A Study in Evaluating Bioequivalence Between Test and Reference Formulations of Vadadustat Tablets in Healthy Adults

A Randomized, Open-Label, Single-Dose, Two-Period Crossover Study in Healthy Adults to Assess Bioequivalence Between Test and Reference Formulations of Vadadustat 150 mg Tablets

This study is to assess the bioequivalence of a test formulation of vadadustat (A) compared to a reference formulation of vadadustat (B)

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: vadadustat reference tablets; Drug: vadadustat test tablets

Detailed Description

This is a randomized, open-label, single-dose, two-period crossover study in healthy adults to assess the bioequivalence of a test formulation of vadadustat compared to the reference formulation of vadadustat. Blood samples for vadadustat PK will be collected at pre-dose (0 hour) and at 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 32, 40, and 48 hours post-dose.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21225
      • Research Site

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:

• Between 18 and 55 years of age, inclusive, at time of informed consent.
• Healthy subjects per Investigator judgment as documented by the medical history, physical examination, vital sign assessments, 12-lead electrocardiogram (ECG), clinical laboratory assessments, and general observations.
• Minimum weight of 45 kg with Body mass index (BMI) between 18 and 29.5 kg/m2, inclusive.
• Understands the procedures and requirements of the study and provides written informed consent and authorization for protected health information disclosure
• Willing and able to comply with the requirements of the study protocol.

Exclusion Criteria:

• Current or past history of cardiovascular, cerebrovascular, pulmonary, gastrointestinal, hematologic, renal, hepatic, immunologic, metabolic, urologic, neurologic, dermatologic, psychiatric, or other major disease, history of cancer (except non-melanoma skin cancer) or history of chemotherapy use.
• Any surgical or medical condition or history that may potentially alter the absorption, metabolism, or excretion of study treatment, such as, but not limited to gastric bypass surgery or gastric or duodenal ulcers.
• History of severe allergic or anaphylactic reactions.
• Chronic daily medication use.
• History of drug abuse
• Excessive alcohol consumption
• Smoking and the use of nicotine-containing products
• Consumption of grapefruit or grapefruit juice, pomelo, star fruit, Seville or Moro (blood) orange, or their associated products
• Participation in another clinical trial or exposure to any investigational agent.
• Donation of blood or significant blood loss or plasma donation.
• Any condition that would interfere with the ability to provide informed consent, comply with study instructions, or which might confound the interpretation of the study results or put the patient at undue risk.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Regimen A; vadadustat reference tablets	Drug: vadadustat reference tablets; oral tablet; Other Names: AKB-6548
EXPERIMENTAL: Regimen B; vadadustat test tablets	Drug: vadadustat test tablets; oral tablet; Other Names: AKB-6548

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)	Baseline visit, 48 hours
Area under plasma concentration-time curve from 0 to infinity (AUCinf)	Baseline visit, 48 hours
Area under plasma concentration-time curve from 0 to last sampling point (AUCall)	Baseline visit, 48 hours
Observed maximum concentration (Cmax)	Baseline visit, 48 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to reach Cmax	Baseline visit, 48 hours
Time to reach Tmax	Baseline visit, 48 hours
Mean residence time (MRT)	Baseline visit, 48 hours
Elimination rate constant (Kel)	Baseline visit, 48 hours
Apparent total body clearance (CL/F)	Baseline visit, 48 hours
Apparent volume of distribution (Vd/F)	Baseline visit, 48 hours
Terminal half-life (t1/2)	Baseline visit, 48 hours

Collaborators and Investigators

• Sponsor: Akebia Therapeutics
• Investigators: Study Director: Akebia, Sponsor GmbH

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 12, 2018
• Primary Completion (ACTUAL): May 23, 2018
• Study Completion (ACTUAL): May 23, 2018

Study Registration Dates

• First Submitted: June 12, 2018
• First Submitted That Met QC Criteria: August 16, 2018
• First Posted (ACTUAL): August 21, 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: vadadustat; HIF; AKB-6548; hypoxia-inducible factor; hypoxia-inducible factor prolyl-hydroxylase inhibitor; HIF-PHI
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Glycine Agents; Glycine
• Other Study ID Numbers: AKB-6548-CI-0027

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