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

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

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.

Study Overview

• Status: Completed
• Conditions: Hepatic Impairment
• Intervention / Treatment: Drug: Vadadustat

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 Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Saint Paul, Minnesota, United States, 55114
      • Prism Clinical Research
  • Texas
    • San Antonio, Texas, United States, 78215
      • American Research Corporation at the University of Texas Liver Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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)	Drug: Vadadustat; Oral tablet; Other Names: AKB-6548

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Akebia Therapeutics
• Investigators: Study Director: Akebia Therapeutics, Akebia Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): June 12, 2018
• Primary Completion (Actual): October 18, 2018
• Study Completion (Actual): October 18, 2018

Study Registration Dates

• First Submitted: December 27, 2018
• First Submitted That Met QC Criteria: January 9, 2019
• First Posted (Actual): January 10, 2019

Study Record Updates

• Last Update Posted (Actual): March 22, 2019
• Last Update Submitted That Met QC Criteria: March 20, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Healthy subjects; Hepatic impairment; Vadadustat; Child-pugh
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: AKB-6548-CI-0024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No