg Fed | 2.750 |
Part 2: Daprodustat 4mg Fasted | 1.750 |
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
Intervention | Milliliters (mL) (Geometric Mean) |
---|---|
Part 2: Daprodustat 4mg Fed | 129676.9 |
Part 2: Daprodustat 4mg Fasted | 119394.6 |
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
Intervention | Millimoles per Liter (mmol/L) (Mean) | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Glucose 24hours | Calcium 24hours | Cholesterol 24hours | Chloride 24hours | HDL cholesterol 24hours | LDL cholesterol 24hours | Potassium 24hours | Phosphate 24hours | Sodium 24hours | Triglycerides 24hours | Urea 24hours | |
Part 1: Daprodustat 2mg*2 | -0.007619 | -0.016144 | -0.043607 | 0.9 | -0.128793 | 0.022818 | 0.04 | -0.102568 | 0.2 | 0.21802 | -0.14000 |
Part 1: Daprodustat 4mg*1 | -0.004270 | -0.015834 | 0.046747 | 0.5 | -0.111397 | 0.099462 | 0.03 | -0.091281 | 0.0 | 0.16385 | -0.29178 |
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
Intervention | Grams per liter (g/L) (Mean) | |
---|---|---|
Albumin 24hours | Protein 24hours | |
Part 1: Daprodustat 2mg*2 | -2.0 | -2.3 |
Part 1: Daprodustat 4mg*1 | -2.0 | -2.1 |
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
Intervention | Micromoles per liter (umol/L) (Mean) | |||
---|---|---|---|---|
Direct bilirubin 24hours | Bilirubin 24hours | Creatinine 24hours | Urate 24hours | |
Part 1: Daprodustat 2mg*2 | 0.268 | 2.615 | 1.7160 | 26.1245 |
Part 1: Daprodustat 4mg*1 | 0.164 | 2.960 | 1.4110 | 25.6222 |
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
Intervention | International unit per liter (IU/L) (Mean) | |||||
---|---|---|---|---|---|---|
ALP 24hours | ALT 24hours | AST 24hours | Creatine kinase 24hours | GGT 24hours | Lactate 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 |
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)
Intervention | Milliseconds (msec) (Mean) | |||||||
---|---|---|---|---|---|---|---|---|
PR Interval, Aggregate 3hours | PR Interval, Aggregate 24hours | QRS Duration, Aggregate 3hours | QRS Duration, Aggregate 24hours | QT interval, Aggregate 3hours | QT interval, Aggregate 24hours | QTcF interval, Aggregate 3hours | QtcF Interval, Aggregate 24hours | |
Part 1: Daprodustat 2mg*2 | -3.3 | 1.4 | -2.8 | -1.6 | 0.0 | -5.2 | 1.2 | -2.4 |
Part 1: Daprodustat 4mg*1 | -3.8 | 0.0 | -1.5 | 0.2 | 0.8 | -5.3 | 1.6 | -3.1 |
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)
Intervention | Beats per minute (Mean) | |
---|---|---|
Mean HR 3hours | Mean HR 24hours | |
Part 1: Daprodustat 2mg*2 | 0.6 | 1.2 |
Part 1: Daprodustat 4mg*1 | 0.2 | 0.8 |
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
Intervention | Billion cells per liter (10^9/L) (Mean) | |
---|---|---|
Platelets 24hours | Leukocytes 24hours | |
Part 1: Daprodustat 2mg*2 | 0.7 | -0.55 |
Part 1: Daprodustat 4mg*1 | 2.0 | -0.53 |
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
Intervention | Percentage of cells (Mean) | ||||
---|---|---|---|---|---|
Basophils 24hours | Eosinophils 24hours | Lymphocytes 24hours | Monocytes 24hours | Neutrophils 24hours | |
Part 1: Daprodustat 2mg*2 | -0.01 | 0.27 | -1.47 | -0.43 | 1.64 |
Part 1: Daprodustat 4mg*1 | 0.00 | 0.25 | -0.86 | -0.33 | 0.94 |
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
Intervention | Grams per Liter (g/L) (Mean) | |
---|---|---|
Hb 24hours | MCHC 24hours | |
Part 1: Daprodustat 2mg*2 | 1.1 | 2.1 |
Part 1: Daprodustat 4mg*1 | 0.8 | 0.8 |
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)
Intervention | Beats per minute (Mean) | |
---|---|---|
Pulse rate 3hours | Pulse rate 24hours | |
Part 1: Daprodustat 2mg*2 | 0.0 | 0.1 |
Part 1: Daprodustat 4mg*1 | 0.7 | 1.0 |
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)
Intervention | Celcius (c) (Mean) | |
---|---|---|
Temperature 3hours | Temperature 24hours | |
Part 1: Daprodustat 2mg*2 | 0.23 | 0.10 |
Part 1: Daprodustat 4mg*1 | 0.22 | 0.05 |
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)
Intervention | Millimeters of mercury (mmHg) (Mean) | |||
---|---|---|---|---|
DBP 3hours | DBP 24hours | SBP 3hours | SBP 24hours | |
Part 1: Daprodustat 2mg*2 | -2.9 | -1.8 | -0.6 | -0.9 |
Part 1: Daprodustat 4mg*1 | -1.5 | 0.1 | -0.4 | 0.2 |
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
Intervention | Participants (Count of Participants) | |
---|---|---|
Any AE | Any SAE | |
Part 1: Daprodustat 2mg*2 | 3 | 0 |
Part 1: Daprodustat 4mg*1 | 1 | 0 |
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
Intervention | Hour*nanogram/milliliter (Geometric Mean) | |
---|---|---|
AUC (0-t) | AUC (0-inf) | |
Part 1: Daprodustat 2mg*2 | 182.8420 | 183.0240 |
Part 1: Daprodustat 4mg*1 | 179.6940 | 179.8710 |
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
Intervention | hour (Geometric Mean) | |
---|---|---|
t1/2 | MRT | |
Part 1: Daprodustat 2mg*2 | 3.2427 | 2.8142 |
Part 1: Daprodustat 4mg*1 | 3.2579 | 2.9637 |
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)
Intervention | Millimoles per Liter (mmol/L) (Mean) | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Glucose, 24hours | Calcium, 24hours | Cholesterol, 24hours | Chloride, 24hours | HDL cholesterol, 24hours | LDL cholesterol, 24hours | Potassium, 24hours | Phosphate, 24hours | Sodium, 24hours | Triglycerides, 24hours | Urea, 24hours | |
Part 2: Daprodustat 4mg (Fasted) | -0.018503 | -0.058217 | -0.094820 | 2.1 | -0.148695 | -0.066805 | 0.19 | -0.080725 | 0.9 | 0.08475 | -0.14875 |
Part 2: Daprodustat 4mg (Fed) | -0.425577 | -0.076929 | -0.172400 | 1.5 | -0.165935 | -0.170245 | 0.06 | -0.029599 | 0.3 | 0.25331 | 0.19040 |
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)
Intervention | Grams per liter (g/L) (Mean) | |
---|---|---|
Albumin 24hours | Protein 24hours | |
Part 2: Daprodustat 4mg (Fasted) | -1.9 | -2.6 |
Part 2: Daprodustat 4mg (Fed) | -3.2 | -3.4 |
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)
Intervention | Micromoles per liter (umol/L) (Mean) | |||
---|---|---|---|---|
Direct bilirubin, 24hours | Bilirubin, 24hours | Creatinine, 24hours | Urate, 24hours | |
Part 2: Daprodustat 4mg (Fasted) | 0.000 | 1.425 | -1.1050 | 21.8093 |
Part 2: Daprodustat 4mg (Fed) | 0.000 | 2.280 | -1.6207 | 23.2963 |
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)
Intervention | International unit per liter (IU/L) (Mean) | |||||
---|---|---|---|---|---|---|
ALP, 24hours | ALT, 24hours | AST, 24hours | Creatine kinase, 24hours | Lactate dehydrogenase, 24hours | GGT, 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 |
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)
Intervention | Beats/minute (Mean) | |
---|---|---|
Mean HR, 3hours | Mean HR, 24hours | |
Part 2: Daprodustat 4mg (Fasted) | 0.0 | 0.6 |
Part 2: Daprodustat 4mg (Fed) | 3.7 | 3.1 |
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)
Intervention | Milliseconds (msec) (Mean) | |||||||
---|---|---|---|---|---|---|---|---|
PR Interval, Aggregate, 3hours | PR Interval, Aggregate, 24hours | QRS Duration, Aggregate, 3hours | QRS Duration, Aggregate, 24hours | QT interval, Aggregate, 3hours | QT Interval, Aggregate, 24hours | QTcF Interval, Aggregate, 3hours | QTcF Interval, Aggregate, 24hours | |
Part 2: Daprodustat 4mg (Fasted) | -2.7 | -3.2 | -0.5 | 2.8 | 1.0 | -2.2 | 1.2 | -1.1 |
Part 2: Daprodustat 4mg (Fed) | -6.2 | -4.0 | -1.5 | -0.8 | -13.0 | -7.3 | -5.3 | -0.6 |
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)
Intervention | Billion cells per liter (10^9/L) (Mean) | |
---|---|---|
Platelets, 24hours | Leukocytes, 24hours | |
Part 2: Daprodustat 4mg (Fasted) | -3.2 | -0.39 |
Part 2: Daprodustat 4mg (Fed) | -10.9 | -0.27 |
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)
Intervention | Percentage of cells (Mean) | ||||
---|---|---|---|---|---|
Basophils, 24hours | Eosinophils, 24hours | Lymphocytes, 24hours | Monocytes, 24hours | Neutrophils, 24hours | |
Part 2: Daprodustat 4mg (Fasted) | -0.17 | -0.49 | -1.14 | -0.03 | 1.83 |
Part 2: Daprodustat 4mg (Fed) | -0.04 | 0.62 | -2.31 | -0.38 | 2.12 |
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)
Intervention | Grams per liter (g/L) (Mean) | |
---|---|---|
Hb 24hours | EMCH concentration 24hours | |
Part 2: Daprodustat 4mg (Fasted) | -1.2 | -0.6 |
Part 2: Daprodustat 4mg (Fed) | -2.1 | 0.4 |
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)
Intervention | Beats per minute (Mean) | |
---|---|---|
Pulse rate, 3hours | Pulse rate, 24hours | |
Part 2: Daprodustat 4mg (Fasted) | -1.5 | 2.9 |
Part 2: Daprodustat 4mg (Fed) | 6.1 | 4.0 |
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)
Intervention | celcius (Mean) | |
---|---|---|
Temperature, 3hours | Temperature, 24hours | |
Part 2: Daprodustat 4mg (Fasted) | 0.13 | 0.03 |
Part 2: Daprodustat 4mg (Fed) | 0.28 | 0.02 |
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)
Intervention | Millimeters of mercury (mmHg) (Mean) | |||
---|---|---|---|---|
DBP, 3hours | DBP, 24hours | SBP, 3hours | SBP, 24hours | |
Part 2: Daprodustat 4mg (Fasted) | 0.2 | 2.8 | -1.3 | 1.3 |
Part 2: Daprodustat 4mg (Fed) | -4.8 | -0.6 | 0.7 | 1.4 |
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
Intervention | Participants (Number) | |
---|---|---|
Any AE | Any SAE | |
Part 2: Daprodustat 4mg (Fasted) | 0 | 0 |
Part 2: Daprodustat 4mg (Fed) | 0 | 0 |
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
Intervention | hour (Geometric Mean) | |
---|---|---|
t1/2 | MRT | |
Daprodustat 4mg Fed | 3.2160 | 3.2420 |
Part 2: Daprodustat 4mg Fasted | 3.2389 | 2.6695 |
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
Intervention | Hour*nanogram/milliliter (Geometric Mean) | |
---|---|---|
AUC (0-t) | AUC (0-inf) | |
Daprodustat 4mg (Fed) | 142.9556 | 143.1156 |
Daprodustat 4mg(Fasted) | 156.4222 | 156.5481 |
Change from Baseline was calculated as the post-dose Week 4 visit value minus the Baseline value. (NCT02969655)
Timeframe: Baseline and Week 4
Intervention | g/dL (Mean) |
---|---|
Daprodustat | -0.42 |
Darbepoetin Alfa | 0.08 |
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
Intervention | Days (Median) |
---|---|
Daprodustat | 28.0 |
The mean hemoglobin during the Evaluation Period was estimated by a statistical model. (NCT02969655)
Timeframe: Weeks 40 to 52
Intervention | Grams per deciliter (g/dL) (Least Squares Mean) |
---|---|
Daprodustat | 10.89 |
Darbepoetin Alfa | 10.83 |
Number of dose adjustments has been presented only for daprodustat. (NCT02969655)
Timeframe: Up to Week 52
Intervention | Dose adjustments (Median) |
---|---|
Daprodustat | 2.0 |
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
Intervention | Episodes (Number) |
---|---|
Daprodustat | 9 |
Darbepoetin Alfa | 12 |
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
Intervention | Participants (Count of Participants) |
---|---|
Daprodustat | 1 |
Darbepoetin Alfa | 2 |
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
Intervention | Percentage of participants (Number) |
---|---|
Daprodustat | 0 |
Darbepoetin Alfa | 0 |
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
Intervention | Percentage of participants (Number) |
---|---|
Daprodustat | 7 |
Darbepoetin Alfa | 8 |
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
Intervention | Percentage of time (Mean) |
---|---|
Daprodustat | 76.81 |
Darbepoetin Alfa | 80.23 |
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
Intervention | Hours*nanograms per milliliter (Geometric Mean) | ||||||
---|---|---|---|---|---|---|---|
1 mg, n=8 | 2 mg, n=24 | 4 mg, n=91 | 6 mg, n=61 | 8 mg, n=38 | 12 mg, n=17 | 18 mg, n=5 | |
Daprodustat | 27.57 | 44.52 | 72.68 | 140.58 | 170.41 | 150.53 | 488.93 |
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
Intervention | g/dL (Mean) | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Week 4, n=133, 134 | Week 8, n=127, 132 | Week 12, n=125, 129 | Week 16, n=124, 129 | Week 20, n=123, 129 | Week 24, n=123, 129 | Week 28, n=123, 129 | Week 32, n=122, 127 | Week 36, n=121, 127 | Week 40, n=120, 125 | Week 44, n=117, 125 | Week 48, n=117, 124 | Week 52,n=115, 120 | |
Daprodustat | -0.42 | -0.45 | -0.42 | -0.38 | -0.09 | 0.07 | 0.03 | 0.16 | 0.17 | 0.03 | 0.03 | -0.01 | -0.16 |
Darbepoetin Alfa | 0.08 | 0.20 | 0.27 | 0.09 | 0.12 | 0.10 | 0.04 | 0.14 | 0.09 | 0.10 | 0.07 | -0.04 | 0.01 |
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)
Intervention | milligrams per day (mg/day) (Median) | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Day 1, n=133 | Week 4, n=133 | Week 8, n=126 | Week 12, n=125 | Week 16, n=123 | Week 20, n=123 | Week 24, n=123 | Week 28, n=123 | Week 32, n=122 | Week 36, n=121 | Week 40, n=119 | Week 44, n=117 | Week 48, n=117 | |
Daprodustat | 4.0 | 4.0 | 4.0 | 6.0 | 6.0 | 6.0 | 6.0 | 6.0 | 6.0 | 6.0 | 6.0 | 6.0 | 6.0 |
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
Intervention | micrograms per week (ug/week) (Median) | |||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Day 1, n=134 | Week 2. n=134 | Week 4, n=134 | Week 6, n=133 | Week 8, n=131 | Week 10, n=129 | Week 12, n=129 | Week 14, n=129 | Week 16, n=129 | Week 18, n=129 | Week 20, n=129 | Week 22, n=128 | Week 24, n=129 | Week 26, n=129 | Week 28, n=127 | Week 30, n=128 | Week 32, n=127 | Week 34, n=127 | Week 36, n=127 | Week 38, n=127 | Week 40, n=125 | Week 42, n=125 | Week 44, n=125 | Week 46, n=125 | Week 48, n=124 | Week 50, n=122 | |
Darbepoetin Alfa | 15.0 | 15.0 | 15.0 | 15.0 | 15.0 | 15.0 | 15.0 | 15.0 | 15.0 | 15.0 | 15.0 | 15.0 | 15.0 | 15.0 | 15.0 | 15.0 | 15.0 | 15.0 | 15.0 | 15.0 | 15.0 | 15.0 | 15.0 | 15.0 | 15.0 | 15.0 |
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
Intervention | g/dL (Mean) | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Baseline (Day 1), n=133, 134 | Week 4, n=133, 134 | Week 8, n=127, 132 | Week 12, n=125, 129 | Week 16, n=124, 129 | Week 20, n=123, 129 | Week 24, n=123, 129 | Week 28, n=123, 129 | Week 32, n=122, 127 | Week 36, n=121, 127 | Week 40, n=120, 125 | Week 44, n=117, 125 | Week 48, n=117, 124 | Week 52,n=115, 120 | |
Daprodustat | 10.94 | 10.52 | 10.50 | 10.53 | 10.57 | 10.85 | 11.01 | 10.97 | 11.10 | 11.12 | 10.97 | 10.98 | 10.94 | 10.79 |
Darbepoetin Alfa | 10.82 | 10.90 | 11.01 | 11.09 | 10.92 | 10.95 | 10.92 | 10.86 | 10.96 | 10.91 | 10.90 | 10.87 | 10.76 | 10.79 |
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
Intervention | Nanograms per milliliter (Geometric Mean) | ||||||
---|---|---|---|---|---|---|---|
1 mg, n=8 | 2 mg, n=24 | 4 mg, n=91 | 6 mg, n=61 | 8 mg, n=38 | 12 mg, n=17 | 18 mg, n=5 | |
Daprodustat | 16.11 | 25.16 | 42.45 | 83.60 | 105.71 | 108.58 | 306.61 |
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
Intervention | Percentage of participants (Number) | |||||||
---|---|---|---|---|---|---|---|---|
<= -2.0 | > -2.0 and <= -1.0 | > -1.0 and <= 0 | > 0 and <= 1.0 | > 1.0 and <= 2.0 | > 2.0 | within +/- 1.0 | over +/- 2.0 | |
Daprodustat | 5 | 21 | 44 | 27 | 4 | 0 | 75 | 5 |
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
Intervention | Percentage of participants (Number) | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Baseline (Day 1), n=133, 134 | Week 4, n=133,134 | Week 8, n=127,132 | Week 12, n=125,129 | Week 16, n=124,129 | Week 20, n=123,129 | Week 24, n=123,129 | Week 28, n=123,129 | Week 32, n=122, 127 | Week 36, n=121,127 | Week 40, n=120,125 | Week 44, n=117,125 | Week 48, n=117,124 | Week 52, n=115,120 | |
