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

Primary Purpose

Hepatic Impairment

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Vadadustat

About this trial

This is an interventional basic science trial for Hepatic Impairment focused on measuring Hepatic impairment, Healthy subjects, Child-pugh, Vadadustat

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Prism Clinical Research
American Research Corporation at the University of Texas Liver Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Vadadustat

Arm 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)

Outcomes

Primary Outcome Measures

Area under the concentration-time curve from dosing to last measurable concentration (AUClast)

Area under the concentration-time curve from dosing to infinity (AUCinf)

Observed maximum concentration (Cmax).

Secondary Outcome Measures

Time to reach Cmax of vadadustat

Apparent total body clearance (CL/F) of vadadustat

Apparent volume of distribution (Vd/F) of vadadustat

Terminal half-life (t1/2) of vadadustat

Time to reach Tmax of vadadustat

Assessment of Treatment-Emergent Adverse Events (TEAEs) as reported by study subjects

Cmax related to free drug (Cmax, free) of Vadadustat Unbound

AUClast related to free drug (AUClast, free) of Vadadustat Unbound

AUCinf related to free drug (AUCinf, free) of Vadadustat Unbound

CL/F related to free drug (CL/Ffree) of Vadadustat Unbound

Terminal half-life (t1/2) of Vadadustat Unbound

The area under the concentration-time curve from dosing to last measurable concentration (AUClast) of Vadadustat metabolites

The area under the concentration-time curve from dosing to infinity (AUCinf) of Vadadustat metabolite

Time to reach Cmax of vadadustat metabolites

Terminal half-life (t1/2) of Vadadustat metabolites

Renal clearance (CLr) of Vadadustat/metabolite(s) Urine

Cumulative amount of drug excreted (Ae) of Vadadustat/metabolite(s) Urine

Cumulative fraction of drug excreted (Fe) of Vadadustat/metabolite(s) Urine

Full Information

NCT ID

NCT03799848

First Posted

December 27, 2018

Last Updated

March 20, 2019

Sponsor

Akebia Therapeutics

1. Study Identification

Unique Protocol Identification Number

NCT03799848

Brief Title

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

2. Study Status

Record Verification Date

March 2019

Overall Recruitment Status

Completed

Study Start Date

June 12, 2018 (Actual)

Primary Completion Date

October 18, 2018 (Actual)

Study Completion Date

October 18, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Akebia Therapeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatic Impairment

Keywords

Hepatic impairment, Healthy subjects, Child-pugh, Vadadustat

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Vadadustat

Arm Type

Experimental

Arm 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)

Intervention Type

Drug

Intervention Name(s)

Vadadustat

Other Intervention Name(s)

AKB-6548

Intervention Description

Oral tablet

Primary Outcome Measure Information:

Title

Area under the concentration-time curve from dosing to last measurable concentration (AUClast)

Time Frame

Day 1, Day 4

Title

Area under the concentration-time curve from dosing to infinity (AUCinf)

Time Frame

Day 1, Day 4

Title

Observed maximum concentration (Cmax).

Time Frame

Day 1, Day 4

Secondary Outcome Measure Information:

Title

Time to reach Cmax of vadadustat

Time Frame

Day 1, Day 4

Title

Apparent total body clearance (CL/F) of vadadustat

Time Frame

Day 1, Day 4

Title

Apparent volume of distribution (Vd/F) of vadadustat

Time Frame

Day 1, Day 4

Title

Terminal half-life (t1/2) of vadadustat

Time Frame

Day 1, Day 4

Title

Time to reach Tmax of vadadustat

Time Frame

Day 1, Day 4

Title

Assessment of Treatment-Emergent Adverse Events (TEAEs) as reported by study subjects

Time Frame

Up to 9 Weeks

Title

Cmax related to free drug (Cmax, free) of Vadadustat Unbound

Time Frame

Day 1, Day 4

Title

AUClast related to free drug (AUClast, free) of Vadadustat Unbound

Time Frame

Day 1, Day 4

Title

AUCinf related to free drug (AUCinf, free) of Vadadustat Unbound

Time Frame

Day 1, Day 4

Title

CL/F related to free drug (CL/Ffree) of Vadadustat Unbound

Time Frame

Day 1, Day 4

Title

Terminal half-life (t1/2) of Vadadustat Unbound

Time Frame

Day 1, Day 4

Title

The area under the concentration-time curve from dosing to last measurable concentration (AUClast) of Vadadustat metabolites

Time Frame

Day 1, Day 4

Title

The area under the concentration-time curve from dosing to infinity (AUCinf) of Vadadustat metabolite

Time Frame

Day 1, Day 4

Title

Time to reach Cmax of vadadustat metabolites

Time Frame

Day 1, Day 4

Title

Terminal half-life (t1/2) of Vadadustat metabolites

Time Frame

Day 1, Day 4

Title

Renal clearance (CLr) of Vadadustat/metabolite(s) Urine

Time Frame

Day 1, Day 4

Title

Cumulative amount of drug excreted (Ae) of Vadadustat/metabolite(s) Urine

Time Frame

Day 1, Day 4

Title

Cumulative fraction of drug excreted (Fe) of Vadadustat/metabolite(s) Urine

Time Frame

Day 1, Day 4

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Akebia Therapeutics

Organizational Affiliation

Akebia Therapeutics

Official's Role

Study Director

Facility Information:

Facility Name

Prism Clinical Research

City

Saint Paul

State/Province

Minnesota

ZIP/Postal Code

55114

Country

United States

Facility Name

American Research Corporation at the University of Texas Liver Institute

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78215

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Undecided

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

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