Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
|
| 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 |
|
| 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| vadadustat | Drug | Oral dose 300 mg |
|
| Measure | Description | Time Frame |
|---|---|---|
| Area under plasma concentration-time curve from 0 to last quantifiable concentration (AUClast) of vadadustat | Up to 10 weeks | |
| Area under plasma concentration-time curve from 0 to infinity (AUCinf) of vadadustat | Up to 10 weeks | |
| Maximum observed plasma concentration (Cmax) of 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 |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Akebia Inc | Sponsor GmbH | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| inVentiv Health Clinique Inc. | Québec | Quebec | G1P A02 | Canada |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| C000624313 | vadadustat |
| D012293 | Rifampin |
| D011339 | Probenecid |
| D003524 | Cyclosporins |
| ID | Term |
|---|---|
| D012294 | Rifamycins |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
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
Not provided
Not provided
Not provided
Not provided
| Rifampin | Drug | IV Rifampin |
|
| Probenecid | Drug | Oral Probenecid |
|
| Cyclosporins | Drug | Oral Cyclosporine |
|
| 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 | Up to 10 weeks |
| Renal clearance (CLr) of vadadustat and vadadustat 1-O-glucuronide excretion in urine for Part 1 Arm 2 (Probenecid) only | 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 | 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 | Up to 10 weeks |
| Area under plasma concentration-time curve from 0 to last quantifiable concentration (AUClast) of vadadustat metabolites | Up to 10 weeks |
| Area under plasma concentration-time curve from 0 to infinity (AUCinf) of vadadustat metabolites | Up to 10 weeks |
| Maximum observed plasma concentration (Cmax) of vadadustat metabolites | Up to 10 weeks |
| Reporting of treatment emergent adverse events as reported by the study subject | Up to 10 weeks |
| D047029 | Lactams, Macrocyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D010456 | Peptides, Cyclic |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |