Drug Interaction PotentiationPhase 1NCT03801733
Drug-Drug Interaction Study of Vadadustat With Rosuvastatin, Sulfasalazine, Pravastatin, Atorvastatin and Simvastatin
A Phase 1 study testing Vadadustat, Simvastatin and Rosuvastatin in people with Drug Interaction Potentiation, run by Akebia Therapeutics at 1 site in Canada.
Trial summary
This is a Phase 1, three-part, open-label study to evaluate vadadustat as a perpetrator in drug-drug interactions with rosuvastatin, sulfasalazine, pravastatin, atorvastatin and simvastatin 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, Simvastatin and Rosuvastatin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 134 participants
- Where
- 1 siteCanada
- Study dates
- 17 Jun 2018to 24 Nov 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; 12. 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, Three-Part, Open-label Study in Healthy Adult Volunteers to Assess Vadadustat as a Perpetrator in Drug-Drug Interactions With Rosuvastatin, Sulfasalazine, Pravastatin, Atorvastatin and Simvastatin
This is a Phase 1, three-part, open-label study to evaluate vadadustat as a perpetrator in drug-drug interactions with rosuvastatin, sulfasalazine, pravastatin, atorvastatin and simvastatin in healthy male and female subjects.
Read the detailed description
This is a Phase 1, three-part, open-label study to evaluate vadadustat as a perpetrator in drug-drug interactions with rosuvastatin, sulfasalazine, pravastatin, atorvastatin, and simvastatin in healthy male and female subjects. Thirty-four (34) subjects will be enrolled in Part 1 (rosuvastatin) and based on review of the PK and safety/tolerability data, a decision will be made on whether to proceed with Part 2. Part 2 consists of 2 arms (sulfasalazine and pravastatin). Twenty-six (26) subjects will be enrolled into each arm. Part 3 consists of 2 arms (atorvastatin and simvastatin). Twenty-four (24) subjects will be enrolled into each arm after enrollment in Part 2 is completed. Subjects will be in the study for up to 72 days, including a 28-day screening period, 6-14 day in clinic period, and a 30-day follow up period post last dose. Blood samples for PK analysis will be collected at pre-defined time points throughout the study.
- Conditions
- Drug Interaction Potentiation
- Being tested
- Vadadustat, Simvastatin, Rosuvastatin, Atorvastatin, Pravastatin
- Keywords
- Vadadustat, Normal Healthy volunteers, Pharmacokinetics, Rosuvastatin, Sulfasalazine, Pravastatin, Atrovastatin, Simvastatin
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 of 600 mg QD
SimvastatinDrug
Oral Simvastatin
RosuvastatinDrug
Oral Rosuvastatin
AtorvastatinDrug
Oral Atorvastatin
PravastatinDrug
Oral Pravastatin
SulfasalazineDrug
Oral Sulfasalazine
| Study group | Role | What they receive |
|---|---|---|
| Rosuvastatin, Vadadustat | Experimental | Part 1: Subjects will receive rosuvastatin 20 mg alone, vadadustat 600 mg alone, followed by rosuvastatin 20 mg in combination with vadadustat 600 mg in a fixed-sequence dosing design. Receives: Drug: Vadadustat; Drug: Rosuvastatin |
| Sulfasalazine. Pravastatin, Vadadustat | Experimental | Part 2, Arm 1: Subjects will receive sulfasalazine 500 mg alone followed by sulfasalazine 500 mg in combination with vadadustat 600 mg once a day in a fixed-sequence dosing design.
Part 2, Arm 2: Subjects will receive pravastatin 40 mg alone followed by pravastatin 40 mg in combination with vadadustat 600 mg once a day in a fixed-sequence dosing design. Receives: Drug: Vadadustat; Drug: Pravastatin; Drug: Sulfasalazine |
| Atorvastatin, Simvastatin, Vadadustat | Experimental | Part 3, Arm 1: Subjects will receive atorvastatin 40 mg alone followed by atorvastatin 40 mg in combination with vadadustat 600 mg once a day in a fixed-sequence dosing design.
