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

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

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.

Study Overview

• Status: Completed
• 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

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Kalamazoo, Michigan, United States, 49007

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Akebia Therapeutics

Study record dates

Study Major Dates

• Study Start: April 1, 2015
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: April 1, 2015
• First Submitted That Met QC Criteria: April 6, 2015
• First Posted (Estimate): April 9, 2015

Study Record Updates

• Last Update Posted (Actual): November 14, 2018
• Last Update Submitted That Met QC Criteria: November 10, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Erythropoietin; Pharmacokinetics; Anemia; Iron; CKD; Bioavailability; End stage renal disease; Chronic kidney disease; Dialysis; Volunteers; Renal impairment; Chronic renal insufficiency; Ferrous sulfate; Oral anemia treatment; Hypoxia-inducible factor
• 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-0013

Plan for Individual participant data (IPD)

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