Dataset Information

Efficacy and safety of daprodustat in Japanese peritoneal dialysis patients.

ABSTRACT: Daprodustat is a hypoxia-inducible factor-prolyl hydroxylase inhibitor for the treatment of anemia of chronic kidney disease. This phase 3 study evaluated the efficacy and safety of daprodustat in an uncontrolled cohort of 56 Japanese peritoneal dialysis patients with anemia over 52 weeks. Subjects received daprodustat 4 mg orally once daily for 4 weeks and the dose was subsequently adjusted every 4 weeks. Mean baseline hemoglobin was 10.9 g/dL (95% CI 10.59, 11.12). Mean hemoglobin reached the target range (11.0-13.0 g/dL) at week 12 and was maintained until week 52. Mean hemoglobin during weeks 40-52 was 12.1 g/dL (95% CI 12.0, 12.2). The most frequent adverse events included nasopharyngitis (29%), catheter-site infection (18%), peritonitis (16%), diarrhea (14%), and nausea (11%). No deaths were reported. Once-daily oral daprodustat treatment was generally well tolerated and mean hemoglobin was achieved and maintained within the target range in Japanese peritoneal dialysis participants.

SUBMITTER: Kanai H

PROVIDER: S-EPMC9290017 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Efficacy and safety of daprodustat in Japanese peritoneal dialysis patients.

Kanai Hidetoshi H Nangaku Masaomi M Nagai Reiko R Okuda Nobuhiko N Kurata Kyo K Nagakubo Takashi T Endo Yukihiro Y Cobitz Alexander A

Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy 20210525 6

Daprodustat is a hypoxia-inducible factor-prolyl hydroxylase inhibitor for the treatment of anemia of chronic kidney disease. This phase 3 study evaluated the efficacy and safety of daprodustat in an uncontrolled cohort of 56 Japanese peritoneal dialysis patients with anemia over 52 weeks. Subjects received daprodustat 4 mg orally once daily for 4 weeks and the dose was subsequently adjusted every 4 weeks. Mean baseline hemoglobin was 10.9 g/dL (95% CI 10.59, 11.12). Mean hemoglobin reached the ...[more]

PMID: 33964183

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Project description:ImportanceDaprodustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, is being evaluated as an oral alternative to conventional erythropoiesis-stimulating agent (ESA) therapy. Few studies of anemia treatment in an incident dialysis (ID) population have been reported.ObjectiveTo evaluate the efficacy and safety of daprodustat vs darbepoetin alfa in treating anemia of chronic kidney disease in ID patients.Design, setting, and participantsThis prospective, randomized, open-label clinical trial was conducted from May 11, 2017, through September 24, 2020, in 90 centers across 14 countries. Patients with advanced CKD were eligible if they planned to start dialysis within 6 weeks from screening or had started and received hemodialysis (HD) or peritoneal dialysis (PD) within 90 days before randomization, had a screening hemoglobin (Hb) concentration of 8.0 to 10.5 g/dL (to convert to grams per liter, multiply by 10) and a randomization Hb of 8.0 to 11.0 g/dL, were ESA-naive or had received limited ESA treatment, and were iron-replete.InterventionsRandomized 1:1 to daprodustat or darbepoetin alfa.Main outcomes and measuresThe primary analysis in the intent-to-treat population evaluated the mean change in Hb concentration from baseline to evaluation period (weeks 28-52) to assess noninferiority of daprodustat vs darbepoetin alfa (noninferiority margin, -0.75 g/dL). The mean monthly intravenous (IV) iron dose from baseline to week 52 was the principal secondary end point. Rates of treatment-emergent and serious adverse events (AEs) were also compared between treatment groups to assess safety and tolerability.ResultsA total of 312 patients (median [IQR] age, 55 [45-65] years; 194 [62%] male) were randomized to either daprodustat (157 patients; median [IQR] age, 52.0 [45-63] years; 96 [61%] male) or darbepoetin alfa (155 patients; median [IQR] age, 56.0 [45-67] years; 98 [63%] male); 306 patients (98%) completed the trial. The mean (SD) Hb concentration during the evaluation period was 10.5 (1.0) g/dL for the daprodustat and 10.6 (0.9) g/dL for the darbepoetin alfa group, with an adjusted mean treatment difference of -0.10 g/dL (95% CI, -0.34 to 0.14 g/dL), indicating noninferiority. There was a reduction in mean monthly IV iron use from baseline to week 52 in both treatment groups; however, daprodustat was not superior compared with darbepoetin alfa in reducing monthly IV iron use (adjusted mean treatment difference, 19.4 mg [95% CI, -11.0 to 49.9 mg]). Adverse event rates were 76% for daprodustat vs 72% for darbepoetin alfa.Conclusions and relevanceThis randomized clinical trial found that daprodustat was noninferior to darbepoetin alfa in treating anemia of CKD and may represent a potential oral alternative to a conventional ESA in the ID population.Trial registrationClinicalTrials.gov Identifier: NCT03029208.

Project description:Background and objectivesDaprodustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis and regulates genes related to iron metabolism. The efficacy (noninferiority) and safety of daprodustat compared with standard therapy (darbepoetin alfa) was evaluated.Design, setting, participants, & measurementsThis was a randomized, phase 3, double-blind, active-control study in Japanese patients receiving hemodialysis with anemia of CKD. Participants' treatment was switched from current erythropoiesis-stimulating agents (ESAs) to daprodustat 4 mg once daily or darbepoetin alfa 10-60 μg once weekly (on the basis of the prestudy ESA dose). Dose was adjusted every 4 weeks for daprodustat or every 2 weeks for darbepoetin alfa, according to a protocol-specified algorithm. The primary end point was mean hemoglobin during weeks 40-52 in the intent-to-treat population.ResultsOf 332 participants screened, 271 participants were randomized (safety evaluation: 271 participants; efficacy evaluation: 267 intent-to-treat population). The mean hemoglobin during weeks 40-52 were maintained within the target range in both groups (10.9 g/dl [95% confidence interval (95% CI), 10.8 to 11.0] for daprodustat, and 10.8 g/dl [95% CI, 10.7 to 11.0] for darbepoetin alfa). Daprodustat was noninferior to darbepoetin alfa, as the lower bound of the confidence interval for the treatment difference (0.1 g/dl; 95% CI, -0.1 to 0.2 g/dl) was greater than the noninferiority criterion of -1.0 g/dl. For most participants, hemoglobin was maintained within the target range (10.0-12.0 g/dl) during weeks 40-52 (88% daprodustat; 90% darbepoetin alfa). Geometric mean hepcidin levels decreased more at week 52 with daprodustat (-37%; 95% CI, -49 to -23) than with darbepoetin alfa (-20%; 95% CI, -36 to -1), and an increase in total iron-binding capacity was observed in the daprodustat group. Frequency of adverse events were generally similar between daprodustat and darbepoetin alfa.ConclusionsOral daprodustat was noninferior to darbepoetin alfa as measured by mean hemoglobin over weeks 40-52 in Japanese patients receiving hemodialysis switched from ESAs.Clinical trial registry name and registration number201754, Clinicaltrials.gov, NCT02969655.

Dataset Information

Efficacy and safety of daprodustat in Japanese peritoneal dialysis patients.

Publications

Efficacy and safety of daprodustat in Japanese peritoneal dialysis patients.

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