Effects of Ferrous Sulfate on the Pharmacokinetics of AKB-6548

Study Overview
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Brief Summary
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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.

Official Title
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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.

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: AKB-6548
* Drug: Ferrous Sulfate


Participation Criteria
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Eligibility Criteria
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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

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

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AKB-6548<br>AKB-6548 | Drug: AKB-6548<br> <br> |
| Experimental: AKB-6548 plus Ferrous Sulfate<br>AKB-6548 plus ferrous sulfate | Drug: AKB-6548<br> <br> Drug: Ferrous Sulfate<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK parameters of AKB-6548: Maximum plasma concentration (Cmax) |  | Multiple timepoint evaluations from pre-dose to 24 hours post-dose | 
| PK parameters of AKB-6548: Area under the curve from time 0 until the last quantifiable concentration (AUC [last]) |  | Multiple timepoint evaluations from pre-dose to 24 hours post-dose | 
| PK parameters of AKB-6548: Area under the concentration-time curve from 0 to infinity (AUCinf) |  | 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: Time to maximum plasma concentration (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: Plasma half life (t1/2) |  | Multiple timepoint evaluations from pre-dose to 24 hours post-dose | 
| PK parameters of AKB-6548: Apparent total systemic clearance (CL/F) |  | Multiple timepoint evaluations from pre-dose to 24 hours post-dose | 
| PK parameters of AKB-6548: Apparent volume of distribution during the terminal elimination phase (VzF) |  | Multiple timepoint evaluations from pre-dose to 24 hours post-dose | 
| PK parameters of AKB-6548 metabolites: Maximum plasma concentration (Cmax) |  | Multiple timepoint evaluations from pre-dose to 24 hours post-dose | 
| PK parameters of AKB-6548 metabolites: Time to maximum plasma concentration (Tmax) |  | Multiple timepoint evaluations from pre-dose to 24 hours post-dose | 
| PK parameters of AKB-6548 metabolites: Terminal elimination rate constant (λz) |  | Multiple timepoint evaluations from pre-dose to 24 hours post-dose | 
| PK parameters of AKB-6548 metabolites: Plasma half life (t1/2) |  | Multiple timepoint evaluations from pre-dose to 24 hours post-dose | 
| PK parameters of AKB-6548 metabolites: Area under the curve from time 0 until the last quantifiable concentration (AUC [last]) |  | Multiple timepoint evaluations from pre-dose to 24 hours post-dose | 
| PK parameters of AKB-6548 metabolites: Area under the concentration-time curve from 0 to infinity (AUCinf) |  | Multiple timepoint evaluations from pre-dose to 24 hours post-dose | 
| Ratio of metabolite to parent drug for maximum plasma concentration (Cmax) |  | Multiple timepoint evaluations from pre-dose to 24 hours post-dose | 
| Ratio of metabolite to parent drug for are under the curve from time 0 until the last quantifiable concentration (AUC [last]) |  | Multiple timepoint evaluations from pre-dose to 24 hours post-dose | 
| Ratio of metabolite to parent drug for area under the concentration-time curve (AUC) |  | Multiple timepoint evaluations from pre-dose to 24 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIF-PHI, Drug-drug interaction, End stage renal disease, Erythropoietin, Pharmacokinetics, Anemia, Chronic kidney disease, CKD, Chronic renal insufficiency, Renal impairment, Ferrous sulfate, Iron, Dialysis, Oral anemia treatment, Hypoxia-induciable factor, HIF, Hypoxia-induciable factor prolyl-hydroxylase inhibitor