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

NCT03801759 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: AKB-6548-CI-0031
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

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.

Conditions

Drug Interaction Potentiation

Keywords

vadadustat; drug interactions; healthy volunteers

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (6)

• 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

Study Arms (3)

Vadadustat, digoxin

EXPERIMENTAL

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; Drug: Digoxin

Vadadustat, adefovir

EXPERIMENTAL

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; Drug: Adefovir

Vadadustat, Furosemide

EXPERIMENTAL

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; Drug: Furosemide

Interventions

Vadadustat DRUG

Oral dose 600 mg

Also known as: AKB 6548

Vadadustat, Furosemide; Vadadustat, adefovir; Vadadustat, digoxin

Furosemide DRUG

Oral Furosemide

Vadadustat, Furosemide

Adefovir DRUG

Oral Adefovir

Vadadustat, adefovir

Digoxin DRUG

Oral Digoxin

Vadadustat, digoxin

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Akebia Therapeutics: lead

Study Sites (1)

inVentiv Health Clinique Inc.

Québec, Quebec, G1P 0A2, Canada

Location

MeSH Terms

Interventions

vadadustat; Furosemide; adefovir; Digoxin

Intervention Hierarchy (Ancestors)

Sulfanilamides; Sulfonamides; Amides; Organic Chemicals; Aniline Compounds; Amines; Sulfones; Sulfur Compounds; Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates

Study Officials

• Akebia Therapeutics

  Sponsor GmbH

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: December 27, 2018
• First Posted: January 11, 2019
• Study Start: July 20, 2018
• Primary Completion: September 30, 2018
• Study Completion: September 30, 2018
• Last Updated: March 22, 2019

Record last verified: 2019-03

Locations

CA (1)