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

Akebia Therapeutics0 sites93 target enrollmentJune 15, 2011

ConditionsAnemia Kidney Disease

InterventionsAKB-6548 Placebo

DrugsAKB-6548 Placebo

Overview

Phase: Phase 2
Intervention: AKB-6548
Conditions: Anemia
Sponsor: Akebia Therapeutics
Enrollment: 93
Primary Endpoint: Absolute Change From Baseline in Hemoglobin (Hgb) to End of Treatment (Week 6)
Status: Completed
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

Brief 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.

Registry

clinicaltrials.gov

Start Date

June 15, 2011

End Date

February 16, 2012

Last Updated

3 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Akebia Therapeutics

Responsible Party

Sponsor

Eligibility Criteria

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

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

Arms & Interventions

AKB-6548 240 mg

Intervention: AKB-6548

AKB-6548 370 mg

Intervention: AKB-6548

AKB-6548 500 mg

Intervention: AKB-6548

AKB-6548 630 mg

Intervention: AKB-6548

Placebo

Intervention: Placebo

Outcomes

Primary Outcomes

Absolute Change From Baseline in Hemoglobin (Hgb) to End of Treatment (Week 6)

Time Frame: Baseline, 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.

Secondary Outcomes

Number of Participants With Clinically Significant Changes From Baseline in Vital Signs Parameter(Up to Week 8 (Follow-up Visit 2 weeks after last dose))
Number of Participants With Clinically Significant Abnormal 12-Electrocardiogram (ECG) Findings(Up to Week 8 (Follow-up Visit 2 weeks after last dose))
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values(Up to Week 8 (Follow-up Visit 2 weeks after last dose))
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)(Baseline, Week 1, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8))
Change From Baseline in Reticulocyte Hgb Content at Week 6(Baseline, Week 6)
Change From Baseline in Absolute Reticulocyte Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)(Baseline, Week 1, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8))
Maximum Change From Baseline in Hgb(Baseline; up to Week 8)
Maximum Change From Baseline in HCT(Baseline; up to Week 8)
Maximum Change From Baseline in RBC Count(Baseline; up to Week 8)
Maximum Change in Absolute Reticulocyte Count From Baseline(Baseline; up to Week 8)
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(Up to Week 6 (End of the Dosing Period))
Number of Participants With Change From Baseline in HCT ≥5.0, 7.5, and 10.0% by the End of Dosing Period(Up to Week 6 (End of The Dosing Period))
Change From Baseline in Total Iron at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)(Baseline, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8))
Number of Participants With Change From Baseline in RBC Count ≥5.0, 7.5, and 10.0% by the End of Dosing Period(Up to Week 6 (End of The Dosing Period))
Change From Baseline in Unsaturated Iron Binding Capacity at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)(Baseline, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8))
Change From Baseline in Iron Saturation at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)(Baseline, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8))
Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)(Baseline, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8))
Change From Baseline in Ferritin at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)(Baseline, Week 2, Week 4, Week 6, Follow-up (up to Week 8))
Change From Baseline in Erythropoietin at Week 2, Week 6, and Follow-up Visit (up to Week 8)(Baseline, Week 2, Week 6, Follow-up Visit (up to Week 8))
Change From Baseline in Hepcidin at Week 6(Baseline, Week 6)
Mean Plasma Vadadustat Concentrations on Week 2 and Week 4(Week 2: Pre-dose and post-dose; Week 4: Pre-dose)
Mean Plasma Vadadustat Acyl-Glucuronide Concentrations on Week 2 and Week 4(Week 2: Pre-dose; Week 4: Pre-dose)
Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval(Baseline, Week 6)
Number of Participants With Change From Baseline in Hgb ≥5.0, 7.5, and 10.0% by the End of Dosing Period(Up to Week 6 (End of The Dosing Period))
Change From Baseline in Hgb at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)(Baseline, Week 1, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8))
Change From Baseline in Hematocrit (HCT) at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)(Baseline, Week 1, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8))
Number of Participants Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(Up to Week 8 (Follow-up Visit 2 weeks after last dose))
Number of Participants With Change From Baseline in Reticulocyte Count ≥6000, 12000, and 18000 Cells/uL by the End of Dosing Period(Up to Week 6 (End of The Dosing Period))