Drug Interaction PotentiationPhase 1NCT03801759
Drug-Drug Interaction Study of Vadadustat With Digoxin, Adefovir and Furosemide
A Phase 1 study testing Vadadustat, Furosemide and Adefovir in people with Drug Interaction Potentiation, run by Akebia Therapeutics at 1 site in Canada.
Trial summary
This is a Phase 1, open-label, 3-arm, fixed sequence, study to evaluate vadadustat as a perpetrator of drug-drug interactions (DDIs) with digoxin, adefovir and furosemide 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, Furosemide and Adefovir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 62 participants
- Where
- 1 siteCanada
- Study dates
- 20 Jul 2018to 30 Sep 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.
- 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 Open-label, Three Arm Study in Healthy Adult Volunteers to Assess Vadadustat as a Perpetrator in Drug-Drug-Interactions With Digoxin, Adefovir and Furosemide
This is a Phase 1, open-label, 3-arm, fixed sequence, study to evaluate vadadustat as a perpetrator of drug-drug interactions (DDIs) with digoxin, adefovir and furosemide in healthy male and female subjects.
Read the detailed description
This is a Phase 1, open-label, 3-arm, fixed sequence, study to evaluate vadadustat as a perpetrator of drug-drug interactions (DDIs) with digoxin, adefovir and furosemide in healthy male and female subjects. Unique subjects will be enrolled into each arm of the study and enrollment will be sequential. The first 20 subjects confirmed to be eligible will be assigned to Arm 1 (digoxin), the next 16 subjects will be assigned to Arm 2 (adefovir) and the next 22 subjects will be assigned to Arm 3 (furosemide). Blood samples for PK analysis will be collected at pre-defined timepoints for each arm throughout the study. Subjects will be on study for up to 80 days, including a 28-day screening period, 7-21 day in clinic period, and a 30-day follow up period post last dose.
- Conditions
- Drug Interaction Potentiation
- Being tested
- Vadadustat, Furosemide, Adefovir, Digoxin
- Keywords
- vadadustat, drug interactions, healthy volunteers
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 600 mg
FurosemideDrug
Oral Furosemide
AdefovirDrug
Oral Adefovir
DigoxinDrug
Oral Digoxin
| Study group | Role | What they receive |
|---|---|---|
| Vadadustat, digoxin | Experimental | Arm 1: Subjects will receive a single oral dose of digoxin 0.5 mg alone, followed by a washout period and repeat doses of vadadustat 600 mg QD alone and in combination with a single dose of digoxin 0.5 mg. Receives: Drug: Vadadustat; Drug: Digoxin |
| Vadadustat, adefovir | Experimental | Arm 2: Subjects will receive a single dose of oral adefovir 10 mg alone, followed by a washout period and repeat doses of vadadustat 600 mg QD alone and in combination with a single dose of adefovir. Receives: Drug: Vadadustat; Drug: Adefovir |
| Vadadustat, Furosemide | Experimental | Arm 3: Subjects will receive a single dose of oral furosemide 40 mg alone, followed by a washout period and repeat doses of vadadustat 600 mg QD alone, and in combination with a single dose of furosemide 40 mg. Receives: Drug: Vadadustat; Drug: Furosemide |
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) for digoxin, adefovir and furosemide
Measured: Up to 12 Weeks
Area under plasma concentration-time curve from 0 to infinity (AUCinf) for digoxin, adefovir and furosemide
Measured: Up to 12 Weeks
Maximum observed plasma concentration (Cmax) for digoxin, adefovir and furosemide
Measured: Up to 12 Weeks
Secondary outcomes (6)
Time to maximum observed plasma concentration (Tmax) for digoxin, adefovir and furosemide
Measured: Up to 12 Weeks
Elimination rate constant (Kel) for digoxin, adefovir and furosemide
Measured: Up to 12 Weeks
Terminal half-life (t½) for digoxin, adefovir and furosemide
Measured: Up to 12 Weeks
Apparent total body clearance (CL/F) for digoxin, adefovir and furosemide
Measured: Up to 12 Weeks
Percent of extrapolated area under the curve from time t to infinity (%AUCextrap) for digoxin, adefovir and furosemide
Measured: Up to 12 Weeks
Reporting of Treatment Emergent Adverse Events (TEAEs) as reported by study subjects
Measured: Up to 12 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 completion30 Sep 2018
- Study completion30 Sep 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
- Non-randomised
- Intervention model
- Sequential
- Model description
- Each arm has fixed sequence design. 1. Arm 1 (n = 20): Digoxin 0.5 mg alone, vadadustat 600 mg alone and digoxin + vadadustat 2. Arm 2 (n = 16): adefovir 10mg alone, vadadustat 600 mg QD alone and adefovir + vadadustat 3. Arm 3 (n=22) : furosemide 40mg alone, vadadustat 600 mg QD alone, and furosemide + vadadustat
- Masking
- None (open label)
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- Akebia Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Akebia Therapeutics, Study director, Sponsor GmbH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03801759
- Sponsor's protocol ID
- AKB-6548-CI-0031
- 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 Open-label, Three Arm Study in Healthy Adult Volunteers to Assess Vadadustat as a Perpetrator in Drug-Drug-Interactions With Digoxin, Adefovir and Furosemide
- ClinicalTrials.gov ID
- NCT03801759
- Acronym / sponsor ID
- AKB-6548-CI-0031
- Conditions
- Drug Interaction Potentiation
- Keywords
- vadadustat, drug interactions, healthy volunteers
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- Akebia TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 20 Jul 2018 (actual)
- Primary completion
- 30 Sep 2018 (actual)
- Study completion
- 30 Sep 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, open-label, 3-arm, fixed sequence, study to evaluate vadadustat as a perpetrator of drug-drug interactions (DDIs) with digoxin, adefovir and furosemide in healthy male and female subjects.
