Clinical trial NCT03789032: Study to Evaluate the Effect of Rabeprazole on the Pharmacokinetics of Vadadustat
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Drug Interaction Potentiation
Pharmacokinetics
Keywords: Vadadustat
Rabeprazole
Pharmacokinetics
Lead sponsor: Akebia Therapeutics
Sponsor class: INDUSTRY
First posted: 2018-12-28
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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.

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 vadadustat
timeFrame: Up to 10 weeks
measure: Area under plasma concentration-time curve from 0 to infinity (AUCinf) for vadadustat
timeFrame: Up to 10 weeks
measure: Maximum observed plasma concentration (Cmax) for vadadustat
timeFrame: Up to 10 weeks
Secondary outcomes:
measure: Time to maximum observed plasma concentration (Tmax) of vadadustat
timeFrame: Up to 10 weeks
measure: Elimination rate constant (Kel) of vadadustat
timeFrame: Up to 10 weeks
measure: Terminal half-life (t½) of vadadustat
timeFrame: Up to 10 weeks
measure: Apparent total body clearance (CL/F) of vadadustat
timeFrame: Up to 10 weeks
measure: Percent of extrapolated area under the curve from time t to infinity (%AUCextrap) of vadadustat
timeFrame: Baseline and end of study
measure: Area under plasma concentration-time curve from 0 to last quantifiable concentration (AUClast) of vadadustat-O-glucuronide
timeFrame: Up to 10 weeks
measure: Area under plasma concentration-time curve from 0 to infinity (AUCinf) of vadadustat-O-glucuronide
timeFrame: Up to 10 weeks
measure: Maximum observed plasma concentration (Cmax) of vadadustat-O-glucuronide
timeFrame: Up to 10 weeks
measure: Reporting of treatment emergent adverse event (TEAE) as reported by study subjects
timeFrame: Up to 10 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: