Drug Interaction Potentiation
Conditions
Keywords
vadadustat, drug interactions, healthy volunteers
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.
Interventions
DRUGVadadustat
Oral dose 600 mg
DRUGFurosemide
Oral Furosemide
DRUGAdefovir
Oral Adefovir
DRUGDigoxin
Oral Digoxin
Sponsors
Akebia Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
NONE
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
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| Apparent total body clearance (CL/F) for digoxin, adefovir and furosemide | Up to 12 Weeks |
| Time to maximum observed plasma concentration (Tmax) 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 |
| Percent of extrapolated area under the curve from time t to infinity (%AUCextrap) 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 |
Countries
Canada
Outcome results
None listed