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

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

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.

Study Overview

• Status: Completed
• Conditions: Pharmacokinetics; Drug Interaction Potentiation
• Intervention / Treatment: Drug: Vadadustat; Drug: Rabeprazole

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Québec City, Quebec, Canada, G1P 0A2
      • inVentiv Health Clinique Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Rabeprazole and Vadadustat; 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; Vadadustat 300 mg; Drug: Rabeprazole; Oral Rabeprazole

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Akebia Therapeutics

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 3, 2018
• Primary Completion (ACTUAL): November 9, 2018
• Study Completion (ACTUAL): November 19, 2018

Study Registration Dates

• First Submitted: December 27, 2018
• First Submitted That Met QC Criteria: December 27, 2018
• First Posted (ACTUAL): December 28, 2018

Study Record Updates

• Last Update Posted (ACTUAL): March 22, 2019
• Last Update Submitted That Met QC Criteria: March 20, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Rabeprazole; Vadadustat
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Rabeprazole
• Other Study ID Numbers: AKB-6548-CI-0033

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No