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

Akebia Therapeutics62 enrolled

Overview

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

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Drug Interaction Potentiation

Interventions

VadadustatDRUG

Oral dose 600 mg

FurosemideDRUG

Oral Furosemide

AdefovirDRUG

Oral Adefovir

DigoxinDRUG

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (1)

inVentiv Health Clinique Inc.

Québec, Quebec, Canada

Outcomes

Primary Outcomes

Area under plasma concentration-time curve from 0 to last quantifiable concentration (AUClast) for digoxin, adefovir and furosemide

Time frame: Up to 12 Weeks

Area under plasma concentration-time curve from 0 to infinity (AUCinf) for digoxin, adefovir and furosemide

Time frame: Up to 12 Weeks

Maximum observed plasma concentration (Cmax) for digoxin, adefovir and furosemide

Time frame: Up to 12 Weeks

Secondary Outcomes

Time to maximum observed plasma concentration (Tmax) for digoxin, adefovir and furosemide

Time frame: Up to 12 Weeks

Elimination rate constant (Kel) for digoxin, adefovir and furosemide

Time frame: Up to 12 Weeks

Terminal half-life (t½) for digoxin, adefovir and furosemide

Time frame: Up to 12 Weeks

Apparent total body clearance (CL/F) for digoxin, adefovir and furosemide

Time frame: Up to 12 Weeks

Percent of extrapolated area under the curve from time t to infinity (%AUCextrap) for digoxin, adefovir and furosemide

Time frame: Up to 12 Weeks

Reporting of Treatment Emergent Adverse Events (TEAEs) as reported by study subjects

Time frame: Up to 12 Weeks

Data from ClinicalTrials.gov

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