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

Akebia Therapeutics

Status and phase: Completed; Phase 1

Conditions: Drug Interaction Potentiation

Treatments: Drug: Furosemide; Drug: Digoxin; Drug: Vadadustat; Drug: Adefovir

Study type: Interventional

Funder types: Industry

Identifiers

NCT03801759

AKB-6548-CI-0031

Details and patient eligibility

About

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.

Full 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.

Enrollment: 62 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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62 participants in 3 patient groups

Vadadustat, digoxin

Experimental group

Description:

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.

Treatment:

Drug: Digoxin

Drug: Vadadustat

Vadadustat, adefovir

Experimental group

Description:

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.

Treatment:

Drug: Vadadustat

Drug: Adefovir

Vadadustat, Furosemide

Experimental group

Description:

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.

Treatment:

Drug: Vadadustat

Drug: Furosemide