scholarly journals P1866TO INVESTIGATE THE EFFICACY AND SAFETY OF MOLIDUSTAT IN NON-DIALYSIS PATIENTS WITH RENAL ANEMIA WHO ARE NOT TREATED WITH ERYTHROPOIESIS-STIMULATING AGENTS: MIYABI ND-C

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Hiroyasu Yamamoto ◽  
Megumi Taguchi ◽  
Kiyoshi Nobori ◽  
Yoshimi Matsuda ◽  
Kazuma Iekushi ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Anemia ◽  
Target Range ◽  
Primary Efficacy ◽  
Efficacy And Safety ◽  
Dialysis Patients ◽  
Evaluation Period ◽  
Starting Dose ◽  
The Mean

Abstract Background and Aims Anemia is a common complication of chronic kidney disease (CKD). A hypoxia-inducible factor prolyl-hydroxylase (HF-PH) inhibitor is developing as a new treatment option of renal anemia. Molidustat, an oral HIF-PH inhibitor, stimulated endogenous production of erythropoietin and was well tolerated in phase IIb clinical trials. The phase III program entitled MolIdustat once dailY improves renal Anemia By Inducing EPO (MIYABI) was conducted in Japan. Method MIYABI Non-Dialysis-Correction (ND-C) of Hb study (up to 52 weeks, randomized, darbepoetin-controlled, open-label) was conducted to investigate the efficacy and safety of molidustat (MO) in non-dialysis patients with renal anemia who are not treated with erythropoiesis-stimulating agents. Study drug doses were titrated regularly with the aim of correcting and maintaining the patients’ Hb values between the target range (11.0-13.0 g/dL). The primary efficacy variables were the mean Hb values during the evaluation period (30-36 weeks) and its change from baseline to demonstrate the non-inferiority of MO to darbepoetin alfa (DA) using a non-inferiority margin of 1.0g/dL. Safety variables included adverse events (AE). Prespecified primary analysis results up to 36 weeks are presented here. Results 82 patients were treated with a starting dose of 25mg of MO and 79 patients were treated with a starting dose of 30μg/2weeks of DA. The mean of baseline Hb values were 9.84 g/dL and 10.00 g/dL in the MO and DA group, respectively. MO increased the mean Hb values (rate of rise from baseline in Hb values at the first dose change up to 8 weeks: mean: 0.086 g/dL/week (95%CI; 0.047, 0.126)) and achieved the lower limit of target range at 12 weeks. MO maintained Hb values after 12 weeks, and for the mean Hb values during the evaluation period, the mean was 11.28 g/dL (95%CI; 11.07, 11.50). As the primary efficacy variables (the changes from baseline of mean Hb values during the evaluation period), the means were 1.45 g/dL (95%CI; 1.21, 1.68) and 1.70 g/dL (95%CI; 1.47, 1.92) in the MO and DA group, respectively. The LS mean difference was -0.38 (95%CI; -0.67, -0.08), therefore the non-inferiority of MO to DA was established. The mean (SD) doses during the study period were 45.33 (28.88) mg/day of MO and 17.87 (12.49) μg/week of DA. The most common maximum dose of MO was 25 mg (26 patients, 31.7%) followed by 75 mg (16 patients, 19.5%) and 50mg (14 patients, 17.1%). AEs were experienced in 84.1% of patients in the MO group and in 91.1% of patients in the DA group up to 36 weeks. The most common AEs occurred ≥ 5% of patients in any group were nasopharyngitis (20.7% and 25.3%, respectively) and worsening of chronic kidney disease (13.4% and 6.3%, respectively). Conclusion Correction and Maintenance effect of MO on the Hb values was investigated and the non-inferiority of MO to DA was established in non-dialysis patients with untreated anemia. The MO showed no new safety concern but further longitudinal investigation will be needed.

scholarly journals P1868TO INVESTIGATE THE EFFICACY AND SAFETY OF MOLIDUSTAT IN NON-DIALYSIS PATIENTS WITH RENAL ANEMIA WHO ARE TREATED WITH ERYTHROPOIESIS-STIMULATING AGENTS: MIYABI ND-M

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Hiroyasu Yamamoto ◽  
Megumi Taguchi ◽  
Kiyoshi Nobori ◽  
Yoshimi Matsuda ◽  
Kazuma Iekushi ◽  
...  
Keyword(s):  
Safety Concern ◽  
Renal Anemia ◽  
Phase Iii ◽  
Target Range ◽  
Primary Efficacy ◽  
Efficacy And Safety ◽  
Dialysis Patients ◽  
Primary Analysis ◽  
Evaluation Period ◽  
The Mean

Abstract Background and Aims Treatment with subcutaneous erythropoiesis-stimulating agent (ESA) is the standard of care for renal anemia in non-dialysis patients. A hypoxia-inducible factor prolyl-hydroxylase (HF-PH) inhibitor is an oral medication and might be a new treatment option of renal anemia. Molidustat mimics the physiological response to hypoxia, thereby stimulating endogenous EPO production by the kidneys. The phase III program entitled MolIdustat once dailY improves renal Anemia By Inducing EPO (MIYABI) was conducted in Japan. Method MIYABI Non-Dialysis- Maintenance (ND-M) of Hb study (up to 52 weeks, randomized, darbepoetin-controlled, open-label) was conducted to investigate the efficacy and safety of molidustat (MO) in non-dialysis patients with renal anemia who are treated with ESAs. A starting dose was in accordance with previous ESA dose and study drug doses were titrated regularly with the aim of maintaining the patients’ Hb values between the target range (11.0-13.0 g/dL). The primary efficacy variables were the mean Hb values during the evaluation period (30-36 weeks) and its change from baseline to demonstrate the non-inferiority of MO to darbepoetin alfa (DA) using a non-inferiority margin of 1.0 g/dL. Safety variables included adverse events. Prespecified primary analysis results up to 36 weeks are presented here. Results 82 patients were treated with MO, starting doses were 25 mg for 27 patients and 50 mg in 55 patients. 82 patients were treated with DA, starting doses were in accordance with previous ESA dose and interval. The mean of baseline Hb values were 11.31 g/dL and 11.27 g/dL in the MO and DA group, respectively. For the mean Hb values during the evaluation period in MO, the mean was 11.67 g/dL (95%CI; 11.48, 11.85) and the mean Hb values of 66 patients (80.5%) were within the target range. As the primary efficacy variables (the changes from baseline of mean Hb values during the evaluation period), the means were 0.35 g/dL (95%CI; 0.12, 0.58) and 0.26 g/dL (95%CI; 0.04, 0.48) in the MO and DA group, respectively. The LS mean difference was 0.13 (95%CI; -0.15, 0.40), therefore the non-inferiority of MO to DA was established. The mean (SD) doses during the study period were 52.16 (32.58) mg/day of MO and 21.33 (12.33) μg/week of DA. AEs were experienced in 87.8% of patients in the MO group and 89.0% of patients in the DA group up to 36 weeks. The most common AEs occurred ≥ 5% of patients in any group were nasopharyngitis (29.3% and 30.5%, respectively) and worsening of chronic kidney disease (12.2% and 7.3%, respectively). Conclusion Maintenance effect of MO on the Hb values was investigated and the non-inferiority of MO to DA was established in non-dialysis patients with anemia treated with ESAs. The MO showed no new safety concern but further longitudinal investigation will be needed.

scholarly journals A Phase 3 Study of Enarodustat (JTZ-951) in Japanese Hemodialysis Patients for Treatment of Anemia in Chronic Kidney Disease: SYMPHONY HD Study

