ClinicalTrials.gov
ClinicalTrials.gov Menu

A Single Dose Study of Oral Vadadustat in Subjects With Normal and Impaired Hepatic Function

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03799848
Recruitment Status : Completed
First Posted : January 10, 2019
Last Update Posted : January 10, 2019
Sponsor:
Information provided by (Responsible Party):
Akebia Therapeutics

Brief Summary:
This is a Phase I open-label study to evaluate the pharmacokinetic (PK) profile of a single oral dose of vadadustat in subjects with hepatic impairment(HI) compared to healthy matched control subjects with normal hepatic function.

Condition or disease Intervention/treatment Phase
Hepatic Impairment Drug: Vadadustat Phase 1

Detailed Description:
This is an open label, parallel-group, single dose, Phase 1 study to evaluate the PK profile, safety, and tolerability of a single oral 450 mg dose of vadadustat in subjects with hepatic impairment relative to control subjects with normal hepatic function. The study will enroll up to 24 subjects in 3 groups of 8 subjects at 2 study sites. Blood samples for vadadustat PK and its metabolites will be collected pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 60, and 72 hours post-dose.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Phase 1, Open-Label, Parallel-Group, Pharmacokinetic Single Dose Study of Oral Vadadustat in Subjects With Normal and Impaired Hepatic Function
Actual Study Start Date : June 4, 2018
Actual Primary Completion Date : November 30, 2018
Actual Study Completion Date : December 31, 2018

Arm Intervention/treatment
Experimental: Vadadustat
Group 1: Subjects with moderately impaired hepatic function (Child-Pugh Class B) Group 2: Normal healthy volunteers Group 3: Subjects with mildly impaired hepatic function (Child-Pugh Class A)
Drug: Vadadustat
Oral tablet
Other Name: AKB-6548




Primary Outcome Measures :
  1. Area under the concentration-time curve from dosing to last measurable concentration (AUClast) [ Time Frame: Day 1, Day 4 ]
  2. Area under the concentration-time curve from dosing to infinity (AUCinf) [ Time Frame: Day 1, Day 4 ]
  3. Observed maximum concentration (Cmax). [ Time Frame: Day 1, Day 4 ]

Secondary Outcome Measures :
  1. Time to reach Cmax of vadadustat [ Time Frame: Day 1, Day 4 ]
  2. Apparent total body clearance (CL/F) of vadadustat [ Time Frame: Day 1, Day 4 ]
  3. Apparent volume of distribution (Vd/F) of vadadustat [ Time Frame: Day 1, Day 4 ]
  4. Terminal half-life (t1/2) of vadadustat [ Time Frame: Day 1, Day 4 ]
  5. Time to reach Tmax of vadadustat [ Time Frame: Day 1, Day 4 ]
  6. Assessment of Treatment-Emergent Adverse Events (TEAEs) as reported by study subjects [ Time Frame: Up to 9 Weeks ]
  7. Cmax related to free drug (Cmax, free) of Vadadustat Unbound [ Time Frame: Day 1, Day 4 ]
  8. AUClast related to free drug (AUClast, free) of Vadadustat Unbound [ Time Frame: Day 1, Day 4 ]
  9. AUCinf related to free drug (AUCinf, free) of Vadadustat Unbound [ Time Frame: Day 1, Day 4 ]
  10. CL/F related to free drug (CL/Ffree) of Vadadustat Unbound [ Time Frame: Day 1, Day 4 ]
  11. Terminal half-life (t1/2) of Vadadustat Unbound [ Time Frame: Day 1, Day 4 ]
  12. The area under the concentration-time curve from dosing to last measurable concentration (AUClast) of Vadadustat metabolites [ Time Frame: Day 1, Day 4 ]
  13. The area under the concentration-time curve from dosing to infinity (AUCinf) of Vadadustat metabolite [ Time Frame: Day 1, Day 4 ]
  14. Time to reach Cmax of vadadustat metabolites [ Time Frame: Day 1, Day 4 ]
  15. Terminal half-life (t1/2) of Vadadustat metabolites [ Time Frame: Day 1, Day 4 ]
  16. Renal clearance (CLr) of Vadadustat/metabolite(s) Urine [ Time Frame: Day 1, Day 4 ]
  17. Cumulative amount of drug excreted (Ae) of Vadadustat/metabolite(s) Urine [ Time Frame: Day 1, Day 4 ]
  18. Cumulative fraction of drug excreted (Fe) of Vadadustat/metabolite(s) Urine [ Time Frame: Day 1, Day 4 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria (All groups):

  • Male or female subjects between ≥18 years and ≤70 years of age
  • Have a body weight ≥45 kg and body mass index (BMI) ≥18.5 kg/m2 to 40.0 kg/m2

Additional Group-Specific Inclusion Criteria:

  • Group 1 (Moderate Hepatic Impairment Subjects):

    • Presence of Moderate hepatic impairment (Child-Pugh Class B)
  • Group 2 (Normal Hepatic Function Subjects):

    • Normal hepatic function
  • Group 3 (Mild Hepatic Impairment Subjects):

    • Presence of mild hepatic impairment ( Child-Pugh Class A)

Exclusion Criteria (all groups):

  • Renal impairment ≥ Stage 3 (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73m2 using the Modification of Diet in Renal Disease (MDRD) study equation)
  • Any history of active malignancy within 2 years prior to or during screening, except for treated basal cell carcinoma of skin, curatively resected squamous cell carcinoma of skin, or cervical carcinoma in situ; any history of tuberculosis and/or prophylaxis for tuberculosis
  • Positive test for human immunodeficiency virus (HIV) antibody at Screening.
  • Hepatic or other organ or cell transplant
  • Subjects with alcoholic cirrhosis must be sober for a minimum of 6 months

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03799848


Locations
United States, Minnesota
Prism Clinical Research
Saint Paul, Minnesota, United States, 55114
United States, Texas
American Research Corporation at the University of Texas Liver Institute
San Antonio, Texas, United States, 78215
Sponsors and Collaborators
Akebia Therapeutics
Investigators
Study Director: Akebia Therapeutics Akebia Therapeutics

Responsible Party: Akebia Therapeutics
ClinicalTrials.gov Identifier: NCT03799848     History of Changes
Other Study ID Numbers: AKB-6548-CI-0024
First Posted: January 10, 2019    Key Record Dates
Last Update Posted: January 10, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Akebia Therapeutics:
Hepatic impairment
Healthy subjects
Child-pugh
Vadadustat

Additional relevant MeSH terms:
Liver Diseases
Digestive System Diseases