Drug Interaction Potentiation
Conditions
Keywords
Healthy volunteers, vadadustat, drug interactions
Brief summary
This is a Phase 1, two-part, open-label study to evaluate the interaction of cyclosporine, probenecid, and rifampin as perpetrators with vadadustat (victim) in healthy male and female subjects.
Detailed description
This is a Phase 1, two-part, open-label study to evaluate the interaction of cyclosporine, probenecid, and rifampin as perpetrators with vadadustat (victim) in healthy male and female subjects. Part 1 consists of 2 arms (cyclosporine and probenecid) and Part 2 consists of 1 arm (rifampin). Twenty (20) unique subjects will be enrolled into each study arm. The PK and safety/tolerability data from Part 1 Arm 1 (cyclosporine) will determine if Part 2 (rifampin) will proceed. Subjects will be on study for up to 72 days, including a 28-day screening period, 6-10 day clinic period, and a 30-day follow-up period post last dose. Blood and/or urine samples for PK analysis will be collected at pre-defined timepoints throughout the study.
Interventions
DRUGvadadustat
Oral dose 300 mg
DRUGRifampin
IV Rifampin
DRUGProbenecid
Oral Probenecid
DRUGCyclosporins
Oral Cyclosporine
Sponsors
Akebia Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
This is a 2 part study. Part 1 Arm 1 is a cross over design to assess the drug-drug interactions of cyclosporine with vadadustat. Part 1 Arm 2 is a fixed sequence design to assess the drug-drug interactions of probenecid with vadadustat. Part 2 is a crossover design to assess the drug-drug interaction of rifampin with 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; History of latent or active tuberculosis (TB). * 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) of vadadustat | Up to 10 weeks |
| Area under plasma concentration-time curve from 0 to infinity (AUCinf) of vadadustat | Up to 10 weeks |
| Maximum observed plasma concentration (Cmax) of vadadustat | Up to 10 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Apparent total body clearance (CL/F) of vadadustat | Up to 10 weeks |
| Percent of extrapolated area under the curve from time t to infinity (%AUCextrap) of vadadustat | Up to 10 weeks |
| Renal clearance (CLr) of vadadustat and vadadustat 1-O-glucuronide excretion in urine for Part 1 Arm 2 (Probenecid) only | Up to 10 weeks |
| Cumulative amount excreted (Ae0-t) of vadadustat and vadadustat 1-O-glucuronide in urine for Part 1 Arm 2 (Probenecid) only | Up to 10 weeks |
| Time to maximum observed plasma concentration (Tmax) of vadadustat | Up to 10 weeks |
| Area under plasma concentration-time curve from 0 to last quantifiable concentration (AUClast) of vadadustat metabolites | Up to 10 weeks |
| Area under plasma concentration-time curve from 0 to infinity (AUCinf) of vadadustat metabolites | Up to 10 weeks |
| Maximum observed plasma concentration (Cmax) of vadadustat metabolites | Up to 10 weeks |
| Reporting of treatment emergent adverse events as reported by the study subject | Up to 10 weeks |
| Fraction (%) of the dose excreted (Fe%0-t) for Part 1 Arm 2 (Probenecid) only of vadadustat and vadadustat 1-O-glucuronide excretion in urine | Up to 10 weeks |
| Elimination rate constant (Kel) of vadadustat | Up to 10 weeks |
| Terminal half-life (t½) of vadadustat | Up to 10 weeks |
Countries
Canada
Outcome results
None listed