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

Akebia Therapeutics

Status and phase: Completed; Phase 1

Conditions: Hepatic Impairment

Treatments: Drug: Vadadustat

Study type: Interventional

Funder types: Industry

Identifiers

NCT03799848

AKB-6548-CI-0024

Details and patient eligibility

About

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.

Full 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.

Enrollment: 24 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

24 participants in 1 patient group

Vadadustat

Experimental group

Description:

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)

Treatment:

Drug: Vadadustat