Drug-Drug Interaction Study of Vadadustat With Cyclosporine, Probenecid and Rifampin

Drug Interaction Potentiation Clinical Trial

Official title:

A Phase 1, Two-Part, Open-label Study in Healthy Adult Volunteers to Assess a Single Dose of Vadadustat as a Victim in Drug-Drug Interactions With Cyclosporine, Probenecid and Rifampin

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03801746
• Other study ID #: AKB-6548-CI-0029
• Status: Completed
• Phase: Phase 1
• Start date: July 20, 2018
• Est. completion date: August 15, 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 1, two-part, open-label study to evaluate the interaction of cyclosporine, probenecid, and rifampin as perpetrators with vadadustat (victim) in healthy male and female subjects.

Description:

This is a Phase 1, two-part, open-label study to evaluate the interaction of cyclosporine, probenecid, and rifampin as perpetrators with vadadustat (victim) in healthy male and female subjects. Part 1 consists of 2 arms (cyclosporine and probenecid) and Part 2 consists of 1 arm (rifampin). Twenty (20) unique subjects will be enrolled into each study arm. The PK and safety/tolerability data from Part 1 Arm 1 (cyclosporine) will determine if Part 2 (rifampin) will proceed. Subjects will be on study for up to 72 days, including a 28-day screening period, 6-10 day clinic period, and a 30-day follow-up period post last dose. Blood and/or urine samples for PK analysis will be collected at pre-defined timepoints throughout the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: August 15, 2018
• Est. primary completion date: August 15, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Healthy Male or female between 18 and 55 years of age, inclusive, at time of informed consent

• Body mass index between 18.0 and 30.0 kg/m2, with a minimum body weight of 45 kg for females and 50 kg for males, inclusive.

Exclusion Criteria:

• Current or past clinically significant history of cardiovascular, cerebrovascular, pulmonary, gastrointestinal, hematologic, renal, hepatic, immunologic, metabolic, urologic, neurologic, dermatologic, psychiatric, or other major disease. History of cancer (except treated non-melanoma skin cancer) or history of chemotherapy use within 5 years prior to Screening; History of latent or active tuberculosis (TB).

• Positive test results for human immunodeficiency virus (HIV) antibody; Positive test results of hepatitis B surface antigen (HBsAg), or positive hepatitis C virus antibody (HCVab) within 3 months prior to screening , or positive test results for human immunodeficiency virus antibody (HIVab) at Screening.

• Taking any prescription medication or over the counter multi-vitamin supplement, or any non-prescription products (including herbal-containing preparations but excluding acetaminophen) within 14 days prior to Day -1.

Related Conditions & MeSH terms

• Drug Interaction Potentiation

Intervention

Drug:
• vadadustat
Oral dose 300 mg
• Rifampin
IV Rifampin
• Probenecid
Oral Probenecid
• Cyclosporins
Oral Cyclosporine

Locations

Country	Name	City	State
Canada	inVentiv Health Clinique Inc.	Québec City	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
Akebia Therapeutics

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area under plasma concentration-time curve from 0 to last quantifiable concentration (AUClast) of vadadustat		Up to 10 weeks
Primary	Area under plasma concentration-time curve from 0 to infinity (AUCinf) of vadadustat		Up to 10 weeks
Primary	Maximum observed plasma concentration (Cmax) of vadadustat		Up to 10 weeks
Secondary	Time to maximum observed plasma concentration (Tmax) of vadadustat		Up to 10 weeks
Secondary	Elimination rate constant (Kel) of vadadustat		Up to 10 weeks
Secondary	Terminal half-life (t½) of vadadustat		Up to 10 weeks
Secondary	Apparent total body clearance (CL/F) of vadadustat		Up to 10 weeks
Secondary	Percent of extrapolated area under the curve from time t to infinity (%AUCextrap) of vadadustat		Up to 10 weeks
Secondary	Renal clearance (CLr) of vadadustat and vadadustat 1-O-glucuronide excretion in urine for Part 1 Arm 2 (Probenecid) only		Up to 10 weeks
Secondary	Cumulative amount excreted (Ae0-t) of vadadustat and vadadustat 1-O-glucuronide in urine for Part 1 Arm 2 (Probenecid) only		Up to 10 weeks
Secondary	Fraction (%) of the dose excreted (Fe%0-t) for Part 1 Arm 2 (Probenecid) only of vadadustat and vadadustat 1-O-glucuronide excretion in urine		Up to 10 weeks
Secondary	Area under plasma concentration-time curve from 0 to last quantifiable concentration (AUClast) of vadadustat metabolites		Up to 10 weeks
Secondary	Area under plasma concentration-time curve from 0 to infinity (AUCinf) of vadadustat metabolites		Up to 10 weeks
Secondary	Maximum observed plasma concentration (Cmax) of vadadustat metabolites		Up to 10 weeks
Secondary	Reporting of treatment emergent adverse events as reported by the study subject		Up to 10 weeks