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This is a Phase 1, fixed sequence, open-label study to evaluate the effect of multiple oral doses of rabeprazole on the pharmacokinetics of a single dose of vadadustat 300 mg in healthy male and female subjects.
This is a Phase 1, fixed sequence, open-label study in healthy adult subjects to evaluate the effect of multiple doses of rabeprazole on the pharmacokinetics of a single dose of vadadustat in healthy male and female subjects. Approximately twenty (20) subjects, with at least 30% female subjects, will be enrolled to ensure 18 evaluable subjects. Subjects will be on study for up to 66 days, including a 28-day screening period, 9-day clinic period, and a 30-day follow- up period post last dose. Subjects who are confirmed eligible and receive at least one dose of study drug will be considered enrolled in the study. Blood samples for PK analysis will be collected at pre-defined time points throughout the study up to 48 hours post administration of vadadustat.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Rabeprazole and Vadadustat | Experimental | Subjects will receive vadadustat 300 mg on day 1, rabeprazole 20 mg every 12 hours on days 2 through 5 and vadadustat 300 mg and rabeprazole on day 6 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Vadadustat | Drug | Vadadustat 300 mg |
| |
| Rabeprazole |
| Measure | Description | Time Frame |
|---|---|---|
| Area under plasma concentration-time curve from 0 to last quantifiable concentration (AUClast) for vadadustat | Up to 10 weeks | |
| Area under plasma concentration-time curve from 0 to infinity (AUCinf) for vadadustat | Up to 10 weeks | |
| Maximum observed plasma concentration (Cmax) for vadadustat | Up to 10 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Time to maximum observed plasma concentration (Tmax) of vadadustat | Up to 10 weeks | |
| Elimination rate constant (Kel) of vadadustat | Up to 10 weeks | |
| Terminal half-life (t½) of vadadustat |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Akebia Therapeutics | Sponsor GmbH | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| inVentiv Health Clinique Inc. | Québec | Quebec | G1P 0A2 | Canada |
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| ID | Term |
|---|---|
| C000624313 | vadadustat |
| D064750 | Rabeprazole |
| ID | Term |
|---|---|
| D053799 | 2-Pyridinylmethylsulfinylbenzimidazoles |
| D013454 | Sulfoxides |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
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This is a single arm fixed sequence study. Subjects will be administered vadadustat on day 1, rabeprazole on days 2 to 5, and vadadustat and rabeprazole on day 6.
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| Drug |
Oral Rabeprazole |
|
| Up to 10 weeks |
| Apparent total body clearance (CL/F) of vadadustat | Up to 10 weeks |
| Percent of extrapolated area under the curve from time t to infinity (%AUCextrap) of vadadustat | Baseline and end of study |
| Area under plasma concentration-time curve from 0 to last quantifiable concentration (AUClast) of vadadustat-O-glucuronide | Up to 10 weeks |
| Area under plasma concentration-time curve from 0 to infinity (AUCinf) of vadadustat-O-glucuronide | Up to 10 weeks |
| Maximum observed plasma concentration (Cmax) of vadadustat-O-glucuronide | Up to 10 weeks |
| Reporting of treatment emergent adverse event (TEAE) as reported by study subjects | Up to 10 weeks |
| D011725 |
| Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001562 | Benzimidazoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |