Drug Interaction Potentiation, Pharmacokinetics
Conditions
Keywords
Vadadustat, Rabeprazole, Pharmacokinetics
Brief summary
This is a Phase 1, fixed sequence, open-label study to evaluate the effect of multiple oral doses of rabeprazole on the pharmacokinetics of a single dose of vadadustat 300 mg in healthy male and female subjects.
Detailed description
This is a Phase 1, fixed sequence, open-label study in healthy adult subjects to evaluate the effect of multiple doses of rabeprazole on the pharmacokinetics of a single dose of vadadustat in healthy male and female subjects. Approximately twenty (20) subjects, with at least 30% female subjects, will be enrolled to ensure 18 evaluable subjects. Subjects will be on study for up to 66 days, including a 28-day screening period, 9-day clinic period, and a 30-day follow- up period post last dose. Subjects who are confirmed eligible and receive at least one dose of study drug will be considered enrolled in the study. Blood samples for PK analysis will be collected at pre-defined time points throughout the study up to 48 hours post administration of vadadustat.
Interventions
DRUGVadadustat
Vadadustat 300 mg
DRUGRabeprazole
Oral Rabeprazole
Sponsors
Akebia Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a single arm fixed sequence study. Subjects will be administered vadadustat on day 1, rabeprazole on days 2 to 5, and vadadustat and rabeprazole on day 6.
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 vadadustat | Up to 10 weeks |
| Area under plasma concentration-time curve from 0 to infinity (AUCinf) for vadadustat | Up to 10 weeks |
| Maximum observed plasma concentration (Cmax) for 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 | Baseline and end of study |
| Area under plasma concentration-time curve from 0 to last quantifiable concentration (AUClast) of vadadustat-O-glucuronide | Up to 10 weeks |
| Time to maximum observed plasma concentration (Tmax) of vadadustat | Up to 10 weeks |
| Maximum observed plasma concentration (Cmax) of vadadustat-O-glucuronide | Up to 10 weeks |
| Reporting of treatment emergent adverse event (TEAE) as reported by study subjects | Up to 10 weeks |
| Area under plasma concentration-time curve from 0 to infinity (AUCinf) of vadadustat-O-glucuronide | 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