Publications by authors named "Alexander Cobitz"
Article Synopsis
- - The ASCEND-NHQ trial investigated the effectiveness of daprodustat in increasing hemoglobin levels and improving fatigue in adults with chronic kidney disease (CKD) stages 3-5, comparing it to a placebo over 28 weeks.
- - Results showed that participants taking daprodustat experienced a significant mean change in hemoglobin (1.58 g/dl) compared to the placebo group (0.19 g/dl), with 77% of daprodustat users achieving a 1 g/dl increase.
- - Additionally, the SF-36 Vitality score (which measures fatigue) improved more for those on daprodustat (7.3 points) than those on placebo (1.
Article Synopsis
- Hyporesponsiveness to erythropoiesis-stimulating agents (ESAs) affects 10-15% of chronic dialysis patients, and a study compared the investigational drug daprodustat with standard ESA treatment to understand the characteristics and predictors of this issue.
- The study recruited 2,964 ESA-treated chronic dialysis patients and defined ESA hyporesponsiveness using specific criteria, finding that about 12% of participants were hyporesponsive.
- Key predictors included geographic region (especially Latin America), lower body mass index, younger age, and certain blood levels, along with additional factors like female sex and a history of heart failure; notably, the geographic finding suggests a need for further research.
Analysis of on-treatment cancer safety events with daprodustat versus conventional erythropoiesis-stimulating agents-post hoc analyses of the ASCEND-ND and ASCEND-D trials.
Ajay K Singh Finnian R McCausland Brian L Claggett Christoph Wanner Andrzej Wiecek Alexander R Cobitz
Nephrol Dial Transplant
July 2023
Article Synopsis
- The ASCEND-ND trial raised concerns about daprodustat having a higher risk of cancer-related adverse events compared to darbepoetin in patients with anemia due to chronic kidney disease (CKD), but this was not seen in the dialysis-focused ASCEND-D trial.* -
- Both trials involved randomizing patients to receive either daprodustat or various types of erythropoiesis-stimulating agents (ESAs), with different dosing schedules, and used statistical models to analyze the safety of the treatments.* -
- The findings indicated that the perceived increased risk of cancer-related adverse events for daprodustat in ASCEND-ND may have been biased due to under-counting of events in the darbepo
Article Synopsis
- The study compared the effectiveness of daprodustat, a new treatment for anemia in chronic kidney disease (CKD) patients on hemodialysis, with the standard treatment, epoetin alfa, in a noninferiority trial over 52 weeks.
- Results showed that daprodustat was as effective as epoetin in improving hemoglobin levels, with 80% of daprodustat patients responding adequately, compared to 64% with epoetin.
- Both treatments had similar rates of adverse events and impacts on blood pressure, while there was no significant difference in monthly intravenous iron use between the two groups.
The coronavirus disease 2019 pandemic has had an unprecedented effect on health and health care and posed challenges to the conduct of clinical trials.Targeted mitigating strategies, on the basis of early and continued data collection from site surveys, limited disruption to the ASCEND trials.Flexibly allowing hemoglobin assessment at local laboratories to inform randomized treatment dosing was key to limiting the discontinuation of treatment.
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- Daprodustat is being tested as an oral alternative to traditional ESAs for treating anemia in patients with chronic kidney disease starting dialysis, with limited past studies on this topic.
- The clinical trial involved a randomized, open-label design across 90 centers in 14 countries, focusing on patients who were either set to begin dialysis soon or had started within the last 90 days.
- The main goal was to compare the effectiveness and safety of daprodustat to darbepoetin alfa by assessing changes in hemoglobin levels and monitoring adverse events over a treatment period of 28 to 52 weeks.
Article Synopsis
- - Daprodustat is a drug being tested for treating anemia in patients with chronic kidney disease, and this study examined how liver impairment affects its metabolism and safety.
- - Participants with mild and moderate liver issues showed increased levels of daprodustat and its metabolites compared to healthy controls, with a 1.5- to 2.0-fold increase in drug exposure.
- - Despite the higher drug levels in those with liver impairment, there were no significant changes in erythropoietin (EPO) levels, and no serious side effects were reported during the study.
Article Synopsis
- Daprodustat is an approved medication for treating anemia in patients with chronic kidney disease (CKD) in Japan, and this analysis focused on its safety profile compared to traditional injectable treatments.
- The study involved data from three phase 3 trials, assessing both dialysis-dependent and nondialysis patients, with an average treatment duration of 365 days for both daprodustat and injectable erythropoiesis-stimulating agents (ESA).
- The findings indicated similar rates of adverse events and serious complications, but more extensive research is necessary to fully understand the long-term risks associated with daprodustat.