Daprodustat | 79 | 65 | 65 | 66 | 64 | 82 | 85 | 85 | 79 | 78 | 77 | 74 | 77 | 77 |
Darbepoetin Alfa | 87 | 80 | 84 | 86 | 80 | 81 | 81 | 82 | 80 | 78 | 80 | 82 | 79 | 80 |
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
Intervention | Percentage of participants (Number) | |
---|---|---|
Responder | Non-responder | |
Daprodustat | 88 | 13 |
Darbepoetin Alfa | 90 | 10 |
(NCT03402386)
Timeframe: Up to Week 24
Intervention | g/dL (Least Squares Mean) |
---|---|
MT-6548 | 11.35 |
(NCT03402386)
Timeframe: Up to Week 24
Intervention | g/dL (Mean) | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Baseline | Week 2 | Week 4 | Week 6 | Week 8 | Week 10 | Week 12 | Week 16 | Week 20 | Week 24 | Week 24 (LOCF) | |
MT-6548 | 10.90 | 10.96 | 10.74 | 10.61 | 10.87 | 10.89 | 11.10 | 11.58 | 11.68 | 11.39 | 11.01 |
(NCT03402386)
Timeframe: Up to Week 24
Intervention | percentage of subjects (Number) | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Baseline | Week 2 | Week 4 | Week 6 | Week 8 | Week 10 | Week 12 | Week 16 | Week 20 | Week 24 | |
MT-6548 | 57.1 | 60.0 | 41.5 | 35.9 | 47.4 | 44.7 | 44.7 | 32.4 | 66.7 | 65.7 |
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
Intervention | Hour*nanogram per milliliter (Geometric Mean) |
---|---|
Daprodustat 1 mg | 35.3199 |
Daprodustat 2 mg | 63.0175 |
Daprodustat 4 mg | 101.9293 |
Daprodustat 6 mg | 152.4966 |
Daprodustat 8 mg | 167.6515 |
Daprodustat 12 mg | 190.0962 |
Daprodustat 18 mg | 435.6847 |
Daprodustat 24 mg | 404.0567 |
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
Intervention | g/dL (Mean) |
---|---|
Daprodustat in ND Participants | 0.47 |
Epoetin Beta Pegol in ND Participants | 0.26 |
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
Intervention | g/dL (Mean) |
---|---|
Daprodustat in PD Participants | -0.09 |
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
Intervention | Days (Median) |
---|---|
Daprodustat in ND Participants | 28.0 |
Epoetin Beta Pegol in ND Participants | 28.0 |
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
Intervention | Days (Median) |
---|---|
Daprodustat in PD Participants | 28.0 |
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
Intervention | Nanogram per milliliter (Geometric Mean) |
---|---|
Daprodustat 1 mg | 17.6522 |
Daprodustat 2 mg | 35.0709 |
Daprodustat 4 mg | 58.6098 |
Daprodustat 6 mg | 81.1851 |
Daprodustat 8 mg | 91.0731 |
Daprodustat 12 mg | 94.1242 |
Daprodustat 18 mg | 197.9290 |
Daprodustat 24 mg | 226.0000 |
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
Intervention | Grams per deciliter (g/dL) (Mean) |
---|---|
Daprodustat in ND Participants | 11.97 |
Epoetin Beta Pegol in ND Participants | 11.86 |
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
Intervention | Milligrams (Mean) |
---|---|
Daprodustat in ND Participants | 967.41 |
Epoetin Beta Pegol in ND Participants | 777.69 |
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
Intervention | Milligrams (Mean) |
---|---|
Daprodustat in PD Participants | 3038.67 |
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
Intervention | Milligrams (Mean) |
---|---|
Daprodustat in ND Participants | 837.37 |
Epoetin Beta Pegol in ND Participants | 747.04 |
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
Intervention | Milligrams (Mean) |
---|---|
Daprodustat in PD Participants | 2468.68 |
Number of dose adjustments in ND participants is presented. (NCT02791763)
Timeframe: Up to Week 52
Intervention | Number of dose adjustments (Median) |
---|---|
Daprodustat in ND Participants | 5.0 |
Epoetin Beta Pegol in ND Participants | 6.0 |
Number of dose adjustments in PD participants is presented. (NCT02791763)
Timeframe: Up to Week 52
Intervention | Number of dose adjustments (Median) |
---|---|
Daprodustat in PD Participants | 5.0 |
Number of episodes with Hgb level of more than 13.0 g/dL in ND participants is presented. (NCT02791763)
Timeframe: Up to week 52
Intervention | Episodes (Number) |
---|---|
Daprodustat in ND Participants | 76 |
Epoetin Beta Pegol in ND Participants | 88 |
Number of episodes with Hgb level of more than 13.0 g/dL in PD participants is presented. (NCT02791763)
Timeframe: Up to week 52
Intervention | Episodes (Number) |
---|---|
Daprodustat in PD Participants | 43 |
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
Intervention | Participants (Count of Participants) |
---|---|
Daprodustat in ND Participants | 17 |
Epoetin Beta Pegol in ND Participants | 11 |
Number of ND participants who had an Hgb level of less than 7.5 g/dL is presented. (NCT02791763)
Timeframe: Up to week 52
Intervention | Participants (Count of Participants) |
---|---|
Daprodustat in ND Participants | 1 |
Epoetin Beta Pegol in ND Participants | 0 |
Number of ND participants who had an Hgb level of more than 13.0 g/dL is presented. (NCT02791763)
Timeframe: Up to week 52
Intervention | Participants (Count of Participants) |
---|---|
Daprodustat in ND Participants | 49 |
Epoetin Beta Pegol in ND Participants | 52 |
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
Intervention | Participants (Count of Participants) |
---|---|
Daprodustat in ND Participants | 34 |
Epoetin Beta Pegol in ND Participants | 28 |
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
Intervention | Participants (Count of Participants) |
---|---|
Daprodustat in ND Participants | 56 |
Epoetin Beta Pegol in ND Participants | 49 |
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
Intervention | Participants (Count of Participants) |
---|---|
Daprodustat in PD Participants | 11 |
Number of PD participants who had an Hgb level of less than 7.5 g/dL is presented. (NCT02791763)
Timeframe: Up to week 52
Intervention | Participants (Count of Participants) |
---|---|
Daprodustat in PD Participants | 0 |
Number of PD participants who had an Hgb level of more than 13.0 g/dL is presented. (NCT02791763)
Timeframe: Up to week 52
Intervention | Participants (Count of Participants) |
---|---|
Daprodustat in PD Participants | 28 |
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
Intervention | Participants (Count of Participants) |
---|---|
Daprodustat in PD Participants | 22 |
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
Intervention | Participants (Count of Participants) |
---|---|
Daprodustat in PD Participants | 33 |
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
Intervention | Percentage of participants (Number) |
---|---|
Daprodustat in ND Participants | 16 |
Epoetin Beta Pegol in ND Participants | 10 |
Percentage of ND participants who had an Hgb level of less than 7.5 g/dL is presented. (NCT02791763)
Timeframe: Up to week 52
Intervention | Percentage of participants (Number) |
---|---|
Daprodustat in ND Participants | 1 |
Epoetin Beta Pegol in ND Participants | 0 |
Percentage of ND participants who had an Hgb level of more than 13.0 g/dL is presented. (NCT02791763)
Timeframe: Up to week 52
Intervention | Percentage of participants (Number) |
---|---|
Daprodustat in ND Participants | 45 |
Epoetin Beta Pegol in ND Participants | 48 |
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
Intervention | Percentage of participants (Number) |
---|---|
Daprodustat in ND Participants | 39 |
Epoetin Beta Pegol in ND Participants | 32 |
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
Intervention | Percentage of participants (Number) |
---|---|
Daprodustat in ND Participants | 52 |
Epoetin Beta Pegol in ND Participants | 45 |
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
Intervention | Percentage of participants (Number) |
---|---|
Daprodustat in PD Participants | 20 |
Percentage of PD participants who had an Hgb level of less than 7.5 g/dL is presented. (NCT02791763)
Timeframe: Up to week 52
Intervention | Percentage of participants (Number) |
---|---|
Daprodustat in PD Participants | 0 |
Percentage of PD participants who had an Hgb level of more than 13.0 g/dL is presented. (NCT02791763)
Timeframe: Up to week 52
Intervention | Percentage of participants (Number) |
---|---|
Daprodustat in PD Participants | 51 |
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
Intervention | Percentage of participants (Number) |
---|---|
Daprodustat in PD Participants | 50 |
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
Intervention | Percentage of participants (Number) |
---|---|
Daprodustat in PD Participants | 60 |
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
Intervention | Percentage of time (Mean) |
---|---|
Daprodustat in ND Participants | 85.44 |
Epoetin Beta Pegol in ND Participants | 80.57 |
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
Intervention | Percentage of time (Mean) |
---|---|
Daprodustat in PD Participants | 85.73 |
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
Intervention | Days (Median) |
---|---|
Daprodustat in ND Participants | 58.0 |
Epoetin Beta Pegol in ND Participants | 57.0 |
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
Intervention | Days (Median) |
---|---|
Daprodustat in PD Participants | 84.0 |
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
Intervention | Micrograms per liter (µg/L) (Mean) | ||||
---|---|---|---|---|---|
Week 4, n=107,109 | Week 16, n=104,105 | Week 28, n=96,93 | Week 40, n=88,87 | Week 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 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
Intervention | µg/L (Mean) | ||||
---|---|---|---|---|---|
Week 4, n=55 | Week 16, n=51 | Week 28, n=48 | Week 40, n=44 | Week 52, n=43 | |
Daprodustat in PD Participants | -36.4 | -81.8 | -89.1 | -74.6 | -63.6 |
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
Intervention | g/dL (Mean) | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Week 4, n=107,109 | Week 8, n=107,109 | Week 12, n=106,107 | Week 16, n=104,105 | Week 20, n=102,103 | Week 24, n=99,99 | Week 28, n=96,93 | Week 32, n=92,90 | Week 36, n=92,88 | Week 40, n=88,87 | Week 44, n=88,86 | Week 48, n=87,83 | Week 52, n=87,81 | |
Daprodustat in ND Participants | 0.47 | 0.71 | 1.04 | 1.45 | 1.39 | 1.41 | 1.54 | 1.60 | 1.49 | 1.44 | 1.43 | 1.61 | 1.56 |
Epoetin Beta Pegol in ND Participants | 0.26 | 0.66 | 1.18 | 1.40 | 1.26 | 1.10 | 1.08 | 1.04 | 1.04 | 1.26 | 1.01 | 1.03 | 1.21 |
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
Intervention | g/dL (Mean) | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Week 4, n=55 | Week 8, n=54 | Week 12, n=52 | Week 16, n=51 | Week 20, n=50 | Week 24, n=49 | Week 28, n=48 | Week 32, n=45 | Week 36, n=45 | Week 40, n=44 | Week 44, n=43 | Week 48, n=43 | Week 52, n=43 | |
Daprodustat in PD Participants | -0.09 | -0.06 | 0.44 | 0.52 | 0.63 | 0.74 | 1.00 | 1.13 | 0.95 | 1.13 | 0.90 | 1.08 | 1.10 |
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
Intervention | Micromoles per liter (µmol/L) (Mean) | ||||
---|---|---|---|---|---|
Week 4, n=107,109 | Week 16, n=104,105 | Week 28, n=96,93 | Week 40, n=88,87 | Week 52, n=87,81 | |
Daprodustat in ND Participants | 0.5 | 0.3 | 0.3 | 0.9 | 0.7 |
Epoetin Beta Pegol in ND Participants | -0.8 | 0.6 | 2.0 | 1.8 | 1.1 |
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
Intervention | µmol/L (Mean) | ||||
---|---|---|---|---|---|
Week 4, n=55 | Week 16, n=51 | Week 28, n=48 | Week 40, n=44 | Week 52, n=43 | |
Daprodustat in PD Participants | -1.2 | -2.4 | -1.0 | -0.4 | 1.0 |
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
Intervention | µmol/L (Mean) | ||||
---|---|---|---|---|---|
Week 4, n=55 | Week 16, n=51 | Week 28, n=48 | Week 40, n=44 | Week 52, n=43 | |
Daprodustat in PD Participants | 6.9 | 9.5 | 11.0 | 11.0 | 9.6 |
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
Intervention | µmol/L (Mean) | ||||
---|---|---|---|---|---|
Week 4, n=107,109 | Week 16, n=104,105 | Week 28, n=96,93 | Week 40, n=88,87 | Week 52, n=87,81 | |
Daprodustat in ND Participants | 6.9 | 9.9 | 9.9 | 8.0 | 7.8 |
Epoetin Beta Pegol in ND Participants | 0.5 | 1.9 | 1.4 | 0.2 | 0.1 |
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
Intervention | Milligrams per day (mg/day) (Median) | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Day 1, n=108 | Week 4, n=106 | Week 8, n=106 | Week 12, n=106 | Week 16, n=103 | Week 20, n=100 | Week 24, n=96 | Week 28, n=94 | Week 32, n=92 | Week 36, n=89 | Week 40, n=88 | Week 44, n=88 | Week 48, n=87 | |
Daprodustat in ND Participants | 4.0 | 4.0 | 4.0 | 4.0 | 4.0 | 4.0 | 4.0 | 4.0 | 4.0 | 4.0 | 4.0 | 4.0 | 4.0 |
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
Intervention | mg/day (Median) | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Day 1, n=55 | Week 4, n=55 | Week 8, n=52 | Week 12, n=52 | Week 16, n=51 | Week 20, n=50 | Week 24, n=48 | Week 28, n=45 | Week 32, n=45 | Week 36, n=45 | Week 40, n=44 | Week 44, n=43 | Week 48, n=43 | |
Daprodustat in PD Participants | 4.0 | 6.0 | 6.0 | 6.0 | 6.0 | 6.0 | 8.0 | 8.0 | 6.0 | 8.0 | 6.0 | 6.0 | 6.0 |
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
Intervention | Micrograms per 4 weeks (Median) | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Day 1, n=109 | Week 4, n=109 | Week 8, n=107 | Week 12, n=105 | Week 16, n=104 | Week 20, n=100 | Week 24, n=97 | Week 28, n=92 | Week 32, n=90 | Week 36, n=88 | Week 40, n=87 | Week 44, n=84 | Week 48, n=82 | |
Epoetin Beta Pegol in ND Participants | 50.0 | 75.0 | 100.0 | 100.0 | 75.0 | 75.0 | 75.0 | 75.0 | 75.0 | 75.0 | 75.0 | 100.0 | 100.0 |
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
Intervention | g/dL (Mean) | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Day 1, n=108,109 | Week 4, n=107,109 | Week 8, n=107,109 | Week 12, n=106,107 | Week 16, n=104,105 | Week 20, n=102,103 | Week 24, n=99,99 | Week 28, n=96,93 | Week 32, n=92,90 | Week 36, n=92,88 | Week 40, n=88,87 | Week 44, n=88,86 | Week 48, n=87,83 | Week 52, n=87,81 | |
Daprodustat in ND Participants | 10.48 | 10.95 | 11.19 | 11.51 | 11.90 | 11.84 | 11.87 | 11.98 | 12.03 | 11.93 | 11.88 | 11.87 | 12.05 | 12.01 |
Epoetin Beta Pegol in ND Participants | 10.68 | 10.94 | 11.34 | 11.84 | 12.07 | 11.96 | 11.80 | 11.83 | 11.80 | 11.81 | 12.00 | 11.75 | 11.80 | 11.99 |
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
Intervention | g/dL (Mean) | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Day 1, n=55 | Week 4, n=55 | Week 8, n=54 | Week 12, n=52 | Week 16, n=51 | Week 20, n=50 | Week 24, n=49 | Week 28, n=48 | Week 32, n=45 | Week 36, n=45 | Week 40, n=44 | Week 44, n=43 | Week 48, n=43 | Week 52, n=43 | |
Daprodustat in PD Participants | 10.85 | 10.77 | 10.83 | 11.36 | 11.42 | 11.54 | 11.69 | 11.95 | 12.07 | 11.90 | 12.12 | 11.92 | 12.10 | 12.12 |
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
Intervention | Participants (Count of Participants) | |||||||
---|---|---|---|---|---|---|---|---|
<=-2.0 | >-2.0 and <=-1.0 | >-1.0 and <=0 | >0 and <=1.0 | >1.0 and <=2.0 | >2.0 | within +/- 1.0 | over +/- 2.0 | |
Daprodustat in ND Participants | 1 | 4 | 28 | 43 | 29 | 2 | 72 | 3 |
Epoetin Beta Pegol in ND Participants | 2 | 3 | 33 | 56 | 15 | 0 | 90 | 1 |
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
Intervention | Participants (Count of Participants) | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Day 1, n=108,109 | Week 4, n=107,109 | Week 8, n=107,109 | Week 12, n=106,107 | Week 16, n=104,105 | Week 20, n=102,103 | Week 24, n=99,99 | Week 28, n=96,93 | Week 32, n=92,90 | Week 36, n=92,88 | Week 40, n=88,87 | Week 44, n=88,86 | Week 48, n=87,83 | Week 52, n=87,81 | |
