Drug-Drug Interaction Study of Vadadustat With Cyclosporine, Probenecid and Rifampin
Phase 1
Completed
- Conditions
- Drug Interaction Potentiation
- Interventions
- Registration Number
- NCT03801746
- Lead Sponsor
- Akebia Therapeutics
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 40
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Vadadustat, Cyclosporine vadadustat Part 1: Arm 1: Subjects will receive vadadustat 300 mg alone and vadadustat 300 mg in combination with oral cyclosporine 500 mg in a crossover design Vadadustat, Cyclosporine Cyclosporins Part 1: Arm 1: Subjects will receive vadadustat 300 mg alone and vadadustat 300 mg in combination with oral cyclosporine 500 mg in a crossover design Vadadustat; Probenecid vadadustat Part 1: Arm 2: Subjects will receive vadadustat 300 mg alone and vadadustat 300 mg in combination with oral Probenecid 500 mg Q12h in a fixed sequence design Vadadustat; Probenecid Probenecid Part 1: Arm 2: Subjects will receive vadadustat 300 mg alone and vadadustat 300 mg in combination with oral Probenecid 500 mg Q12h in a fixed sequence design Vadadustat and Rifampin vadadustat Part 2: Subjects will receive vadadustat 300 mg alone and vadadustat 300 mg in combination with IV rifampin 600 mg in a cross-over design Vadadustat and Rifampin Rifampin Part 2: Subjects will receive vadadustat 300 mg alone and vadadustat 300 mg in combination with IV rifampin 600 mg in a cross-over design
- Primary Outcome Measures
Name Time Method Area under plasma concentration-time curve from 0 to last quantifiable concentration (AUClast) of vadadustat Up to 10 weeks Area under plasma concentration-time curve from 0 to infinity (AUCinf) of vadadustat Up to 10 weeks Maximum observed plasma concentration (Cmax) of vadadustat Up to 10 weeks
- Secondary Outcome Measures
Name Time Method Elimination rate constant (Kel) of vadadustat Up to 10 weeks Terminal half-life (t½) of vadadustat Up to 10 weeks Time to maximum observed plasma concentration (Tmax) of vadadustat Up to 10 weeks Maximum observed plasma concentration (Cmax) of vadadustat metabolites Up to 10 weeks Reporting of treatment emergent adverse events as reported by the study subject Up to 10 weeks Apparent total body clearance (CL/F) of vadadustat Up to 10 weeks Percent of extrapolated area under the curve from time t to infinity (%AUCextrap) of vadadustat Up to 10 weeks Renal clearance (CLr) of vadadustat and vadadustat 1-O-glucuronide excretion in urine for Part 1 Arm 2 (Probenecid) only Up to 10 weeks 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 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 Area under plasma concentration-time curve from 0 to last quantifiable concentration (AUClast) of vadadustat metabolites Up to 10 weeks Area under plasma concentration-time curve from 0 to infinity (AUCinf) of vadadustat metabolites Up to 10 weeks
Trial Locations
- Locations (1)
inVentiv Health Clinique Inc.
🇨🇦Québec City, Quebec, Canada