Drug-Drug Interaction Study of Vadadustat With Rosuvastatin, Sulfasalazine, Pravastatin, Atorvastatin and Simvastatin

Drug Interaction Potentiation Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03801733
• Other study ID #: AKB 6548 CI 0030
• Status: Completed
• Phase: Phase 1
• Start date: June 17, 2018
• Est. completion date: November 24, 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, 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 134
• Est. completion date: November 24, 2018
• Est. primary completion date: November 24, 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; 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.

Related Conditions & MeSH terms

• Drug Interaction Potentiation

Intervention

Drug:
• Vadadustat
Oral dose of 600 mg QD
• Simvastatin
Oral Simvastatin
• Rosuvastatin
Oral Rosuvastatin
• Atorvastatin
Oral Atorvastatin
• Pravastatin
Oral Pravastatin
• Sulfasalazine
Oral Sulfasalazine

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 time 0 to last quantifiable concentration (AUClast) of rosuvastatin, sulfasalazine, pravastatin and simvastatin		Up to 10 weeks
Primary	Area under plasma concentration-time curve from time 0 to infinity (AUCinf) of rosuvastatin, sulfasalazine, pravastatin and simvastatin		Up to 10 weeks
Primary	Maximum observed plasma concentration (Cmax) of rosuvastatin. sulfasalazine, pravastatin, atorvastatin and simvastatin		Up to 10 weeks
Primary	Area under plasma concentration-time curve (AUCtau) of atorvastatin		Up to 10 weeks
Secondary	Time to maximum observed plasma concentration (Tmax) of rosuvastatin, sulfasalazine, pravastatin, atorvastatin, and simvastatin		Up to 10 weeks
Secondary	Elimination rate constant (Kel) of rosuvastatin, sulfasalazine, pravastatin, atorvastatin, and simvastatin		Up to 10 weeks
Secondary	Terminal half-life (t½) of rosuvastatin, sulfasalazine, pravastatin, atorvastatin, and simvastatin		Up to 10 weeks
Secondary	Apparent total body clearance (CL/F) of rosuvastatin, sulfasalazine, pravastatin, atorvastatin, and simvastatin		Up to 10 weeks
Secondary	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
Secondary	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
Secondary	Area under plasma concentration-time curve from time 0 to infinity (AUCinf) of sulfasalazine metabolites, sulfapyridine and 5-ASA (mesalamine		Up to 10 weeks
Secondary	Maximum observed plasma concentration (Cmax) of sulfasalazine metabolites, sulfapyridine and 5-ASA (mesalamine		Up to 10 weeks
Secondary	Time to maximum observed plasma concentration (Tmax) of sulfasalazine metabolites, sulfapyridine and 5-ASA (mesalamine		Up to 10 weeks
Secondary	Elimination rate constant (Kel) of sulfasalazine metabolites, sulfapyridine and 5-ASA (mesalamine		Up to 10 weeks
Secondary	Terminal half-life (t½) of sulfasalazine metabolites, sulfapyridine and 5-ASA (mesalamine		Up to 10 weeks
Secondary	Area under the plasma concentration-time curve for a dosing interval (AUCtau) of atorvastatin metabolites, o-hydroxyatorvastatin; p-hydroxyatorvastatin		Up to 10 weeks
Secondary	Maximum observed plasma concentration (Cmax) of atorvastatin metabolites, o-hydroxyatorvastatin; p-hydroxyatorvastatin		Up to 10 weeks
Secondary	Time to maximum observed plasma concentration (Tmax) of atorvastatin metabolites, o-hydroxyatorvastatin; p-hydroxyatorvastatin		Up to 10 weeks
Secondary	Area under plasma concentration-time curve from time 0 to last quantifiable concentration (AUClast) of simvastatin metabolite		Up to 10 weeks
Secondary	Area under plasma concentration-time curve from time 0 to infinity (AUCinf) of simvastatin metabolite		Up to 10 weeks
Secondary	Maximum observed plasma concentration (Cmax) of simvastatin metabolite		Up to 10 weeks
Secondary	Time to maximum observed plasma concentration (Tmax) of simvastatin metabolite		Up to 10 weeks
Secondary	Elimination rate constant (Kel) of simvastatin metabolite		Up to 10 weeks
Secondary	Terminal half-life (t½), of simvastatin metabolite		Up to 10 weeks
Secondary	Reporting of treatment emergent adverse events (TEAE) as reported by the study subjects		Up to 10 weeks