Daprodustat in ND Participants | 29 | 43 | 64 | 78 | 84 | 88 | 86 | 77 | 79 | 79 | 78 | 71 | 75 | 67 |
Epoetin Beta Pegol in ND Participants | 36 | 48 | 73 | 85 | 80 | 85 | 85 | 73 | 67 | 70 | 72 | 68 | 62 | 59 |
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
Intervention | Participants (Count of Participants) | |
---|---|---|
Responder | Non-Responder | |
Daprodustat in ND Participants | 81 | 7 |
Epoetin Beta Pegol in ND Participants | 80 | 7 |
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
Intervention | Participants (Count of Participants) | |||||||
---|---|---|---|---|---|---|---|---|
<=-2.0 | >-2.0 and <=-1.0 | >-1.0 and <=0 | >0 and <=1.0 | >1.0 and <=2.0 | >2.0 | within +/- 1.0 | over +/- 2.0 | |
Daprodustat in PD Participants | 0 | 10 | 20 | 20 | 4 | 1 | 41 | 1 |
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
Intervention | Participants (Count of Participants) | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Day 1, n=55 | Week 4, n=55 | Week 8, n=54 | Week 12, n=52 | Week 16, n=51 | Week 20, n=50 | Week 24, n=49 | Week 28, n=48 | Week 32, n=45 | Week 36, n=45 | Week 40, n=44 | Week 44, n=43 | Week 48, n=43 | Week 52, n=43 | |
Daprodustat in PD Participants | 28 | 25 | 26 | 32 | 32 | 38 | 36 | 39 | 34 | 36 | 34 | 33 | 36 | 38 |
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
Intervention | Percent change (Geometric Mean) | ||||
---|---|---|---|---|---|
Week 4, n=99,100 | Week 16, n=86,99 | Week 28, n=81,85 | Week 40, n=76,80 | Week 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 | -3.73 | 7.61 | 9.54 | 10.13 |
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
Intervention | Percent change (Geometric Mean) | ||||
---|---|---|---|---|---|
Week 4, n=53 | Week 16, n=48 | Week 28, n=39 | Week 40, n=39 | Week 52, n=40 | |
Daprodustat in PD Participants | -49.79 | -62.59 | -65.37 | -67.91 | -54.77 |
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
Intervention | Percent change (Geometric Mean) | ||||
---|---|---|---|---|---|
Week 4, n=107,109 | Week 16, n=104,105 | Week 28, n=96,93 | Week 40, n=88,87 | Week 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 | -0.3 | 10.6 | 12.5 | 7.0 |
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
Intervention | Percent change (Geometric Mean) | ||||
---|---|---|---|---|---|
Week 4, n=55 | Week 16, n=51 | Week 28, n=48 | Week 40, n=44 | Week 52, n=43 | |
Daprodustat in PD Participants | -19.2 | -29.1 | -22.6 | -19.5 | -14.7 |
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
Intervention | Percentage of participants (Number) | |||||||
---|---|---|---|---|---|---|---|---|
<=-2.0 | >-2.0 and <=-1.0 | >-1.0 and <=0 | >0 and <=1.0 | >1.0 and <=2.0 | >2.0 | within +/- 1.0 | over +/- 2.0 | |
Daprodustat in ND Participants | 1 | 4 | 26 | 40 | 27 | 2 | 67 | 3 |
Epoetin Beta Pegol in ND Participants | 2 | 3 | 30 | 51 | 14 | 0 | 83 | 1 |
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
Intervention | Percentage of Participants (Number) | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Day 1, n=108,109 | Week 4, n=107,109 | Week 8, n=107,109 | Week 12, n=106,107 | Week 16, n=104,105 | Week 20, n=102,103 | Week 24, n=99,99 | Week 28, n=96,93 | Week 32, n=92,90 | Week 36, n=92,88 | Week 40, n=88,87 | Week 44, n=88,86 | Week 48, n=87,83 | Week 52, n=87,81 | |
Daprodustat in ND Participants | 27 | 40 | 60 | 74 | 81 | 86 | 87 | 80 | 86 | 86 | 89 | 81 | 86 | 77 |
Epoetin Beta Pegol in ND Participants | 33 | 44 | 67 | 79 | 76 | 83 | 86 | 78 | 74 | 80 | 83 | 79 | 75 | 73 |
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
Intervention | Percentage of participants (Number) | |
---|---|---|
Responder | Non-Responder | |
Daprodustat in ND Participants | 92 | 8 |
Epoetin Beta Pegol in ND Participants | 92 | 8 |
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
Intervention | Percentage of Participants (Number) | |||||||
---|---|---|---|---|---|---|---|---|
<=-2.0 | >-2.0 and <=-1.0 | >-1.0 and <=0 | >0 and <=1.0 | >1.0 and <=2.0 | >2.0 | within +/- 1.0 | over +/- 2.0 | |
Daprodustat in PD Participants | 0 | 18 | 36 | 36 | 7 | 2 | 75 | 2 |
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
Intervention | Percentage of Participants (Number) | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Day 1, n=55 | Week 4, n=55 | Week 8, n=54 | Week 12, n=52 | Week 16, n=51 | Week 20, n=50 | Week 24, n=49 | Week 28, n=48 | Week 32, n=45 | Week 36, n=45 | Week 40, n=44 | Week 44, n=43 | Week 48, n=43 | Week 52, n=43 | |
Daprodustat in PD Participants | 51 | 45 | 48 | 62 | 63 | 76 | 73 | 81 | 76 | 80 | 77 | 77 | 84 | 88 |
(NCT03439137)
Timeframe: Up to Week 24
Intervention | g/dL (Least Squares Mean) |
---|---|
MT-6548 | 10.61 |
Darbepoetin Alfa | 10.65 |
(NCT03439137)
Timeframe: Up to Week 52
Intervention | g/dL (Least Squares Mean) |
---|---|
MT-6548 | 10.42 |
Darbepoetin Alfa | 10.62 |
(NCT03439137)
Timeframe: Up to Week 52
Intervention | g/dL (Mean) | |||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Baseline | Week 2 | Week 4 | Week 6 | Week 8 | Week 10 | Week 12 | Week 16 | Week 20 | Week 24 | Week 28 | Week 32 | Week 36 | Week 40 | Week 44 | Week 48 | Week 52 | Week 52 (LOCF) | |
Darbepoetin Alfa | 10.73 | 10.85 | 10.88 | 10.83 | 10.84 | 10.86 | 10.90 | 10.80 | 10.65 | 10.63 | 10.66 | 10.77 | 10.75 | 10.67 | 10.64 | 10.63 | 10.63 | 10.61 |
MT-6548 | 10.73 | 10.61 | 10.38 | 10.24 | 10.24 | 10.24 | 10.43 | 10.57 | 10.69 | 10.65 | 10.58 | 10.60 | 10.49 | 10.53 | 10.54 | 10.50 | 10.47 | 10.24 |
(NCT03439137)
Timeframe: Up to Week 52
Intervention | percentage of subjects (Number) | ||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Baseline | Week 2 | Week 4 | Week 6 | Week 8 | Week 10 | Week 12 | Week 16 | Week 20 | Week 24 | Week 28 | Week 32 | Week 36 | Week 40 | Week 44 | Week 48 | Week 52 | |
Darbepoetin Alfa | 78.9 | 81.3 | 83.0 | 84.3 | 85.4 | 81.5 | 86.6 | 84.6 | 74.0 | 75.7 | 77.3 | 79.5 | 78.9 | 81.6 | 85.6 | 79.7 | 86.5 |
MT-6548 | 81.5 | 75.0 | 63.7 | 58.1 | 56.0 | 56.7 | 61.9 | 68.8 | 73.6 | 75.4 | 70.5 | 73.3 | 67.5 | 77.0 | 74.6 | 72.9 | 75.7 |
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
Intervention | g/dL (Least Squares Mean) |
---|---|
Vadadustat | 1.42 |
Darbepoetin Alfa | 1.50 |
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
Intervention | Grams per deciliter (g/dL) (Least Squares Mean) |
---|---|
Vadadustat | 1.26 |
Darbepoetin Alfa | 1.58 |
"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
Intervention | Weeks (Median) |
---|---|
Vadadustat | 31.71 |
Darbepoetin Alfa | 45.36 |
"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
Intervention | Weeks (Median) |
---|---|
Vadadustat | 22.00 |
Darbepoetin Alfa | 58.14 |
"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
Intervention | Weeks (Median) |
---|---|
Vadadustat | 18.50 |
Darbepoetin Alfa | 54.07 |
"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
Intervention | Weeks (Median) |
---|---|
Vadadustat | 27.14 |
Darbepoetin Alfa | 47.00 |
"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
Intervention | Weeks (Median) |
---|---|
Vadadustat | 26.21 |
Darbepoetin Alfa | 46.64 |
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
Intervention | g/dL (Least Squares Mean) |
---|---|
Vadadustat | 0.23 |
Darbepoetin Alfa | 0.41 |
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
Intervention | Grams per deciliter (g/dL) (Least Squares Mean) |
---|---|
Vadadustat | 0.19 |
Darbepoetin Alfa | 0.36 |
"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
Intervention | Weeks (Median) |
---|---|
Vadadustat | 50.79 |
Darbepoetin Alfa | 50.43 |
"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
Intervention | Weeks (Median) |
---|---|
Vadadustat | 46.14 |
Darbepoetin Alfa | 47.64 |
"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
Intervention | Weeks (Median) |
---|---|
Vadadustat | 44.57 |
Darbepoetin Alfa | 43.57 |
"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
Intervention | Weeks (Median) |
---|---|
Vadadustat | 43.29 |
Darbepoetin Alfa | 45.21 |
"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
Intervention | Weeks (Median) |
---|---|
Vadadustat | 48.86 |
Darbepoetin Alfa | 48.00 |
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
Intervention | g/dL (Least Squares Mean) |
---|---|
Vadadustat | 1.52 |
Darbepoetin Alfa | 1.48 |
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
Intervention | g/dL (Least Squares Mean) |
---|---|
Vadadustat | 1.43 |
Darbepoetin Alfa | 1.38 |
"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
Intervention | Weeks (Median) |
---|---|
Vadadustat | 46.57 |
Darbepoetin Alfa | 47.79 |
"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
Intervention | Weeks (Median) |
---|---|
Vadadustat | 48.29 |
Darbepoetin Alfa | 41.86 |
"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
Intervention | Weeks (Median) |
---|---|
Vadadustat | 45.86 |
Darbepoetin Alfa | 41.86 |
"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
Intervention | Weeks (Median) |
---|---|
Vadadustat | 37.64 |
Darbepoetin Alfa | 41.43 |
"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
Intervention | Weeks (Median) |
---|---|
Vadadustat | 45.71 |
Darbepoetin Alfa | 46.71 |
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
Intervention | g/dL (Least Squares Mean) |
---|---|
Vadadustat | 0.43 |
Darbepoetin Alfa | 0.44 |
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
Intervention | Grams per deciliter (g/dL) (Least Squares Mean) |
---|---|
Vadadustat | 0.41 |
Darbepoetin Alfa | 0.42 |
"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
Intervention | Weeks (Median) |
---|---|
Vadadustat | 57.71 |
Darbepoetin Alfa | 62.14 |
"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
Intervention | Weeks (Median) |
---|---|
Vadadustat | 48.29 |
Darbepoetin Alfa | 54.21 |
"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
Intervention | Weeks (Median) |
---|---|
Vadadustat | 45.57 |
Darbepoetin Alfa | 50.29 |
"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
Intervention | Weeks (Median) |
---|---|
Vadadustat | 48.29 |
Darbepoetin Alfa | 49.29 |
"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
Intervention | Weeks (Median) |
---|---|
Vadadustat | 53.21 |
Darbepoetin Alfa | 58.00 |
(NCT03461146)
Timeframe: Up to Week 24
Intervention | g/dL (Least Squares Mean) |
---|---|
MT-6548 | 10.75 |
(NCT03461146)
Timeframe: Up to Week 24
Intervention | days (Mean) |
---|---|
MT-6548 | 67.2 |
(NCT03461146)
Timeframe: Up to Week 24
Intervention | g/dL (Mean) | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Baseline | Week 2 | Week 4 | Week 6 | Week 8 | Week 10 | Week 12 | Week 16 | Week 20 | Week 24 | Week 24 (LOCF) | |
MT-6548 | 9.15 | 9.25 | 9.53 | 9.90 | 10.33 | 10.56 | 10.68 | 11.17 | 11.08 | 11.03 | 10.56 |
(NCT03461146)
Timeframe: Up to Week 24
Intervention | percentage of subjects (Number) | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Baseline | Week 2 | Week 4 | Week 6 | Week 8 | Week 10 | Week 12 | Week 16 | Week 20 | Week 24 | |
MT-6548 | 16.7 | 21.7 | 36.4 | 47.6 | 55.0 | 63.2 | 68.4 | 63.2 | 78.9 | 73.7 |
(NCT03461146)
Timeframe: Up to Week 6
Intervention | g/dL/week (Mean) | |
---|---|---|
Calculated based on Hb at baseline and Week 4 | Calculated based on Hb up to Week6 | |
MT-6548 | 0.05 | 0.09 |
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)
Intervention | Participants (Count of Participants) |
---|---|
AKB-6548 240 mg | 0 |
AKB-6548 370 mg | 0 |
AKB-6548 500 mg | 0 |
AKB-6548 630 mg | 0 |
Placebo | 0 |
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)
Intervention | Participants (Count of Participants) |
---|---|
AKB-6548 240 mg | 0 |
AKB-6548 370 mg | 0 |
AKB-6548 500 mg | 0 |
AKB-6548 630 mg | 0 |
Placebo | 0 |
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)
Intervention | Participants (Count of Participants) |
---|---|
AKB-6548 240 mg | 0 |
AKB-6548 370 mg | 0 |
AKB-6548 500 mg | 0 |
AKB-6548 630 mg | 0 |
Placebo | 0 |
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
Intervention | Grams per deciliter (g/dL) (Mean) | |
---|---|---|
Baseline | Change from Baseline at Week 6 | |
AKB-6548 240 mg | 9.46 | 0.77 |
AKB-6548 370 mg | 9.93 | 0.73 |
AKB-6548 500 mg | 9.86 | 1.25 |
AKB-6548 630 mg | 9.67 | 1.43 |
Placebo | 9.83 | -0.03 |
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)
Intervention | 10^6 cells/μL (Mean) | |||||
---|---|---|---|---|---|---|
Baseline | Change from Baseline to Week 1 | Change from Baseline to Week 2 | Change from Baseline to Week 4 | Change from Baseline to Week 6 | Change from Baseline to Follow-up Visit (up to Week 8) | |
AKB-6548 240 mg | 0.0766 | 0.0022 | 0.0012 | 0.0029 | -0.0020 | -0.0042 |
AKB-6548 370 mg | 0.0569 | 0.0134 | 0.0196 | 0.0128 | 0.0116 | 0.0015 |
AKB-6548 500 mg | 0.0811 | 0.0259 | 0.0346 | 0.0234 | 0.0061 | -0.0152 |
AKB-6548 630 mg | 0.0674 | 0.0289 | 0.0292 | 0.0206 | 0.0047 | -0.0119 |
Placebo | 0.0700 | 0.0010 | -0.0015 | -0.0023 | -0.0004 | -0.0035 |
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)
Intervention | ng/mL (Mean) | |||
---|---|---|---|---|
Baseline | Change from Baseline to Week 2 | Change from Baseline to Week 6 | Change from Baseline to Follow-up Visit (up to Week 8) | |
AKB-6548 240 mg | 18.011 | -3.538 | -3.050 | -3.853 |
AKB-6548 370 mg | 4.339 | 0.606 | -1.013 | -0.563 |
AKB-6548 500 mg | 7.287 | 1.142 | -3.329 | -2.061 |
AKB-6548 630 mg | 8.826 | -2.483 | -0.372 | -4.844 |
Placebo | 6.963 | -0.850 | -1.492 | -2.650 |
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)
Intervention | Nanograms per milliliter (ng/mL) (Mean) | ||||
---|---|---|---|---|---|
Baseline | Change from Baseline to Week 2 | Change from Baseline to Week 4 | Change from Baseline to Week 6 | Change from Baseline to Follow-up Visit (up to Week 8) | |
AKB-6548 240 mg | 349.5 | -66.0 | -69.8 | -65.5 | -50.4 |
AKB-6548 370 mg | 245.8 | -41.7 | -48.7 | -59.4 | -37.7 |
AKB-6548 500 mg | 332.3 | -72.0 | -89.6 | -88.9 | -86.1 |
AKB-6548 630 mg | 240.2 | -58.9 | -80.6 | -86.6 | -27.4 |
Placebo | 200.8 | -12.9 | -20.5 | -19.6 | -20.2 |
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)
Intervention | Percentage of red blood cells in blood (Mean) | |||||
---|---|---|---|---|---|---|
Baseline | Change from Baseline to Week 1 | Change from Baseline to Week 2 | Change from Baseline to Week 4 | Change from Baseline to Week 6 | Change from Baseline to Follow-up Visit (up to Week 8) | |
AKB-6548 240 mg | 29.0 | 0.5 | 0.2 | 1.7 | 1.8 | 1.9 |
AKB-6548 370 mg | 29.6 | 0.2 | 0.1 | 0.6 | 2.1 | 0.7 |
AKB-6548 500 mg | 30.4 | 1.2 | 1.6 | 3.1 | 3.4 | 2.4 |
AKB-6548 630 mg | 29.6 | 1.6 | 1.5 | 3.4 | 4.3 | 2.8 |
Placebo | 29.8 | 0.2 | 0.3 | 0.1 | -0.4 | 0.0 |
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
Intervention | ng/mL (Mean) | |
---|---|---|
Baseline | Change from Baseline at Week 6 | |
AKB-6548 240 mg | 326.35 | -28.64 |
AKB-6548 370 mg | 241.03 | -90.91 |
AKB-6548 500 mg | 242.51 | -85.01 |
AKB-6548 630 mg | 282.75 | -144.90 |
Placebo | 258.29 | -32.54 |
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)
Intervention | g/dL (Mean) | |||||
---|---|---|---|---|---|---|
Baseline | Change from Baseline to Week 1 | Change from Baseline to Week 2 | Change from Baseline to Week 4 | Change from Baseline to Week 6 | Change from Baseline to Follow-up Visit (up to Week 8) | |
AKB-6548 240 mg | 9.46 | 0.06 | 0.16 | 0.54 | 0.77 | 0.78 |
AKB-6548 370 mg | 9.93 | -0.12 | 0.00 | 0.36 | 0.73 | 0.40 |
AKB-6548 500 mg | 9.86 | 0.28 | 0.54 | 0.85 | 1.25 | 1.04 |
AKB-6548 630 mg | 9.67 | 0.29 | 0.53 | 1.06 | 1.43 | 1.01 |
Placebo | 9.83 | 0.04 | 0.14 | 0.08 | -0.03 | 0.06 |
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)
Intervention | Percentage of saturation (Mean) | ||||
---|---|---|---|---|---|
Baseline | Change from Baseline to Week 2 | Change from Baseline to Week 4 | Change from Baseline to Week 6 | Change from Baseline to Follow-up Visit (up to Week 8) | |
AKB-6548 240 mg | 30.4 | -1.5 | -1.9 | -0.3 | -4.1 |
AKB-6548 370 mg | 32.4 | -3.8 | -2.3 | -3.8 | -3.9 |
AKB-6548 500 mg | 31.4 | 1.4 | -3.7 | -2.3 | 0.5 |
AKB-6548 630 mg | 26.5 | 0.6 | -0.2 | -4.6 | 1.6 |
Placebo | 27.7 | -0.9 | -0.2 | -2.1 | 1.2 |
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)
Intervention | 10^6 cells/microliter (10^6 cells/μL) (Mean) | |||||
---|---|---|---|---|---|---|
Baseline | Change from Baseline to Week 1 | Change from Baseline to Week 2 | Change from Baseline to Week 4 | Change from Baseline to Week 6 | Change from Baseline to Follow-up Visit (up to Week 8) | |
AKB-6548 240 mg | 3.21 | -0.01 | 0.02 | 0.16 | 0.17 | 0.24 |
AKB-6548 370 mg | 3.38 | -0.07 | -0.05 | 0.01 | 0.18 | 0.06 |
AKB-6548 500 mg | 3.37 | 0.09 | 0.14 | 0.26 | 0.39 | 0.30 |
AKB-6548 630 mg | 3.25 | 0.04 | 0.11 | 0.27 | 0.41 | 0.26 |
Placebo | 3.34 | -0.02 | 0.03 | 0.02 | -0.02 | 0.01 |
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
Intervention | Picogram (Mean) | |
---|---|---|
Baseline | Change From Baseline at Week 6 | |
AKB-6548 240 mg | 31.02 | 0.37 |
AKB-6548 370 mg | 31.44 | 0.29 |
AKB-6548 500 mg | 30.26 | 0.06 |
AKB-6548 630 mg | 31.54 | 0.15 |
Placebo | 30.73 | 0.03 |
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)
Intervention | Micrograms per deciliter (µg/dL) (Mean) | ||||
---|---|---|---|---|---|
Baseline | Change from Baseline to Week 2 | Change from Baseline to Week 4 | Change from Baseline to Week 6 | Change from Baseline to Follow-up Visit (up to Week 8) | |
AKB-6548 240 mg | 66.0 | -1.8 | -1.5 | 3.6 | -7.4 |
AKB-6548 370 mg | 77.8 | -3.7 | 4.0 | 2.8 | -7.5 |
AKB-6548 500 mg | 76.1 | 10.9 | -1.6 | 3.7 | 0.9 |
AKB-6548 630 mg | 60.7 | 10.4 | 13.2 | 0.7 | 6.2 |
Placebo | 67.6 | -4.1 | -2.2 | -8.6 | 3.4 |
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)
Intervention | µg/dL (Mean) | ||||
---|---|---|---|---|---|
Baseline | Change from Baseline to Week 2 | Change from Baseline to Week 4 | Change from Baseline to Week 6 | Change from Baseline to Follow-up Visit (up to Week 8) | |
AKB-6548 240 mg | 219.4 | 9.2 | 12.9 | 18.8 | 7.8 |
AKB-6548 370 mg | 245.8 | 18.7 | 30.1 | 36.8 | 8.7 |
AKB-6548 500 mg | 249.2 | 28.1 | 29.9 | 33.0 | 0.2 |
AKB-6548 630 mg | 231.8 | 31.7 | 50.5 | 50.3 | 10.2 |
Placebo | 243.1 | -5.5 | -5.9 | -9.9 | 4.1 |
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)
Intervention | µg/dL (Mean) | ||||
---|---|---|---|---|---|
Baseline | Change from Baseline to Week 2 | Change from Baseline to Week 4 | Change from Baseline to Week 6 | Change from Baseline to Follow-up Visit (up to Week 8) | |
AKB-6548 240 mg | 153.4 | 10.9 | 14.4 | 15.3 | 15.1 |
AKB-6548 370 mg | 168.0 | 22.4 | 26.1 | 34.0 | 16.2 |
AKB-6548 500 mg | 173.1 | 17.2 | 31.5 | 29.3 | -0.7 |
AKB-6548 630 mg | 171.2 | 21.3 | 37.4 | 49.6 | 3.9 |
Placebo | 175.5 | -1.5 | -3.7 | -1.3 | 0.7 |
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
Intervention | Percentage of red blood cells (Mean) | |
---|---|---|
Baseline | Maximum change from Baseline (up to Week 8) | |
AKB-6548 240 mg | 29.0 | 2.94 |
AKB-6548 370 mg | 29.6 | 2.56 |
AKB-6548 500 mg | 30.4 | 4.43 |
AKB-6548 630 mg | 29.6 | 4.84 |
Placebo | 29.8 | 1.89 |
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
Intervention | g/dL (Mean) | |
---|---|---|
Baseline | Maximum change from Baseline (up to Week 8) | |
AKB-6548 240 mg | 9.46 | 1.04 |
AKB-6548 370 mg | 9.93 | 0.82 |
AKB-6548 500 mg | 9.86 | 1.44 |
AKB-6548 630 mg | 9.67 | 1.54 |
Placebo | 9.83 | 0.59 |
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
Intervention | 10^6 cells/μL (Mean) | |
---|---|---|
Baseline | Maximum change from Baseline (up to Week 8) | |
AKB-6548 240 mg | 3.21 | 0.31 |
AKB-6548 370 mg | 3.38 | 0.22 |
AKB-6548 500 mg | 3.37 | 0.44 |
AKB-6548 630 mg | 3.25 | 0.44 |
Placebo | 3.34 | 0.18 |
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
Intervention | 10^6 cells/μL (Mean) | |
---|---|---|
Baseline | Maximum Change from Baseline (up to Week 8) | |
AKB-6548 240 mg | 0.0766 | 0.013 |
AKB-6548 370 mg | 0.0569 | 0.028 |
AKB-6548 500 mg | 0.0811 | 0.040 |
AKB-6548 630 mg | 0.0674 | 0.042 |
Placebo | 0.0700 | 0.011 |
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
Intervention | Milliseconds (Mean) | |||||||
---|---|---|---|---|---|---|---|---|
Baseline PR Interval | Change from Baseline PR Interval | Baseline QRS Duration | Change from Baseline QRS Duration | Baseline QT Interval | Change from Baseline QT Interval | Baseline QTC Interval | Change from Baseline QTC Interval | |
AKB-6548 240 mg | 156.7 | -0.8 | 94.9 | 4.1 | 412.0 | 3.8 | 424.9 | 5.1 |
AKB-6548 370 mg | 174.6 | 2.2 | 113.8 | 2.0 | 421.4 | 7.8 | 436.3 | 3.6 |
AKB-6548 500 mg | 172.8 | 11.4 | 97.1 | -1.3 | 419.0 | -1.6 | 445.1 | -5.8 |
AKB-6548 630 mg | 187.8 | -11.7 | 94.5 | 1.4 | 406.9 | 4.5 | 427.6 | -1.6 |
Placebo | 175.8 | -0.4 | 94.6 | -1.6 | 419.1 | 11.0 | 435.6 | 3.3 |
Plasma samples were collected for the analysis. (NCT01381094)
Timeframe: Week 2: Pre-dose; Week 4: Pre-dose
Intervention | μg/mL (Mean) | |
---|---|---|
Week 2 Pre-Dose | Week 4 Pre-Dose | |
AKB-6548 240 mg | 1848.4 | 1999.3 |
AKB-6548 370 mg | 2708.5 | 2687.5 |
AKB-6548 500 mg | 5900.1 | 6866.9 |
AKB-6548 630 mg | 6425.0 | 7960.8 |
Plasma samples were collected for the analysis. (NCT01381094)
Timeframe: Week 2: Pre-dose and post-dose; Week 4: Pre-dose
Intervention | μg/mL (Mean) | ||
---|---|---|---|
Week 2 Pre-Dose | Week 2 Post-Dose | Week 4 Pre-Dose | |
AKB-6548 240 mg | 4358.28 | 17036.82 | 4698.21 |
AKB-6548 370 mg | 6640.04 | 21371.63 | 7884.56 |
AKB-6548 500 mg | 10791.79 | 39892.00 | 14274.80 |
AKB-6548 630 mg | 12443.17 | 41656.11 | 17700.17 |
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)
Intervention | Participants (Count of Participants) | |
---|---|---|
TEAEs | SAEs | |
AKB-6548 240 mg | 9 | 2 |
AKB-6548 370 mg | 6 | 3 |
AKB-6548 500 mg | 8 | 1 |
AKB-6548 630 mg | 11 | 1 |
Placebo | 11 | 1 |
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)
Intervention | Participants (Count of Participants) | |||
---|---|---|---|---|
Change from Baseline in Hgb ≥0.4 g/dL | Change from Baseline in Hgb ≥0.6 g/dL | Change from Baseline in Hgb ≥0.8 g/dL | Change from Baseline in Hgb ≥1.0 g/dL | |
AKB-6548 240 mg | 3 | 3 | 3 | 5 |
AKB-6548 370 mg | 2 | 2 | 2 | 6 |
AKB-6548 500 mg | 2 | 0 | 3 | 11 |
AKB-6548 630 mg | 1 | 1 | 1 | 14 |
Placebo | 2 | 0 | 0 | 2 |
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)
Intervention | Participants (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 mg | 4 | 1 | 4 |
AKB-6548 370 mg | 3 | 0 | 6 |
AKB-6548 500 mg | 2 | 0 | 9 |
AKB-6548 630 mg | 0 | 4 | 11 |
Placebo | 1 | 1 | 1 |
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)
Intervention | Participants (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 mg | 4 | 4 | 5 |
AKB-6548 370 mg | 3 | 3 | 5 |
AKB-6548 500 mg | 1 | 3 | 11 |
AKB-6548 630 mg | 1 | 1 | 14 |
Placebo | 2 | 0 | 2 |
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)
Intervention | Participants (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 mg | 4 | 2 | 2 |
AKB-6548 370 mg | 3 | 2 | 4 |
AKB-6548 500 mg | 2 | 3 | 8 |
AKB-6548 630 mg | 3 | 1 | 11 |
Placebo | 1 | 0 | 1 |
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)
Intervention | Participants (Count of Participants) | ||
---|---|---|---|
Change from Baseline in Reticulocytes ≥6000 cells/uL | Change from Baseline in Reticulocytes ≥12000 cells/uL | Change from Baseline in Reticulocytes ≥18000 cells/uL | |
AKB-6548 240 mg | 1 | 1 | 2 |
AKB-6548 370 mg | 1 | 3 | 5 |
AKB-6548 500 mg | 4 | 0 | 4 |
AKB-6548 630 mg | 2 | 3 | 5 |
Placebo | 3 | 1 | 2 |
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
Intervention | G/dL (Mean) |
---|---|
All Participants | 0.79 |
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
Intervention | Days (Median) |
---|---|
All Participants | 84 |
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
Intervention | Episodes (Number) |
---|---|
All Participants | 7 |
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
Intervention | Participants (Count of Participants) |
---|---|
All Participants | 1 |
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
Intervention | Participants (Count of Participants) |
---|---|
All Participants | 0 |
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
Intervention | Participants (Count of Participants) |
---|---|
All Participants | 3 |
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
Intervention | Days (Median) |
---|---|
All Participants | 57.0 |
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
Intervention | Hour*nanogram per milliliter (h*ng/mL) (Geometric Mean) | |
---|---|---|
AUC (0-4), Week 24, n=1,8,8,5,2,1,1 | AUC (0-4), All, n=1,12,22,13,3,1,1 | |
GSK1278863 1 mg | 43.3100 | 43.3100 |
GSK1278863 12 mg | 749.4583 | 749.4583 |
GSK1278863 18 mg | 126.2883 | 126.2883 |
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
Intervention | Hour*nanogram per milliliter (h*ng/mL) (Geometric Mean) | ||
---|---|---|---|
AUC (0-4), Week 12, n=0,4,14,8,1,0,0 | AUC (0-4), Week 24, n=1,8,8,5,2,1,1 | AUC (0-4), All, n=1,12,22,13,3,1,1 | |
GSK1278863 2 mg | 25.7228 | 33.8941 | 30.9164 |
GSK1278863 4 mg | 95.1319 | 86.3702 | 91.8474 |
GSK1278863 6 mg | 200.6036 | 133.3020 | 171.4229 |
GSK1278863 8 mg | 233.3933 | 437.0983 | 354.6083 |
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
Intervention | Microgram per liter (µg/L) (Mean) | ||
---|---|---|---|
Week 4 | Week 12 | Week 24 | |
All Participants | -80.11 | -126.29 | -107.03 |
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
Intervention | G/dL (Mean) | |||||
---|---|---|---|---|---|---|
Week 4 | Week 8 | Week 12 | Week 16 | Week 20 | Week 24 | |
All Participants | 0.79 | 1.66 | 1.98 | 2.28 | 2.24 | 2.01 |
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
Intervention | Micromoles per liter (µmol/L) (Mean) | ||
---|---|---|---|
Week 4 | Week 12 | Week 24 | |
All Participants | -0.8123 | 2.0916 | 1.4584 |
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
Intervention | umol/L (Mean) | ||
---|---|---|---|
Week 4 | Week 12 | Week 24 | |
All Participants | 8.5904 | 10.8611 | 9.3388 |
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
Intervention | mg (Median) | ||||||
---|---|---|---|---|---|---|---|
Day 1 | Week 4 | Week 8 | Week 12 | Week 16 | Week 20 | Week 12 to 24 | |
All Participants | 4.0 | 4.0 | 4.0 | 4.0 | 4.0 | 4.0 | 4.00 |
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
Intervention | G/dL (Mean) | ||||||
---|---|---|---|---|---|---|---|
Day 1 | Week 4 | Week 8 | Week 12 | Week 16 | Week 20 | Week 24 | |
All Participants | 9.10 | 9.90 | 10.76 | 11.09 | 11.38 | 11.34 | 11.12 |
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
Intervention | ng/mL (Geometric Mean) | |
---|---|---|
Cmax, Week 24, n=1,8,8,5,2,1,1 | Cmax, All, n=1,12,22,13,3,1,1 | |
GSK1278863 1 mg | 27.5000 | 27.5000 |
GSK1278863 12 mg | 311.0000 | 311.0000 |
GSK1278863 18 mg | 93.4000 | 93.4000 |
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
Intervention | ng/mL (Geometric Mean) | ||
---|---|---|---|
Cmax, Week 12, n=0,4,14,8,1,0,0 | Cmax, Week 24, n=1,8,8,5,2,1,1 | Cmax, All, n=1,12,22,13,3,1,1 | |
GSK1278863 2 mg | 13.9578 | 18.3448 | 16.7474 |
GSK1278863 4 mg | 57.6572 | 44.8853 | 52.6391 |
GSK1278863 6 mg | 122.9883 | 100.2261 | 113.6784 |
GSK1278863 8 mg | 179.0000 | 202.9384 | 194.6229 |
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
Intervention | Mg (Mean) | |
---|---|---|
Quarter 1; n= 3 | Quarter 2; n= 4 | |
All Participants | 231.61 | 217.19 |
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
Intervention | Participants (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 Participants | 0 | 0 | 4 | 13 | 11 | 0 |
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
Intervention | Participants (Count of Participants) | ||||||
---|---|---|---|---|---|---|---|
Day 1, within range | Week 4, within range | Week 8, within range | Week 12, within range | Week 16, within range | Week 20, within range | Week 24, within range | |
All Participants | 3 | 13 | 20 | 18 | 17 | 20 | 23 |
The number of participants who used iron (both IV and oral iron) during the treatment period were summarized. (NCT02829320)
Timeframe: Up to Week 24
Intervention | Participants (Count of Participants) | ||
---|---|---|---|
Oral iron | Intravenous iron | Any iron medication | |
All Participants | 9 | 4 | 12 |
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
Intervention | Participants (Count of Participants) | ||||||
---|---|---|---|---|---|---|---|
Any dose adjustments | Number of dose adjustments=0 | Number of dose adjustments=1 | Number of dose adjustments=2 | Number of dose adjustments=3 | Number of dose adjustments=4 | Number of dose adjustments=5 or more | |
All Participants | 21 | 7 | 9 | 7 | 4 | 1 | 0 |
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
Intervention | Percentage of hepcidin (Geometric Mean) | ||
---|---|---|---|
Week 4, n=26 | Week 12, n=22 | Week 24, n=21 | |
All Participants | -64.78 | -61.74 | -55.67 |
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
Intervention | Percentage of transferrin (Geometric Mean) | ||
---|---|---|---|
Week 4 | Week 12 | Week 24 | |
All Participants | -23.06 | -15.31 | -10.07 |
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)
Intervention | milli-international units (mIU)/mL (Mean) |
---|---|
Day 1, Baseline | |
Roxadustat 2.0 mg/kg BIW | 9.00 |
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)
Intervention | milli-international units (mIU)/mL (Mean) | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Day 1, Baseline | Change at Day 26, 1 Hour | Change at Day 26, 2 Hour | Change at Day 26, 3 Hour | Change at Day 26, 4 Hour | Change at Day 26, 6 Hour | Change at Day 26, 8 Hour | Change at Day 26, 12 Hour | Change at Day 26, 18 Hour | Change at Day 26, 24 Hour | Change at Day 26, 48 Hour | Change at Day 26, 72 Hour | |
Roxadustat 1.0 mg/kg TIW | 13.30 | -1.50 | -0.85 | -0.95 | -0.45 | 8.05 | 57.95 | 81.80 | 37.30 | 22.35 | 0.55 | -2.85 |
Roxadustat 2.0 mg/kg TIW | 8.50 | 0.00 | -0.60 | 2.30 | 29.70 | 132.80 | 462.00 | 492.00 | 176.90 | 33.90 | -0.50 | -1.50 |
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)
Intervention | milli-international units (mIU)/mL (Mean) | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Day 1, Baseline | Change at Day 29, 1 Hour | Change at Day 29, 2 Hour | Change at Day 29, 3 Hour | Change at Day 29, 4 Hour | Change at Day 29, 6 Hour | Change at Day 29, 8 Hour | Change at Day 29, 12 Hour | Change at Day 29, 18 Hour | Change at Day 29, 24 Hour | Change at Day 29, 48 Hour | Change at Day 29, 72 Hour | |
Roxadustat 1.0 mg/kg BIW | 13.46 | -1.08 | -1.27 | -0.55 | 12.03 | 66.85 | 135.08 | 77.35 | 43.80 | 10.18 | -5.17 | -2.93 |
