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

Overview

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.

Full Title of Study: “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

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Sequential Assignment
    • Primary Purpose: Basic Science
    • Masking: None (Open Label)
  • Study Primary Completion Date: November 24, 2018

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

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

Arms, Groups and Cohorts

  • Experimental: Rosuvastatin, Vadadustat
    • Part 1: Subjects will receive rosuvastatin 20 mg alone, vadadustat 600 mg alone, followed by rosuvastatin 20 mg in combination with vadadustat 600 mg in a fixed-sequence dosing design.
  • Experimental: Sulfasalazine. Pravastatin, Vadadustat
    • Part 2, Arm 1: Subjects will receive sulfasalazine 500 mg alone followed by sulfasalazine 500 mg in combination with vadadustat 600 mg once a day in a fixed-sequence dosing design. Part 2, Arm 2: Subjects will receive pravastatin 40 mg alone followed by pravastatin 40 mg in combination with vadadustat 600 mg once a day in a fixed-sequence dosing design.
  • Experimental: Atorvastatin, Simvastatin, Vadadustat
    • Part 3, Arm 1: Subjects will receive atorvastatin 40 mg alone followed by atorvastatin 40 mg in combination with vadadustat 600 mg once a day in a fixed-sequence dosing design. Part 3, Arm 2: 24 subjects will receive simvastatin 40 mg alone followed by simvastatin 40 mg in combination with vadadustat 600 mg once a day in a fixed-sequence dosing design.

Clinical Trial Outcome Measures

Primary Measures

  • Area under plasma concentration-time curve from time 0 to last quantifiable concentration (AUClast) of rosuvastatin, sulfasalazine, pravastatin and simvastatin
    • Time Frame: Up to 10 weeks
  • Area under plasma concentration-time curve from time 0 to infinity (AUCinf) of rosuvastatin, sulfasalazine, pravastatin and simvastatin
    • Time Frame: Up to 10 weeks
  • Maximum observed plasma concentration (Cmax) of rosuvastatin. sulfasalazine, pravastatin, atorvastatin and simvastatin
    • Time Frame: Up to 10 weeks
  • Area under plasma concentration-time curve (AUCtau) of atorvastatin
    • Time Frame: Up to 10 weeks

Secondary Measures

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

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 55 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Akebia Therapeutics
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Akebia Inc, Study Director, Akebia Therapeutics

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.