The ASCEND-ND trial: study design and participant characteristics.
Nephrol Dial Transplant
October 2022
Article Synopsis
- Anaemia is a common issue for patients with chronic kidney disease (CKD), and it's crucial to evaluate new treatments like daprodustat compared to the existing drug, darbepoetin alfa.
- The ASCEND-ND trial involved 3,872 adult participants across 39 countries, focusing on those with specific hemoglobin levels and assessing various health characteristics related to CKD.
- The study aims to determine the effectiveness and safety of daprodustat in treating CKD-related anaemia in patients not on dialysis, providing important insights into managing this condition.
Article Synopsis
- Daprodustat, a new oral treatment for anemia in chronic kidney disease (CKD) patients not on dialysis, was compared to the standard treatment darbepoetin alfa in a phase 3 clinical trial to evaluate effectiveness and safety.* -
- The study included 3872 participants, revealing that daprodustat resulted in a slightly higher increase in hemoglobin levels (0.74 g/dL) compared to darbepoetin alfa (0.66 g/dL), meeting noninferiority benchmarks for effectiveness.* -
- Cardiovascular safety outcomes showed daprodustat was also noninferior to darbepoetin alfa, with similar rates of major adverse cardiovascular events (19.5% vs. 19
Article Synopsis
- A phase 3 trial compared the effectiveness of an oral drug called daprodustat to injectable erythropoiesis-stimulating agents (ESAs) in increasing hemoglobin levels in CKD patients on dialysis with low hemoglobin.
- Results showed that daprodustat increased hemoglobin by an average of 0.28 g/dL, while the ESA group had an increase of 0.10 g/dL, indicating that daprodustat was noninferior to ESAs.
- Cardiovascular events were similar in both groups, with 25.2% of daprodustat patients and 26.7% of ESA patients experiencing major adverse events, confirming dap
Article Synopsis
- Daprodustat, an oral medication being tested for treating anemia in chronic kidney disease, has undergone a study assessing its absorption, distribution, and excretion after both oral and IV doses in healthy men.
- The study found that about 95% of the radiolabeled substance was recovered by day 5, primarily through feces, indicating it is mostly eliminated via the liver and intestines rather than the kidneys.
- Daprodustat showed moderate oral bioavailability (about 66%) and low tissue distribution, with no serious side effects reported, suggesting it is generally well tolerated.
Article Synopsis
- Daprodustat, a medication that inhibits a specific enzyme, was tested for its effectiveness in treating anemia in Japanese patients undergoing peritoneal dialysis over a year-long study.
- The study involved 56 participants who started with an average hemoglobin level of 10.9 g/dL, which increased to the target range of 11.0-13.0 g/dL by week 12 and was maintained throughout the study.
- Common side effects included nasopharyngitis and infections, but overall, daprodustat was well tolerated, with no reported deaths during the study.
Article Synopsis
- The ASCEND-D trial aims to compare the effectiveness and cardiovascular safety of the prolyl hydroxylase inhibitor daprodustat against traditional treatments (epoetin alfa and darbepoetin alfa) in patients with anemia related to chronic kidney disease (CKD).
- Over 2,900 patients were randomly assigned to this study, with a focus on demographic and clinical characteristics, and the group showed a median age of 58 years, predominantly male, and high rates of diabetes and cardiovascular history.
- The results of the trial will help determine whether daprodustat is a viable alternative for managing anemia in CKD patients, contributing to the broader understanding of treatment options in this population.
Article Synopsis
- Daprodustat is an oral medication designed to stimulate red blood cell production by preventing the breakdown of a protein that helps respond to low oxygen levels; its safety and effectiveness were evaluated in a year-long study involving Japanese patients with anemia due to chronic kidney disease (CKD).
- The study involved 299 patients who were not on dialysis and compared daprodustat with another treatment, CERA, with adjustments made to dosages based on patients' hemoglobin levels.
- Results showed that the mean hemoglobin levels after the 40-52 week period were similar for both treatments, with daprodustat at 12.0 g/dL and CERA at 11.9 g/dL, and both treatments
Article Synopsis
- - Daprodustat is an oral medication being compared to darbepoetin alfa (an existing treatment) for its effectiveness in treating anemia in Japanese patients undergoing hemodialysis due to chronic kidney disease (CKD).
- - The study, a phase 3 randomized trial, found that daprodustat maintained hemoglobin levels similarly to darbepoetin alfa, showing it to be noninferior, meaning it is just as effective.
- - Additionally, daprodustat demonstrated a greater decrease in hepcidin levels and an increase in total iron-binding capacity, suggesting enhanced iron metabolism compared to darbepoetin alfa, with most participants experiencing similar rates of side effects.