2021 ◽  
pp. 1-9
Author(s):  
Tadao Akizawa ◽  
Masaomi Nangaku ◽  
Takuhiro Yamaguchi ◽  
Ryosuke Koretomo ◽  
Kazuo Maeda ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Binding Capacity ◽  
Hypoxia Inducible Factor ◽  
Intravenous Iron ◽  
Target Range ◽  
Maintenance Hemodialysis ◽  
Phase 3 ◽  
Evaluation Period ◽  
The Mean

<b><i>Introduction:</i></b> Enarodustat (JTZ-951) is a new oral hypoxia-inducible factor-prolyl hydroxylase inhibitor for the treatment of anemia in chronic kidney disease (CKD). We conducted a phase 3 study to compare the efficacy and safety of enarodustat with darbepoetin alfa (DA) in Japanese anemic patients with CKD receiving maintenance hemodialysis. <b><i>Methods:</i></b> Subjects receiving maintenance hemodialysis were randomly assigned at a 1:1 ratio to receive oral enarodustat once daily or intravenous DA every week for 24 weeks with dose adjustment every 4 weeks to maintain hemoglobin (Hb) within a target range (≥10.0 to &#x3c;12.0 g/dL). The primary efficacy endpoint was difference in mean Hb level between arms during the evaluation period defined as weeks 20–24 (noninferiority margin: −1.0 g/dL). Intravenous iron preparations were prohibited during the screening period and during weeks 0–4. <b><i>Results:</i></b> The mean Hb level of each arm during the evaluation period was 10.73 g/dL (95% confidence interval [CI]: 10.56, 10.91) in the enarodustat arm and 10.85 g/dL (95% CI: 10.72, 10.98) in the DA arm. The difference in the mean Hb level between arms was −0.12 g/dL (95% CI: −0.33, 0.10), confirming the noninferiority of enarodustat to DA. The mean Hb level of each arm was maintained within the target range during the treatment period. Increased total iron-binding capacity and serum iron and decreased hepcidin were observed through week 4 in the enarodustat arm albeit after switching from erythropoiesis-stimulating agents. No apparent safety concerns of enarodustat were observed compared with DA. <b><i>Discussion/Conclusion:</i></b> Enarodustat was noninferior to DA for the treatment of anemia in CKD patients receiving maintenance hemodialysis and was generally well tolerated over 24 weeks.

scholarly journals Efficacy and Safety of Molidustat for Anemia in ESA-Naive Nondialysis Patients: A Randomized, Phase 3 Trial

2021 ◽  
pp. 1-13
Author(s):  
Hiroyasu Yamamoto ◽  
Kiyoshi Nobori ◽  
Yoshimi Matsuda ◽  
Yasuhiro Hayashi ◽  
Takanori Hayasaki ◽  
...  
Keyword(s):  
Japanese Patients ◽  
Renal Anemia ◽  
Target Range ◽  
Efficacy And Safety ◽  
Open Label ◽  
Phase 3 ◽  
Once Daily ◽  
Evaluation Period ◽  
The Mean ◽  
Change In Mean

