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

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

Detailed Description
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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.

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: vadadustat reference tablets
* Drug: vadadustat test tablets


Participation Criteria
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Eligibility Criteria
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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.

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
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Regimen A<br>vadadustat reference tablets | Drug: vadadustat reference tablets<br>* oral tablet<br>* Other names: AKB-6548;|
| Experimental: Regimen B<br>vadadustat test tablets | Drug: vadadustat test tablets<br>* oral tablet<br>* Other names: AKB-6548;|

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) |  | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hypoxia-inducible factor, hypoxia-inducible factor prolyl-hydroxylase inhibitor, HIF-PHI, HIF, vadadustat, AKB-6548