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Phase 1 Drug-Drug Interaction Study of Vadadustat With Cyclosporine, Probenecid and Rifampin

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ClinicalTrials.gov Identifier: NCT03801746
Recruitment Status : Active, not recruiting
First Posted : January 11, 2019
Last Update Posted : January 11, 2019
Sponsor:
Information provided by (Responsible Party):
Akebia Therapeutics

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.

Condition or disease Intervention/treatment Phase
Drug Interaction Potentiation Drug: vadadustat Drug: Rifampin Drug: Probenecid Drug: Cyclosporins Phase 1

Detailed Description:
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. Part 1 consists of 2 arms (cyclosporine and probenecid) and Part 2 consists of 1 arm (rifampin). Twenty (20) unique subjects will be enrolled into each study arm. The PK and safety/tolerability data from Part 1 Arm 1 (cyclosporine) will determine if Part 2 (rifampin) will proceed. Subjects will be on study for up to 72 days, including a 28-day screening period, 6-10 day clinic period, and a 30-day follow-up period post last dose. Blood and/or urine samples for PK analysis will be collected at pre-defined timepoints throughout the study.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: 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
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: A Phase 1, Two-Part, Open-label Study in Healthy Adult Volunteers to Assess a Single Dose of Vadadustat as a Victim in Drug-Drug Interactions With Cyclosporine, Probenecid and Rifampin
Actual Study Start Date : July 20, 2018
Estimated Primary Completion Date : January 30, 2019
Estimated Study Completion Date : February 24, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Drug Reactions

Arm Intervention/treatment
Experimental: Vadadustat, Cyclosporine
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
Oral dose 300 mg
Other Name: AKB 6548

Drug: Cyclosporins
Oral Cyclosporine

Experimental: Vadadustat; Probenecid
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
Oral dose 300 mg
Other Name: AKB 6548

Drug: Probenecid
Oral Probenecid

Experimental: Vadadustat and Rifampin
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
Oral dose 300 mg
Other Name: AKB 6548

Drug: Rifampin
IV Rifampin




Primary Outcome Measures :
  1. Area under plasma concentration-time curve from 0 to last quantifiable concentration (AUClast) of vadadustat [ Time Frame: Up to 10 weeks ]
  2. Area under plasma concentration-time curve from 0 to infinity (AUCinf) of vadadustat [ Time Frame: Up to 10 weeks ]
  3. Maximum observed plasma concentration (Cmax) of vadadustat [ Time Frame: Up to 10 weeks ]

Secondary Outcome Measures :
  1. Time to maximum observed plasma concentration (Tmax) of vadadustat [ Time Frame: Up to 10 weeks ]
  2. Elimination rate constant (Kel) of vadadustat [ Time Frame: Up to 10 weeks ]
  3. Terminal half-life (t½) of vadadustat [ Time Frame: Up to 10 weeks ]
  4. Apparent total body clearance (CL/F) of vadadustat [ Time Frame: Up to 10 weeks ]
  5. Percent of extrapolated area under the curve from time t to infinity (%AUCextrap) of vadadustat [ Time Frame: Up to 10 weeks ]
  6. Renal clearance (CLr) of vadadustat and vadadustat 1-O-glucuronide excretion in urine for Part 1 Arm 2 (Probenecid) only [ Time Frame: Up to 10 weeks ]
  7. Cumulative amount excreted (Ae0-t) of vadadustat and vadadustat 1-O-glucuronide in urine for Part 1 Arm 2 (Probenecid) only [ Time Frame: Up to 10 weeks ]
  8. Fraction (%) of the dose excreted (Fe%0-t) for Part 1 Arm 2 (Probenecid) only of vadadustat and vadadustat 1-O-glucuronide excretion in urine [ Time Frame: Up to 10 weeks ]
  9. Area under plasma concentration-time curve from 0 to last quantifiable concentration (AUClast) of vadadustat metabolites [ Time Frame: Up to 10 weeks ]
  10. Area under plasma concentration-time curve from 0 to infinity (AUCinf) of vadadustat metabolites [ Time Frame: Up to 10 weeks ]
  11. Maximum observed plasma concentration (Cmax) of vadadustat metabolites [ Time Frame: Up to 10 weeks ]
  12. Reporting of treatment emergent adverse events as reported by the study subject [ Time Frame: Up to 10 weeks ]


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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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; 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03801746


Locations
Canada, Quebec
inVentiv Health Clinique Inc.
Québec City, Quebec, Canada, G1P A02
Sponsors and Collaborators
Akebia Therapeutics
Investigators
Study Director: Akebia Inc Sponsor GmbH

Responsible Party: Akebia Therapeutics
ClinicalTrials.gov Identifier: NCT03801746     History of Changes
Other Study ID Numbers: AKB-6548-CI-0029
First Posted: January 11, 2019    Key Record Dates
Last Update Posted: January 11, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Akebia Therapeutics:
Healthy volunteers
vadadustat
drug interactions

Additional relevant MeSH terms:
Cyclosporins
Cyclosporine
Rifampin
Probenecid
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Antirheumatic Agents
Calcineurin Inhibitors
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP2C8 Inducers
Cytochrome P-450 CYP2C19 Inducers
Cytochrome P-450 CYP2C9 Inducers
Cytochrome P-450 CYP3A Inducers
Uricosuric Agents
Gout Suppressants
Renal Agents