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

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ClinicalTrials.gov Identifier: NCT03801759
Recruitment Status : Completed
First Posted : January 11, 2019
Last Update Posted : March 22, 2019
Sponsor:
Information provided by (Responsible Party):
Akebia Therapeutics

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
Drug Interaction Potentiation Drug: Vadadustat Drug: Furosemide Drug: Adefovir Drug: Digoxin 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 62 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

Each arm has fixed sequence design.

  1. Arm 1 (n = 20): Digoxin 0.5 mg alone, vadadustat 600 mg alone and digoxin + vadadustat
  2. Arm 2 (n = 16): adefovir 10mg alone, vadadustat 600 mg QD alone and adefovir + vadadustat
  3. 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 : July 20, 2018
Actual Primary Completion Date : September 30, 2018
Actual Study Completion Date : September 30, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Drug Reactions

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 Name: 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 Name: 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 Name: AKB 6548

Drug: Furosemide
Oral Furosemide




Primary Outcome Measures :
  1. Area under plasma concentration-time curve from 0 to last quantifiable concentration (AUClast) for digoxin, adefovir and furosemide [ Time Frame: Up to 12 Weeks ]
  2. Area under plasma concentration-time curve from 0 to infinity (AUCinf) for digoxin, adefovir and furosemide [ Time Frame: Up to 12 Weeks ]
  3. Maximum observed plasma concentration (Cmax) for digoxin, adefovir and furosemide [ Time Frame: Up to 12 Weeks ]

Secondary Outcome Measures :
  1. Time to maximum observed plasma concentration (Tmax) for digoxin, adefovir and furosemide [ Time Frame: Up to 12 Weeks ]
  2. Elimination rate constant (Kel) for digoxin, adefovir and furosemide [ Time Frame: Up to 12 Weeks ]
  3. Terminal half-life (t½) for digoxin, adefovir and furosemide [ Time Frame: Up to 12 Weeks ]
  4. Apparent total body clearance (CL/F) for digoxin, adefovir and furosemide [ Time Frame: Up to 12 Weeks ]
  5. Percent of extrapolated area under the curve from time t to infinity (%AUCextrap) for digoxin, adefovir and furosemide [ Time Frame: Up to 12 Weeks ]
  6. Reporting of Treatment Emergent Adverse Events (TEAEs) as reported by study subjects [ Time Frame: Up to 12 Weeks ]


Information from the National Library of Medicine

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

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.

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): NCT03801759


Locations
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Canada, Quebec
inVentiv Health Clinique Inc.
Québec City, Quebec, Canada, G1P 0A2
Sponsors and Collaborators
Akebia Therapeutics
Investigators
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Study Director: Akebia Therapeutics Sponsor GmbH

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Responsible Party: Akebia Therapeutics
ClinicalTrials.gov Identifier: NCT03801759     History of Changes
Other Study ID Numbers: AKB-6548-CI-0031
First Posted: January 11, 2019    Key Record Dates
Last Update Posted: March 22, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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:
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Furosemide
Adefovir
Adefovir dipivoxil
Digoxin
Glycine
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Sodium Potassium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Anti-Arrhythmia Agents
Cardiotonic Agents
Enzyme Inhibitors
Protective Agents
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Anti-Retroviral Agents
Glycine Agents
Neurotransmitter Agents