Clinical trial NCT02327546: Effects of Ferrous Sulfate on the Pharmacokinetics of AKB-6548
Official title: An Open-Label, Randomized, Single-Dose Study to Evaluate the Effects of 325 mg Ferrous Sulfate Tablet (65 mg Iron) on the Pharmacokinetics of 450 mg Dose of AKB-6548 in Healthy Male Volunteers.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Pharmacokinetics
Anemia
Chronic kidney disease
CKD
Chronic renal insufficiency
Renal impairment
Ferrous sulfate
Iron
Drug-drug interaction
End stage renal disease
Dialysis
Erythropoietin
Oral anemia treatment
Hypoxia-induciable factor
HIF
Hypoxia-induciable factor prolyl-hydroxylase inhibitor
HIF-PHI
Lead sponsor: Akebia Therapeutics
Sponsor class: INDUSTRY
First posted: 2014-12-30
Enrollment: 10
Sex: MALE
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 assess the single-dose bioavailability of AKB-6548 with ferrous sulfate relative to AKB-6548 in healthy volunteers.


Eligibility criteria: Inclusion Criteria:

* Healthy male subjects 18 to 55 years of age with a body mass index between 18 and 30 kg/m2
* Participants and their partners must use a highly effective form of contraception during the study and for 1 month following discharge from the Clinical Research Unit (CRU)
* Subjects must discontinue all iron preparations for 14 days prior to study drug administration

Exclusion Criteria:

* Current or past history of cardiovascular, cerebrovascular, pulmonary, renal or liver disease
* Positive serology results for HBsAg, HCV, and HIV at Screening
* Renal impairment (estimated glomerular filtration rate (eGFR) of \<65mL/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: PK parameters of AKB-6548: Maximum plasma concentration (Cmax)
timeFrame: Multiple timepoint evaluations from pre-dose to 24 hours post-dose
measure: PK parameters of AKB-6548: Area under the curve from time 0 until the last quantifiable concentration (AUC [last])
timeFrame: Multiple timepoint evaluations from pre-dose to 24 hours post-dose
measure: PK parameters of AKB-6548: Area under the concentration-time curve from 0 to infinity (AUCinf)
timeFrame: Multiple timepoint evaluations from pre-dose to 24 hours post-dose
Secondary outcomes:
measure: PK parameters of AKB-6548: Time to maximum plasma concentration (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: Plasma half life (t1/2)
timeFrame: Multiple timepoint evaluations from pre-dose to 24 hours post-dose
measure: PK parameters of AKB-6548: Apparent total systemic clearance (CL/F)
timeFrame: Multiple timepoint evaluations from pre-dose to 24 hours post-dose
measure: PK parameters of AKB-6548: Apparent volume of distribution during the terminal elimination phase (VzF)
timeFrame: Multiple timepoint evaluations from pre-dose to 24 hours post-dose
measure: PK parameters of AKB-6548 metabolites: Maximum plasma concentration (Cmax)
timeFrame: Multiple timepoint evaluations from pre-dose to 24 hours post-dose
measure: PK parameters of AKB-6548 metabolites: Time to maximum plasma concentration (Tmax)
timeFrame: Multiple timepoint evaluations from pre-dose to 24 hours post-dose
measure: PK parameters of AKB-6548 metabolites: Terminal elimination rate constant (λz)
timeFrame: Multiple timepoint evaluations from pre-dose to 24 hours post-dose
measure: PK parameters of AKB-6548 metabolites: Plasma half life (t1/2)
timeFrame: Multiple timepoint evaluations from pre-dose to 24 hours post-dose
measure: PK parameters of AKB-6548 metabolites: Area under the curve from time 0 until the last quantifiable concentration (AUC [last])
timeFrame: Multiple timepoint evaluations from pre-dose to 24 hours post-dose
measure: PK parameters of AKB-6548 metabolites: Area under the concentration-time curve from 0 to infinity (AUCinf)
timeFrame: Multiple timepoint evaluations from pre-dose to 24 hours post-dose
measure: Ratio of metabolite to parent drug for maximum plasma concentration (Cmax)
timeFrame: Multiple timepoint evaluations from pre-dose to 24 hours post-dose
measure: Ratio of metabolite to parent drug for are under the curve from time 0 until the last quantifiable concentration (AUC [last])
timeFrame: Multiple timepoint evaluations from pre-dose to 24 hours post-dose
measure: Ratio of metabolite to parent drug for area under the concentration-time curve (AUC)
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: