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

Phase 1

Completed

• Conditions: Healthy
• Interventions: 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

• Registration Number: NCT02412449
• Lead Sponsor: Akebia Therapeutics

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2015-04
• Primary Completion: 2015-04
• Study Completion: 2015-04
• Study First Submitted: 2015-04-01
• Study First Submitted QC: 2015-04-06
• Study First Posted: 2015-04-09
• Status Verified: 2018-11
• Last Update Submitted: 2018-11-10
• Last Update Posted: 2018-11-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 18

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Treatment A	AKB-6548 tablet, reference formulation given in the fasted state	AKB-6548
Treatment B	AKB-6548 tablet, test formulation given in the fasted state.	AKB-6548
Treatment C	AKB-6548 tablet, test formulation given in the fed state	AKB-6548

Primary Outcome Measures

Name	Time	Method
Bioavailability endpoints: Maximum observed plasma concentration (Cmax) of AKB-6548	Multiple timepoint evaluations from pre-dose to 24 hours post-dose
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
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

Name	Time	Method
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: 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: 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