Drug-Drug Interaction Study of Vadadustat With Cyclosporine, Probenecid and Rifampin

NCT03801746 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: AKB-6548-CI-0029
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1, two-part, open-label study to evaluate the interaction of cyclosporine, probenecid, and rifampin as perpetrators with vadadustat (victim) in healthy male and female subjects.

Conditions

Drug Interaction Potentiation

Keywords

Healthy volunteers; vadadustat; drug interactions

Outcome Measures

Primary Outcomes (3)

• Area under plasma concentration-time curve from 0 to last quantifiable concentration (AUClast) of vadadustat

  Up to 10 weeks

• Area under plasma concentration-time curve from 0 to infinity (AUCinf) of vadadustat

  Up to 10 weeks

• Maximum observed plasma concentration (Cmax) of vadadustat

  Up to 10 weeks

Secondary Outcomes (12)

• Time to maximum observed plasma concentration (Tmax) of vadadustat

  Up to 10 weeks

• Elimination rate constant (Kel) of vadadustat

  Up to 10 weeks

• Terminal half-life (t½) of vadadustat

  Up to 10 weeks

• Apparent total body clearance (CL/F) of vadadustat

  Up to 10 weeks

• Percent of extrapolated area under the curve from time t to infinity (%AUCextrap) of vadadustat

  Up to 10 weeks

Study Arms (3)

Vadadustat, Cyclosporine

EXPERIMENTAL

Part 1: Arm 1: Subjects will receive vadadustat 300 mg alone and vadadustat 300 mg in combination with oral cyclosporine 500 mg in a crossover design

Drug: vadadustat; Drug: Cyclosporins

Vadadustat; Probenecid

EXPERIMENTAL

Part 1: Arm 2: Subjects will receive vadadustat 300 mg alone and vadadustat 300 mg in combination with oral Probenecid 500 mg Q12h in a fixed sequence design

Drug: vadadustat; Drug: Probenecid

Vadadustat and Rifampin

EXPERIMENTAL

Part 2: Subjects will receive vadadustat 300 mg alone and vadadustat 300 mg in combination with IV rifampin 600 mg in a cross-over design

Drug: vadadustat; Drug: Rifampin

Interventions

vadadustat DRUG

Oral dose 300 mg

Also known as: AKB 6548

Vadadustat and Rifampin; Vadadustat, Cyclosporine; Vadadustat; Probenecid

Rifampin DRUG

IV Rifampin

Vadadustat and Rifampin

Probenecid DRUG

Oral Probenecid

Vadadustat; Probenecid

Cyclosporins DRUG

Oral Cyclosporine

Vadadustat, Cyclosporine

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; 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; Rifampin; Probenecid; Cyclosporins

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Peptides, Cyclic; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Akebia Inc

  Sponsor GmbH

  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 2 part study. Part 1 Arm 1 is a cross over design to assess the drug-drug interactions of cyclosporine with vadadustat. Part 1 Arm 2 is a fixed sequence design to assess the drug-drug interactions of probenecid with vadadustat. Part 2 is a crossover design to assess the drug-drug interaction of rifampin with vadadustat

Study Record Dates

• First Submitted: December 27, 2018
• First Posted: January 11, 2019
• Study Start: July 20, 2018
• Primary Completion: August 15, 2018
• Study Completion: August 15, 2018
• Last Updated: March 22, 2019

Record last verified: 2019-03

Locations

CA (1)