Relative Bioavailability of Two Formulations of AKB-6548 and the Food Effect of a New Tablet in Healthy Adult Subjects

Study Overview
=================
Brief Summary
-----------------
The primary purpose of this study is to compare the PK parameters of a single dose of a test tablet formulation of AKB-6548 relative to a single dose of the reference AKB-6548 tablet formulation, both treatments administered without food, and to compare the PK parameters of the test tablet formulation given under fed and fasted conditions.

Official Title
-----------------
A Randomized, Open-Label, Single-Dose, Three-Period Crossover Study in Healthy Adults to Assess the Relative Bioavailability of Test and Reference Formulations of AKB-6548 Tablets and to Evaluate the Effect of Food on the Bioavailability of AKB-6548

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: AKB-6548 tablet, reference formulation given in the fasted state
* Drug: AKB-6548 tablet, test formulation given in the fasted state.
* Drug: AKB-6548 tablet, test formulation given in the fed state


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy male and female subjects between 18 and 55 years of age, inclusive, and with a body mass index between 18 and 30 kg/m2, inclusive. Exclusion Criteria: Current or past history of cardiovascular, cerebrovascular, pulmonary, renal or liver disease. Positive serology results for HBsAg, HCV, and HIV at Screening. Significant renal impairment as evidenced by an estimated glomerular filtration rate (eGFR) of <65 mL/min Known active cancer (except non-melanoma skin cancer) or history of chemotherapy use within the previous 24 months. Current or past history of gastric or duodenal ulcers or other diseases of the GI tract (including gastric bypass surgeries) that could interfere with absorption of study drug. Subjects with a known history of smoking and/or have used nicotine or nicotine-containing products within the past 6 months.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A<br>AKB-6548 | Drug: AKB-6548 tablet, reference formulation given in the fasted state<br> <br> |
| Experimental: Treatment B<br>AKB-6548 | Drug: AKB-6548 tablet, test formulation given in the fasted state.<br> <br> |
| Experimental: Treatment C<br>AKB-6548 | Drug: AKB-6548 tablet, test formulation given in the fed state<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bioavailability endpoints: Area under the plasma concentration-time curve from 0 to last quantifiable concentration (AUC 0-t) of AKB-6548 |  | Multiple timepoint evaluations from pre-dose to 24 hours post-dose | 
| Bioavailability endpoints: Area under the concentration time curve from time 0 to infinity (AUC 0-inf) of AKB-6548 |  | Multiple timepoint evaluations from pre-dose to 24 hours post-dose | 
| Bioavailability endpoints: Maximum observed plasma concentration (Cmax) of AKB-6548 |  | Multiple timepoint evaluations from pre-dose to 24 hours post-dose | 
| Food Effect Endpoint: AKB-6548 AUC 0-t for the fed versus fasted administration of AKB-6548 tablets |  | Multiple timepoint evaluations from pre-dose to 24 hours post-dose | 
| Food Effect Endpoint: AKB-6548 AUC 0-inf for the fed versus fasted administration of AKB-6548 tablets |  | Multiple timepoint evaluations from pre-dose to 24 hours post-dose | 
| Food Effect Endpoint: AKB-6548 Cmax for the fed versus fasted administration of AKB-6548 tablets |  | Multiple timepoint evaluations from pre-dose to 24 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK Parameters of AKB-6548: Maximum observed plasma concentration (Cmax) |  | Multiple timepoint evaluations from pre-dose to 24 hours post-dose | 
| PK Parameters of AKB-6548: Time to reach Cmax (Tmax) |  | Multiple timepoint evaluations from pre-dose to 24 hours post-dose | 
| PK Parameters of AKB-6548: Terminal elimination rate constant (λz) |  | Multiple timepoint evaluations from pre-dose to 24 hours post-dose | 
| PK Parameters of AKB-6548: Terminal elimination half-life (t1/2) |  | Multiple timepoint evaluations from pre-dose to 24 hours post-dose | 
| PK Parameters of AKB-6548: Area under the plasma concentration-time curve from 0 to last quantifiable concentration (AUC 0-t) |  | Multiple timepoint evaluations from pre-dose to 24 hours post-dose | 
| PK Parameters of AKB-6548: AUC from time 0 to infinity (AUC 0-inf) |  | Multiple timepoint evaluations from pre-dose to 24 hours post-dose | 
| AKB-6548: Apparent oral clearance (CL/F) |  | Multiple timepoint evaluations from pre-dose to 24 hours post-dose | 
| AKB-6548: Apparent volume of distribution during the terminal phase (Vz/F) |  | Multiple timepoint evaluations from pre-dose to 24 hours post-dose | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pharmacokinetics, Anemia, Chronic kidney disease, CKD, Renal impairment, Chronic renal insufficiency, Ferrous sulfate, Iron, End stage renal disease, Dialysis, Oral anemia treatment, Bioavailability, Erythropoietin, Hypoxia-inducible factor, Volunteers