Article Synopsis
- Daprodustat, a medication aimed at treating anemia in chronic kidney disease (CKD) patients undergoing hemodialysis, was studied for its effectiveness when given three times a week compared to standard daily doses.
- A total of 103 hemodialysis patients, with hemoglobin levels between 9.0 to 11.5 g/dL, were randomized to receive different doses of daprodustat or a placebo over 29 days.
- The results showed that daprodustat increased hemoglobin levels in a dose-dependent manner, was well tolerated, and established important dosing guidelines for further long-term studies in CKD treatment.
Article Synopsis
- Current treatments for anemia in chronic kidney disease (CKD) include iron supplements, blood transfusions, and erythropoietin replacement but have limitations; daprodustat is a new oral medication in Phase 3 trials that may overcome some of these issues.
- The study aimed to evaluate the pharmacokinetics (how the drug behaves in the body) of daprodustat in different groups: those with normal kidney function, CKD patients not on dialysis, and those on hemodialysis (HD) or peritoneal dialysis (PD).
- Results showed similar pharmacokinetic properties for daprodustat across all patient groups, indicating consistent absorption and metabolism, even in those undergoing dialysis. *
Article Synopsis
- Daprodustat is an oral medication aimed at treating anemia in patients with chronic kidney disease, specifically focusing on those undergoing hemodialysis and not using erythropoiesis-stimulating agents.
- In a 24-week clinical trial, 28 Japanese patients were given daprodustat starting at 4 mg daily, which successfully raised their hemoglobin levels from a baseline of 9.10 g/dL to the target range of 10.0 to 12.0 g/dL by week 8.
- Throughout the study, daprodustat maintained these hemoglobin levels without introducing any new safety issues among the participants.
Introduction: Cardiovascular (CV) morbidity and mortality are excessively high among hemodialysis (HD) patients. Anemia is a common complication of chronic kidney disease (CKD) and a known risk factor for CV events. To understand the impact of the recent regulatory and guideline changes in anemia management, we examined regional CV event rates in high-risk and erythropoiesis-stimulating agent (ESA)-hyporesponsive HD patients.
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- - This study examined the effects of daprodustat, a new oral medication for anemia in chronic kidney disease, focusing on its impact on hemoglobin levels and safety compared to traditional treatments like erythropoietin (rhEPO).
- - Participants (216) on hemodialysis were switched from rhEPO to daprodustat at varying doses and their hemoglobin levels were monitored over 24 weeks, with initial results showing significant hemoglobin increases in the daprodustat group during the first 4 weeks.
- - While both treatment groups showed similar hemoglobin levels after 24 weeks, daprodustat's safety profile was consistent with patients on hemodialysis, suggesting it could be a viable
Article Synopsis
- - The study evaluated the safety and effectiveness of daprodustat, a new oral medication, for treating anemia in patients with chronic kidney disease (CKD) not on dialysis over a 24-week period.
- - In the trial involving 252 patients, those taking daprodustat achieved average hemoglobin levels similar to those receiving standard care with rhEPO, and maintained target hemoglobin levels better than the control group for a majority of the study period.
- - Overall, daprodustat was found to be a viable option for managing anemia in CKD patients, showing effectiveness and a safety profile in line with expectations for this population.
Article Synopsis
- Hyporesponsiveness to rhEPO in chronic kidney disease patients on hemodialysis is a significant concern, leading researchers to investigate daprodustat as a potential treatment to address this issue.
- A phase 2a study involved 15 participants with anemia on hemodialysis, taking daprodustat over 16 weeks, with the goal of maintaining hemoglobin levels between 10.0-11.5 g/dl.
- Results showed that 29% of subjects experienced meaningful increases in hemoglobin, and while many had adverse effects, most were mild to moderate with no new safety concerns raised.
Background: A combination of safety concerns and labeling changes impacted use of erythropoiesis-stimulating agents (ESAs) in renal anemia. Data regarding contemporary utilization in pre-dialysis chronic kidney disease (CKD) are lacking.
Methods: Electronic healthcare records and medical claims data of pre-dialysis CKD patients were aggregated from a large US managed care provider (2011-13).
Article Synopsis
- The study aimed to evaluate daprodustat's ability to cause drug-drug interactions with the CYP2C8 enzyme and OATP1B1 transporter using pioglitazone and rosuvastatin as test drugs.
- Results showed that daprodustat did not significantly affect the plasma levels of pioglitazone and rosuvastatin, suggesting low interaction potential as a perpetrator.
- However, when daprodustat was taken with trimethoprim, a weak CYP2C8 inhibitor, its plasma concentration increased by 48%, indicating a moderate increase in absorption with the presence of weak inhibitors.