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)
Intervention | milli-international units (mIU)/mL (Mean) | ||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Day 1, Baseline | Change at Day 26, 1 Hour | Change at Day 26, 2 Hour | Change at Day 26, 3 Hour | Change at Day 26, 4 Hour | Change at Day 26, 6 Hour | Change at Day 26, 8 Hour | Change at Day 26, 12 Hour | Change at Day 26, 18 Hour | Change at Day 26, 24 Hour | Change at Day 26, 48 Hour | Change at Day 26, 72 Hour | Change at Day 29, 1 Hour | Change at Day 29, 2 Hour | Change at Day 29, 3 Hour | Change at Day 29, 4 Hour | Change at Day 29, 6 Hour | Change at Day 29, 8 Hour | Change at Day 29, 12 Hour | Change at Day 29, 18 Hour | Change at Day 29, 24 Hour | Change at Day 29, 48 Hour | Change at Day 29, 72 Hour | |
Placebo | 13.75 | 0.17 | 0.67 | -1.27 | 0.50 | 0.33 | 0.20 | -1.30 | 0.87 | 2.60 | -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 |
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
Intervention | mIU/mL (Mean) | ||||
---|---|---|---|---|---|
Baseline | Change at 4 Hour | Change at 8 Hour | Change at 12 Hour | Change at 24 Hour | |
Roxadustat 0.7 mg/kg TIW | 8.30 | 2.80 | 66.70 | 66.25 | 10.05 |
Roxadustat 1.5 mg/kg BIW | 9.55 | 2.10 | 100.40 | 147.15 | 107.65 |
Roxadustat 2.0 mg/kg BIW | 10.45 | 1.00 | 42.05 | 201.10 | 461.05 |
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)
Intervention | g/dL (Mean) | |
---|---|---|
Baseline | Change at Day 26-29 | |
Placebo | 10.10 | -0.05 |
Roxadustat 0.7 mg/kg BIW | 10.32 | 0.25 |
Roxadustat 0.7 mg/kg TIW | 10.03 | 0.60 |
Roxadustat 1.0 mg/kg BIW | 9.18 | 0.44 |
Roxadustat 1.0 mg/kg TIW | 10.35 | 0.21 |
Roxadustat 1.5 mg/kg BIW | 10.28 | 1.22 |
Roxadustat 1.5 mg/kg TIW | 10.08 | 1.65 |
Roxadustat 2.0 mg/kg BIW | 9.97 | 1.35 |
Roxadustat 2.0 mg/kg TIW | 9.93 | 1.75 |
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)
Intervention | g/dL (Mean) | |
---|---|---|
Baseline | Change at Week 8 | |
Placebo | 10.10 | 0.04 |
Roxadustat 0.7 mg/kg BIW | 10.32 | 0.59 |
Roxadustat 0.7 mg/kg TIW | 10.03 | 0.24 |
Roxadustat 1.0 mg/kg BIW | 9.18 | 0.50 |
Roxadustat 1.0 mg/kg TIW | 10.35 | 0.05 |
Roxadustat 1.5 mg/kg BIW | 10.28 | 0.79 |
Roxadustat 1.5 mg/kg TIW | 10.08 | 1.31 |
Roxadustat 2.0 mg/kg BIW | 9.97 | 1.21 |
Roxadustat 2.0 mg/kg TIW | 9.93 | 1.52 |
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)
Intervention | Participants (Count of Participants) | ||
---|---|---|---|
Day 26-29 | Week 8 | Week 16 | |
Placebo | 3 | 6 | 8 |
Roxadustat 0.7 mg/kg BIW | 1 | 5 | 7 |
Roxadustat 0.7 mg/kg TIW | 6 | 7 | 7 |
Roxadustat 1.0 mg/kg BIW | 1 | 3 | 3 |
Roxadustat 1.0 mg/kg TIW | 1 | 2 | 2 |
Roxadustat 1.5 mg/kg BIW | 8 | 8 | 9 |
Roxadustat 1.5 mg/kg TIW | 10 | 10 | 10 |
Roxadustat 2.0 mg/kg BIW | 7 | 9 | 9 |
Roxadustat 2.0 mg/kg TIW | 9 | 11 | 11 |
(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)
Intervention | nanograms (ng)/milliliter (mL) (Mean) | ||||
---|---|---|---|---|---|
Day 3 | Day 8 | Day 15 | Day 22 | Day 26 | |
Roxadustat 0.7 mg/kg TIW | 394.800 | 203.535 | 195.483 | 153.903 | 331.640 |
Roxadustat 1.5 mg/kg TIW | 260.027 | 168.955 | 247.945 | 163.100 | 223.140 |
Roxadustat 2.0 mg/kg TIW | 422.700 | 297.500 | 175.570 | 239.600 | 508.889 |
(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)
Intervention | nanograms (ng)/milliliter (mL) (Mean) | ||||
---|---|---|---|---|---|
Day 4 | Day 8 | Day 15 | Day 22 | Day 29 | |
Roxadustat 0.7 mg/kg BIW | 28.596 | 19.884 | 22.997 | 36.432 | 14.332 |
Roxadustat 2.0 mg/kg BIW | 283.067 | 291.856 | 358.400 | 171.833 | 193.622 |
Roxadustat 1.5 mg/kg BIW | 168.310 | 125.185 | 134.116 | 147.323 | 150.599 |
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])
Intervention | Participants (Count of Participants) | ||||
---|---|---|---|---|---|
Any TEAEs | Serious TEAEs | Severe TEAEs | Drug-Related TEAEs | TEAEs Leading to Treatment Discontinuation | |
Placebo | 13 | 1 | 1 | 3 | 1 |
Roxadustat 0.7 mg/kg BIW | 3 | 0 | 0 | 1 | 0 |
Roxadustat 0.7 mg/kg TIW | 9 | 4 | 3 | 2 | 0 |
Roxadustat 1.0 mg/kg BIW | 7 | 0 | 1 | 2 | 0 |
Roxadustat 1.0 mg/kg TIW | 5 | 0 | 0 | 1 | 1 |
Roxadustat 1.5 mg/kg BIW | 9 | 0 | 0 | 3 | 0 |
Roxadustat 1.5 mg/kg TIW | 7 | 0 | 1 | 3 | 0 |
Roxadustat 2.0 mg/kg BIW | 7 | 0 | 1 | 3 | 1 |
Roxadustat 2.0 mg/kg TIW | 5 | 0 | 0 | 1 | 0 |
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
Intervention | Micromoles per Liter (Least Squares Mean) |
---|---|
0.5 mg GSK1278863 | 4.3 |
2 mg GSK1278863 | 6.2 |
5 mg GSK1278863 | 2.5 |
rhEPO | 0.3 |
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
Intervention | Ratio (Least Squares Mean) |
---|---|
0.5 mg GSK1278863 | 6.4 |
2 mg GSK1278863 | 11.7 |
5 mg GSK1278863 | 1.3 |
rhEPO | -0.1 |
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
Intervention | Micromoles per Liter (Least Squares Mean) |
---|---|
0.5 mg GSK1278863 | 3.2 |
2 mg GSK1278863 | 3.7 |
5 mg GSK1278863 | 5.2 |
rhEPO | 1.3 |
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
Intervention | Units per liter (U/L) (Least Squares Mean) |
---|---|
0.5 mg GSK1278863 | 4.368 |
2 mg GSK1278863 | 3.263 |
5 mg GSK1278863 | 181.948 |
rhEPO | 393.159 |
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
Intervention | Nanograms per liter (ng/L) (Least Squares Mean) |
---|---|
0.5 mg GSK1278863 | 23.21 |
2 mg GSK1278863 | 21.52 |
5 mg GSK1278863 | 53.85 |
rhEPO | 20.59 |
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
Intervention | Grams per liter (Least Squares Mean) |
---|---|
0.5 mg GSK1278863 | 0.105 |
2 mg GSK1278863 | 0.155 |
5 mg GSK1278863 | 0.221 |
rhEPO | 0.059 |
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
Intervention | Micrograms per liter (Least Squares Mean) |
---|---|
0.5 mg GSK1278863 | 76.7 |
2 mg GSK1278863 | -1.6 |
5 mg GSK1278863 | -76.7 |
rhEPO | -38.0 |
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
Intervention | Milligrams 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 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
Intervention | Micrograms per liter (mcg/L) (Least Squares Mean) |
---|---|
0.5 mg GSK1278863 | 204.88 |
2 mg GSK1278863 | 150.29 |
5 mg GSK1278863 | 16.42 |
rhEPO | -45.47 |
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
Intervention | g/dL (Mean) |
---|---|
0.5 mg GSK1278863 | 0.53 |
2 mg GSK1278863 | 0.55 |
5 mg GSK1278863 | 0.40 |
rhEPO | 0.35 |
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
Intervention | Grams per deciliter (g/dL) (Mean) |
---|---|
0.5 mg GSK1278863 | -1.130 |
2 mg GSK1278863 | -1.070 |
5 mg GSK1278863 | 0.212 |
rhEPO | -0.273 |
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
Intervention | Participants (Count of Participants) |
---|---|
0.5 mg GSK1278863 | 1 |
2 mg GSK1278863 | 2 |
5 mg GSK1278863 | 0 |
rhEPO | 0 |
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)
Intervention | Participants (Count of Participants) |
---|---|
0.5 mg GSK1278863 | 0 |
2 mg GSK1278863 | 0 |
5 mg GSK1278863 | 0 |
rhEPO | 0 |
Residual standard deviation was derived by linear regression. Hgb of participants was recorded over 4 weeks (NCT01587924)
Timeframe: Up to 4 weeks
Intervention | g/L (Mean) |
---|---|
0.5 mg GSK1278863 | 0.24 |
2 mg GSK1278863 | 0.26 |
5 mg GSK1278863 | 0.26 |
rhEPO | 0.20 |
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
Intervention | 10^12 cells per Liter (Giga cells per L) (Mean) | |||
---|---|---|---|---|
Week 1 | Week 2 | Week 3 | Week 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 |
rhEPO | 0.02 | 0.18 | 0.01 | -0.03 |
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
Intervention | Percentage change (Mean) | |||
---|---|---|---|---|
Week 1 | Week 2 | Week 3 | Week 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 GSK1278863 | 0.03 | -0.08 | -0.06 | -0.03 |
rhEPO | -0.08 | -0.14 | -0.35 | -0.29 |
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
Intervention | Percentage (Mean) | |||
---|---|---|---|---|
Week 1 | Week 2 | Week 3 | Week 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 |
rhEPO | 0.20 | 2.02 | 0.24 | -0.22 |
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
Intervention | Nanograms per milliliter (ng/mL) (Mean) | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
GSK1278863, Week 2, 7-11h | GSK1278863, Week 4, 3h | M2, Week 2, 7-11h | M2, Week 4, 3h | M3, Week 2, 7-11h | M3, Week 4, 3h | M4, Week 2, 7-11h | M4, Week 4, 3h | M5, Week 2, 7-11h | M5, Week 4, 3h | M6, Week 2, 7-11h | M6, Week 4, 3h | M13, Week 2, 7-11h | M13, Week 4, 3h | |
0.5 mg GSK1278863 | 0.2292 | 3.3113 | 0.4582 | 0.6780 | 0.6386 | 0.7921 | 0.2156 | 0.6016 | 0.1546 | 0.1995 | 0.1776 | 0.3235 | 0.4875 | 0.4651 |
2 mg GSK1278863 | 3.3148 | 17.9009 | 1.5468 | 2.0382 | 2.1188 | 2.2857 | 0.8121 | 1.8355 | 0.5511 | 0.7132 | 0.6956 | 1.0626 | 1.4014 | 1.3623 |
5 mg GSK1278863 | 5.6170 | 34.7253 | 4.3165 | 7.4288 | 5.6935 | 8.4582 | 2.3216 | 6.1856 | 1.4581 | 1.9972 | 1.8957 | 3.4569 | 3.9647 | 5.3494 |
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
Intervention | Days (Median) | |
---|---|---|
Within +/- 0.5 g/dL | Within +/- 1 g/dL | |
0.5 mg GSK1278863 | 12.82 | 27.71 |
2 mg GSK1278863 | 14.34 | 20.79 |
5 mg GSK1278863 | 24.41 | 28.00 |
rhEPO | 21.15 | 28.00 |
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
Intervention | Participants (Count of Participants) | ||
---|---|---|---|
Post Baseline Hgb <8.0 | >=2g/dL Hgb increase post Baseline | Post Baseline Hgb >=13.0 | |
0.5 mg GSK1278863 | 1 | 0 | 0 |
2 mg GSK1278863 | 1 | 1 | 0 |
5 mg GSK1278863 | 0 | 1 | 1 |
rhEPO | 0 | 0 | 0 |
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
Intervention | Participants (Count of Participants) | |||||
---|---|---|---|---|---|---|
DBP, low | DBP, high | SBP, low | SBP, high | HR, low | HR, high | |
0.5 mg GSK1278863 | 1 | 2 | 0 | 10 | 0 | 0 |
2 mg GSK1278863 | 2 | 2 | 1 | 9 | 0 | 0 |
5 mg GSK1278863 | 2 | 0 | 0 | 6 | 0 | 3 |
rhEPO | 3 | 2 | 1 | 10 | 0 | 2 |
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
Intervention | Participants (Count of Participants) | |
---|---|---|
Any AE | Any SAE | |
0.5 mg GSK1278863 | 9 | 0 |
2 mg GSK1278863 | 7 | 2 |
5 mg GSK1278863 | 1 | 0 |
rhEPO | 6 | 2 |
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
Intervention | Participants (Count of Participants) | |
---|---|---|
Abnormal, clinically significant | Abnormal, not clinically significant | |
0.5 mg GSK1278863 | 10 | 5 |
2 mg GSK1278863 | 12 | 6 |
5 mg GSK1278863 | 8 | 9 |
rhEPO | 12 | 6 |
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
Intervention | g/dL (Least Squares Mean) |
---|---|
Placebo | 0.153 |
GSK1278863, 0.5 mg | 0.137 |
GSK1278863, 2 mg | 0.474 |
GSK1278863, 5 mg | 1.069 |
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
Intervention | gram per decilitre (g/dL) (Mean) |
---|---|
Placebo | -0.148 |
GSK1278863, 0.5 mg | 0.132 |
GSK1278863, 2 mg | 0.463 |
GSK1278863, 5 mg | 1.010 |
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
Intervention | Participants (Count of Participants) |
---|---|
Placebo | 1 |
GSK1278863, 0.5 mg | 1 |
GSK1278863, 2 mg | 0 |
GSK1278863, 5 mg | 0 |
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
Intervention | Milliseconds (msec) (Mean) | |||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
PR Interval, Day 1 | PR Interval, Week 2 | PR Interval, Week 4 | PR Interval, Week 6 | QRS Duration, Day 1 | QRS Duration, Week 2 | QRS Duration, Week 4 | QRS Duration, Week 6 | Uncorrected QT Interval, Day 1 | Uncorrected QT Interval, Week 2 | Uncorrected QT Interval, Week 4 | Uncorrected QT Interval, Week 6 | QTc Interval (Bazett's), Day 1 | QTc Interval (Bazett's), Week 2 | QTc Interval (Bazett's), Week 4 | QTc Interval (Bazett's), Week 6 | QTc Interval (Fridericias's), Day 1 | QTc Interval (Fridericias's), Week 2 | QTc Interval (Fridericias's), Week 4 | QTc Interval (Fridericias's), Week 6 | |
GSK1278863, 0.5 mg | 164.727 | 187.002 | 180.000 | 183.314 | 101.227 | 101.111 | 104.205 | 104.729 | 432.455 | 422.837 | 413.333 | 428.077 | 446.712 | 440.390 | 434.590 | 441.622 | 441.424 | 434.178 | 427.103 | 436.666 |
GSK1278863, 2 mg | 165.313 | 172.909 | 174.875 | 175.321 | 99.532 | 102.328 | 103.965 | 101.811 | 405.541 | 408.936 | 411.859 | 396.778 | 435.351 | 428.144 | 429.480 | 429.983 | 424.970 | 421.124 | 422.943 | 418.161 |
GSK1278863, 5 mg | 177.630 | 176.875 | 176.000 | 179.307 | 106.444 | 106.556 | 104.392 | 105.617 | 426.074 | 419.444 | 423.255 | 417.686 | 437.593 | 431.500 | 426.549 | 431.700 | 433.815 | 426.944 | 424.961 | 426.591 |
Placebo | 160.750 | 165.961 | 161.689 | 153.914 | 99.750 | 107.647 | 101.467 | 96.186 | 412.000 | 411.804 | 413.111 | 404.500 | 430.833 | 440.843 | 435.556 | 444.771 | 424.417 | 430.549 | 427.711 | 430.357 |
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
Intervention | International Units per litre (IU/L) (Mean) | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
ALT, Day 1 | ALT, Week 2 | ALT, Week 4 | ALT, Week 6 | ALP, Day 1 | ALP, Week 2 | ALP, Week 4 | ALP, Week 6 | AST, Day 1 | AST, Week 2 | AST, Week 4 | AST, Week 6 | CK, Day 1 | CK, Week 2 | CK, Week 4 | CK, Week 6 | |
GSK1278863, 0.5 mg | 13.8 | 12.4 | 14.6 | 14.9 | 95.6 | 91.5 | 90.4 | 89.2 | 19.1 | 17.5 | 18.2 | 20.1 | 132.4 | 130.8 | 114.2 | 132.2 |
GSK1278863, 2 mg | 18.8 | 20.1 | 22.2 | 16.9 | 97.7 | 92.2 | 92.6 | 87.1 | 22.9 | 26.1 | 26.7 | 21.4 | 159.4 | 150.2 | 136.4 | 137.4 |
GSK1278863, 5 mg | 16.2 | 14.1 | 13.2 | 16.5 | 85.9 | 87.2 | 90.1 | 92.4 | 18.7 | 19.0 | 17.4 | 19.8 | 94.4 | 100.0 | 83.1 | 130.9 |
Placebo | 11.8 | 10.8 | 11.4 | 10.1 | 86.6 | 84.3 | 84.1 | 83.9 | 16.7 | 16.1 | 15.6 | 15.2 | 101.6 | 86.7 | 94.4 | 90.6 |
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
Intervention | G/L (Mean) | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Albumin, Day 1 | Albumin, Week 2 | Albumin, Week 4 | Albumin, Week 6 | Apolipoprotein A1, Day 1 | Apolipoprotein A1, Week 2 | Apolipoprotein A1, Week 4 | Apolipoprotein A1, Week 6 | Apolipoprotein Total, Day 1 | Apolipoprotein Total, Week 2 | Apolipoprotein Total, Week 4 | Apolipoprotein Total, Week 6 | Total Protein, Day 1 | Total Protein, Week 2 | Total Protein, Week 4 | Total Protein, Week 6 | |
GSK1278863, 0.5 mg | 40.9 | 40.3 | 41.3 | 39.9 | 1.515 | 1.472 | 1.452 | 1.501 | 0.936 | 0.901 | 0.888 | 0.872 | 71.1 | 70.1 | 71.8 | 69.7 |
GSK1278863, 2 mg | 39.7 | 38.8 | 39.1 | 40.6 | 1.461 | 1.469 | 1.436 | 1.468 | 0.788 | 0.733 | 0.724 | 0.757 | 68.5 | 66.4 | 66.9 | 68.3 |
GSK1278863, 5 mg | 39.8 | 40.1 | 39.2 | 38.9 | 1.572 | 1.370 | 1.405 | 1.492 | 0.792 | 0.751 | 0.743 | 0.776 | 67.7 | 68.3 | 67.6 | 66.9 |
Placebo | 39.8 | 40.8 | 40.6 | 40.0 | 1.481 | 1.418 | 1.482 | 1.472 | 0.794 | 0.754 | 0.720 | 0.732 | 69.4 | 70.8 | 70.7 | 69.8 |
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
Intervention | 10^9 cells/L (Mean) | |||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Basophils, Day 1 | Basophils, Week 1 | Basophils, Week 2 | Basophils, Week 3 | Basophils, Week 4 | Basophils, Week 6 | Eosinophils, Day 1 | Eosinophils, Week 1 | Eosinophils, Week 2 | Eosinophils, Week 3 | Eosinophils, Week 4 | Eosinophils, Week 6 | Lymphocytes, Day 1 | Lymphocytes, Week 1 | Lymphocytes, Week 2 | Lymphocytes, Week 3 | Lymphocytes, Week 4 | Lymphocytes, Week 6 | Monocytes, Day 1 | Monocytes, Week 1 | Monocytes, Week 2 | Monocytes, Week 3 | Monocytes, Week 4 | Monocytes, Week 6 | Total Neutrophils, Day 1 | Total Neutrophils, Week 1 | Total Neutrophils, Week 2 | Total Neutrophils, Week 3 | Total Neutrophils, Week 4 | Total Neutrophils, Week 6 | Platelet Count, Day 1 | Platelet Count, Week 1 | Platelet Count, Week 2 | Platelet Count, Week 3 | Platelet Count, Week 4 | Platelet Count, Week 6 | WBC count (absolute), Day 1 | WBC count (absolute), Week 1 | WBC count (absolute), Week 2 | WBC count (absolute), Week 3 | WBC count (absolute), Week 4 | WBC count (absolute), Week 6 | |