Part 3, Arm 2: 24 subjects will receive simvastatin 40 mg alone followed by simvastatin 40 mg in combination with vadadustat 600 mg once a day in a fixed-sequence dosing design. Receives: Drug: Vadadustat; Drug: Simvastatin; Drug: Atorvastatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under plasma concentration-time curve from time 0 to last quantifiable concentration (AUClast) of rosuvastatin, sulfasalazine, pravastatin and simvastatin
Measured: Up to 10 weeks
Area under plasma concentration-time curve from time 0 to infinity (AUCinf) of rosuvastatin, sulfasalazine, pravastatin and simvastatin
Measured: Up to 10 weeks
Maximum observed plasma concentration (Cmax) of rosuvastatin. sulfasalazine, pravastatin, atorvastatin and simvastatin
Measured: Up to 10 weeks
Area under plasma concentration-time curve (AUCtau) of atorvastatin
Measured: Up to 10 weeks
Secondary outcomes (21)
Time to maximum observed plasma concentration (Tmax) of rosuvastatin, sulfasalazine, pravastatin, atorvastatin, and simvastatin
Measured: Up to 10 weeks
Elimination rate constant (Kel) of rosuvastatin, sulfasalazine, pravastatin, atorvastatin, and simvastatin
Measured: Up to 10 weeks
Terminal half-life (t½) of rosuvastatin, sulfasalazine, pravastatin, atorvastatin, and simvastatin
Measured: Up to 10 weeks
Apparent total body clearance (CL/F) of rosuvastatin, sulfasalazine, pravastatin, atorvastatin, and simvastatin
Measured: Up to 10 weeks
Percentage of extrapolated area under the curve from time t to infinity (%AUCextrap or Residual Area) of rosuvastatin, sulfasalazine, pravastatin, atorvastatin, and simvastatin
Measured: Up to 10 weeks
Area under plasma concentration-time curve from time 0 to last quantifiable concentration (AUClast) of sulfasalazine metabolites, sulfapyridine and 5-ASA (mesalamine
Measured: Up to 10 weeks
Area under plasma concentration-time curve from time 0 to infinity (AUCinf) of sulfasalazine metabolites, sulfapyridine and 5-ASA (mesalamine
Measured: Up to 10 weeks
Maximum observed plasma concentration (Cmax) of sulfasalazine metabolites, sulfapyridine and 5-ASA (mesalamine
Measured: Up to 10 weeks
Time to maximum observed plasma concentration (Tmax) of sulfasalazine metabolites, sulfapyridine and 5-ASA (mesalamine
Measured: Up to 10 weeks
Elimination rate constant (Kel) of sulfasalazine metabolites, sulfapyridine and 5-ASA (mesalamine
Measured: Up to 10 weeks
Terminal half-life (t½) of sulfasalazine metabolites, sulfapyridine and 5-ASA (mesalamine
Measured: Up to 10 weeks
Area under the plasma concentration-time curve for a dosing interval (AUCtau) of atorvastatin metabolites, o-hydroxyatorvastatin; p-hydroxyatorvastatin
Measured: Up to 10 weeks
Maximum observed plasma concentration (Cmax) of atorvastatin metabolites, o-hydroxyatorvastatin; p-hydroxyatorvastatin
Measured: Up to 10 weeks
Time to maximum observed plasma concentration (Tmax) of atorvastatin metabolites, o-hydroxyatorvastatin; p-hydroxyatorvastatin
Measured: Up to 10 weeks
Area under plasma concentration-time curve from time 0 to last quantifiable concentration (AUClast) of simvastatin metabolite
Measured: Up to 10 weeks
Area under plasma concentration-time curve from time 0 to infinity (AUCinf) of simvastatin metabolite
Measured: Up to 10 weeks
Maximum observed plasma concentration (Cmax) of simvastatin metabolite
Measured: Up to 10 weeks
Time to maximum observed plasma concentration (Tmax) of simvastatin metabolite
Measured: Up to 10 weeks
Elimination rate constant (Kel) of simvastatin metabolite
Measured: Up to 10 weeks
Terminal half-life (t½), of simvastatin metabolite
Measured: Up to 10 weeks
Reporting of treatment emergent adverse events (TEAE) as reported by the study subjects
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 start17 Jun 2018
- Primary completion24 Nov 2018
- Study completion24 Nov 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 three-part sequential design study. Part 2 will be initiated based upon the outcome of Part 1 and Part 3 will be initiated after completion of Part 2.
