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

Phase 1

Completed

• Conditions: Hepatic Impairment
• Interventions: Drug: Vadadustat

• Registration Number: NCT03799848
• Lead Sponsor: Akebia Therapeutics

Brief Summary

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

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.

Study Timeline

• Study Start: 2018-06-12
• Primary Completion: 2018-10-18
• Study Completion: 2018-10-18
• Study First Submitted: 2018-12-27
• Study First Submitted QC: 2019-01-09
• Study First Posted: 2019-01-10
• Status Verified: 2019-03
• Last Update Submitted: 2019-03-20
• Last Update Posted: 2019-03-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Vadadustat	Vadadustat	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)

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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
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
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

Trial Locations

Locations (2)

American Research Corporation at the University of Texas Liver Institute; 🇺🇸 San Antonio, Texas, United States

Prism Clinical Research; 🇺🇸 Saint Paul, Minnesota, United States