GSK1278863, 0.5 mg | 0.035 | 0.023 | 0.022 | 0.031 | 0.033 | 0.029 | 0.205 | 0.189 | 0.223 | 0.212 | 0.190 | 0.229 | 1.662 | 1.673 | 1.741 | 1.765 | 1.736 | 1.491 | 0.345 | 0.375 | 0.339 | 0.388 | 0.388 | 0.336 | 4.808 | 4.670 | 4.523 | 4.789 | 5.238 | 4.061 | 229.9 | 219.8 | 230.1 | 237.3 | 255.8 | 207.9 | 7.06 | 6.92 | 6.84 | 7.18 | 7.57 | 6.14 |
GSK1278863, 2 mg | 0.025 | 0.034 | 0.024 | 0.024 | 0.023 | 0.023 | 0.165 | 0.126 | 0.122 | 0.105 | 0.124 | 0.134 | 1.473 | 1.677 | 1.356 | 1.475 | 1.428 | 1.427 | 0.319 | 0.371 | 0.305 | 0.362 | 0.365 | 0.350 | 4.533 | 4.203 | 4.121 | 4.181 | 4.315 | 4.126 | 219.2 | 225.8 | 209.7 | 208.5 | 215.3 | 217.9 | 6.51 | 6.42 | 5.93 | 6.14 | 6.26 | 6.06 |
GSK1278863, 5 mg | 0.025 | 0.030 | 0.029 | 0.026 | 0.024 | 0.024 | 0.141 | 0.169 | 0.112 | 0.122 | 0.146 | 0.150 | 1.602 | 1.676 | 1.533 | 1.461 | 1.330 | 1.466 | 0.373 | 0.452 | 0.383 | 0.418 | 0.367 | 0.430 | 4.614 | 5.337 | 4.746 | 5.011 | 4.539 | 4.891 | 223.5 | 238.8 | 229.9 | 224.6 | 240.5 | 227.1 | 6.76 | 7.67 | 6.80 | 7.04 | 6.42 | 6.97 |
Placebo | 0.023 | 0.023 | 0.026 | 0.027 | 0.027 | 0.024 | 0.226 | 0.212 | 0.204 | 0.216 | 0.191 | 0.202 | 1.844 | 1.842 | 1.629 | 1.813 | 1.795 | 1.739 | 0.384 | 0.418 | 0.400 | 0.452 | 0.305 | 0.369 | 4.654 | 5.076 | 4.305 | 4.588 | 3.834 | 4.163 | 199.9 | 204.8 | 211.3 | 211.5 | 184.6 | 195.1 | 7.14 | 7.56 | 6.57 | 7.11 | 6.16 | 6.50 |
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
Intervention | Millimol per Litre (MMOL/L) (Mean) | |||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Calcium, Day 1 | Calcium, Week 2 | Calcium, Week 4 | Calcium, Week 6 | Chloride, Day 1 | Chloride, Week 2 | Chloride, Week 4 | Chloride, Week 6 | Cholesterol, Day 1 | Cholesterol, Week 2 | Cholesterol, Week 4 | Cholesterol, Week 6 | Glucose, Day 1 | Glucose, Week 2 | Glucose, Week 4 | Glucose, Week 6 | Phosphorus, inorganic, Day 1 | Phosphorus, inorganic, Week 2 | Phosphorus, inorganic, Week 4 | Phosphorus, inorganic, Week 6 | Potassium, Day 1 | Potassium, Week 2 | Potassium, Week 4 | Potassium, Week 6 | Sodium, Day 1 | Sodium, Week 2 | Sodium, Week 4 | Sodium, Week 6 | |
GSK1278863, 0.5 mg | 2.296 | 2.298 | 2.302 | 2.331 | 103.1 | 104.2 | 105.0 | 105.3 | 4.632 | 4.623 | 4.448 | 4.520 | 9.11 | 8.48 | 9.03 | 8.34 | 1.364 | 1.421 | 1.388 | 1.345 | 4.65 | 4.61 | 4.61 | 4.58 | 137.8 | 137.9 | 139.2 | 139.4 |
GSK1278863, 2 mg | 2.259 | 2.331 | 2.301 | 2.309 | 103.9 | 103.6 | 104.0 | 103.8 | 4.088 | 3.800 | 3.776 | 3.928 | 9.46 | 9.64 | 8.63 | 9.14 | 1.403 | 1.435 | 1.403 | 1.366 | 4.65 | 4.71 | 4.56 | 4.70 | 137.5 | 138.2 | 138.5 | 137.9 |
GSK1278863, 5 mg | 2.335 | 2.347 | 2.348 | 2.322 | 104.7 | 103.1 | 106.4 | 104.2 | 4.411 | 4.282 | 4.091 | 4.406 | 7.75 | 9.42 | 6.71 | 7.81 | 1.313 | 1.285 | 1.244 | 1.203 | 4.63 | 4.62 | 4.42 | 4.65 | 138.6 | 137.5 | 140.2 | 138.8 |
Placebo | 2.258 | 2.299 | 2.274 | 2.255 | 105.4 | 105.6 | 106.6 | 106.7 | 4.147 | 3.997 | 3.893 | 3.944 | 6.97 | 6.78 | 6.49 | 8.88 | 1.325 | 1.309 | 1.293 | 1.319 | 4.57 | 4.67 | 4.54 | 4.56 | 140.1 | 139.8 | 140.6 | 140.3 |
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
Intervention | Micromol/L (Mean) | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Creatinine, Day 1 | Creatinine, Week 2 | Creatinine, Week 4 | Creatinine, Week 6 | Direct bilirubin, Day 1 | Direct bilirubin, Week 2 | Direct bilirubin, Week 4 | Direct bilirubin, Week 6 | Indirect bilirubin, Day 1 | Indirect bilirubin, Week 2 | Indirect bilirubin, Week 4 | Indirect bilirubin, Week 6 | Total bilirubin, Day 1 | Total bilirubin, Week 2 | Total bilirubin, Week 4 | Total bilirubin, Week 6 | |
GSK1278863, 0.5 mg | 237.05 | 245.16 | 250.10 | 238.07 | 2.1 | 1.7 | 1.8 | 1.8 | 4.4 | 4.5 | 4.2 | 5.0 | 6.5 | 6.1 | 6.0 | 6.8 |
GSK1278863, 2 mg | 274.34 | 267.07 | 254.86 | 254.86 | 2.1 | 1.8 | 1.9 | 1.8 | 4.4 | 4.8 | 4.8 | 4.8 | 6.5 | 6.6 | 6.7 | 6.5 |
GSK1278863, 5 mg | 237.43 | 217.84 | 209.76 | 219.50 | 1.6 | 2.1 | 1.9 | 2.1 | 4.6 | 4.6 | 4.9 | 3.8 | 6.2 | 6.7 | 6.8 | 5.9 |
Placebo | 250.67 | 235.92 | 242.21 | 244.43 | 1.9 | 1.5 | 1.6 | 1.8 | 4.0 | 5.1 | 4.3 | 4.4 | 5.9 | 6.6 | 5.9 | 6.1 |
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
Intervention | Beats per minute (Mean) | |||||
---|---|---|---|---|---|---|
Heart rate, Day 1 | Heart rate, Week 1 | Heart rate, Week 2 | Heart rate, Week 3 | Heart rate, Week 4 | Heart rate, Week 6 | |
GSK1278863, 0.5 mg | 68.4 | 69.5 | 67.5 | 69.8 | 68.5 | 67.6 |
GSK1278863, 2 mg | 69.1 | 69.4 | 66.9 | 68.7 | 67.9 | 68.0 |
GSK1278863, 5 mg | 67.8 | 69.4 | 67.6 | 66.9 | 65.4 | 68.9 |
Placebo | 68.4 | 68.7 | 68.9 | 71.9 | 67.9 | 71.0 |
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
Intervention | G/L (Mean) | |||||
---|---|---|---|---|---|---|
Mean Corpuscle Hgb, Day 1 | Mean Corpuscle Hgb, Week 1 | Mean Corpuscle Hgb, Week 2 | Mean Corpuscle Hgb, Week 3 | Mean Corpuscle Hgb, Week 4 | Mean Corpuscle Hgb, Week 6 | |
GSK1278863, 0.5 mg | 330.9 | 330.1 | 329.9 | 329.5 | 328.8 | 330.7 |
GSK1278863, 2 mg | 330.2 | 330.8 | 331.3 | 331.2 | 329.6 | 331.4 |
GSK1278863, 5 mg | 328.4 | 328.0 | 326.5 | 326.0 | 326.1 | 328.2 |
Placebo | 328.6 | 329.3 | 327.3 | 328.4 | 329.6 | 326.4 |
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
Intervention | Femtolitre (FL) (Mean) | |||||
---|---|---|---|---|---|---|
Mean Corpuscle Volume, Day 1 | Mean Corpuscle Volume, Week 1 | Mean Corpuscle Volume, Week 2 | Mean Corpuscle Volume, Week 3 | Mean Corpuscle Volume, Week 4 | Mean Corpuscle Volume, Week 6 | |
GSK1278863, 0.5 mg | 92.4 | 92.7 | 92.8 | 93.1 | 93.4 | 94.1 |
GSK1278863, 2 mg | 94.8 | 94.6 | 95.5 | 95.6 | 96.1 | 95.8 |
GSK1278863, 5 mg | 94.2 | 95.3 | 95.4 | 95.9 | 95.7 | 95.1 |
Placebo | 93.8 | 93.6 | 93.9 | 93.6 | 93.9 | 94.1 |
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
Intervention | Ratio (Mean) | |||||
---|---|---|---|---|---|---|
Reticulocytes, Day 1 | Reticulocytes, Week 1 | Reticulocytes, Week 2 | Reticulocytes, Week 3 | Reticulocytes, Week 4 | Reticulocytes, Week 6 | |
GSK1278863, 0.5 mg | 0.0179 | 0.0198 | 0.0201 | 0.0189 | 0.0187 | 0.0196 |
GSK1278863, 2 mg | 0.0208 | 0.0256 | 0.0224 | 0.0229 | 0.0203 | 0.0161 |
GSK1278863, 5 mg | 0.0188 | 0.0284 | 0.0268 | 0.0232 | 0.0236 | 0.0142 |
Placebo | 0.0183 | 0.0185 | 0.0178 | 0.0191 | 0.0174 | 0.0154 |
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
Intervention | Millimeter mercury (mmHg) (Mean) | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Systolic blood pressure, Day 1 | Systolic blood pressure, Week 1 | Systolic blood pressure, Week 2 | Systolic blood pressure, Week 3 | Systolic blood pressure, Week 4 | Systolic blood pressure, Week 6 | Diastolic blood pressure, Day 1 | Diastolic blood pressure, Week 1 | Diastolic blood pressure, Week 2 | Diastolic blood pressure, Week 3 | Diastolic blood pressure, Week 4 | Diastolic blood pressure, Week 6 | |
GSK1278863, 0.5 mg | 135.5 | 136.0 | 129.4 | 133.5 | 133.1 | 131.7 | 69.0 | 68.8 | 68.6 | 69.5 | 68.2 | 67.2 |
GSK1278863, 2 mg | 134.0 | 134.6 | 129.9 | 133.0 | 134.2 | 135.0 | 68.2 | 67.4 | 66.0 | 66.5 | 66.2 | 66.6 |
GSK1278863, 5 mg | 140.1 | 137.8 | 139.1 | 131.7 | 135.4 | 130.4 | 71.7 | 71.5 | 72.7 | 66.9 | 68.9 | 70.1 |
Placebo | 132.9 | 132.3 | 128.4 | 130.2 | 132.6 | 134.3 | 69.9 | 66.9 | 67.7 | 67.7 | 68.9 | 70.3 |
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
Intervention | mg/MMOL (Mean) | |||
---|---|---|---|---|
Urine Total Protein/Creatinine ratio, Day 1 | Urine Total Protein/Creatinine ratio, Week 2 | Urine Total Protein/Creatinine ratio, Week 4 | Urine Total Protein/Creatinine ratio, Week 6 | |
GSK1278863, 0.5 mg | 205.73 | 207.82 | 169.31 | 162.81 |
GSK1278863, 2 mg | 342.39 | 194.14 | 196.37 | 175.16 |
GSK1278863, 5 mg | 211.58 | 149.08 | 219.47 | 160.01 |
Placebo | 226.00 | 170.41 | 114.71 | 232.80 |
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
Intervention | 10^9 cells/L (Mean) | ||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Basophils, Week 1 | Basophils, Week 2 | Basophils, Week 3 | Basophils, Week 4 | Basophils, Week 6 | Eosinophils, Week 1 | Eosinophils, Week 2 | Eosinophils, Week 3 | Eosinophils, Week 4 | Eosinophils, Week 6 | Lymphocytes, Week 1 | Lymphocytes, Week 2 | Lymphocytes, Week 3 | Lymphocytes, Week 4 | Lymphocytes, Week 6 | Monocytes, Week 1 | Monocytes, Week 2 | Monocytes, Week 3 | Monocytes, Week 4 | Monocytes, Week 6 | Total Neutrophils, Week 1 | Total Neutrophils, Week 2 | Total Neutrophils, Week 3 | Total Neutrophils, Week 4 | Total Neutrophils, Week 6 | Platelet count, Week 1 | Platelet count, Week 2 | Platelet count, Week 3 | Platelet count, Week 4 | Platelet count, Week 6 | WBC count (absolute), Week 1 | WBC count (absolute), Week 2 | WBC count (absolute), Week 3 | WBC count (absolute), Week 4 | WBC count (absolute), Week 6 | |
GSK1278863, 0.5 mg | -0.011 | -0.013 | -0.005 | -0.000 | -0.003 | -0.014 | 0.021 | 0.012 | -0.004 | 0.034 | 0.024 | 0.062 | 0.072 | 0.030 | -0.086 | 0.042 | 0.029 | 0.075 | 0.070 | 0.006 | 0.027 | -0.217 | -0.101 | 0.493 | -0.278 | -7.375 | -10.500 | -3.333 | 12.417 | -14.071 | 0.050 | -0.136 | 0.046 | 0.567 | -0.336 |
GSK1278863, 2 mg | 0.008 | -0.001 | -0.001 | -0.003 | -0.003 | -0.029 | -0.013 | -0.040 | -0.028 | -0.018 | 0.126 | -0.176 | -0.028 | -0.082 | -0.083 | 0.032 | -0.044 | 0.015 | 0.005 | -0.010 | -0.362 | -0.400 | -0.373 | -0.239 | -0.428 | 6.056 | 0.200 | -7.412 | -0.563 | 2.063 | -0.211 | -0.625 | -0.435 | -0.344 | -0.538 |
GSK1278863, 5 mg | 0.003 | 0.004 | 0.002 | -0.001 | -0.001 | 0.023 | -0.031 | -0.018 | 0.011 | 0.009 | 0.048 | -0.036 | 0.021 | -0.081 | 0.025 | 0.096 | 0.025 | 0.054 | -0.007 | 0.066 | 0.457 | 0.086 | 0.335 | -0.148 | 0.215 | 14.500 | 12.941 | 8.176 | 22.500 | 10.647 | 0.639 | 0.050 | 0.394 | -0.206 | 0.329 |
Placebo | -0.000 | 0.004 | 0.004 | 0.005 | -0.000 | -0.014 | -0.033 | -0.014 | -0.020 | -0.012 | -0.002 | -0.234 | -0.050 | -0.137 | -0.186 | 0.034 | 0.009 | 0.060 | -0.039 | -0.012 | 0.422 | 0.155 | 0.014 | -0.394 | -0.229 | 4.833 | 16.375 | 14.118 | -1.357 | 8.933 | 0.422 | -0.100 | 0.018 | -0.579 | -0.443 |
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
Intervention | msec (Mean) | ||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
PR Interval, Week 2 | PR Interval, Week 4 | PR Interval, Week 6 | QRS Duration, Week 2 | QRS Duration, Week 4 | QRS Duration, Week 6 | Uncorrected QT Interval, Week 2 | Uncorrected QT Interval, Week 4 | Uncorrected QT Interval, Week 6 | QTc Interval (Bazett's), Week 2 | QTc Interval (Bazett's), Week 4 | QTc Interval (Bazett's), Week 6 | QTc Interval (Fridericias's), Week 2 | QTc Interval (Fridericias's), Week 4 | QTc Interval (Fridericias's), Week 6 | |
GSK1278863, 0.5 mg | 3.6 | 1.8 | 0.5 | -0.0 | 1.8 | 0.2 | -1.9 | -10.9 | -2.4 | 3.4 | -0.8 | 2.9 | 1.7 | -4.2 | 1.0 |
GSK1278863, 2 mg | 2.5 | 3.1 | -0.2 | 0.4 | 1.3 | -1.9 | 3.1 | 5.4 | -6.7 | -4.0 | -1.8 | 0.0 | -1.7 | 0.5 | -2.4 |
GSK1278863, 5 mg | -0.6 | -2.0 | 1.3 | 4.6 | 2.3 | 3.5 | 5.8 | 8.8 | 3.2 | 1.7 | -1.9 | 3.3 | 3.0 | 1.6 | 3.2 |
Placebo | -1.2 | -2.6 | -5.8 | 2.5 | -0.4 | -0.3 | -10.8 | -2.9 | -7.9 | 7.9 | 2.5 | 11.4 | 1.6 | 1.0 | 4.6 |
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
Intervention | Units per litre (U/L) (Mean) | ||||
---|---|---|---|---|---|
Week 2, 4-8 Hours Post-Dose | Week 2, 5-9 Hours, Post Dose | Week 2, 7-11 Hours, Post Dose | Week 4, Pre-dose | Week 4, 3 Hour Post-Dose | |
GSK1278863, 0.5 mg | 1.022 | 1.027 | 0.538 | 0.014 | 1.039 |
GSK1278863, 2 mg | 3.622 | 4.612 | 6.630 | 0.814 | -0.075 |
GSK1278863, 5 mg | 13.267 | 15.800 | 20.100 | 2.975 | 2.102 |
Placebo | 0.721 | 1.541 | 0.437 | 6.644 | 6.346 |
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
Intervention | mcg/L (Mean) | |
---|---|---|
Week 2 | Week 4 | |
GSK1278863, 0.5 mg | -20.0 | -35.8 |
GSK1278863, 2 mg | -38.6 | -8.2 |
GSK1278863, 5 mg | -58.8 | -101.8 |
Placebo | 2.6 | -24.3 |
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
Intervention | Beats per minute (Mean) | ||||
---|---|---|---|---|---|
Heart rate, Week 1 | Heart rate, Week 2 | Heart rate, Week 3 | Heart rate, Week 4 | Heart rate, Week 6 | |
GSK1278863, 0.5 mg | 1.375 | -1.310 | 0.976 | 1.111 | -0.167 |
GSK1278863, 2 mg | 0.315 | -1.333 | 0.412 | -0.500 | -0.458 |
GSK1278863, 5 mg | 1.632 | -0.500 | -0.510 | -2.020 | 0.917 |
Placebo | 0.296 | 0.412 | 3.392 | -1.167 | 1.854 |
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
Intervention | Ratio (Mean) | |||||||
---|---|---|---|---|---|---|---|---|
Hematocrit, Week 1 | Hematocrit, Week 2 | Hematocrit, Week 3 | Hematocrit, Week 4 | Reticulocyte, Week 1 | Reticulocyte, Week 2 | Reticulocyte, Week 3 | Reticulocyte, Week 4 | |
GSK1278863, 0.5 mg | -0.29 | 0.11 | -0.56 | -0.14 | 0.24 | 0.32 | 0.23 | 0.11 |
GSK1278863, 2 mg | -0.35 | 0.24 | 0.08 | 1.16 | 0.46 | 0.12 | 0.15 | -0.07 |
GSK1278863, 5 mg | 0.39 | 1.64 | 2.11 | 3.38 | 0.95 | 0.85 | 0.45 | 0.49 |
Placebo | -0.15 | 0.35 | -0.24 | -0.50 | 0.05 | 0.01 | 0.13 | -0.07 |
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
Intervention | Microgram per Litre (mcg/L) (Mean) | |
---|---|---|
Week 2 | Week 4 | |
GSK1278863, 0.5 mg | -23.46 | -22.16 |
GSK1278863, 2 mg | -75.24 | -77.34 |
GSK1278863, 5 mg | -120.31 | -143.09 |
Placebo | 10.19 | -2.62 |
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
Intervention | miligram per litre (mg/L) (Mean) | |
---|---|---|
Week 2 | Week 4 | |
GSK1278863, 0.5 mg | 2.35 | 0.65 |
GSK1278863, 2 mg | -1.00 | -2.09 |
GSK1278863, 5 mg | 4.32 | 1.76 |
Placebo | 6.13 | 0.21 |
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
Intervention | G/L (Mean) | ||||
---|---|---|---|---|---|
Mean Corpuscle Hgb Concentration, Week 1 | Mean Corpuscle Hgb Concentration, Week 2 | Mean Corpuscle Hgb Concentration, Week 3 | Mean Corpuscle Hgb Concentration, Week 4 | Mean Corpuscle Hgb Concentration, Week 6 | |
GSK1278863, 0.5 mg | -0.688 | -0.214 | -0.462 | -1.417 | -1.714 |
GSK1278863, 2 mg | 0.222 | 0.750 | 0.294 | -1.375 | 0.438 |
GSK1278863, 5 mg | -0.389 | -2.111 | -2.588 | -2.625 | -0.353 |
Placebo | 0.667 | -0.875 | 0.647 | 2.429 | -1.200 |
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
Intervention | FL (Mean) | ||||
---|---|---|---|---|---|
Mean Corpuscle Volume, Week 1 | Mean Corpuscle Volume, Week 2 | Mean Corpuscle Volume, Week 3 | Mean Corpuscle Volume, Week 4 | Mean Corpuscle Volume, Week 6 | |
GSK1278863, 0.5 mg | 0.125 | -0.214 | -0.231 | 0.083 | -0.071 |
GSK1278863, 2 mg | -0.222 | 0.125 | 0.118 | 0.188 | -0.125 |
GSK1278863, 5 mg | 0.278 | 0.944 | 1.176 | 1.188 | 0.353 |
Placebo | -0.222 | 0.188 | -0.235 | -0.143 | -0.133 |
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
Intervention | 10^12 cells /L (Mean) | |||
---|---|---|---|---|
Week 1 | Week 2 | Week 3 | Week 4 | |
GSK1278863, 0.5 mg | -0.03 | 0.03 | -0.02 | 0.01 |
GSK1278863, 2 mg | -0.03 | 0.01 | -0.02 | 0.09 |
GSK1278863, 5 mg | 0.04 | 0.14 | 0.16 | 0.33 |
Placebo | -0.01 | 0.02 | -0.03 | -0.05 |
