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Completed

NCT Number: NCT01381094

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

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.

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Key information

Conditions

Anemia Chronic Disease Disease Attributes Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Hematologic Diseases Hemic and Lymphatic Diseases Kidney Disease Kidney Diseases Male Urogenital Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Renal Insufficiency Renal Insufficiency, Chronic Urogenital Diseases Urologic Diseases

Age range

18 year–79 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Pine Bluff, Arkansas, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

AKB-6548

Drug

oral dose administered once daily for 42 days

Placebo

Drug

oral Placebo administered once daily for 42 days

Primary outcomes

  1. 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

  1. 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)

    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.

  2. 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)

    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.

  3. 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)

    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.

  4. 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)

    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.

  5. Change From Baseline in Reticulocyte Hgb Content at Week 6

    Time frame: Baseline, 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.

  6. Maximum Change From Baseline in Hgb

    Time frame: Baseline; up to Week 8

    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.

  7. Maximum Change From Baseline in HCT

    Time frame: Baseline; up to Week 8

    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.

  8. Maximum Change From Baseline in RBC Count

    Time frame: Baseline; up to Week 8

    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.

  9. Maximum Change in Absolute Reticulocyte Count From Baseline

    Time frame: Baseline; up to Week 8

    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.

  10. 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)

    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.

  11. 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)

    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.

  12. 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)

    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.

  13. 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)

    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.

  14. 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)

    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.

  15. 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)

    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.

  16. 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)

    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.

  17. 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)

    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.

  18. 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)

    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.

  19. 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)

    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.

  20. 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)

    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.

  21. Change From Baseline in Hepcidin at Week 6

    Time frame: Baseline, 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.

  22. Mean Plasma Vadadustat Concentrations on Week 2 and Week 4

    Time frame: Week 2: Pre-dose and post-dose; Week 4: Pre-dose

    Plasma samples were collected for the analysis.

  23. Mean Plasma Vadadustat Acyl-Glucuronide Concentrations on Week 2 and Week 4

    Time frame: Week 2: Pre-dose; Week 4: Pre-dose

    Plasma samples were collected for the analysis.

  24. 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)

    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.

  25. 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)

    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.

  26. 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)

    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.

  27. Mean Change From Baseline in PR Interval, QT Interval, QRS Interval, and QT Corrected (QTc) Interval

    Time frame: Baseline, Week 6

    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).

  28. 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)

    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.

Sponsors and collaborators

Lead sponsor

Akebia Therapeutics

Industry

Registry information

Official study 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

Important dates

Study start
2011
Primary completion
2012
Study completion
2012
First posted
Jun 27, 2011
Registry last updated
Jul 1, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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