- Masking
- None (open label)
- Enrolment
- 134 participants (actual)
Sponsor and investigators
- Lead sponsor
- Akebia Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Akebia Inc, Study director, Akebia Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03801733
- Sponsor's protocol ID
- AKB 6548 CI 0030
- 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, Three-Part, Open-label Study in Healthy Adult Volunteers to Assess Vadadustat as a Perpetrator in Drug-Drug Interactions With Rosuvastatin, Sulfasalazine, Pravastatin, Atorvastatin and Simvastatin
- ClinicalTrials.gov ID
- NCT03801733
- Acronym / sponsor ID
- AKB 6548 CI 0030
- Conditions
- Drug Interaction Potentiation
- Keywords
- Vadadustat, Normal Healthy volunteers, Pharmacokinetics, Rosuvastatin, Sulfasalazine, Pravastatin, Atrovastatin, Simvastatin
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 134 participants (actual)
- Lead sponsor
- Akebia TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 17 Jun 2018 (actual)
- Primary completion
- 24 Nov 2018 (actual)
- Study completion
- 24 Nov 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, three-part, open-label study to evaluate vadadustat as a perpetrator in drug-drug interactions with rosuvastatin, sulfasalazine, pravastatin, atorvastatin and simvastatin in healthy male and female subjects.
Detailed description
This is a Phase 1, three-part, open-label study to evaluate vadadustat as a perpetrator in drug-drug interactions with rosuvastatin, sulfasalazine, pravastatin, atorvastatin, and simvastatin in healthy male and female subjects. Thirty-four (34) subjects will be enrolled in Part 1 (rosuvastatin) and based on review of the PK and safety/tolerability data, a decision will be made on whether to proceed with Part 2. Part 2 consists of 2 arms (sulfasalazine and pravastatin). Twenty-six (26) subjects will be enrolled into each arm. Part 3 consists of 2 arms (atorvastatin and simvastatin). Twenty-four (24) subjects will be enrolled into each arm after enrollment in Part 2 is completed. Subjects will be in the study for up to 72 days, including a 28-day screening period, 6-14 day in clinic period, and a 30-day follow up period post last dose. Blood samples for PK analysis will be collected at pre-defined time points 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 three-part sequential design study. Part 2 will be initiated based upon the outcome of Part 1 and Part 3 will be initiated after completion of Part 2.
| Arm | Type | Receives |
|---|---|---|
| Rosuvastatin, Vadadustat | Experimental | Drug: Vadadustat, Drug: RosuvastatinPart 1: Subjects will receive rosuvastatin 20 mg alone, vadadustat 600 mg alone, followed by rosuvastatin 20 mg in combination with vadadustat 600 mg in a fixed-sequence dosing design. |
| Sulfasalazine. Pravastatin, Vadadustat | Experimental | Drug: Vadadustat, Drug: Pravastatin, Drug: SulfasalazinePart 2, Arm 1: Subjects will receive sulfasalazine 500 mg alone followed by sulfasalazine 500 mg in combination with vadadustat 600 mg once a day in a fixed-sequence dosing design. Part 2, Arm 2: Subjects will receive pravastatin 40 mg alone followed by pravastatin 40 mg in combination with vadadustat 600 mg once a day in a fixed-sequence dosing design. |
| Atorvastatin, Simvastatin, Vadadustat | Experimental | Drug: Vadadustat, Drug: Simvastatin, Drug: AtorvastatinPart 3, Arm 1: Subjects will receive atorvastatin 40 mg alone followed by atorvastatin 40 mg in combination with vadadustat 600 mg once a day in a fixed-sequence dosing design. Part 3, Arm 2: 24 subjects will receive simvastatin 40 mg alone followed by simvastatin 40 mg in combination with vadadustat 600 mg once a day in a fixed-sequence dosing 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; 12. 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 of 600 mg QD | Drug | Atorvastatin, Simvastatin, Vadadustat, Rosuvastatin, Vadadustat, Sulfasalazine. Pravastatin, Vadadustat |
| SimvastatinOral Simvastatin | Drug | Atorvastatin, Simvastatin, Vadadustat |
| RosuvastatinOral Rosuvastatin | Drug | Rosuvastatin, Vadadustat |