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
Intervention | mmHg (Mean) | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Systolic blood pressure, Week 1 | Systolic blood pressure, Week 2 | Systolic blood pressure, Week 3 | Systolic blood pressure, Week 4 | Systolic blood pressure, Week 6 | Diastolic blood pressure, Week 1 | Diastolic blood pressure, Week 2 | Diastolic blood pressure, Week 3 | Diastolic blood pressure, Week 4 | Diastolic blood pressure, Week 6 | |
GSK1278863, 0.5 mg | 1.167 | -5.786 | -1.643 | -0.944 | -2.458 | 0.521 | -0.024 | 0.857 | -0.111 | -1.312 |
GSK1278863, 2 mg | 0.565 | -5.284 | -2.206 | 0.844 | 1.656 | -0.750 | -2.206 | -1.755 | -1.615 | -1.281 |
GSK1278863, 5 mg | -2.368 | 1.241 | -5.216 | -1.510 | -6.451 | -0.193 | 1.963 | -2.627 | -0.667 | 0.529 |
Placebo | -0.519 | -3.373 | -1.529 | 0.854 | 0.125 | -3.037 | -1.608 | -1.647 | -0.625 | 1.396 |
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
Intervention | micromol/L (Mean) | |
---|---|---|
Week 2 | Week 4 | |
GSK1278863, 0.5 mg | -1.1 | -1.7 |
GSK1278863, 2 mg | -1.3 | -0.4 |
GSK1278863, 5 mg | 0.4 | -0.4 |
Placebo | 0.4 | 0.6 |
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
Intervention | Micromol per litre (micromol/L) (Mean) | |
---|---|---|
Week 2 | Week 4 | |
GSK1278863, 0.5 mg | -1.6 | 0.3 |
GSK1278863, 2 mg | 2.9 | 5.1 |
GSK1278863, 5 mg | 5.9 | 8.3 |
Placebo | 0.6 | -0.5 |
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
Intervention | Grams per litre (G/L) (Mean) | |
---|---|---|
Week 2 | Week 4 | |
GSK1278863, 0.5 mg | -0.100 | 0.028 |
GSK1278863, 2 mg | 0.153 | 0.294 |
GSK1278863, 5 mg | 0.141 | 0.388 |
Placebo | -0.017 | 0.011 |
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
Intervention | Percentage of transferrin saturation (Mean) | |
---|---|---|
Week 2 | Week 4 | |
GSK1278863, 0.5 mg | -1.5 | -3.1 |
GSK1278863, 2 mg | -3.7 | -2.6 |
GSK1278863, 5 mg | -2.1 | -3.4 |
Placebo | 0.7 | 1.5 |
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
Intervention | Nanogram per litre (ng/L) (Mean) | ||||
---|---|---|---|---|---|
WEEK 2, 4-8 HOURS POST-DOSE | WEEK 2, 5-9 HOURS, POST DOSE | WEEK 2, 7-11 HOURS, POST DOSE | WEEK 4, PRE-DOSE | WEEK 4, 3 HOUR POST-DOSE | |
GSK1278863, 0.5 mg | -17.23 | -18.21 | -30.56 | 65.89 | 0.77 |
GSK1278863, 2 mg | -19.55 | -11.80 | -17.88 | -7.47 | -3.87 |
GSK1278863, 5 mg | 20.38 | 8.38 | 14.40 | -1.48 | 5.56 |
Placebo | -12.09 | -23.04 | -41.40 | -39.69 | -43.33 |
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
Intervention | G/L (Mean) | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Albumin, Week 2 | Albumin, Week 4 | Albumin, Week 6 | Apolipoprotein A1, Week 2 | Apolipoprotein A1, Week 4 | Apolipoprotein A1, Week 6 | Apolipoprotein total, Week 2 | Apolipoprotein total, Week 4 | Apolipoprotein total, Week 6 | Total protein, Week 2 | Total protein, Week 4 | Total 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 | -0.6 | 0.1 | -0.023 | -0.025 | -0.011 | -0.051 | -0.055 | 0.014 | -1.3 | -0.8 | -0.3 |
GSK1278863, 5 mg | -0.4 | -0.6 | -1.0 | -0.197 | -0.163 | -0.076 | -0.048 | -0.024 | 0.009 | -0.2 | 0.2 | -0.6 |
Placebo | 0.7 | 0.4 | 0.2 | -0.045 | -0.011 | -0.009 | -0.016 | -0.036 | -0.007 | 1.1 | 0.5 | 0.4 |
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
Intervention | IU/L (Mean) | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
ALT, Week 2 | ALT, Week 4 | ALT, Week 6 | ALP, Week 2 | ALP, Week 4 | ALP, Week 6 | AST, Week 2 | AST, Week 4 | AST, Week 6 | CK, Week 2 | CK, Week 4 | CK, Week 6 | |
GSK1278863, 0.5 mg | -1.2 | 0.7 | 0.7 | -2.8 | -4.8 | -6.4 | -1.7 | -0.5 | -0.1 | 7.9 | -8.5 | -9.4 |
GSK1278863, 2 mg | 3.9 | 6.0 | 0.4 | -1.2 | -0.8 | -5.7 | 4.7 | 5.1 | -0.3 | 1.2 | -12.6 | -5.1 |
GSK1278863, 5 mg | -1.9 | -2.8 | 0.5 | 2.7 | 2.6 | 4.9 | 0.1 | -1.1 | 1.4 | 4.4 | -7.5 | 40.4 |
Placebo | -1.1 | 0.1 | -1.3 | 0.8 | 1.1 | -1.9 | -0.9 | -1.3 | -1.6 | -18.7 | -21.4 | -19.1 |
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
Intervention | MMOL/L (Mean) | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Calcium, Week 2 | Calcium, Week 4 | Calcium, Week 6 | Chloride, Week 2 | Chloride, Week 4 | Chloride, Week 6 | Cholesterol, Week 2 | Cholesterol, Week 4 | Cholesterol, Week 6 | Glucose, Week 2 | Glucose, Week 4 | Glucose, Week 6 | Inorganic phosphorus, Week 2 | Inorganic phosphorus, Week 4 | Inorganic phosphorus, Week 6 | Potassium, Week 2 | Potassium, Week 4 | Potassium, Week 6 | Sodium, Week 2 | Sodium, Week 4 | Sodium, Week 6 | |
GSK1278863, 0.5 mg | 0.017 | 0.008 | 0.019 | 0.9 | 1.8 | 1.9 | -0.150 | -0.195 | -0.223 | -0.59 | -0.21 | 0.53 | 0.065 | 0.015 | -0.031 | 0.01 | -0.02 | -0.05 | 0.1 | 1.6 | 1.3 |
GSK1278863, 2 mg | 0.032 | -0.000 | -0.001 | -0.5 | -0.1 | -0.1 | -0.256 | -0.288 | -0.040 | 0.13 | -0.88 | -0.57 | 0.032 | 0.000 | -0.009 | 0.08 | -0.04 | 0.06 | 0.3 | 0.6 | 0.1 |
GSK1278863, 5 mg | 0.014 | 0.010 | -0.014 | -1.5 | 0.9 | -1.3 | -0.244 | -0.285 | 0.029 | 1.67 | -0.51 | 0.59 | 0.026 | -0.032 | -0.074 | -0.02 | -0.23 | 0.01 | -0.9 | 1.3 | -0.1 |
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
Intervention | MMOL/L (Mean) | |||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Calcium, Week 2 | Calcium, Week 4 | Calcium, Week 6 | Chloride, Week 2 | Chloride, Week 4 | Chloride, Week 6 | Cholesterol, Week 1 | Cholesterol, Week 2 | Cholesterol, Week 4 | Cholesterol, Week 6 | Glucose, Week 2 | Glucose, Week 4 | Glucose, Week 6 | Inorganic phosphorus, Week 2 | Inorganic phosphorus, Week 4 | Inorganic phosphorus, Week 6 | Potassium, Week 2 | Potassium, Week 4 | Potassium, Week 6 | Sodium, Week 2 | Sodium, Week 4 | Sodium, Week 6 | |
Placebo | 0.044 | 0.021 | 0.000 | 0.0 | 1.4 | 1.1 | 0.050 | -0.029 | -0.136 | -0.134 | 0.35 | 0.01 | 1.89 | 0.012 | 0.025 | 0.003 | 0.10 | 0.05 | 0.05 | -0.3 | 0.5 | -0.2 |
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
Intervention | Micromol/L (Mean) | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Creatinine, Week 2 | Creatinine, Week 4 | Creatinine, Week 6 | Direct bilirubin, Week 2 | Direct bilirubin, Week 4 | Direct bilirubin, Week 6 | Indirect bilirubin, Week 2 | Indirect bilirubin, Week 4 | Indirect bilirubin, Week 6 | Total bilirubin, Week 2 | Total bilirubin, Week 4 | Total bilirubin, Week 6 | |
GSK1278863, 0.5 mg | -0.99 | 1.65 | -5.01 | -0.3 | -0.2 | -0.5 | 0.1 | -0.2 | 0.9 | -0.3 | -0.5 | 0.4 |
GSK1278863, 2 mg | 10.78 | -1.44 | 7.24 | -0.4 | -0.2 | -0.4 | 0.5 | 0.5 | 0.3 | 0.1 | 0.2 | -0.1 |
GSK1278863, 5 mg | -2.60 | -16.96 | -7.23 | 0.4 | 0.2 | 0.5 | -0.1 | 0.5 | -0.7 | 0.2 | 0.7 | -0.2 |
Placebo | -1.41 | 11.79 | 0.71 | -0.5 | -0.6 | -0.4 | 1.2 | 0.4 | 0.4 | 0.7 | -0.1 | 0.0 |
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
Intervention | MG/MMOL (Mean) | ||
---|---|---|---|
Urine Total Protein/Creatinine ratio, Week 2 | Urine Total Protein/Creatinine ratio, Week 4 | Urine Total Protein/Creatinine ratio, Week 6 | |
GSK1278863, 0.5 mg | -38.83 | 17.43 | -26.73 |
GSK1278863, 2 mg | -115.28 | -99.40 | -72.19 |
GSK1278863, 5 mg | -77.98 | 39.90 | -41.40 |
Placebo | 3.44 | -20.56 | 47.22 |
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).
Intervention | nanogram per millilitre (ng/mL) (Geometric Mean) | |||||
---|---|---|---|---|---|---|
GSK1278863 | M2 | M3 | M4 | M5 | M6 | |
GSK1278863, 0.5 mg | 2.68 | 1.03 | 1.23 | 0.721 | 0.296 | 0.455 |
GSK1278863, 2 mg | 12.8 | 3.83 | 4.45 | 2.74 | 1.08 | 1.74 |
GSK1278863, 5 mg | 35.7 | 10.3 | 11.8 | 7.29 | 2.81 | 4.43 |
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)
Intervention | ng*hour/mL (Geometric Mean) | |||||
---|---|---|---|---|---|---|
GSK1278863 | M2 | M3 | M4 | M5 | M6 | |
GSK1278863, 0.5 mg | 10.3 | 13.0 | 17.8 | 5.54 | 4.64 | 5.34 |
GSK1278863, 2 mg | 51.1 | 51.9 | 67.1 | 22.0 | 17.3 | 21.5 |
GSK1278863, 5 mg | 148 | 140 | 175 | 63.4 | 43.5 | 56.3 |
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
Intervention | Participants (Count of Participants) | ||||
---|---|---|---|---|---|
Decrease/increase of < 0.5 g/dL | Increase of >=0.5 g/dL | Increase of >=1 g/dL | Increase of >=1.5 g/dL | Increase of >=2 g/dL | |
GSK1278863, 0.5 mg | 12 | 4 | 1 | 0 | 0 |
GSK1278863, 2 mg | 12 | 6 | 2 | 0 | 0 |
GSK1278863, 5 mg | 4 | 14 | 9 | 5 | 1 |
Placebo | 16 | 3 | 1 | 0 | 0 |
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
Intervention | Participants (Count of Participants) | ||
---|---|---|---|
<8.0 | >=8.0-<13.0 and >=2.0 decrease | >=8.0-<13.0 and >=2.0 increase | |
GSK1278863, 0.5 mg | 0 | 0 | 1 |
GSK1278863, 2 mg | 1 | 0 | 1 |
GSK1278863, 5 mg | 0 | 0 | 0 |
Placebo | 0 | 1 | 0 |
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
Intervention | Participants (Count of Participants) | |
---|---|---|
Any AEs | Any SAEs | |
GSK1278863, 0.5 mg | 10 | 0 |
GSK1278863, 2 mg | 5 | 2 |
GSK1278863, 5 mg | 6 | 1 |
Placebo | 9 | 1 |
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
Intervention | Percentage of participants (Number) | ||||
---|---|---|---|---|---|
Decrease/increase of < 0.5 g/dL | Increase of >=0.5 g/dL | Increase of >=1 g/dL | Increase of >=1.5 g/dL | Increase of >=2 g/dL | |
GSK1278863, 0.5 mg | 75 | 25 | 6 | 0 | 0 |
GSK1278863, 2 mg | 67 | 33 | 11 | 0 | 0 |
GSK1278863, 5 mg | 22 | 78 | 50 | 28 | 6 |
Placebo | 84 | 16 | 5 | 0 | 0 |
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
Intervention | Units of blood per participant (Median) |
---|---|
Placebo | 1.0 |
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
Intervention | Participants (Count of Participants) |
---|---|
Vadadustat | 1 |
Placebo | 0 |
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
Intervention | Participants (Count of Participants) |
---|---|
Vadadustat | 0 |
Placebo | 0 |
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
Intervention | Participants (Count of Participants) |
---|---|
Vadadustat | 0 |
Placebo | 0 |
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
Intervention | Percentage of participants (Number) |
---|---|
Vadadustat | 54.9 |
Placebo | 10.3 |
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
Intervention | Percentage of participants (Number) |
---|---|
Vadadustat | 33.3 |
Placebo | 7.7 |
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
Intervention | Percentage of participants (Number) |
---|---|
Vadadustat | 41.5 |
Placebo | 19 |
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
Intervention | Percentage of participants (Number) |
---|---|
Vadadustat | 50 |
Placebo | 7.9 |
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
Intervention | Percentage of participants (Number) |
---|---|
Vadadustat | 44.1 |
Placebo | 11.1 |
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
Intervention | Percentage of participants (Number) |
---|---|
Vadadustat | 44.9 |
Placebo | 13.9 |
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
Intervention | Percentage of participants (Number) |
---|---|
Vadadustat | 0 |
Placebo | 1.4 |
"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
Intervention | Percentage of participants (Number) |
---|---|
Vadadustat | 59.6 |
Placebo | 88.9 |
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
Intervention | Weeks (Mean) |
---|---|
Vadadustat | 21.6 |
Placebo | 21.2 |
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
Intervention | Percentage of red blood cells in blood (Mean) | ||||||||
---|---|---|---|---|---|---|---|---|---|
Baseline | Week 2 | Week 4 | Week 6 | Week 8 | Week 12 | Week 16 | Week 19 | Week 20 | |
Placebo | 30.3 | 29.7 | 29.7 | 29.4 | 29.3 | 30.2 | 30.3 | 30.7 | 30.4 |
Vadadustat | 30.4 | 31.2 | 32.4 | 33.1 | 33.2 | 33.5 | 34 | 33.7 | 33.6 |
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
Intervention | g/dL (Mean) | ||||||||
---|---|---|---|---|---|---|---|---|---|
Baseline | Week 2 | Week 4 | Week 6 | Week 8 | Week 12 | Week 16 | Week 19 | Week 20 | |
Placebo | 9.96 | 9.74 | 9.7 | 9.6 | 9.6 | 9.82 | 9.83 | 9.93 | 9.93 |
Vadadustat | 9.94 | 10.02 | 10.35 | 10.61 | 10.66 | 10.87 | 10.79 | 10.74 | 10.88 |
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
Intervention | 10^6 cells per microliter (Mean) | ||||||||
---|---|---|---|---|---|---|---|---|---|
Baseline | Week 2 | Week 4 | Week 6 | Week 8 | Week 12 | Week 16 | Week 19 | Week 20 | |
Placebo | 3.34 | 3.25 | 3.24 | 3.2 | 3.21 | 3.27 | 3.29 | 3.32 | 3.33 |
Vadadustat | 3.38 | 3.39 | 3.51 | 3.57 | 3.61 | 3.68 | 3.69 | 3.67 | 3.7 |
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
Intervention | 10^6 cells per microliter (Mean) | ||||||||
---|---|---|---|---|---|---|---|---|---|
Baseline | Week 2 | Week 4 | Week 6 | Week 8 | Week 12 | Week 16 | Week 19 | Week 20 | |
Placebo | 1.97 | 1.91 | 2.06 | 2.07 | 2.09 | 2 | 1.96 | 1.92 | 2.1 |
Vadadustat | 2.12 | 2.74 | 2.44 | 2.32 | 2.05 | 2.02 | 2.13 | 2.21 | 2.17 |
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
Intervention | Percentage of red blood cells in blood (Mean) | ||||||||
---|---|---|---|---|---|---|---|---|---|
Baseline | Week 2 | Week 4 | Week 6 | Week 8 | Week 12 | Week 16 | Week 19 | Week 20 | |
Placebo | 30.3 | -0.6 | -0.5 | -1 | -1 | -0.3 | -0.1 | 0 | 0.1 |
Vadadustat | 30.4 | 0.8 | 2 | 2.5 | 2.7 | 3 | 3.3 | 3.1 | 3 |
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
Intervention | g/dL (Mean) | ||||||||
---|---|---|---|---|---|---|---|---|---|
Baseline | Week 2 | Week 4 | Week 6 | Week 8 | Week 12 | Week 16 | Week 19 | Week 20 | |
Placebo | 9.96 | -0.22 | -0.25 | -0.41 | -0.4 | -0.2 | -0.18 | -0.16 | -0.08 |
Vadadustat | 9.94 | 0.1 | 0.39 | 0.63 | 0.69 | 0.9 | 0.76 | 0.73 | 0.88 |
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
Intervention | 10^6 cells per microliter (Mean) | ||||||||
---|---|---|---|---|---|---|---|---|---|
Baseline | Week 2 | Week 4 | Week 6 | Week 8 | Week 12 | Week 16 | Week 19 | Week 20 | |
Placebo | 3.34 | -0.08 | -0.08 | -0.14 | -0.14 | -0.08 | -0.06 | -0.04 | -0.01 |
Vadadustat | 3.38 | 0.02 | 0.12 | 0.18 | 0.23 | 0.3 | 0.28 | 0.26 | 0.3 |
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
Intervention | 10^6 cells per microliter (Mean) | ||||||||
---|---|---|---|---|---|---|---|---|---|
Baseline | Week 2 | Week 4 | Week 6 | Week 8 | Week 12 | Week 16 | Week 19 | Week 20 | |
Placebo | 1.97 | -0.07 | 0.06 | 0.08 | 0.06 | 0.02 | -0.03 | -0.05 | 0.12 |
Vadadustat | 2.12 | 0.61 | 0.29 | 0.19 | -0.08 | -0.12 | 0.03 | 0.07 | 0.03 |
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
Intervention | Doses/participants (Mean) |
---|---|
Epoetin Alfa | |
Vadadustat | 1.7 |
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
Intervention | Doses/participants (Mean) | |
---|---|---|
Epoetin Alfa | Darbepoetin Alfa | |
Placebo | 2.8 | 4.3 |
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
Intervention | Participants (Count of Participants) | ||
---|---|---|---|
Hematology | Serum chemistry | Urinalysis | |
Placebo | 0 | 0 | 0 |
Vadadustat | 0 | 1 | 0 |
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
Intervention | Participants (Count of Participants) | |
---|---|---|
TEAEs | Treatment-emergent SAEs | |
Placebo | 29 | 11 |
Vadadustat | 58 | 33 |
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
Intervention | Percentage of participants (Number) | |
---|---|---|
Epoetin Alfa | Darbepoetin Alfa | |
Placebo | 12.5 | 4.2 |
Vadadustat | 4.4 | 0 |
30 reviews available for glycine and Anemia
Article | Year |
---|---|
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.
