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Drug-Drug Interaction Study of Vadadustat With Digoxin, Adefovir and Furosemide

Sponsor
Akebia Therapeutics (Industry)
Overall Status
Completed
CT.gov ID
NCT03801759
Collaborator
(none)
62
Enrollment
1
Location
3
Arms
2.4
Actual Duration (Months)
26.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase 1, open-label, 3-arm, fixed sequence, study to evaluate vadadustat as a perpetrator of drug-drug interactions (DDIs) with digoxin, adefovir and furosemide in healthy male and female subjects.

Condition or Disease Intervention/Treatment Phase
Phase 1

Detailed Description

This is a Phase 1, open-label, 3-arm, fixed sequence, study to evaluate vadadustat as a perpetrator of drug-drug interactions (DDIs) with digoxin, adefovir and furosemide in healthy male and female subjects. Unique subjects will be enrolled into each arm of the study and enrollment will be sequential. The first 20 subjects confirmed to be eligible will be assigned to Arm 1 (digoxin), the next 16 subjects will be assigned to Arm 2 (adefovir) and the next 22 subjects will be assigned to Arm 3 (furosemide). Blood samples for PK analysis will be collected at pre-defined timepoints for each arm throughout the study. Subjects will be on study for up to 80 days, including a 28-day screening period, 7-21 day in clinic period, and a 30-day follow up period post last dose.

Study Design

Study Type:
Interventional
Actual Enrollment :
62 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Intervention Model Description:
Each arm has fixed sequence design. Arm 1 (n = 20): Digoxin 0.5 mg alone, vadadustat 600 mg alone and digoxin + vadadustat Arm 2 (n = 16): adefovir 10mg alone, vadadustat 600 mg QD alone and adefovir + vadadustat Arm 3 (n=22) : furosemide 40mg alone, vadadustat 600 mg QD alone, and furosemide + vadadustatEach arm has fixed sequence design. Arm 1 (n = 20): Digoxin 0.5 mg alone, vadadustat 600 mg alone and digoxin + vadadustat Arm 2 (n = 16): adefovir 10mg alone, vadadustat 600 mg QD alone and adefovir + vadadustat Arm 3 (n=22) : furosemide 40mg alone, vadadustat 600 mg QD alone, and furosemide + vadadustat
Masking:
None (Open Label)
Primary Purpose:
Basic Science
Official Title:
A Phase 1 Open-label, Three Arm Study in Healthy Adult Volunteers to Assess Vadadustat as a Perpetrator in Drug-Drug-Interactions With Digoxin, Adefovir and Furosemide
Actual Study Start Date :
Jul 20, 2018
Actual Primary Completion Date :
Sep 30, 2018
Actual Study Completion Date :
Sep 30, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: Vadadustat, digoxin

Arm 1: Subjects will receive a single oral dose of digoxin 0.5 mg alone, followed by a washout period and repeat doses of vadadustat 600 mg QD alone and in combination with a single dose of digoxin 0.5 mg.

Drug: Vadadustat
Oral dose 600 mg
Other Names:
  • AKB 6548

    • Drug: Digoxin
    Oral Digoxin
    Experimental: Vadadustat, adefovir

    Arm 2: Subjects will receive a single dose of oral adefovir 10 mg alone, followed by a washout period and repeat doses of vadadustat 600 mg QD alone and in combination with a single dose of adefovir.

    Drug: Vadadustat
    Oral dose 600 mg
    Other Names:
  • AKB 6548

    • Drug: Adefovir
    Oral Adefovir
    Experimental: Vadadustat, Furosemide

    Arm 3: Subjects will receive a single dose of oral furosemide 40 mg alone, followed by a washout period and repeat doses of vadadustat 600 mg QD alone, and in combination with a single dose of furosemide 40 mg.

    Drug: Vadadustat
    Oral dose 600 mg
    Other Names:
  • AKB 6548

    • Drug: Furosemide
    Oral Furosemide

    Outcome Measures

    Primary Outcome Measures

    1. Area under plasma concentration-time curve from 0 to last quantifiable concentration (AUClast) for digoxin, adefovir and furosemide [Up to 12 Weeks]

    2. Area under plasma concentration-time curve from 0 to infinity (AUCinf) for digoxin, adefovir and furosemide [Up to 12 Weeks]

    3. Maximum observed plasma concentration (Cmax) for digoxin, adefovir and furosemide [Up to 12 Weeks]

    Secondary Outcome Measures

    1. Time to maximum observed plasma concentration (Tmax) for digoxin, adefovir and furosemide [Up to 12 Weeks]

    2. Elimination rate constant (Kel) for digoxin, adefovir and furosemide [Up to 12 Weeks]

    3. Terminal half-life (t½) for digoxin, adefovir and furosemide [Up to 12 Weeks]

    4. Apparent total body clearance (CL/F) for digoxin, adefovir and furosemide [Up to 12 Weeks]

    5. Percent of extrapolated area under the curve from time t to infinity (%AUCextrap) for digoxin, adefovir and furosemide [Up to 12 Weeks]

    6. Reporting of Treatment Emergent Adverse Events (TEAEs) as reported by study subjects [Up to 12 Weeks]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 55 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:

    • Healthy Male or female between 18 and 55 years of age, inclusive, at time of informed consent.

    • Body mass index between 18.0 and 30.0 kg/m2, with a minimum body weight of 45 kg for females and 50 kg for males, inclusive.

    Exclusion Criteria:

    • Current or past clinically significant history of cardiovascular, cerebrovascular, pulmonary, gastrointestinal, hematologic, renal, hepatic, immunologic, metabolic, urologic, neurologic, dermatologic, psychiatric, or other major disease. History of cancer (except treated non-melanoma skin cancer) or history of chemotherapy use within 5 years prior to Screening.

    • Positive test results for human immunodeficiency virus (HIV) antibody; Positive test results of hepatitis B surface antigen (HBsAg), or positive hepatitis C virus antibody (HCVab) within 3 months prior to screening; or positive test results for human immunodeficiency virus antibody (HIVab) at Screening

    • Taking any prescription medication or over the counter multi-vitamin supplement, or any non-prescription products (including herbal-containing preparations but excluding acetaminophen) within 14 days prior to Day -1.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 inVentiv Health Clinique Inc. Québec City Quebec Canada G1P 0A2

    Sponsors and Collaborators

    • Akebia Therapeutics

    Investigators

    • Study Director: Akebia Therapeutics, Sponsor GmbH

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Akebia Therapeutics
    ClinicalTrials.gov Identifier:
    NCT03801759
    Other Study ID Numbers:
    • AKB-6548-CI-0031
    First Posted:
    Jan 11, 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
    vadadustat
    drug interactions
    healthy volunteers
    Additional relevant MeSH terms:
    Adefovir
    Digoxin
    Furosemide

    Study Results

    No Results Posted as of Mar 22, 2019