16-Week Repeat Oral Dose Study of AKB-6548 for Anemia in Participants With End Stage Renal Disease (ESRD) Requiring Chronic Hemodialysis
- Registration Number
- NCT02260193
- Lead Sponsor
- Akebia Therapeutics
- Brief Summary
The purpose of this study is to evaluate the hemoglobin response (efficacy), safety, and tolerability of orally administered AKB-6548 in participants with end stage renal disease undergoing chronic hemodialysis.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 94
- 18 to 79 years inclusive
- Chronic Kidney Disease (CKD) Stage 5 on chronic hemodialysis for at least 3 months
- Anemia secondary to CKD treated with erythropoiesis stimulating agent and intravenous iron
Key
- Body mass index >44.0 kilograms per meter squared (kg/m^2)
- Transfusion within 8 weeks prior to Screening
- Alanine transaminase or total bilirubin >1.25x ULN
- Uncontrolled hypertension
- Class III or IV congestive heart failure
- Myocardial infarction, acute coronary syndrome, stroke or transient ischemic attack within 6 months prior to Screening
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description AKB-6548, starting dose 2 AKB-6548 - AKB-6548, starting dose 1 AKB-6548 - AKB-6548, starting dose 3 AKB-6548 -
- Primary Outcome Measures
Name Time Method Change From Pre-dose Average in Hemoglobin (Hgb) Level to The Mid-study Average Pre-dose (Screening, Second Screening, and Baseline), Week 7, and Week 8 Change from pre-dose average was calculated by the mid-study average minus the pre-dose average. The pre-dose average was defined as the average of the 3 Hgb values that were obtained before dosing at the first screening visit, the second screening visit, and the Baseline visit; the mid-study average was defined as the average of the 2 Hgb values that were obtained at the Week 7 and Week 8 visits.
Change From Pre-dose Average in Hgb Level to The End-of-study Average Pre-dose, Week 15, and Week 16 Change from pre-dose average was calculated by the end-of-study average minus the pre-dose average. The pre-dose average was defined as the average of the 3 Hgb values that were obtained before dosing at the first screening visit, the second screening visit, and the Baseline visit; the end-of-study average was defined as the average of the 2 Hgb values that were obtained at the Week 15 and Week 16 visits.
Change From Mid-study Average in Hgb Level to The End-of-study Average Week 7, Week 8, Week 15, and Week 16 Change from mid-study average was calculated by the end-of-study average minus the mid-study average. The mid-study average was defined as the average of the 2 Hgb values that were obtained at the Week 7 and Week 8 visits; the end-of-study average was defined as the average of the 2 Hgb values that were obtained at the Week 15 and Week 16 visits.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Absolute Reticulocyte Count Baseline, Week 4, Week 8, Week 12, and Week 16 Change from Baseline was calculated as the visit value minus the Baseline value. Baseline absolute reticulocyte count was defined as the last observation before the first dose of study medication.
Change From Baseline in Transferrin Saturation (TSAT) Baseline, Week 4, Week 8, Week 12, and Week 16 Change from Baseline was calculated as (visit value minus the Baseline value)/ Baseline value x 100. Baseline TSAT was defined as the last observation before the first dose of study medication.
Mean Plasma Concentrations of Vadadustat-Acyl-Glucuronide Metabolite Pre-dialysis and post-dialysis on Week 2 and Week 16 Blood samples for determination of plasma levels of Vadadustat were drawn just before and 10 minutes after completion of the dialysis session.
Change From Baseline in Hematocrit Baseline, Week 4, Week 8, Week 12, and Week 16 Change from Baseline was calculated as the visit value minus the Baseline value. Baseline Hematocrit was defined as the last observation before the first dose of study medication.
Change From Baseline in Red Blood Cell (RBC) Count Baseline, Week 4, Week 8, Week 12, and Week 16 Change from Baseline was calculated as the visit value minus the Baseline value. Baseline RBC Count was defined as the average of the three samples obtained prior to dosing.
Change From Baseline in Percent Reticulocyte Count Baseline, Week 4, Week 8, Week 12, and Week 16 Change from Baseline was calculated as (visit value minus the Baseline value)/ Baseline value x 100. Baseline percent reticulocyte count was defined as the last observation before the first dose of study medication.
Change From Baseline in Ferritin Baseline, Week 4, Week 8, Week 12, and Week 16 Change from Baseline was calculated as the visit value minus the Baseline value. Baseline ferritin was defined as the last observation before the first dose of study medication.
Change From Baseline in Hepcidin Baseline, Week 8, and Week 16 Change from Baseline was calculated as the visit value minus the Baseline value. Baseline hepcidin was defined as the last observation before the first dose of study medication.
Change From Baseline in Total Iron-Binding Capacity (TIBC) Baseline, Week 4, Week 8, Week 12, and Week 16 Change from Baseline was calculated as the visit value minus the Baseline value. Baseline TIBC was defined as the last observation before the first dose of study medication.
Change From Baseline in Iron Baseline, Week 4, Week 8, Week 12, and Week 16 Change from Baseline was calculated as the visit value minus the Baseline value. Baseline iron was defined as the last observation before the first dose of study medication.
Change From Baseline in Reticulocyte Hgb Content Baseline, Week 2, Week 4, Week 8, and Week 16 Change from Baseline was calculated as the visit value minus the Baseline value. Baseline reticulocyte Hgb content was defined as the average of the three samples obtained prior to dosing.
Number of Participants Who Received Erythropoiesis-stimulating Agent (ESA) Rescue Therapy Up to Week 16 ESA rescue therapy was administered in participants with Hgb ≤12.5 g/dL, and was stopped when Hgb reached ≥13.0 g/dL.
Number of Participants With Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) Findings Up to Week 20 A standard 12-lead ECG was performed following dosing in a supine position for approximately 5 minutes. ECGs were taken prior to vital sign assessments, circulatory access cannulation, and blood draws when possible. Clinical significance was determined by the investigator.
Change From Baseline in Hgb Baseline, Week 4, Week 8, Week 12, and Week 16 Change from Baseline was calculated as the visit value minus the Baseline value. Baseline Hgb was defined as the average of the three samples obtained prior to dosing.
Number of Participants Who Received Blood Transfusion Rescue Therapy Up to Week 16 Blood transfusion rescue therapy was administered in participants with Hgb ≤12.5 g/dL, and was stopped when Hgb reached ≥13.0 g/dL.
Mean Plasma Concentrations of Vadadustat-O-Glucuronide Metabolite Pre-dialysis and post-dialysis on Week 2 and Week 16 Blood samples for determination of plasma levels of Vadadustat were drawn just before and 10 minutes after completion of the dialysis session.
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs Up to Week 20 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.
Mean Plasma Concentrations of Vadadustat Pre-dialysis and post-dialysis on Week 2 and Week 16 Blood samples for determination of plasma levels of Vadadustat were drawn just before and 10 minutes after completion of the dialysis session.
Number of Participants Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Up to Week 20 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, lifethreatening, in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, and congenital anomaly/birth defect.
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values Up to Week 20 Parameters assessed for laboratory values included hematology, serum chemistry, urinalysis, iron indices, C-reactive protein, lipid profile, biomarkers, and pregnancy tests. The investigator was responsible for reviewing laboratory results for clinically significant changes.