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

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

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.

Study Overview

• Status: Completed
• Conditions: Drug Interaction Potentiation
• Intervention / Treatment: Drug: Vadadustat; Drug: Digoxin; Drug: Adefovir; Drug: Furosemide

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 Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Québec City, Quebec, Canada, G1P 0A2
      • inVentiv Health Clinique Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NON_RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under plasma concentration-time curve from 0 to last quantifiable concentration (AUClast) for digoxin, adefovir and furosemide	Up to 12 Weeks
Area under plasma concentration-time curve from 0 to infinity (AUCinf) for digoxin, adefovir and furosemide	Up to 12 Weeks
Maximum observed plasma concentration (Cmax) for digoxin, adefovir and furosemide	Up to 12 Weeks

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Akebia Therapeutics

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 20, 2018
• Primary Completion (ACTUAL): September 30, 2018
• Study Completion (ACTUAL): September 30, 2018

Study Registration Dates

• First Submitted: December 27, 2018
• First Submitted That Met QC Criteria: January 9, 2019
• First Posted (ACTUAL): January 11, 2019

Study Record Updates

• Last Update Posted (ACTUAL): March 22, 2019
• Last Update Submitted That Met QC Criteria: March 20, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: vadadustat; healthy volunteers; drug interactions
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Protective Agents; Natriuretic Agents; Cardiotonic Agents; Membrane Transport Modulators; Diuretics; Sodium Potassium Chloride Symporter Inhibitors; Digoxin; Furosemide; Adefovir
• Other Study ID Numbers: AKB-6548-CI-0031

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No