| AtorvastatinOral Atorvastatin | Drug | Atorvastatin, Simvastatin, Vadadustat |
| PravastatinOral Pravastatin | Drug | Sulfasalazine. Pravastatin, Vadadustat |
| SulfasalazineOral Sulfasalazine | Drug | Sulfasalazine. Pravastatin, Vadadustat |
Primary outcome
Area under plasma concentration-time curve from time 0 to last quantifiable concentration (AUClast) of rosuvastatin, sulfasalazine, pravastatin and simvastatin
Time frame: Up to 10 weeks
Area under plasma concentration-time curve from time 0 to infinity (AUCinf) of rosuvastatin, sulfasalazine, pravastatin and simvastatin
Time frame: Up to 10 weeks
Maximum observed plasma concentration (Cmax) of rosuvastatin. sulfasalazine, pravastatin, atorvastatin and simvastatin
Time frame: Up to 10 weeks
Area under plasma concentration-time curve (AUCtau) of atorvastatin
Time frame: Up to 10 weeks
21 secondary outcomes
Time to maximum observed plasma concentration (Tmax) of rosuvastatin, sulfasalazine, pravastatin, atorvastatin, and simvastatin
Time frame: Up to 10 weeks
Elimination rate constant (Kel) of rosuvastatin, sulfasalazine, pravastatin, atorvastatin, and simvastatin
Time frame: Up to 10 weeks
Terminal half-life (t½) of rosuvastatin, sulfasalazine, pravastatin, atorvastatin, and simvastatin
Time frame: Up to 10 weeks
Apparent total body clearance (CL/F) of rosuvastatin, sulfasalazine, pravastatin, atorvastatin, and simvastatin
Time frame: Up to 10 weeks
Percentage of extrapolated area under the curve from time t to infinity (%AUCextrap or Residual Area) of rosuvastatin, sulfasalazine, pravastatin, atorvastatin, and simvastatin
Time frame: Up to 10 weeks
Area under plasma concentration-time curve from time 0 to last quantifiable concentration (AUClast) of sulfasalazine metabolites, sulfapyridine and 5-ASA (mesalamine
Time frame: Up to 10 weeks
Area under plasma concentration-time curve from time 0 to infinity (AUCinf) of sulfasalazine metabolites, sulfapyridine and 5-ASA (mesalamine
Time frame: Up to 10 weeks
Maximum observed plasma concentration (Cmax) of sulfasalazine metabolites, sulfapyridine and 5-ASA (mesalamine
Time frame: Up to 10 weeks
Time to maximum observed plasma concentration (Tmax) of sulfasalazine metabolites, sulfapyridine and 5-ASA (mesalamine
Time frame: Up to 10 weeks
Elimination rate constant (Kel) of sulfasalazine metabolites, sulfapyridine and 5-ASA (mesalamine
Time frame: Up to 10 weeks
Terminal half-life (t½) of sulfasalazine metabolites, sulfapyridine and 5-ASA (mesalamine
Time frame: Up to 10 weeks
Area under the plasma concentration-time curve for a dosing interval (AUCtau) of atorvastatin metabolites, o-hydroxyatorvastatin; p-hydroxyatorvastatin
Time frame: Up to 10 weeks
Maximum observed plasma concentration (Cmax) of atorvastatin metabolites, o-hydroxyatorvastatin; p-hydroxyatorvastatin
Time frame: Up to 10 weeks
Time to maximum observed plasma concentration (Tmax) of atorvastatin metabolites, o-hydroxyatorvastatin; p-hydroxyatorvastatin
Time frame: Up to 10 weeks
Area under plasma concentration-time curve from time 0 to last quantifiable concentration (AUClast) of simvastatin metabolite
Time frame: Up to 10 weeks
Area under plasma concentration-time curve from time 0 to infinity (AUCinf) of simvastatin metabolite
Time frame: Up to 10 weeks
Maximum observed plasma concentration (Cmax) of simvastatin metabolite
Time frame: Up to 10 weeks
Time to maximum observed plasma concentration (Tmax) of simvastatin metabolite
Time frame: Up to 10 weeks
Elimination rate constant (Kel) of simvastatin metabolite
Time frame: Up to 10 weeks
Terminal half-life (t½), of simvastatin metabolite
Time frame: Up to 10 weeks
Reporting of treatment emergent adverse events (TEAE) as reported by the study subjects
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
Akebia Therapeutics
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, Simvastatin and Rosuvastatin 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 time 0 to last quantifiable concentration (AUClast) of rosuvastatin, sulfasalazine, pravastatin and simvastatin (time frame: Up to 10 weeks). The study lists 4 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.