Clinical trial NCT03799848: A Single Dose Study of Oral Vadadustat in Subjects With Normal and Impaired Hepatic Function
Official title: Phase 1, Open-Label, Parallel-Group, Pharmacokinetic Single Dose Study of Oral Vadadustat in Subjects With Normal and Impaired Hepatic Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic Impairment
Keywords: Hepatic impairment
Healthy subjects
Child-pugh
Vadadustat
Lead sponsor: Akebia Therapeutics
Sponsor class: INDUSTRY
First posted: 2019-01-10
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

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.

Eligibility 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

Primary outcomes:
measure: Area under the concentration-time curve from dosing to last measurable concentration (AUClast)
timeFrame: Day 1, Day 4
measure: Area under the concentration-time curve from dosing to infinity (AUCinf)
timeFrame: Day 1, Day 4
measure: Observed maximum concentration (Cmax).
timeFrame: Day 1, Day 4
Secondary outcomes:
measure: Time to reach Cmax of vadadustat
timeFrame: Day 1, Day 4
measure: Apparent total body clearance (CL/F) of vadadustat
timeFrame: Day 1, Day 4
measure: Apparent volume of distribution (Vd/F) of vadadustat
timeFrame: Day 1, Day 4
measure: Terminal half-life (t1/2) of vadadustat
timeFrame: Day 1, Day 4
measure: Time to reach Tmax of vadadustat
timeFrame: Day 1, Day 4
measure: Assessment of Treatment-Emergent Adverse Events (TEAEs) as reported by study subjects
timeFrame: Up to 9 Weeks
measure: Cmax related to free drug (Cmax, free) of Vadadustat Unbound
timeFrame: Day 1, Day 4
measure: AUClast related to free drug (AUClast, free) of Vadadustat Unbound
timeFrame: Day 1, Day 4
measure: AUCinf related to free drug (AUCinf, free) of Vadadustat Unbound
timeFrame: Day 1, Day 4
measure: CL/F related to free drug (CL/Ffree) of Vadadustat Unbound
timeFrame: Day 1, Day 4
measure: Terminal half-life (t1/2) of Vadadustat Unbound
timeFrame: Day 1, Day 4
measure: The area under the concentration-time curve from dosing to last measurable concentration (AUClast) of Vadadustat metabolites
timeFrame: Day 1, Day 4
measure: The area under the concentration-time curve from dosing to infinity (AUCinf) of Vadadustat metabolite
timeFrame: Day 1, Day 4
measure: Time to reach Cmax of vadadustat metabolites
timeFrame: Day 1, Day 4
measure: Terminal half-life (t1/2) of Vadadustat metabolites
timeFrame: Day 1, Day 4
measure: Renal clearance (CLr) of Vadadustat/metabolite(s) Urine
timeFrame: Day 1, Day 4
measure: Cumulative amount of drug excreted (Ae) of Vadadustat/metabolite(s) Urine
timeFrame: Day 1, Day 4
measure: Cumulative fraction of drug excreted (Fe) of Vadadustat/metabolite(s) Urine
timeFrame: Day 1, Day 4
Other outcomes:
Locations:
city: Saint Paul
country: United States
facility: Prism Clinical Research
state: Minnesota
city: San Antonio
country: United States
facility: American Research Corporation at the University of Texas Liver Institute
state: Texas
Study officials:
affiliation: Akebia Therapeutics
name: Akebia Therapeutics
role: STUDY_DIRECTOR
References: