Clinical trial NCT03801733: Drug-Drug Interaction Study of Vadadustat With Rosuvastatin, Sulfasalazine, Pravastatin, Atorvastatin and Simvastatin
Official title: A Phase 1, Three-Part, Open-label Study in Healthy Adult Volunteers to Assess Vadadustat as a Perpetrator in Drug-Drug Interactions With Rosuvastatin, Sulfasalazine, Pravastatin, Atorvastatin and Simvastatin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Drug Interaction Potentiation
Keywords: Vadadustat
Normal Healthy volunteers
Pharmacokinetics
Rosuvastatin
Sulfasalazine
Pravastatin
Atrovastatin
Simvastatin
Lead sponsor: Akebia Therapeutics
Sponsor class: INDUSTRY
First posted: 2019-01-11
Enrollment: 134
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 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.
Primary purpose: BASIC_SCIENCE

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.

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; 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.

Primary outcomes:
measure: Area under plasma concentration-time curve from time 0 to last quantifiable concentration (AUClast) of rosuvastatin, sulfasalazine, pravastatin and simvastatin
timeFrame: Up to 10 weeks
measure: Area under plasma concentration-time curve from time 0 to infinity (AUCinf) of rosuvastatin, sulfasalazine, pravastatin and simvastatin
timeFrame: Up to 10 weeks
measure: Maximum observed plasma concentration (Cmax) of rosuvastatin. sulfasalazine, pravastatin, atorvastatin and simvastatin
timeFrame: Up to 10 weeks
measure: Area under plasma concentration-time curve (AUCtau) of atorvastatin
timeFrame: Up to 10 weeks
Secondary outcomes:
measure: Time to maximum observed plasma concentration (Tmax) of rosuvastatin, sulfasalazine, pravastatin, atorvastatin, and simvastatin
timeFrame: Up to 10 weeks
measure: Elimination rate constant (Kel) of rosuvastatin, sulfasalazine, pravastatin, atorvastatin, and simvastatin
timeFrame: Up to 10 weeks
measure: Terminal half-life (t½) of rosuvastatin, sulfasalazine, pravastatin, atorvastatin, and simvastatin
timeFrame: Up to 10 weeks
measure: Apparent total body clearance (CL/F) of rosuvastatin, sulfasalazine, pravastatin, atorvastatin, and simvastatin
timeFrame: Up to 10 weeks
measure: Percentage of extrapolated area under the curve from time t to infinity (%AUCextrap or Residual Area) of rosuvastatin, sulfasalazine, pravastatin, atorvastatin, and simvastatin
timeFrame: Up to 10 weeks
measure: Area under plasma concentration-time curve from time 0 to last quantifiable concentration (AUClast) of sulfasalazine metabolites, sulfapyridine and 5-ASA (mesalamine
timeFrame: Up to 10 weeks
measure: Area under plasma concentration-time curve from time 0 to infinity (AUCinf) of sulfasalazine metabolites, sulfapyridine and 5-ASA (mesalamine
timeFrame: Up to 10 weeks
measure: Maximum observed plasma concentration (Cmax) of sulfasalazine metabolites, sulfapyridine and 5-ASA (mesalamine
timeFrame: Up to 10 weeks
measure: Time to maximum observed plasma concentration (Tmax) of sulfasalazine metabolites, sulfapyridine and 5-ASA (mesalamine
timeFrame: Up to 10 weeks
measure: Elimination rate constant (Kel) of sulfasalazine metabolites, sulfapyridine and 5-ASA (mesalamine
timeFrame: Up to 10 weeks
measure: Terminal half-life (t½) of sulfasalazine metabolites, sulfapyridine and 5-ASA (mesalamine
timeFrame: Up to 10 weeks
measure: Area under the plasma concentration-time curve for a dosing interval (AUCtau) of atorvastatin metabolites, o-hydroxyatorvastatin; p-hydroxyatorvastatin
timeFrame: Up to 10 weeks
measure: Maximum observed plasma concentration (Cmax) of atorvastatin metabolites, o-hydroxyatorvastatin; p-hydroxyatorvastatin
timeFrame: Up to 10 weeks
measure: Time to maximum observed plasma concentration (Tmax) of atorvastatin metabolites, o-hydroxyatorvastatin; p-hydroxyatorvastatin
timeFrame: Up to 10 weeks
measure: Area under plasma concentration-time curve from time 0 to last quantifiable concentration (AUClast) of simvastatin metabolite
timeFrame: Up to 10 weeks
measure: Area under plasma concentration-time curve from time 0 to infinity (AUCinf) of simvastatin metabolite
timeFrame: Up to 10 weeks
measure: Maximum observed plasma concentration (Cmax) of simvastatin metabolite
timeFrame: Up to 10 weeks
measure: Time to maximum observed plasma concentration (Tmax) of simvastatin metabolite
timeFrame: Up to 10 weeks
measure: Elimination rate constant (Kel) of simvastatin metabolite
timeFrame: Up to 10 weeks
measure: Terminal half-life (t½), of simvastatin metabolite
timeFrame: Up to 10 weeks
measure: Reporting of treatment emergent adverse events (TEAE) as reported by the study subjects
timeFrame: Up to 10 weeks
Other outcomes:
Locations:
city: Québec City
country: Canada
facility: InVentiv Health Clinique Inc.
state: Quebec
Study officials:
affiliation: Akebia Therapeutics
name: Akebia Inc
role: STUDY_DIRECTOR
References: