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

Hepatic Impairment Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03799848
• Other study ID #: AKB-6548-CI-0024
• Status: Completed
• Phase: Phase 1
• Start date: June 12, 2018
• Est. completion date: October 18, 2018

Study information

• Verified date: March 2019
• Source: Akebia Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: October 18, 2018
• Est. primary completion date: October 18, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Hepatic Impairment
• Liver Diseases

Intervention

Drug:
• Vadadustat
Oral tablet

Locations

Country	Name	City	State
United States	Prism Clinical Research	Saint Paul	Minnesota
United States	American Research Corporation at the University of Texas Liver Institute	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Akebia Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

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