A Single Dose Study of Oral Vadadustat in Subjects With Normal and Impaired Hepatic Function

Study Overview
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Brief Summary
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This is a Phase I open-label study to evaluate the pharmacokinetic (PK) profile of a single oral dose of vadadustat in subjects with hepatic impairment(HI) compared to healthy matched control subjects with normal hepatic function.

Detailed Description
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This is an open label, parallel-group, single dose, Phase 1 study to evaluate the PK profile, safety, and tolerability of a single oral 450 mg dose of vadadustat in subjects with hepatic impairment relative to control subjects with normal hepatic function. The study will enroll up to 24 subjects in 3 groups of 8 subjects at 2 study sites. Blood samples for vadadustat PK and its metabolites will be collected pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 60, and 72 hours post-dose.

Official Title
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Phase 1, Open-Label, Parallel-Group, Pharmacokinetic Single Dose Study of Oral Vadadustat in Subjects With Normal and Impaired Hepatic Function

Conditions
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Hepatic Impairment

Intervention / Treatment
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* Drug: Vadadustat


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (All groups): Male or female subjects between ≥18 years and ≤70 years of age Have a body weight ≥45 kg and body mass index (BMI) ≥18.5 kg/m2 to 40.0 kg/m2 Additional Group-Specific Inclusion Criteria: Group 1 (Moderate Hepatic Impairment Subjects): Presence of Moderate hepatic impairment (Child-Pugh Class B) Group 2 (Normal Hepatic Function Subjects): Normal hepatic function Group 3 (Mild Hepatic Impairment Subjects): Presence of mild hepatic impairment ( Child-Pugh Class A) Exclusion Criteria (all groups): Renal impairment ≥ Stage 3 (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73m2 using the Modification of Diet in Renal Disease (MDRD) study equation) Any history of active malignancy within 2 years prior to or during screening, except for treated basal cell carcinoma of skin, curatively resected squamous cell carcinoma of skin, or cervical carcinoma in situ; any history of tuberculosis and/or prophylaxis for tuberculosis Positive test for human immunodeficiency virus (HIV) antibody at Screening. Hepatic or other organ or cell transplant Subjects with alcoholic cirrhosis must be sober for a minimum of 6 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

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: Basic Science
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vadadustat<br>Group 1: Subjects with moderately impaired hepatic function (Child-Pugh Class B) Group 2: Normal healthy volunteers Group 3: Subjects with mildly impaired hepatic function (Child-Pugh Class A) | Drug: Vadadustat<br>* Oral tablet<br>* Other names: AKB-6548;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration-time curve from dosing to last measurable concentration (AUClast) |  | Day 1, Day 4 | 
| Area under the concentration-time curve from dosing to infinity (AUCinf) |  | Day 1, Day 4 | 
| Observed maximum concentration (Cmax). |  | Day 1, Day 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to reach Cmax of vadadustat |  | Day 1, Day 4 | 
| Apparent total body clearance (CL/F) of vadadustat |  | Day 1, Day 4 | 
| Apparent volume of distribution (Vd/F) of vadadustat |  | Day 1, Day 4 | 
| Terminal half-life (t1/2) of vadadustat |  | Day 1, Day 4 | 
| Time to reach Tmax of vadadustat |  | Day 1, Day 4 | 
| Assessment of Treatment-Emergent Adverse Events (TEAEs) as reported by study subjects |  | Up to 9 Weeks | 
| Cmax related to free drug (Cmax, free) of Vadadustat Unbound |  | Day 1, Day 4 | 
| AUClast related to free drug (AUClast, free) of Vadadustat Unbound |  | Day 1, Day 4 | 
| AUCinf related to free drug (AUCinf, free) of Vadadustat Unbound |  | Day 1, Day 4 | 
| CL/F related to free drug (CL/Ffree) of Vadadustat Unbound |  | Day 1, Day 4 | 
| Terminal half-life (t1/2) of Vadadustat Unbound |  | Day 1, Day 4 | 
| The area under the concentration-time curve from dosing to last measurable concentration (AUClast) of Vadadustat metabolites |  | Day 1, Day 4 | 
| The area under the concentration-time curve from dosing to infinity (AUCinf) of Vadadustat metabolite |  | Day 1, Day 4 | 
| Time to reach Cmax of vadadustat metabolites |  | Day 1, Day 4 | 
| Terminal half-life (t1/2) of Vadadustat metabolites |  | Day 1, Day 4 | 
| Renal clearance (CLr) of Vadadustat/metabolite(s) Urine |  | Day 1, Day 4 | 
| Cumulative amount of drug excreted (Ae) of Vadadustat/metabolite(s) Urine |  | Day 1, Day 4 | 
| Cumulative fraction of drug excreted (Fe) of Vadadustat/metabolite(s) Urine |  | Day 1, Day 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatic impairment, Healthy subjects, Child-pugh, Vadadustat