<b><i>Introduction:</i></b> Molidustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that predominantly induces renal production of erythropoietin (EPO). Molidustat was evaluated for the treatment of anemia associated with chronic kidney disease (CKD) in the “Molidustat Once Daily Improves Renal Anemia by Inducing EPO” (MIYABI) program, which comprises 5 phase 3 clinical trials. The present MIYABI Non-Dialysis Correction (ND-C) study investigated the efficacy and safety of molidustat in Japanese patients with renal anemia who were not undergoing dialysis and were not receiving erythropoiesis-stimulating agent (ESA) treatment. <b><i>Methods:</i></b> This was a 52-week, randomized (1:1), open-label, active-control, parallel-group, multicenter, phase 3 study in Japanese patients with renal anemia associated with CKD (stages 3–5). Molidustat or the ESA darbepoetin alfa (hereinafter referred to as darbepoetin) were initiated at 25 mg once daily or 30 μg every 2 weeks, respectively, and doses were regularly titrated to correct and to maintain hemoglobin (Hb) levels in the target range of ≥11.0 g/dL and &#x3c;13.0 g/dL. The primary efficacy outcome was the mean Hb level and its change from baseline during the evaluation period (weeks 30–36). The safety outcomes included evaluation of all adverse events. <b><i>Results:</i></b> In total, 162 patients were randomized to receive molidustat (<i>n</i> = 82) or darbepoetin (<i>n</i> = 80). Baseline characteristics were generally well balanced between treatment groups. The mean (standard deviation) Hb levels at baseline were 9.84 (0.64) g/dL for molidustat and 10.00 (0.61) g/dL for darbepoetin. The mean (95% confidence interval [CI]) for mean Hb levels during the evaluation period for molidustat (11.28 [11.07, 11.50] g/dL) and darbepoetin (11.70 [11.50, 11.90] g/dL) was within the target range. Based on a noninferiority margin of 1.0 g/dL, molidustat was noninferior to darbepoetin in the change in mean Hb level during the evaluation period from baseline; the least-squares mean (95% CI) difference (molidustat-darbepoetin) was −0.38 (−0.67, −0.08) g/dL. The proportion of patients who reported at least 1 treatment-emergent adverse event (TEAE) was 93.9% for molidustat and 93.7% for darbepoetin. Most TEAEs were mild (54.9% for molidustat and 63.3% for darbepoetin) or moderate (22.0% for molidustat and 22.8% for darbepoetin) in intensity. There were 3 deaths in the molidustat group and 1 in the darbepoetin group. <b><i>Discussion/Conclusion:</i></b> In the MIYABI ND-C study, molidustat appeared to be an efficacious and generally well-tolerated alternative to darbepoetin for the treatment of renal anemia in Japanese patients who were not undergoing dialysis and were not receiving ESA treatment.

scholarly journals EFFICACY AND SAFETY OF IRON (III)–HYDROXIDE SUCROSE COMPLEX IN CORRECTION OF ANEMIA STAGE 5D CHRONIC KIDNEYDISEASE HEMODIALYSIS PATIENTS NOT TREATED BY ERYTHROPOIESIS–STIMULATING AGENTS (PROSPECTIVEANALYSIS)

2014 ◽  
pp. 64-69
Author(s):  
І. О. Dudar ◽  
I. I. Gonchar ◽  
І. М. Shifris ◽  
Е. К. Krasjuk ◽  
V. М. Savchuk ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Iron Deficiency ◽  
Adverse Events ◽  
Transferrin Saturation ◽  
Hemodialysis Patients ◽  
Renal Anemia ◽  
Efficacy And Safety ◽  
Dialysis Patients ◽  
Regular Hemodialysis

The aim of study was to evaluat the efficacy and safety ofSUFER® (iron (III) sucrose complex) in correction of anemia stage 5D chronic kidney disease hemodialysis patients. Methods. This study included thirty patients undergoing regular hemodialysis (mean age 48,81±3,24 years, mean duration of dialysis 30,43±9,25 months) with renal anemia and iron deficiency. All patients were treated with SUFER® intravenously 200 mg three times a week. Correction dose was determined according to the manufacturer’s recommendations. Results. Mean level offerritin was significantly increased from 125,15 ± 21,46 ng / ml to 375,56 ± 64,12 ng / ml (p <0,001), transferrin saturation – from 17,48 ± 2,71% to 38,21 ± 4,90 ng / ml (p <0,001). 23 (76.67%) patients achieved target levels offerritin and transferrin, 12 (40% ) adverse events. Conclusions. SUFER® is effective and safety drug in dialysis patients.

scholarly journals Peginesatide to Manage Anemia in Chronic Kidney Disease Patients on Peritoneal Dialysis

2015 ◽  
Vol 35 (4) ◽  
pp. 481-489 ◽  
Author(s):  
Raja Zabaneh ◽  
Simon D. Roger ◽  
Mohamed El-Shahawy ◽  
Michael Roppolo ◽  
Grant Runyan ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Adverse Event ◽  
Peritoneal Dialysis ◽  
Kidney Disease ◽  
Common Adverse Event ◽  
Erythropoietin Receptor ◽  
Open Label ◽  
Evaluation Period ◽  
Red Blood Cell Transfusions ◽  
The Mean