Detailed description
This is a Phase 1, open-label, 3-arm, fixed sequence, study to evaluate vadadustat as a perpetrator of drug-drug interactions (DDIs) with digoxin, adefovir and furosemide in healthy male and female subjects. Unique subjects will be enrolled into each arm of the study and enrollment will be sequential. The first 20 subjects confirmed to be eligible will be assigned to Arm 1 (digoxin), the next 16 subjects will be assigned to Arm 2 (adefovir) and the next 22 subjects will be assigned to Arm 3 (furosemide). Blood samples for PK analysis will be collected at pre-defined timepoints for each arm throughout the study. Subjects will be on study for up to 80 days, including a 28-day screening period, 7-21 day in clinic period, and a 30-day follow up period post last dose.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Each arm has fixed sequence design. 1. Arm 1 (n = 20): Digoxin 0.5 mg alone, vadadustat 600 mg alone and digoxin + vadadustat 2. Arm 2 (n = 16): adefovir 10mg alone, vadadustat 600 mg QD alone and adefovir + vadadustat 3. Arm 3 (n=22) : furosemide 40mg alone, vadadustat 600 mg QD alone, and furosemide + vadadustat
| Arm | Type | Receives |
|---|---|---|
| Vadadustat, digoxin | Experimental | Drug: Vadadustat, Drug: DigoxinArm 1: Subjects will receive a single oral dose of digoxin 0.5 mg alone, followed by a washout period and repeat doses of vadadustat 600 mg QD alone and in combination with a single dose of digoxin 0.5 mg. |
| Vadadustat, adefovir | Experimental | Drug: Vadadustat, Drug: AdefovirArm 2: Subjects will receive a single dose of oral adefovir 10 mg alone, followed by a washout period and repeat doses of vadadustat 600 mg QD alone and in combination with a single dose of adefovir. |
| Vadadustat, Furosemide | Experimental | Drug: Vadadustat, Drug: FurosemideArm 3: Subjects will receive a single dose of oral furosemide 40 mg alone, followed by a washout period and repeat doses of vadadustat 600 mg QD alone, and in combination with a single dose of furosemide 40 mg. |
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.
- 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 600 mg | Drug | Vadadustat, Furosemide, Vadadustat, adefovir, Vadadustat, digoxin |
| FurosemideOral Furosemide | Drug | Vadadustat, Furosemide |
| AdefovirOral Adefovir | Drug | Vadadustat, adefovir |
| DigoxinOral Digoxin | Drug | Vadadustat, digoxin |
Primary outcome
Area under plasma concentration-time curve from 0 to last quantifiable concentration (AUClast) for digoxin, adefovir and furosemide
Time frame: Up to 12 Weeks
Area under plasma concentration-time curve from 0 to infinity (AUCinf) for digoxin, adefovir and furosemide
Time frame: Up to 12 Weeks
Maximum observed plasma concentration (Cmax) for digoxin, adefovir and furosemide
Time frame: Up to 12 Weeks
6 secondary outcomes
Time to maximum observed plasma concentration (Tmax) for digoxin, adefovir and furosemide
Time frame: Up to 12 Weeks
Elimination rate constant (Kel) for digoxin, adefovir and furosemide
Time frame: Up to 12 Weeks
Terminal half-life (t½) for digoxin, adefovir and furosemide
Time frame: Up to 12 Weeks
Apparent total body clearance (CL/F) for digoxin, adefovir and furosemide
Time frame: Up to 12 Weeks
Percent of extrapolated area under the curve from time t to infinity (%AUCextrap) for digoxin, adefovir and furosemide
Time frame: Up to 12 Weeks
Reporting of Treatment Emergent Adverse Events (TEAEs) as reported by study subjects
Time frame: Up to 12 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 Therapeutics 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, Furosemide and Adefovir 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) for digoxin, adefovir and furosemide (time frame: Up to 12 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.