- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01381094
42-Day Repeat Oral Dose Study of AKB-6548 in Participants With Chronic Kidney Disease and Anemia
June 7, 2022 updated by: Akebia Therapeutics
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
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
93
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Arkansas
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Pine Bluff, Arkansas, United States
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California
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Covina, California, United States
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Los Angeles, California, United States
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Lynwood, California, United States
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Riverside, California, United States
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San Dimas, California, United States
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Whittier, California, United States
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Florida
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Coral Springs, Florida, United States
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Lauderdale Lakes, Florida, United States
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Miami, Florida, United States
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Ocala, Florida, United States
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Georgia
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Augusta, Georgia, United States
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Macon, Georgia, United States
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Kansas
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Wichita, Kansas, United States
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Louisiana
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Shreveport, Louisiana, United States
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Massachusetts
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Springfield, Massachusetts, United States
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Michigan
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Detroit, Michigan, United States
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Pontiac, Michigan, United States
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Warren, Michigan, United States
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New York
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Bethpage, New York, United States
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Mineola, New York, United States
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North Carolina
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Wilmington, North Carolina, United States
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Oklahoma
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Oklahoma City, Oklahoma, United States
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Tennessee
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Knoxville, Tennessee, United States
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Texas
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Austin, Texas, United States
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Fort Worth, Texas, United States
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Houston, Texas, United States
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San Antonio, Texas, United States
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 79 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Placebo Comparator: Placebo
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oral Placebo administered once daily for 42 days
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Experimental: AKB-6548 240 mg
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oral dose administered once daily for 42 days
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Experimental: AKB-6548 370 mg
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oral dose administered once daily for 42 days
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Experimental: AKB-6548 500 mg
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oral dose administered once daily for 42 days
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Experimental: AKB-6548 630 mg
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oral dose administered once daily for 42 days
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Absolute Change From Baseline in Hemoglobin (Hgb) to End of Treatment (Week 6)
Time Frame: Baseline, Week 6
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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.
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Baseline, Week 6
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in Hgb at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)
Time Frame: Baseline, Week 1, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)
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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.
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Baseline, Week 1, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)
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Change From Baseline in Hematocrit (HCT) at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)
Time Frame: Baseline, Week 1, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)
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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.
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Baseline, Week 1, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)
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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)
Time Frame: Baseline, Week 1, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)
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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.
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Baseline, Week 1, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)
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Change From Baseline in Absolute Reticulocyte Count at Week 1, Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)
Time Frame: Baseline, Week 1, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)
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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.
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Baseline, Week 1, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)
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Change From Baseline in Reticulocyte Hgb Content at Week 6
Time Frame: Baseline, Week 6
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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.
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Baseline, Week 6
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Maximum Change From Baseline in Hgb
Time Frame: Baseline; up to Week 8
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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.
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Baseline; up to Week 8
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Maximum Change From Baseline in HCT
Time Frame: Baseline; up to Week 8
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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.
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Baseline; up to Week 8
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Maximum Change From Baseline in RBC Count
Time Frame: Baseline; up to Week 8
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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.
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Baseline; up to Week 8
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Maximum Change in Absolute Reticulocyte Count From Baseline
Time Frame: Baseline; up to Week 8
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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.
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Baseline; up to Week 8
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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
Time Frame: Up to Week 6 (End of the Dosing Period)
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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.
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Up to Week 6 (End of the Dosing Period)
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Number of Participants With Change From Baseline in Hgb ≥5.0, 7.5, and 10.0% by the End of Dosing Period
Time Frame: Up to Week 6 (End of The Dosing Period)
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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.
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Up to Week 6 (End of The Dosing Period)
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Number of Participants With Change From Baseline in HCT ≥5.0, 7.5, and 10.0% by the End of Dosing Period
Time Frame: Up to Week 6 (End of The Dosing Period)
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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.
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Up to Week 6 (End of The Dosing Period)
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Number of Participants With Change From Baseline in RBC Count ≥5.0, 7.5, and 10.0% by the End of Dosing Period
Time Frame: Up to Week 6 (End of The Dosing Period)
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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.
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Up to Week 6 (End of The Dosing Period)
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Number of Participants With Change From Baseline in Reticulocyte Count ≥6000, 12000, and 18000 Cells/uL by the End of Dosing Period
Time Frame: Up to Week 6 (End of The Dosing Period)
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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.
