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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
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| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Vadadustat | Drug | Oral dose of 600 mg QD |
|
| Measure | Description | Time Frame |
|---|---|---|
| Area under plasma concentration-time curve from time 0 to last quantifiable concentration (AUClast) of rosuvastatin, sulfasalazine, pravastatin and simvastatin | Up to 10 weeks | |
| Area under plasma concentration-time curve from time 0 to infinity (AUCinf) of rosuvastatin, sulfasalazine, pravastatin and simvastatin | Up to 10 weeks | |
| Maximum observed plasma concentration (Cmax) of rosuvastatin. sulfasalazine, pravastatin, atorvastatin and simvastatin | Up to 10 weeks | |
| Area under plasma concentration-time curve (AUCtau) of atorvastatin | Up to 10 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Time to maximum observed plasma concentration (Tmax) of rosuvastatin, sulfasalazine, pravastatin, atorvastatin, and simvastatin | Up to 10 weeks | |
| Elimination rate constant (Kel) of rosuvastatin, sulfasalazine, pravastatin, atorvastatin, and simvastatin |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Akebia Inc | Akebia Therapeutics | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| InVentiv Health Clinique Inc. | Québec | Quebec | G1P A02 | Canada |
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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.
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| Simvastatin | Drug | Oral Simvastatin |
|
| Rosuvastatin | Drug | Oral Rosuvastatin |
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| Atorvastatin | Drug | Oral Atorvastatin |
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| Pravastatin | Drug | Oral Pravastatin |
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| Sulfasalazine | Drug | Oral Sulfasalazine |
|
| Up to 10 weeks |
| Terminal half-life (t½) of rosuvastatin, sulfasalazine, pravastatin, atorvastatin, and simvastatin | Up to 10 weeks |
| Apparent total body clearance (CL/F) of rosuvastatin, sulfasalazine, pravastatin, atorvastatin, and simvastatin | 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 | 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 | Up to 10 weeks |
| Area under plasma concentration-time curve from time 0 to infinity (AUCinf) of sulfasalazine metabolites, sulfapyridine and 5-ASA (mesalamine | Up to 10 weeks |
| Maximum observed plasma concentration (Cmax) of sulfasalazine metabolites, sulfapyridine and 5-ASA (mesalamine | Up to 10 weeks |
| Time to maximum observed plasma concentration (Tmax) of sulfasalazine metabolites, sulfapyridine and 5-ASA (mesalamine | Up to 10 weeks |
| Elimination rate constant (Kel) of sulfasalazine metabolites, sulfapyridine and 5-ASA (mesalamine | Up to 10 weeks |
| Terminal half-life (t½) of sulfasalazine metabolites, sulfapyridine and 5-ASA (mesalamine | Up to 10 weeks |
| Area under the plasma concentration-time curve for a dosing interval (AUCtau) of atorvastatin metabolites, o-hydroxyatorvastatin; p-hydroxyatorvastatin | Up to 10 weeks |
| Maximum observed plasma concentration (Cmax) of atorvastatin metabolites, o-hydroxyatorvastatin; p-hydroxyatorvastatin | Up to 10 weeks |
| Time to maximum observed plasma concentration (Tmax) of atorvastatin metabolites, o-hydroxyatorvastatin; p-hydroxyatorvastatin | Up to 10 weeks |
| Area under plasma concentration-time curve from time 0 to last quantifiable concentration (AUClast) of simvastatin metabolite | Up to 10 weeks |
| Area under plasma concentration-time curve from time 0 to infinity (AUCinf) of simvastatin metabolite | Up to 10 weeks |
| Maximum observed plasma concentration (Cmax) of simvastatin metabolite | Up to 10 weeks |
| Time to maximum observed plasma concentration (Tmax) of simvastatin metabolite | Up to 10 weeks |
| Elimination rate constant (Kel) of simvastatin metabolite | Up to 10 weeks |
| Terminal half-life (t½), of simvastatin metabolite | Up to 10 weeks |
| Reporting of treatment emergent adverse events (TEAE) as reported by the study subjects | Up to 10 weeks |
| ID | Term |
|---|---|
| C000624313 | vadadustat |
| D019821 | Simvastatin |
| D000068718 | Rosuvastatin Calcium |
| D000069059 | Atorvastatin |
| D017035 | Pravastatin |
| D012460 | Sulfasalazine |
| ID | Term |
|---|---|
| D008148 | Lovastatin |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
| D013449 | Sulfonamides |
| D000577 | Amides |
| D005464 | Fluorobenzenes |
| D006845 | Hydrocarbons, Fluorinated |
| D006846 | Hydrocarbons, Halogenated |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011758 | Pyrroles |
| D001393 | Azoles |
| D006538 | Heptanoic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |
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