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

Phase 1

Completed

• Conditions: Drug Interaction Potentiation
• Interventions: Drug: Vadadustat; Drug: Furosemide; Drug: Digoxin; Drug: Adefovir

• Registration Number: NCT03801759
• Lead Sponsor: 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.

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 Timeline

• Study Start: 2018-07-20
• Primary Completion: 2018-09-30
• Study Completion: 2018-09-30
• Study First Submitted: 2018-12-27
• Study First Submitted QC: 2019-01-09
• Study First Posted: 2019-01-11
• Status Verified: 2019-03
• Last Update Submitted: 2019-03-20
• Last Update Posted: 2019-03-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 62

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Vadadustat, digoxin	Vadadustat	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.
Vadadustat, Furosemide	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.
Vadadustat, digoxin	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.
Vadadustat, adefovir	Vadadustat	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.
Vadadustat, adefovir	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.
Vadadustat, Furosemide	Vadadustat	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.

Primary Outcome Measures

Name	Time	Method
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
Area under plasma concentration-time curve from 0 to last quantifiable concentration (AUClast) for digoxin, adefovir and furosemide	Up to 12 Weeks

Secondary Outcome Measures

Name	Time	Method
Time to maximum observed plasma concentration (Tmax) for digoxin, adefovir and furosemide	Up to 12 Weeks
Apparent total body clearance (CL/F) 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
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
Percent of extrapolated area under the curve from time t to infinity (%AUCextrap) for digoxin, adefovir and furosemide	Up to 12 Weeks

Trial Locations

Locations (1)

inVentiv Health Clinique Inc.; 🇨🇦 Québec City, Quebec, Canada