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

Sponsor
Akebia Therapeutics (Industry)
Overall Status
Completed
CT.gov ID
NCT03799848
Collaborator
(none)
24
Enrollment
2
Locations
1
Arm
4.2
Actual Duration (Months)
12
Patients Per Site
2.9
Patients Per Site Per Month

Study Details

Study Description

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
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 Design

Study Type:
Interventional
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 :
Jun 12, 2018
Actual Primary Completion Date :
Oct 18, 2018
Actual Study Completion Date :
Oct 18, 2018

Arms and Interventions

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 Names:
  • AKB-6548

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Area under the concentration-time curve from dosing to last measurable concentration (AUClast) [Day 1, Day 4]

    2. Area under the concentration-time curve from dosing to infinity (AUCinf) [Day 1, Day 4]

    3. Observed maximum concentration (Cmax). [Day 1, Day 4]

    Secondary Outcome Measures

    1. Time to reach Cmax of vadadustat [Day 1, Day 4]

    2. Apparent total body clearance (CL/F) of vadadustat [Day 1, Day 4]

    3. Apparent volume of distribution (Vd/F) of vadadustat [Day 1, Day 4]

    4. Terminal half-life (t1/2) of vadadustat [Day 1, Day 4]

    5. Time to reach Tmax of vadadustat [Day 1, Day 4]

    6. Assessment of Treatment-Emergent Adverse Events (TEAEs) as reported by study subjects [Up to 9 Weeks]

    7. Cmax related to free drug (Cmax, free) of Vadadustat Unbound [Day 1, Day 4]

    8. AUClast related to free drug (AUClast, free) of Vadadustat Unbound [Day 1, Day 4]

    9. AUCinf related to free drug (AUCinf, free) of Vadadustat Unbound [Day 1, Day 4]

    10. CL/F related to free drug (CL/Ffree) of Vadadustat Unbound [Day 1, Day 4]

    11. Terminal half-life (t1/2) of Vadadustat Unbound [Day 1, Day 4]

    12. The area under the concentration-time curve from dosing to last measurable concentration (AUClast) of Vadadustat metabolites [Day 1, Day 4]

    13. The area under the concentration-time curve from dosing to infinity (AUCinf) of Vadadustat metabolite [Day 1, Day 4]

    14. Time to reach Cmax of vadadustat metabolites [Day 1, Day 4]

    15. Terminal half-life (t1/2) of Vadadustat metabolites [Day 1, Day 4]

    16. Renal clearance (CLr) of Vadadustat/metabolite(s) Urine [Day 1, Day 4]

    17. Cumulative amount of drug excreted (Ae) of Vadadustat/metabolite(s) Urine [Day 1, Day 4]

    18. Cumulative fraction of drug excreted (Fe) of Vadadustat/metabolite(s) Urine [Day 1, Day 4]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 70 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Prism Clinical Research Saint Paul Minnesota United States 55114
    2 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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Akebia Therapeutics
    ClinicalTrials.gov Identifier:
    NCT03799848
    Other Study ID Numbers:
    • AKB-6548-CI-0024
    First Posted:
    Jan 10, 2019
    Last Update Posted:
    Mar 22, 2019
    Last Verified:
    Mar 1, 2019
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    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

    Study Results

    No Results Posted as of Mar 22, 2019