♦BackgroundPeginesatide is a novel, synthetic, peptide-based pegylated erythropoiesis-stimulating agent that is designed specifically to stimulate the erythropoietin receptor. The purpose of the present study was to assess, for the first time, the efficacy and safety of peginesatide in chronic kidney disease (CKD) patients receiving peritoneal dialysis (PD) and previously on epoetin treatment.♦MethodsIn this open-label multicenter study, 59 PD patients with CKD were converted from epoetin (alfa or beta) to once-monthly peginesatide. Doses were titrated to maintain hemoglobin levels between 10 g/dL and 12 g/dL during the 25 weeks of the study. The primary endpoint was change from baseline in mean hemoglobin values during the evaluation period (weeks 20 – 25).♦ResultsThe mean hemoglobin value during the evaluation period was 11.3 ± 1.07 g/dL, and the mean change from baseline was 0.10 ± 1.15 g/dL (95% confidence limits: –0.24, 0.44 g/dL). During the evaluation period, most patients maintained hemoglobin levels between 10 g/dL and 12 g/dL (63.0%) and within ±1.0 g/dL of baseline (60.9%). The median weekly epoetin dose at baseline was 96.0 U/kg, and the median starting peginesatide dose was 0.047 mg/kg. Forty-three patients (72.9%) completed the study. Six patients (10.2%) received red blood cell transfusions. The observed adverse event profile was consistent with underlying conditions in the PD patient population. The most common adverse event was peritonitis (20.3%), a complication commonly associated with PD. Four deaths occurred during the study (2 related to septic shock, and 1 each to myocardial ischemia and myasthenia gravis).♦ConclusionsIn this study, once-monthly peginesatide maintained hemoglobin levels in PD patients after conversion from epoetin.

SP344THE EFFICACY AND SAFETY OF BCD-131 IN TREATMENT OF RENAL ANEMIA IN CHRONIC KIDNEY DISEASE

2019 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Maria Morozova ◽  
Daria Bolsun ◽  
Arina Zinkina-Orihan ◽  
Yulia Linkova ◽  
Roman Ivanov
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Anemia ◽  
Efficacy And Safety

scholarly journals Long-Term Efficacy and Safety of Molidustat for Anemia in Chronic Kidney Disease: DIALOGUE Extension Studies

2019 ◽  
Vol 49 (4) ◽  
pp. 271-280 ◽  
Author(s):  
Tadao Akizawa ◽  
Iain C. Macdougall ◽  
Jeffrey S. Berns ◽  
Thomas Bernhardt ◽  
Gerald Staedtler ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Hypoxia Inducible Factor ◽  
Efficacy And Safety ◽  
Open Label ◽  
Multicenter Studies ◽  
Parallel Group ◽  
The Mean ◽  
Term Management

Background: Molidustat, a novel hypoxia-inducible factor-prolyl hydroxylase inhibitor, is being investigated for the treatment of anemia associated with chronic kidney disease (CKD). The efficacy and safety of molidustat were recently evaluated in three 16-week phase 2b studies. Here, we report the results of two long-term extension studies of molidustat. Methods: Both studies were parallel-group, open-label, multicenter studies of ≤36 months’ duration, in patients with anemia due to CKD, and included an erythropoiesis-stimulating agent as active control. One study enrolled patients not receiving dialysis (n = 164), and the other enrolled patients receiving hemodialysis (n = 88). The primary efficacy variable for both studies was change in blood hemoglobin (Hb) level from baseline to each post-baseline visit, and safety outcomes included adverse events (AEs). Results: In patients not on dialysis, the mean ± SD Hb concentrations at baseline were 11.28 ± 0.55 g/dL for molidustat and 11.08 ± 0.51 g/dL for darbepoetin. The mean ± SD blood Hb concentrations throughout the study (defined as mean of each patient’s overall study Hb levels) were 11.10 ± 0.508 and 10.98 ± 0.571 g/dL in patients treated with molidustat and darbepoetin, respectively. Similar proportions of patients reported at least one AE in the molidustat (85.6%) and darbepoetin (85.7%) groups. In patients on dialysis, mean ± SD Hb levels at baseline were 10.40 ± 0.70 and 10.52 ± 0.53 g/dL in the molidustat and epoetin groups, respectively. The mean ± SD blood Hb concentrations during the study were 10.37 ± 0.56 g/dL in the molidustat group and 10.52 ± 0.47 g/dL in the epoetin group. Proportions of patients who reported at least one AE were 91.2% in the molidustat group and 93.3% in the epoetin group. Conclusions: Molidustat was well tolerated for up to 36 months and appears to be an effective alternative to darbepoetin and epoetin in the long-term management of anemia associated with CKD.

MO889COST OF ILLNESS OF CHRONIC KIDNEY DISEASE IN LEBANON: FROM THE SOCIETAL PERSPECTIVE

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Mabel Aoun ◽  
Elie Helou ◽  
Ghassan Sleilaty ◽  
Dania Nehme Chelala
Keyword(s):  
Chronic Kidney Disease ◽  
Peritoneal Dialysis ◽  
Kidney Disease ◽  
Kidney Transplant ◽  
Cost Of Illness ◽  
Medical Costs ◽  
Health Policies ◽  
Dialysis Patients ◽  
Transplant Patients ◽  
The Mean

Abstract Background and Aims Chronic Kidney Disease (CKD) is the 12th leading cause of death worldwide and a high societal burden. Cost-of-illness studies of CKD are scarce in developing countries. Identifying factors associated with the highest cost can help decision makers adapt health policies and sustain kidney health services, especially in limited resources' settings. This study aims to estimate the cost of illness of CKD in Lebanon, from the early stages of CKD until dialysis and kidney transplant and identify cost components related to the highest financial burden. Method This is a cross-sectional study of all CKD patients who presented to two nephrology clinics during the first two weeks of November 2020. The sample size required for the study to be representative was 154 patients. The medical and administrative records were reviewed to collect the demographics and CKD characteristics of patients as well as the direct medical costs (medications, diagnostic tests, hospitalizations, inpatient care, outpatient care), direct non-medical costs (transportation) and indirect costs (productivity losses) for one year between 1st June 2019 and 1st June 2020. Kruskal Wallis test was used to compare the costs between different CKD stages and categories. The study got the approval of the ethics committee of Saint-Joseph University. Results The sample included a total of 160 patients: 102 non-dialysis CKD patients, 40 hemodialysis, 8 peritoneal dialysis and 10 kidney transplant patients. Their mean age was 66.74 ±15.36 years, 57.5% were males and 42.5% diabetics. The mean number of daily medications was 8.75 ±3.38, mean frequency of blood tests per year 6.86 ±6.4 and mean number of hospital admissions per year 0.79 ±1.43. The mean total annual cost of CKD per patient across all categories was assessed at 19,900,164 ±27,893,591 Lebanese Pounds (1 $USD= 1515 LP in 2019). Statistical analysis showed a higher total cost among dialysis patients compared to other categories of CKD (p&lt;0.001), higher cost of medications in transplant patients (p&lt;0.001) and higher cost of technique modality in peritoneal dialysis patients (p&lt;0.001). These differences are summarized in Figure 1. Conclusion Similar to previous studies from other countries, this cost of illness analysis showed a high burden of dialysis annual costs compared to non-dialysis CKD and transplant patients. It revealed as well a great burden of medications' costs at the level of dialysis and transplantation. It is thus crucial that governments and health policies in low- and middle-income countries target interventions that prevent end-stage kidney disease, reduce medications' costs and most of all create programs that encourage kidney transplantation.

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