Clinical trial NCT03801746: Drug-Drug Interaction Study of Vadadustat With Cyclosporine, Probenecid and Rifampin
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Drug Interaction Potentiation
Keywords: Healthy volunteers
vadadustat
drug interactions
Lead sponsor: Akebia Therapeutics
Sponsor class: INDUSTRY
First posted: 2019-01-11
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: This is a 2 part study. Part 1 Arm 1 is a cross over design to assess the drug-drug interactions of cyclosporine with vadadustat. Part 1 Arm 2 is a fixed sequence design to assess the drug-drug interactions of probenecid with vadadustat. Part 2 is a crossover design to assess the drug-drug interaction of rifampin with vadadustat
Primary purpose: BASIC_SCIENCE

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Area under plasma concentration-time curve from 0 to last quantifiable concentration (AUClast) of vadadustat
timeFrame: Up to 10 weeks
measure: Area under plasma concentration-time curve from 0 to infinity (AUCinf) of vadadustat
timeFrame: Up to 10 weeks
measure: Maximum observed plasma concentration (Cmax) of vadadustat
timeFrame: Up to 10 weeks
Secondary outcomes:
measure: Time to maximum observed plasma concentration (Tmax) of vadadustat
timeFrame: Up to 10 weeks
measure: Elimination rate constant (Kel) of vadadustat
timeFrame: Up to 10 weeks
measure: Terminal half-life (t½) of vadadustat
timeFrame: Up to 10 weeks
measure: Apparent total body clearance (CL/F) of vadadustat
timeFrame: Up to 10 weeks
measure: Percent of extrapolated area under the curve from time t to infinity (%AUCextrap) of vadadustat
timeFrame: Up to 10 weeks
measure: Renal clearance (CLr) of vadadustat and vadadustat 1-O-glucuronide excretion in urine for Part 1 Arm 2 (Probenecid) only
timeFrame: Up to 10 weeks
measure: Cumulative amount excreted (Ae0-t) of vadadustat and vadadustat 1-O-glucuronide in urine for Part 1 Arm 2 (Probenecid) only
timeFrame: Up to 10 weeks
measure: 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
timeFrame: Up to 10 weeks
measure: Area under plasma concentration-time curve from 0 to last quantifiable concentration (AUClast) of vadadustat metabolites
timeFrame: Up to 10 weeks
measure: Area under plasma concentration-time curve from 0 to infinity (AUCinf) of vadadustat metabolites
timeFrame: Up to 10 weeks
measure: Maximum observed plasma concentration (Cmax) of vadadustat metabolites
timeFrame: Up to 10 weeks
measure: Reporting of treatment emergent adverse events as reported by the study subject
timeFrame: Up to 10 weeks
Other outcomes:
Locations:
city: Québec City
country: Canada
facility: inVentiv Health Clinique Inc.
state: Quebec
Study officials:
affiliation: Sponsor GmbH
name: Akebia Inc
role: STUDY_DIRECTOR
References: