Study to Evaluate the Effect of Rabeprazole on the Pharmacokinetics of Vadadustat

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Drug Interaction Potentiation, Pharmacokinetics

Intervention / Treatment
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* Drug: Vadadustat
* Drug: Rabeprazole


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rabeprazole and Vadadustat<br>Subjects will receive vadadustat 300 mg on day 1, rabeprazole 20 mg every 12 hours on days 2 through 5 and vadadustat 300 mg and rabeprazole on day 6 | Drug: Vadadustat<br>* Vadadustat 300 mg<br>Drug: Rabeprazole<br>* Oral Rabeprazole<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to maximum observed plasma concentration (Tmax) of vadadustat |  | Up to 10 weeks | 
| Elimination rate constant (Kel) of vadadustat |  | Up to 10 weeks | 
| Terminal half-life (t½) of vadadustat |  | Up to 10 weeks | 
| 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 | 
| Area under plasma concentration-time curve from 0 to infinity (AUCinf) of vadadustat-O-glucuronide |  | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vadadustat, Rabeprazole, Pharmacokinetics