42-Day Repeat Oral Dose Study of AKB-6548 in Participants With Chronic Kidney Disease and Anemia

Anemia Clinical Trial

Official title:

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 (CKD), Stages 3 and 4

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01381094
• Other study ID #: AKB-6548-CI-0005
• Status: Completed
• Phase: Phase 2
• Start date: June 15, 2011
• Est. completion date: February 16, 2012

Study information

• Verified date: June 2022
• Source: Akebia Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the dose response (efficacy), pharmacodynamic response, pharmacokinetics, safety, and tolerability of orally administered AKB-6548 in pre-dialysis participants with anemia with repeat dosing for 42 days.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 93
• Est. completion date: February 16, 2012
• Est. primary completion date: February 16, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

Key Inclusion Criteria:

• 18 to 79 years of age, inclusive

• Chronic Kidney Disease (eGFR <60 mL/min), not yet on dialysis

• Hemoglobin (Hgb) = 10.5 g/dL

• Transferring saturation = 20%

• Ferritin = 50 ng/mL

Key Exclusion Criteria:

• Body mass index >42

• Red blood cell transfusion within 12 weeks

• Androgen therapy within the previous 21 days prior to study dosing

• Therapy with any approved or experimental erythropoiesis stimulating agent (ESA) within the 11 weeks prior to the Screening visit

• Participants meeting the criteria of ESA resistance within the previous 4 months

• Individual doses of intravenous iron of greater than 250 mg within the past 21 days

• Aspartate aminotransferase or alanine aminotransferase >1.8x upper limit of normal (ULN)

• Alkaline phosphatase >2x ULN

• Total bilirubin >1.5x ULN

• Uncontrolled hypertension

• New York Heart Association Class III or IV congestive heart failure

• Myocardial infarction, acute coronary syndrome, or stroke within 6 months prior to dosing

Related Conditions & MeSH terms

• Anemia
• Kidney Disease
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• AKB-6548
oral dose administered once daily for 42 days
• Placebo
oral Placebo administered once daily for 42 days

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Akebia Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Absolute Change From Baseline in Hemoglobin (Hgb) to End of Treatment (Week 6)	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.	Baseline, Week 6
Secondary	Change From Baseline in Hgb at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)	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.	Baseline, Week 1, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)
Secondary	Change From Baseline in Hematocrit (HCT) at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)	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.	Baseline, Week 1, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)
Secondary	Change From Baseline in Red Blood Cell (RBC) Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)	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.	Baseline, Week 1, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)
Secondary	Change From Baseline in Absolute Reticulocyte Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)	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.	Baseline, Week 1, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)
Secondary	Change From Baseline in Reticulocyte Hgb Content at Week 6	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.	Baseline, Week 6
Secondary	Maximum Change From Baseline in Hgb	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.	Baseline; up to Week 8
Secondary	Maximum Change From Baseline in HCT	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.	Baseline; up to Week 8
Secondary	Maximum Change From Baseline in RBC Count	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.	Baseline; up to Week 8
Secondary	Maximum Change in Absolute Reticulocyte Count From Baseline	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.	Baseline; up to Week 8
Secondary	Number of Participants With Absolute Change From Baseline in Hgb = 0.4, 0.6, 0.8, and 1.0 g/dL at the End of Dosing Period	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.	Up to Week 6 (End of the Dosing Period)
Secondary	Number of Participants With Change From Baseline in Hgb =5.0, 7.5, and 10.0% by the End of Dosing Period	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.	Up to Week 6 (End of The Dosing Period)
Secondary	Number of Participants With Change From Baseline in HCT =5.0, 7.5, and 10.0% by the End of Dosing Period	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.	Up to Week 6 (End of The Dosing Period)
Secondary	Number of Participants With Change From Baseline in RBC Count =5.0, 7.5, and 10.0% by the End of Dosing Period	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.	Up to Week 6 (End of The Dosing Period)
Secondary	Number of Participants With Change From Baseline in Reticulocyte Count =6000, 12000, and 18000 Cells/uL by the End of Dosing Period	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.	Up to Week 6 (End of The Dosing Period)
Secondary	Change From Baseline in Total Iron at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)	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.	Baseline, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)
Secondary	Change From Baseline in Unsaturated Iron Binding Capacity at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)	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.	Baseline, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)
Secondary	Change From Baseline in Iron Saturation at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)	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.	Baseline, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)
Secondary	Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)	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.	Baseline, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)
Secondary	Change From Baseline in Ferritin at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)	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.	Baseline, Week 2, Week 4, Week 6, Follow-up (up to Week 8)
Secondary	Change From Baseline in Erythropoietin at Week 2, Week 6, and Follow-up Visit (up to Week 8)	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.	Baseline, Week 2, Week 6, Follow-up Visit (up to Week 8)
Secondary	Change From Baseline in Hepcidin at Week 6	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.	Baseline, Week 6
Secondary	Mean Plasma Vadadustat Concentrations on Week 2 and Week 4	Plasma samples were collected for the analysis.	Week 2: Pre-dose and post-dose; Week 4: Pre-dose
Secondary	Mean Plasma Vadadustat Acyl-Glucuronide Concentrations on Week 2 and Week 4	Plasma samples were collected for the analysis.	Week 2: Pre-dose; Week 4: Pre-dose
Secondary	Number of Participants Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	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.	Up to Week 8 (Follow-up Visit 2 weeks after last dose)
Secondary	Number of Participants With Clinically Significant Changes From Baseline in Vital Signs Parameter	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.	Up to Week 8 (Follow-up Visit 2 weeks after last dose)
Secondary	Number of Participants With Clinically Significant Abnormal 12-Electrocardiogram (ECG) Findings	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.	Up to Week 8 (Follow-up Visit 2 weeks after last dose)
Secondary	Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval	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).	Baseline, Week 6
Secondary	Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values	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.	Up to Week 8 (Follow-up Visit 2 weeks after last dose)