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.
Topics: Anemia; Ferritins; Glycine; Hemoglobins; Hepcidins; Humans; Iron; Isoquinolines; Renal Insufficiency | 2022 |
The role of roxadustat in chronic kidney disease patients complicated with anemia.
Topics: Anemia; Glycine; Humans; Iron; Isoquinolines; Renal Insufficiency, Chronic | 2023 |
Roxadustat: Do we know all the answers?
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.
Topics: Anemia; Cardiovascular Diseases; Cholesterol, LDL; Glycine; Hematinics; Hemoglobins; Humans; Iron; R | 2023 |
Hypoxia-Inducible Factor Activators in Renal Anemia: Current Clinical Experience.
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.
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.
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.
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.
Topics: Anemia; Barbiturates; Forecasting; Glycine; Humans; Hypoxia-Inducible Factor-Proline Dioxygenases; I | 2021 |
Vadadustat: First Approval.
Topics: Adult; Anemia; Clinical Trials as Topic; Drug Approval; Drug Development; Glycine; History, 21st Cen | 2020 |
Daprodustat: First Approval.
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.
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.
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?
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.
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.
Topics: Anemia; China; Glycine; Humans; Isoquinolines | 2021 |
Roxadustat for the treatment of anemia in patients with chronic kidney diseases: a meta-analysis.
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.
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.
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.
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.
Topics: Anemia; Barbiturates; Glycine; Hemoglobins; Hepcidins; Humans; Hypoxia-Inducible Factor-Proline Diox | 2018 |
Roxadustat: First Global Approval.
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.
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.
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.
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.
Topics: Anemia; Animals; Cobalt; Doping in Sports; Erythropoiesis; GATA Transcription Factors; Glycine; Hema | 2012 |
DETERMINATION OF RED BLOOD CELL LIFE SPAN.
Topics: Anemia; Carbon Isotopes; Chromium Isotopes; Erythrocytes; Glycine; Hemoglobins; Hemoglobins, Abnorma | 1964 |
[ON THE SHUNT HYPERBILIRUBINEMIA].
Topics: Anemia; Anemia, Hypochromic; Anemia, Pernicious; Anemia, Sickle Cell; Bilirubin; Blood Chemical Anal | 1964 |
Endogenous carbon monoxide production.
Topics: Anemia; Animals; Bilirubin; Carbon Isotopes; Carbon Monoxide; Dogs; Erythrocytes; Glycine; Heme; Hem | 1970 |
52 trials available for glycine and Anemia
Article | Year |
---|---|
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).
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.
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.
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.
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.
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.
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.
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.
Topics: Aged; Anemia; Barbiturates; Cardiovascular Diseases; Darbepoetin alfa; Epoetin Alfa; Female; Glycine | 2021 |
Daprodustat for the Treatment of Anemia in Patients Not Undergoing Dialysis.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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).
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.
Topics: Anemia; Darbepoetin alfa; Double-Blind Method; Erythropoietin; Glycine; Hematinics; Hemoglobins; Hum | 2021 |
Safety and Efficacy of Vadadustat for Anemia in Patients Undergoing Dialysis.
Topics: Aged; Anemia; Cardiovascular Diseases; Darbepoetin alfa; Female; Glycine; Hematinics; Hemoglobins; H | 2021 |
Safety and Efficacy of Vadadustat for Anemia in Patients Undergoing Dialysis.
Topics: Aged; Anemia; Cardiovascular Diseases; Darbepoetin alfa; Female; Glycine; Hematinics; Hemoglobins; H | 2021 |
Safety and Efficacy of Vadadustat for Anemia in Patients Undergoing Dialysis.
Topics: Aged; Anemia; Cardiovascular Diseases; Darbepoetin alfa; Female; Glycine; Hematinics; Hemoglobins; H | 2021 |
Safety and Efficacy of Vadadustat for Anemia in Patients Undergoing Dialysis.
Topics: Aged; Anemia; Cardiovascular Diseases; Darbepoetin alfa; Female; Glycine; Hematinics; Hemoglobins; H | 2021 |
Vadadustat in Patients with Anemia and Non-Dialysis-Dependent CKD.
Topics: Administration, Oral; Aged; Anemia; Cardiovascular Diseases; Darbepoetin alfa; Female; Glycine; Hema | 2021 |
Vadadustat in Patients with Anemia and Non-Dialysis-Dependent CKD.
Topics: Administration, Oral; Aged; Anemia; Cardiovascular Diseases; Darbepoetin alfa; Female; Glycine; Hema | 2021 |
Vadadustat in Patients with Anemia and Non-Dialysis-Dependent CKD.
Topics: Administration, Oral; Aged; Anemia; Cardiovascular Diseases; Darbepoetin alfa; Female; Glycine; Hema | 2021 |
Vadadustat in Patients with Anemia and Non-Dialysis-Dependent CKD.
Topics: Administration, Oral; Aged; Anemia; Cardiovascular Diseases; Darbepoetin alfa; Female; Glycine; Hema | 2021 |
Efficacy and safety of daprodustat in Japanese peritoneal dialysis patients.
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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Topics: Acidosis; Adult; Aged; Anemia; Cholesterol; Double-Blind Method; Female; Glycine; Hematinics; Hemogl | 2019 |
Roxadustat Treatment for Anemia in Patients Undergoing Long-Term Dialysis.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Topics: Aged; Anemia; Barbiturates; Erythropoietin; Female; Glycine; Hemoglobins; Humans; Hypoxia-Inducible | 2016 |
Roxadustat (FG-4592): Correction of Anemia in Incident Dialysis Patients.
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.
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.
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.
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.
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.
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.
Topics: Aged; Anemia; Barbiturates; Dose-Response Relationship, Drug; Double-Blind Method; Erythropoietin; F | 2017 |
103 other studies available for glycine and Anemia
Article | Year |
---|---|
Ixazomib, lenalidomide, and dexamethasone combination in "real-world" clinical practice in patients with relapsed/refractory multiple myeloma.
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.
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.
Topics: Anemia; Glycine; Humans; Picolinic Acids; Renal Dialysis; Renal Insufficiency, Chronic | 2021 |
Targeting ineffective hematopoiesis in myelodysplastic syndromes.
Topics: Aged; Anemia; Blood Transfusion; Disease Management; Female; Glycine; Hematinics; Hematopoiesis; Hum | 2022 |
Daprodustat for anaemia in CKD.
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.
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
Topics: Anemia; Animals; Erythropoietin; Glycine; Hypoxia; Isoquinolines; Kidney; Mice; Procollagen-Proline | 2022 |
Therapeutic Effect of Roxadustat on Patients With Posttransplant Anemia.
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)?
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.
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?
Topics: Anemia; Barbiturates; Cell Hypoxia; Glycine; Humans; Hypoxia; Renal Insufficiency, Chronic | 2022 |
Daprodustat prevents cyclosporine-A-mediated anemia and peritubular capillary loss.
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.
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.
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.
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.
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.
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.
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.
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.
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?
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.
Topics: Anemia; Glycine; Humans; Isoquinolines; Peritoneal Dialysis; Prospective Studies; Renal Insufficienc | 2023 |
Roxadustat treatment for erythropoiesis-stimulating agent-hyporesponsive anemia in maintenance hemodialysis patients.
Topics: Anemia; Erythropoiesis; Glycine; Hematinics; Hemoglobins; Humans; Interleukin-6; Iron; Isoquinolines | 2023 |
A new approach to treating renal anaemia.
Topics: Anemia; Glycine; Humans; Isoquinolines; Renal Dialysis | 2019 |
Stabilizing HIF to Ameliorate Anemia.
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.
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.
Topics: Anemia; Animals; Basic Helix-Loop-Helix Transcription Factors; Cell Line; Erythropoiesis; Erythropoi | 2020 |
Roxadustat for Anemia in Patients with Chronic Kidney Disease.
Topics: Anemia; Glycine; Humans; Isoquinolines; Renal Dialysis; Renal Insufficiency, Chronic | 2020 |
Roxadustat for Anemia in Patients with Chronic Kidney Disease.
Topics: Anemia; Glycine; Humans; Isoquinolines; Renal Dialysis; Renal Insufficiency, Chronic | 2020 |
Roxadustat for Anemia in Patients with Chronic Kidney Disease.
Topics: Anemia; Glycine; Humans; Isoquinolines; Renal Dialysis; Renal Insufficiency, Chronic | 2020 |
Roxadustat for Anemia in Patients with Chronic Kidney Disease.
Topics: Anemia; Glycine; Humans; Isoquinolines; Renal Dialysis; Renal Insufficiency, Chronic | 2020 |
Roxadustat for Anemia in Patients with Chronic Kidney Disease. Reply.
Topics: Anemia; Glycine; Humans; Isoquinolines; Renal Insufficiency, Chronic | 2020 |
Roxadustat for Anemia in Patients with Chronic Kidney Disease. Reply.
Topics: Anemia; Glycine; Humans; Isoquinolines; Renal Insufficiency, Chronic | 2020 |
New Approaches for Anemia in MDS.
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.
Topics: Anemia; Darbepoetin alfa; Double-Blind Method; Glycine; Humans; Isoquinolines; Japan; Renal Dialysis | 2020 |
Authors' Reply.
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.
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.
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.
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.
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.
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.
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.
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.
Topics: Anemia; Glycine; Humans; Picolinic Acids; Renal Insufficiency, Chronic | 2021 |
[Roxadustat (Evrenzo
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.
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.
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.
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.
Topics: Anemia; Ficus; Glycine; Humans; Isoquinolines; Renal Insufficiency, Chronic | 2021 |
Hematologic complications in a patient with Glycine soja polyagglutination following fresh frozen plasma transfusion.
Topics: Anemia; Blood Transfusion; Glycine; Hemolysis; Humans; Male; Methicillin-Resistant Staphylococcus au | 2017 |
Roxadustat in the treatment of anaemia in chronic kidney disease.
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.
Topics: Administration, Oral; Anemia; Animals; Cisplatin; Click Chemistry; Erythropoietin; Female; Fluoresce | 2018 |
Roxadustat: another drug that causes pulmonary hypertension? Report of first human case.
Topics: Aged; Anemia; Dose-Response Relationship, Drug; Echocardiography, Doppler; Female; Glycine; Humans; | 2019 |
Roxadustat and Anemia of Chronic Kidney Disease.
Topics: Anemia; Glycine; Humans; Isoquinolines; Renal Dialysis; Renal Insufficiency, Chronic | 2019 |
Deal watch: AstraZeneca bets on FibroGen's anaemia drug.
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.
Topics: Anemia; Drug Industry; Glycine; Humans; Hypoxia-Inducible Factor-Proline Dioxygenases; Isoquinolines | 2013 |
Targeting the hypoxia-sensing pathway in clinical hematology.
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.
Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Acyl Coenzyme A; Amino Acid Metabolism, I | 2015 |
The Dawning of a New Day in CKD Anemia Care?
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.
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.
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.
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.
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.
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.
Topics: Anemia; Animals; Erythrocytes; Glycine; Mice; Neoplasms, Experimental | 1958 |
Glycine in hypochromic microcytic anemia.
Topics: Anemia; Anemia, Hypochromic; Glycine; Humans | 1959 |
Formiminoglutamicaciduria in humans with megaloblastic anemia: diminution by methionine or glycine.
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].
Topics: Alanine; Amino Acids; Anemia; Anemia, Aplastic; Glutamates; Glycine; Humans; Hydroxyproline; Serine; | 1962 |
[Ferroglycine sulfate in the therapy of hypochromic anemia in infants].
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.
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.
Topics: Anemia; Animals; Bone Marrow; Bone Marrow Cells; Carbon Isotopes; Epoetin Alfa; Erythropoietin; Glyc | 1964 |
IDIOPATHIC DYSERYTHROPOIETIC JAUNDICE.
Topics: Anemia; Bile Pigments; Bilirubin; Blood Cell Count; Bone Marrow Examination; Clinical Enzyme Tests; | 1964 |
HEME SYNTHESIS IN NORMAL AND GENETICALLY ANEMIC MICE.
Topics: Anemia; Carbon Isotopes; Erythropoiesis; Genetics; Glycine; Heme; Hemoglobins; Levulinic Acids; Meta | 1964 |
THE EARLY APPEARING BILIRUBIN: EVIDENCE FOR TWO COMPONENTS.
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.
Topics: Anemia; Anemia, Hypochromic; Anemia, Iron-Deficiency; Bile Pigments; Glycine; Heme; Humans; Leukemia | 1964 |
Clinical trials with a new antianemic agent, acidiron.
Topics: Aged; Anemia; Disease; Glycine; Humans; Iron | 1955 |
Erythrocyte destruction in sickle-cell anemia: simultaneous N15-hemin and N15-stercobilin studies.
Topics: Anemia; Anemia, Sickle Cell; Bile Pigments; Erythrocytes; Glycine; Hemin; Humans | 1955 |
Dyserythropoietic anemia and thrombocytopenia due to a novel mutation in GATA-1.
Topics: Amino Acid Substitution; Anemia; Arginine; Child, Preschool; DNA-Binding Proteins; Erythroid-Specifi | 2005 |
Carbon monoxide production associated with ineffective erythropoiesis.
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.
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)].
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.
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.
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].
Topics: Acetates; Amino Acids; Anemia; Animals; Asparagine; Blood Protein Electrophoresis; gamma-Globulins; | 1967 |
Orthohydroxyhippuric (salicyluric) acid--its physiologic and clinical significance.
Topics: Anemia; Animals; Cattle; Dihydroxyphenylalanine; Dogs; Down Syndrome; Fever; Glycine; Humans; Hypert | 1974 |
Urea inhibition of lactate dehydrogenase. A convenient routine procedure.
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.
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].
Topics: Acid-Base Equilibrium; Anemia; Animals; Bicarbonates; Blood Proteins; Bone Marrow; Carbon Dioxide; E | 1973 |
Hemoglobin G Hsi-Tsou: 79 Asp to Gly.
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].
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.
Topics: Alanine; Anemia; Anemia, Sideroblastic; Blood Cell Count; Child, Preschool; Chromatography; Chromato | 1971 |
Detection of an inhibitor of hemoglobin synthesis in rat plasma.
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.
Topics: Anemia; Anemia, Hypochromic; Animals; Carbon Isotopes; Carbon Monoxide; Erythrocyte Aging; Erythrocy | 1970 |
Glycine decarboxylation as an assay for erythrocyte aminolevulinic acid synthesis.
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].
Topics: Anemia; Animals; Animals, Newborn; Cattle; Cattle Diseases; Glycine; Iron; Swine; Swine Diseases | 1967 |
Marrow defect in idiopathic ineffective erythropoiesis.
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.
Topics: Acetates; Amino Acids; Anemia; Animals; Dogs; Erythropoietin; Glycine; Hemorrhage; Iron; Kidney; Lev | 1968 |
Heme biosynthesis in copper deficient swine.
Topics: Amino Acids; Anemia; Animals; Carbon Isotopes; Copper; Deficiency Diseases; Erythrocytes; Globins; G | 1968 |
Uptake of labelled amino acids into human erythrocytes in disease.
Topics: Acute Disease; Alanine; Amino Acids; Anemia; Bronchitis; Bronchopneumonia; Carbon Isotopes; Erythroc | 1968 |
Liquid-scintillation radioassay of 14C-labeled hemoglobin in a thixotropic gel.
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.
Topics: Anemia; Animals; Bile; Bile Acids and Salts; Cholesterol; Chromatography, Thin Layer; Colorimetry; D | 1969 |
Heme and porphyrin synthesis by porphyric bovine erythrocytes.
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].
Topics: Anemia; Anemia, Macrocytic; Glycine; Humans; Lead Poisoning; Methemoglobinemia; Porphyrias; Porphyri | 1965 |