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

March 20, 2019 updated by: Akebia Therapeutics

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
40

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Quebec
      • Québec City, Quebec, Canada, G1P A02
        • inVentiv Health Clinique Inc.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 Names:
  • 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 Names:
  • 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 Names:
  • AKB 6548
Drug: Rifampin
IV Rifampin

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Area under plasma concentration-time curve from 0 to last quantifiable concentration (AUClast) of vadadustat
Time Frame: Up to 10 weeks
Up to 10 weeks
Area under plasma concentration-time curve from 0 to infinity (AUCinf) of vadadustat
Time Frame: Up to 10 weeks
Up to 10 weeks
Maximum observed plasma concentration (Cmax) of vadadustat
Time Frame: Up to 10 weeks
Up to 10 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Time to maximum observed plasma concentration (Tmax) of vadadustat
Time Frame: Up to 10 weeks
Up to 10 weeks
Elimination rate constant (Kel) of vadadustat
Time Frame: Up to 10 weeks
Up to 10 weeks
Terminal half-life (t½) of vadadustat
Time Frame: Up to 10 weeks
Up to 10 weeks
Apparent total body clearance (CL/F) of vadadustat
Time Frame: Up to 10 weeks
Up to 10 weeks
Percent of extrapolated area under the curve from time t to infinity (%AUCextrap) of vadadustat
Time Frame: Up to 10 weeks
Up to 10 weeks
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
Up to 10 weeks
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
Up to 10 weeks
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
Up to 10 weeks
Area under plasma concentration-time curve from 0 to last quantifiable concentration (AUClast) of vadadustat metabolites
Time Frame: Up to 10 weeks
Up to 10 weeks
Area under plasma concentration-time curve from 0 to infinity (AUCinf) of vadadustat metabolites
Time Frame: Up to 10 weeks
Up to 10 weeks
Maximum observed plasma concentration (Cmax) of vadadustat metabolites
Time Frame: Up to 10 weeks
Up to 10 weeks
Reporting of treatment emergent adverse events as reported by the study subject
Time Frame: Up to 10 weeks
Up to 10 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Akebia Therapeutics

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Akebia Inc, Sponsor GmbH

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 20, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 15, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 15, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 27, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 9, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 11, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 22, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 20, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • AKB-6548-CI-0029

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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