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Up to Week 6 (End of The Dosing Period)
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Change From Baseline in Total Iron at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)
Time Frame: Baseline, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)
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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.
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Baseline, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)
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Change From Baseline in Unsaturated Iron Binding Capacity at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)
Time Frame: Baseline, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)
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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.
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Baseline, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)
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Change From Baseline in Iron Saturation at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)
Time Frame: Baseline, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)
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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.
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Baseline, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)
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Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)
Time Frame: Baseline, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)
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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.
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Baseline, Week 2, Week 4, Week 6, Follow-up Visit (up to Week 8)
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Change From Baseline in Ferritin at Week 2, Week 4, Week 6, and Follow-up Visit (up to Week 8)
Time Frame: Baseline, Week 2, Week 4, Week 6, Follow-up (up to Week 8)
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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.
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Baseline, Week 2, Week 4, Week 6, Follow-up (up to Week 8)
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Change From Baseline in Erythropoietin at Week 2, Week 6, and Follow-up Visit (up to Week 8)
Time Frame: Baseline, Week 2, Week 6, Follow-up Visit (up to Week 8)
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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.
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Baseline, Week 2, Week 6, Follow-up Visit (up to Week 8)
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Change From Baseline in Hepcidin at Week 6
Time Frame: Baseline, Week 6
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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.
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Baseline, Week 6
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Mean Plasma Vadadustat Concentrations on Week 2 and Week 4
Time Frame: Week 2: Pre-dose and post-dose; Week 4: Pre-dose
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Plasma samples were collected for the analysis.
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Week 2: Pre-dose and post-dose; Week 4: Pre-dose
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Mean Plasma Vadadustat Acyl-Glucuronide Concentrations on Week 2 and Week 4
Time Frame: Week 2: Pre-dose; Week 4: Pre-dose
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Plasma samples were collected for the analysis.
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Week 2: Pre-dose; Week 4: Pre-dose
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Number of Participants Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time Frame: Up to Week 8 (Follow-up Visit 2 weeks after last dose)
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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.
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Up to Week 8 (Follow-up Visit 2 weeks after last dose)
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Number of Participants With Clinically Significant Changes From Baseline in Vital Signs Parameter
Time Frame: Up to Week 8 (Follow-up Visit 2 weeks after last dose)
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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.
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Up to Week 8 (Follow-up Visit 2 weeks after last dose)
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Number of Participants With Clinically Significant Abnormal 12-Electrocardiogram (ECG) Findings
Time Frame: Up to Week 8 (Follow-up Visit 2 weeks after last dose)
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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.
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Up to Week 8 (Follow-up Visit 2 weeks after last dose)
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Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval
Time Frame: Baseline, Week 6
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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).
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Baseline, Week 6
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Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values
Time Frame: Up to Week 8 (Follow-up Visit 2 weeks after last dose)
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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.
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Up to Week 8 (Follow-up Visit 2 weeks after last dose)
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Natale P, Palmer SC, Jaure A, Hodson EM, Ruospo M, Cooper TE, Hahn D, Saglimbene VM, Craig JC, Strippoli GF. Hypoxia-inducible factor stabilisers for the anaemia of chronic kidney disease. Cochrane Database Syst Rev. 2022 Aug 25;8(8):CD013751. doi: 10.1002/14651858.CD013751.pub2.
- Martin ER, Smith MT, Maroni BJ, Zuraw QC, deGoma EM. Clinical Trial of Vadadustat in Patients with Anemia Secondary to Stage 3 or 4 Chronic Kidney Disease. Am J Nephrol. 2017;45(5):380-388. doi: 10.1159/000464476. Epub 2017 Mar 25.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
June 15, 2011
Primary Completion (Actual)
February 16, 2012
Study Completion (Actual)
February 16, 2012
Study Registration Dates
First Submitted
June 23, 2011
First Submitted That Met QC Criteria
June 23, 2011
First Posted (Estimate)
June 27, 2011
Study Record Updates
Last Update Posted (Actual)
July 1, 2022
Last Update Submitted That Met QC Criteria
June 7, 2022
Last Verified
June 1, 2022
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- AKB-6548-CI-0005
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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