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

NCT03801733 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: AKB 6548 CI 0030
• Study Type: interventional
• Target: 134
• Locations: 1 country
• Sites: 1

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.

Conditions

Drug Interaction Potentiation

Keywords

Vadadustat; Normal Healthy volunteers; Pharmacokinetics; Rosuvastatin; Sulfasalazine; Pravastatin; Atrovastatin; Simvastatin

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (21)

• Time to maximum observed plasma concentration (Tmax) of rosuvastatin, sulfasalazine, pravastatin, atorvastatin, and simvastatin

  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

• 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

Study Arms (3)

Rosuvastatin, Vadadustat

EXPERIMENTAL

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.

Drug: Vadadustat; Drug: Rosuvastatin

Sulfasalazine. Pravastatin, Vadadustat

EXPERIMENTAL

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.

Drug: Vadadustat; Drug: Pravastatin; Drug: Sulfasalazine

Atorvastatin, Simvastatin, Vadadustat

EXPERIMENTAL

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.

Drug: Vadadustat; Drug: Simvastatin; Drug: Atorvastatin

Interventions

Vadadustat DRUG

Oral dose of 600 mg QD

Also known as: AKB 6548

Atorvastatin, Simvastatin, Vadadustat; Rosuvastatin, Vadadustat; Sulfasalazine. Pravastatin, Vadadustat

Simvastatin DRUG

Oral Simvastatin

Atorvastatin, Simvastatin, Vadadustat

Rosuvastatin DRUG

Oral Rosuvastatin

Rosuvastatin, Vadadustat

Atorvastatin DRUG

Oral Atorvastatin

Atorvastatin, Simvastatin, Vadadustat

Pravastatin DRUG

Oral Pravastatin

Sulfasalazine. Pravastatin, Vadadustat

Sulfasalazine DRUG

Oral Sulfasalazine

Sulfasalazine. Pravastatin, Vadadustat

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Akebia Therapeutics: lead

Study Sites (1)

InVentiv Health Clinique Inc.

Québec, Quebec, G1P A02, Canada

Location

MeSH Terms

Interventions

vadadustat; Simvastatin; Rosuvastatin Calcium; Atorvastatin; Pravastatin; Sulfasalazine

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Sulfonamides; Amides; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrroles; Azoles; Heptanoic Acids; Fatty Acids; Lipids

Study Officials

• Akebia Inc

  Akebia Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: December 27, 2018
• First Posted: January 11, 2019
• Study Start: June 17, 2018
• Primary Completion: November 24, 2018
• Study Completion: November 24, 2018
• Last Updated: March 22, 2019

Record last verified: 2019-03

Locations

CA (1)