Drug Interaction PotentiationPhase 1NCT03801746
Drug-Drug Interaction Study of Vadadustat With Cyclosporine, Probenecid and Rifampin
A Phase 1 study testing vadadustat, Rifampin and Probenecid in people with Drug Interaction Potentiation, run by Akebia Therapeutics at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Drug Interaction Potentiation
- What is being tested?
- vadadustat, Rifampin and Probenecid
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteCanada
- Study dates
- 20 Jul 2018to 15 Aug 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- Drug Interaction Potentiation
- Being tested
- vadadustat, Rifampin, Probenecid, Cyclosporins
- Keywords
- Healthy volunteers, vadadustat, drug interactions
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
vadadustatDrug
Also called AKB 6548
Oral dose 300 mg
RifampinDrug
IV Rifampin
ProbenecidDrug
Oral Probenecid
CyclosporinsDrug
Oral Cyclosporine
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: Drug: vadadustat; Drug: Rifampin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under plasma concentration-time curve from 0 to last quantifiable concentration (AUClast) of vadadustat
Measured: Up to 10 weeks
Area under plasma concentration-time curve from 0 to infinity (AUCinf) of vadadustat
Measured: Up to 10 weeks
Maximum observed plasma concentration (Cmax) of vadadustat
Measured: Up to 10 weeks
Secondary outcomes (12)
Time to maximum observed plasma concentration (Tmax) of vadadustat
Measured: Up to 10 weeks
Elimination rate constant (Kel) of vadadustat
Measured: Up to 10 weeks
Terminal half-life (t½) of vadadustat
Measured: Up to 10 weeks
Apparent total body clearance (CL/F) of vadadustat
Measured: Up to 10 weeks
Percent of extrapolated area under the curve from time t to infinity (%AUCextrap) of vadadustat
Measured: Up to 10 weeks
Renal clearance (CLr) of vadadustat and vadadustat 1-O-glucuronide excretion in urine for Part 1 Arm 2 (Probenecid) only
Measured: 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
Measured: 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
Measured: Up to 10 weeks
Area under plasma concentration-time curve from 0 to last quantifiable concentration (AUClast) of vadadustat metabolites
Measured: Up to 10 weeks
Area under plasma concentration-time curve from 0 to infinity (AUCinf) of vadadustat metabolites
Measured: Up to 10 weeks
Maximum observed plasma concentration (Cmax) of vadadustat metabolites
Measured: Up to 10 weeks
Reporting of treatment emergent adverse events as reported by the study subject
Measured: Up to 10 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2019
- Study start20 Jul 2018
- Primary completion15 Aug 2018
- Study completion15 Aug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Drug Interaction PotentiationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Sequential
- 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)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Akebia Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Akebia Inc, Study director, Sponsor GmbH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03801746
- Sponsor's protocol ID
- AKB-6548-CI-0029
- Status last verified
- Mar 2019
- First submitted
- 27 Dec 2018
- Last updated
- 22 Mar 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03801746
- Acronym / sponsor ID
- AKB-6548-CI-0029
- Conditions
- Drug Interaction Potentiation
- Keywords
- Healthy volunteers, vadadustat, drug interactions
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Akebia TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 20 Jul 2018 (actual)
- Primary completion
- 15 Aug 2018 (actual)
- Study completion
- 15 Aug 2018 (actual)
- First posted
- 11 Jan 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
- 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
| Arm | Type | Receives |
|---|---|---|
| Vadadustat, Cyclosporine | Experimental | Drug: vadadustat, Drug: CyclosporinsPart 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 |
| Vadadustat; Probenecid | Experimental | Drug: vadadustat, Drug: ProbenecidPart 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 |
| Vadadustat and Rifampin | Experimental | Drug: vadadustat, Drug: RifampinPart 2: Subjects will receive vadadustat 300 mg alone and vadadustat 300 mg in combination with IV rifampin 600 mg in a cross-over design |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| vadadustatAlso: AKB 6548Oral dose 300 mg | Drug | Vadadustat and Rifampin, Vadadustat, Cyclosporine, Vadadustat; Probenecid |
| RifampinIV Rifampin | Drug | Vadadustat and Rifampin |
| ProbenecidOral Probenecid | Drug | Vadadustat; Probenecid |
| CyclosporinsOral Cyclosporine | Drug | Vadadustat, Cyclosporine |
Primary outcome
Area under plasma concentration-time curve from 0 to last quantifiable concentration (AUClast) of vadadustat
Time frame: Up to 10 weeks
Area under plasma concentration-time curve from 0 to infinity (AUCinf) of vadadustat
Time frame: Up to 10 weeks
Maximum observed plasma concentration (Cmax) of vadadustat
Time frame: Up to 10 weeks
12 secondary outcomes
Time to maximum observed plasma concentration (Tmax) of vadadustat
Time frame: Up to 10 weeks
Elimination rate constant (Kel) of vadadustat
Time frame: Up to 10 weeks
Terminal half-life (t½) of vadadustat
Time frame: Up to 10 weeks
Apparent total body clearance (CL/F) of vadadustat
Time frame: 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
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
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
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
Area under plasma concentration-time curve from 0 to last quantifiable concentration (AUClast) of vadadustat metabolites
Time frame: Up to 10 weeks
Area under plasma concentration-time curve from 0 to infinity (AUCinf) of vadadustat metabolites
Time frame: Up to 10 weeks
Maximum observed plasma concentration (Cmax) of vadadustat metabolites
Time frame: Up to 10 weeks
Reporting of treatment emergent adverse events as reported by the study subject
Time frame: Up to 10 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2019.
- Individual participant dataSharing planned: Undecided
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Akebia Inc study director
Sponsor GmbH
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing vadadustat, Rifampin and Probenecid in people with Drug Interaction Potentiation, run by Akebia Therapeutics at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area under plasma concentration-time curve from 0 to last quantifiable concentration (AUClast) of vadadustat (time frame: Up to 10 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Mar 2019.