Clinical trial NCT02412449: Relative Bioavailability of Two Formulations of AKB-6548 and the Food Effect of a New Tablet in Healthy Adult Subjects
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: 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
Lead sponsor: Akebia Therapeutics
Sponsor class: INDUSTRY
First posted: 2015-04-09
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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.


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.

Primary outcomes:
measure: Bioavailability endpoints: Area under the plasma concentration-time curve from 0 to last quantifiable concentration (AUC 0-t) of AKB-6548
timeFrame: Multiple timepoint evaluations from pre-dose to 24 hours post-dose
measure: Bioavailability endpoints: Area under the concentration time curve from time 0 to infinity (AUC 0-inf) of AKB-6548
timeFrame: Multiple timepoint evaluations from pre-dose to 24 hours post-dose
measure: Bioavailability endpoints: Maximum observed plasma concentration (Cmax) of AKB-6548
timeFrame: Multiple timepoint evaluations from pre-dose to 24 hours post-dose
measure: Food Effect Endpoint: AKB-6548 AUC 0-t for the fed versus fasted administration of AKB-6548 tablets
timeFrame: Multiple timepoint evaluations from pre-dose to 24 hours post-dose
measure: Food Effect Endpoint: AKB-6548 AUC 0-inf for the fed versus fasted administration of AKB-6548 tablets
timeFrame: Multiple timepoint evaluations from pre-dose to 24 hours post-dose
measure: Food Effect Endpoint: AKB-6548 Cmax for the fed versus fasted administration of AKB-6548 tablets
timeFrame: Multiple timepoint evaluations from pre-dose to 24 hours post-dose
Secondary outcomes:
measure: PK Parameters of AKB-6548: Maximum observed plasma concentration (Cmax)
timeFrame: Multiple timepoint evaluations from pre-dose to 24 hours post-dose
measure: PK Parameters of AKB-6548: Time to reach Cmax (Tmax)
timeFrame: Multiple timepoint evaluations from pre-dose to 24 hours post-dose
measure: PK Parameters of AKB-6548: Terminal elimination rate constant (λz)
timeFrame: Multiple timepoint evaluations from pre-dose to 24 hours post-dose
measure: PK Parameters of AKB-6548: Terminal elimination half-life (t1/2)
timeFrame: Multiple timepoint evaluations from pre-dose to 24 hours post-dose
measure: PK Parameters of AKB-6548: Area under the plasma concentration-time curve from 0 to last quantifiable concentration (AUC 0-t)
timeFrame: Multiple timepoint evaluations from pre-dose to 24 hours post-dose
measure: PK Parameters of AKB-6548: AUC from time 0 to infinity (AUC 0-inf)
timeFrame: Multiple timepoint evaluations from pre-dose to 24 hours post-dose
measure: AKB-6548: Apparent oral clearance (CL/F)
timeFrame: Multiple timepoint evaluations from pre-dose to 24 hours post-dose
measure: AKB-6548: Apparent volume of distribution during the terminal phase (Vz/F)
timeFrame: Multiple timepoint evaluations from pre-dose to 24 hours post-dose
Other outcomes:
Locations:
city: Kalamazoo
country: United States
state: Michigan
Study officials:
affiliation: Sponsor GmbH
name: Akebia Therapeutics
role: STUDY_DIRECTOR
References: