Drug Interaction Potentiation
Conditions
Keywords
Vadadustat, Normal Healthy volunteers, Pharmacokinetics, Rosuvastatin, Sulfasalazine, Pravastatin, Atrovastatin, Simvastatin
Brief summary
This is a Phase 1, three-part, open-label study to evaluate vadadustat as a perpetrator in drug-drug interactions with rosuvastatin, sulfasalazine, pravastatin, atorvastatin and simvastatin in healthy male and female subjects.
Detailed description
This is a Phase 1, three-part, open-label study to evaluate vadadustat as a perpetrator in drug-drug interactions with rosuvastatin, sulfasalazine, pravastatin, atorvastatin, and simvastatin in healthy male and female subjects. Thirty-four (34) subjects will be enrolled in Part 1 (rosuvastatin) and based on review of the PK and safety/tolerability data, a decision will be made on whether to proceed with Part 2. Part 2 consists of 2 arms (sulfasalazine and pravastatin). Twenty-six (26) subjects will be enrolled into each arm. Part 3 consists of 2 arms (atorvastatin and simvastatin). Twenty-four (24) subjects will be enrolled into each arm after enrollment in Part 2 is completed. Subjects will be in the study for up to 72 days, including a 28-day screening period, 6-14 day in clinic period, and a 30-day follow up period post last dose. Blood samples for PK analysis will be collected at pre-defined time points throughout the study.
Interventions
DRUGVadadustat
Oral dose of 600 mg QD
DRUGSimvastatin
Oral Simvastatin
DRUGRosuvastatin
Oral Rosuvastatin
DRUGAtorvastatin
Oral Atorvastatin
DRUGPravastatin
Oral Pravastatin
DRUGSulfasalazine
Oral Sulfasalazine
Sponsors
Akebia Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
This is a three-part sequential design study. Part 2 will be initiated based upon the outcome of Part 1 and Part 3 will be initiated after completion of Part 2.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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; 12. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Area under plasma concentration-time curve from time 0 to last quantifiable concentration (AUClast) of rosuvastatin, sulfasalazine, pravastatin and simvastatin | Up to 10 weeks |
| Area under plasma concentration-time curve from time 0 to infinity (AUCinf) of rosuvastatin, sulfasalazine, pravastatin and simvastatin | Up to 10 weeks |
| Maximum observed plasma concentration (Cmax) of rosuvastatin. sulfasalazine, pravastatin, atorvastatin and simvastatin | Up to 10 weeks |
| Area under plasma concentration-time curve (AUCtau) of atorvastatin | Up to 10 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of extrapolated area under the curve from time t to infinity (%AUCextrap or Residual Area) of rosuvastatin, sulfasalazine, pravastatin, atorvastatin, and simvastatin | Up to 10 weeks |
| Area under plasma concentration-time curve from time 0 to last quantifiable concentration (AUClast) of sulfasalazine metabolites, sulfapyridine and 5-ASA (mesalamine | Up to 10 weeks |
| Area under plasma concentration-time curve from time 0 to infinity (AUCinf) of sulfasalazine metabolites, sulfapyridine and 5-ASA (mesalamine | Up to 10 weeks |
| Maximum observed plasma concentration (Cmax) of sulfasalazine metabolites, sulfapyridine and 5-ASA (mesalamine | Up to 10 weeks |
| Time to maximum observed plasma concentration (Tmax) of sulfasalazine metabolites, sulfapyridine and 5-ASA (mesalamine | Up to 10 weeks |
| Elimination rate constant (Kel) of sulfasalazine metabolites, sulfapyridine and 5-ASA (mesalamine | Up to 10 weeks |
| Terminal half-life (t½) of sulfasalazine metabolites, sulfapyridine and 5-ASA (mesalamine | Up to 10 weeks |
| Area under the plasma concentration-time curve for a dosing interval (AUCtau) of atorvastatin metabolites, o-hydroxyatorvastatin; p-hydroxyatorvastatin | Up to 10 weeks |
| Time to maximum observed plasma concentration (Tmax) of rosuvastatin, sulfasalazine, pravastatin, atorvastatin, and simvastatin | Up to 10 weeks |
| Time to maximum observed plasma concentration (Tmax) of atorvastatin metabolites, o-hydroxyatorvastatin; p-hydroxyatorvastatin | Up to 10 weeks |
| Area under plasma concentration-time curve from time 0 to last quantifiable concentration (AUClast) of simvastatin metabolite | Up to 10 weeks |
| Area under plasma concentration-time curve from time 0 to infinity (AUCinf) of simvastatin metabolite | Up to 10 weeks |
| Maximum observed plasma concentration (Cmax) of simvastatin metabolite | Up to 10 weeks |
| Time to maximum observed plasma concentration (Tmax) of simvastatin metabolite | Up to 10 weeks |
| Elimination rate constant (Kel) of simvastatin metabolite | Up to 10 weeks |
| Terminal half-life (t½), of simvastatin metabolite | Up to 10 weeks |
| Reporting of treatment emergent adverse events (TEAE) as reported by the study subjects | Up to 10 weeks |
| Maximum observed plasma concentration (Cmax) of atorvastatin metabolites, o-hydroxyatorvastatin; p-hydroxyatorvastatin | Up to 10 weeks |
| Elimination rate constant (Kel) of rosuvastatin, sulfasalazine, pravastatin, atorvastatin, and simvastatin | Up to 10 weeks |
| Terminal half-life (t½) of rosuvastatin, sulfasalazine, pravastatin, atorvastatin, and simvastatin | Up to 10 weeks |
| Apparent total body clearance (CL/F) of rosuvastatin, sulfasalazine, pravastatin, atorvastatin, and simvastatin | Up to 10 weeks |
Countries
Canada
Outcome results
None listed