A Study in Evaluating Bioequivalence of Test and Reference Vadadustat 450 MG and 150 MG Tablets and to Determine Food Effect on the 450 MG Tablet

A Randomized, Open-Label, Single-Dose, Three-Period Six-Sequence Crossover Study in Healthy Adults to Assess Bioequivalence Between Test and Reference Vadadustat 450 mg and 150 mg Tablets and to Determine Food Effect on the 450 mg Vadadustat Tablet.

This is a healthy volunteers study to assess the bioequivalence of vadadustat 450 mg tablets (Test A) compared to three 150mg tablets (Reference B). The study will also assess the effect of food on the bioavailability of vadadustat 450 mg tablet.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: vadadustat

Detailed Description

This is a randomized, open-label, single-dose, three-period crossover study in healthy adults to assess the bioequivalence of 3 X 150 mg vadadustat tablets (Test) compared to a single 450 mg vadadustat tablet (reference). Blood samples for vadadustat PK will be collected at pre-dose (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 9, 12, 18, 24, 32, 40, and 48 hours post-dose. The study will also assess the effect of food on vadadustat bioavailability by evaluating the pharmacokinetics of the 450 mg tablet in fed and fasted subjects.

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21225
      • Paraxel International

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:

• Male or female subjects between ≥18 years and ≤55 years of age
• 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.
• Have a body weight ≥50 kg and body mass index (BMI) ≥18.5 kg/m2 to 29.5 kg/m2 inclusive
• Understands the procedures, provides ICF and willing to comply with study requirements
• 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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Treatment A; vadadustat 3 X 150 mg Tablets in fasted subjects	Drug: vadadustat; Vadadustat Tablets; Other Names: AKB-6548
ACTIVE_COMPARATOR: Treatment B; Vadadustat 1 X 450 mg Tablets in fasted subjects	Drug: vadadustat; Vadadustat Tablets; Other Names: AKB-6548
ACTIVE_COMPARATOR: Treatment C; vadadustat 1 X 450 mg Tablets in fed subjects	Drug: vadadustat; Vadadustat Tablets; Other Names: AKB-6548

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Bioequivalence - Area under plasma concentration-time curve from 0 to last quantifiable concentration (AUClast)	Baseline visit, 48 hours
Bioequivalence - Area under plasma concentration-time curve from 0 to infinity (AUCinf)	Baseline visit, 48 hours
Bioequivalence - Area under plasma concentration-time curve from 0 to last sampling point (AUCall)	Baseline visit, 48 hours
Bioequivalence - Observed Maximum concentration (Cmax)	Baseline visit, 48 hours
Measure Food Effect - Area under plasma concentration-time curve from 0 to last quantifiable concentration (AUClast)	Baseline visit, 48 hours
Measure Food Effect - 2. Area under plasma concentration-time curve from 0 to infinity (AUCinf)	Baseline visit, 48 hours
Measure Food Effect - 2.3. 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
Percentage of extrapolated area under the curve from time t to infinity (AUCextrap or Residual Area)	Baseline visit, 48 hours

Collaborators and Investigators

• Sponsor: Akebia Therapeutics

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 3, 2018
• Primary Completion (ACTUAL): October 16, 2018
• Study Completion (ACTUAL): October 16, 2018

Study Registration Dates

• First Submitted: August 31, 2018
• First Submitted That Met QC Criteria: September 4, 2018
• First Posted (ACTUAL): September 5, 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; bioequivalence; healthy volunteers; Vadadustat
• Other Study ID Numbers: AKB-6548-CI-0028

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