Clinical trial NCT03801759: Drug-Drug Interaction Study of Vadadustat With Digoxin, Adefovir and Furosemide
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Drug Interaction Potentiation
Keywords: vadadustat
drug interactions
healthy volunteers
Lead sponsor: Akebia Therapeutics
Sponsor class: INDUSTRY
First posted: 2019-01-11
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 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
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Area under plasma concentration-time curve from 0 to last quantifiable concentration (AUClast) for digoxin, adefovir and furosemide
timeFrame: Up to 12 Weeks
measure: Area under plasma concentration-time curve from 0 to infinity (AUCinf) for digoxin, adefovir and furosemide
timeFrame: Up to 12 Weeks
measure: Maximum observed plasma concentration (Cmax) for digoxin, adefovir and furosemide
timeFrame: Up to 12 Weeks
Secondary outcomes:
measure: Time to maximum observed plasma concentration (Tmax) for digoxin, adefovir and furosemide
timeFrame: Up to 12 Weeks
measure: Elimination rate constant (Kel) for digoxin, adefovir and furosemide
timeFrame: Up to 12 Weeks
measure: Terminal half-life (t½) for digoxin, adefovir and furosemide
timeFrame: Up to 12 Weeks
measure: Apparent total body clearance (CL/F) for digoxin, adefovir and furosemide
timeFrame: Up to 12 Weeks
measure: Percent of extrapolated area under the curve from time t to infinity (%AUCextrap) for digoxin, adefovir and furosemide
timeFrame: Up to 12 Weeks
measure: Reporting of Treatment Emergent Adverse Events (TEAEs) as reported by study subjects
timeFrame: Up to 12 Weeks
Other outcomes:
Locations:
city: Québec City
country: Canada
facility: inVentiv Health Clinique Inc.
state: Quebec
Study officials:
affiliation: Sponsor GmbH
name: Akebia Therapeutics
role: STUDY_DIRECTOR
References: