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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1309-3456 | Other Identifier | Universal Trial Number |
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The study aims to test if a new medicine called etavopivat potentially affects other medicines in healthy participants. The purpose of the study is to investigate whether the use of etavopivat affects the breakdown and metabolism of commonly used medicines in the body. During the study, participants will receive etavopivat and five different medicines that are already approved and available on the market, and which can be prescribed by doctors. These marketed medicines are called substrate drugs and they are: digoxin, pitavastatin, metformin, midazolam, and rosuvastatin. During a period of the study, participants will take 2 tablets of etavopivat daily for 10 consecutive days. The study will last for about 34 to 64 days.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Period 1: digoxin+pitavastatin+metformin | Experimental | Participants will receive a single dose of oral digoxin, pitavastatin and metformin. |
|
| Period 1: midazolam+rosuvastatin | Experimental | Participants will receive a single dose of oral midazolam and rosuvastatin. |
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| Period 2: etavopivat+midazolam | Experimental | Participants will receive a daily dose of oral etavopivat and single dose of oral midazolam. |
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| Period 2: etavopivat+midazolam+rosuvastatin | Experimental | Participants will receive a daily dose of oral etavopivat, single dose of oral midazolam and rosuvastatin. |
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| Period 2: etavopivat+digoxin+pitavastatin+metformin | Experimental | Participants will receive a daily dose of oral etavopivat, single dose of oral digoxin, pitavastatin and metformin. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Etavopivat | Drug | Participants will receive a daily dose of etavopivat orally. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Cmax, digoxin, SD: Maximum observed digoxin plasma concentration with and without etavopivat at steady state | Measured as picograms per milliliter (pg/mL). | Day 1 and day 3 after digoxin administration |
| AUC0-inf, digoxin, SD: Area under the digoxin plasma concentration-time curve from 0 hours and extrapolated to infinity with and without etavopivat at steady state | Measured as hours*picograms per milliliter (h*pg/mL). | Day 1 and day 3 after digoxin administration |
| Cmax, rosuvastatin, SD: Maximum observed rosuvastatin plasma concentration with and without etavopivat at steady state | Measured as pg/mL. | Day 1 after rosuvastatin administration |
| AUC0-inf, rosuvastatin, SD: Area under the rosuvastatin plasma concentration-time curve from 0 hours and extrapolated to infinity with and without etavopivat at steady state | Measured as h*pg/mL. | Day 1 after rosuvastatin administration |
| Cmax, midazolam, SD: Maximum observed midazolam plasma concentration without etavopivat, with a single dose of etavopivat, and with etavopivat at steady state | Measured as pg/mL. | Day 1 after midazolam administration |
| AUC0-inf, midazolam, SD: Area under the midazolam plasma concentration-time curve from 0 hours and extrapolated to infinity without etavopivat, with a single dose of etavopivat, and with etavopivat at steady state | Measured as h*pg/mL. | Day 1 after midazolam administration |
| Measure | Description | Time Frame |
|---|---|---|
| AUC0-last, digoxin, SD: Area under the digoxin plasma concentration-time curve from 0 hours to the last quantifiable concentration with and without etavopivat at steady state | Measured as h*pg/mL. | Day 1 and day 3 after digoxin administration |
| t1/2, digoxin, SD: Terminal half-life for digoxin with and without etavopivat at steady state |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Transparency (dept. 2834) | Novo Nordisk A/S | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| ICON-Salt Lake City | Salt Lake City | Utah | 84124 | United States |
According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
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| ID | Term |
|---|---|
| D013789 | Thalassemia |
| ID | Term |
|---|---|
| D000745 | Anemia, Hemolytic, Congenital |
| D000743 | Anemia, Hemolytic |
| D000740 | Anemia |
| D006402 | Hematologic Diseases |
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| ID | Term |
|---|---|
| D004077 | Digoxin |
| C108475 | pitavastatin |
| D008687 | Metformin |
| D008874 | Midazolam |
| D000068718 | Rosuvastatin Calcium |
| ID | Term |
|---|---|
| D004071 | Digitalis Glycosides |
| D002298 | Cardenolides |
| D002301 | Cardiac Glycosides |
| D002297 | Cardanolides |
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| Digoxin | Drug | Participants will receive a single dose of digoxin orally. |
|
| Pitavastatin | Drug | Participants will receive a single dose of pitavastatin orally. |
|
| Metformin | Drug | Participants will receive a single dose of metformin orally. |
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| Midazolam | Drug | Participants will receive a single dose of midazolam orally. |
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| Rosuvastatin | Drug | Participants will receive a single dose of rosuvastatin orally. |
|
| Cmax, pitavastatin, SD: Maximum observed pitavastatin plasma concentration with and without etavopivat at steady state | Measured as nanograms per milliliter (ng/mL). | Day 1 and day 3 after pitavastatin administration |
| AUC0-inf, pitavastatin, SD: Area under the pitavastatin plasma concentration-time curve from 0 hours and extrapolated to infinity with and without etavopivat at steady state | Measured as hours*nanograms per milliliter(h*ng/mL). | Day 1 and day 3 after pitavastatin administration |
| Cmax, metformin, SD: Maximum observed metformin plasma concentration with and without etavopivat at steady state | Measured as ng/mL. | Day 1 and day 3 after metformin administration |
| AUC0-inf, metformin, SD: Area under the metformin plasma concentration-time curve from 0 hours and extrapolated to infinity with and without etavopivat at steady state | Measured as h*ng/mL. | Day 1 and day 3 after metformin administration |
Measured as hours. |
| Day 1 and day 3 after digoxin administration |
| tmax, digoxin, SD: Time to maximum observed digoxin plasma concentration with and without etavopivat at steady state | Measured as hours. | Day 1 and day 3 after digoxin administration |
| CL/Fdigoxin, SD: Apparent plasma clearance of digoxin with and without etavopivat at steady state | Measured as liters per hour (L/h). | Day 1 and day 3 after digoxin administration |
| Vz/Fdigoxin, SD: Apparent volume of distribution of digoxin with and without etavopivat at steady state based on plasma concentration values | Measured as liters (L). | Day 1 and day 3 after digoxin administration |
| AUC0-last, rosuvastatin, SD: Area under the rosuvastatin plasma concentration-time curve from 0 hours to the last quantifiable concentration with and without etavopivat at steady state | Measured as h*pg/mL. | Day 1 after rosuvastatin administration |
| t1/2, rosuvastatin, SD: Terminal half-life for rosuvastatin with and without etavopivat at steady state | Measured as hours. | Day 1 after rosuvastatin administration |
| tmax, rosuvastatin, SD: Time to maximum observed rosuvastatin plasma concentration with and without etavopivat at steady state | Measured as hours. | Day 1 after rosuvastatin administration |
| CL/Frosuvastatin, SD: Apparent plasma clearance of rosuvastatin with and without etavopivat at steady state | Measured as L/h. | Day 1 after rosuvastatin administration |
| Vz/Frosuvastatin, SD: Apparent volume of distribution of rosuvastatin with and without etavopivat at steady state based on plasma concentration values | Measured as L. | Day 1 after rosuvastatin administration |
| AUC0-last, midazolam, SD: Area under the midazolam plasma concentration-time curve from 0 hours to the last quantifiable concentration without etavopivat, with a single dose of etavopivat, and with etavopivat at steady state | Measured as h*pg/mL. | Day 1 after midazolam administration |
| t1/2, midazolam, SD: Terminal half-life for midazolam without etavopivat, with a single dose of etavopivat, and with etavopivat at steady state | Measured as hours. | Day 1 after midazolam administration |
| tmax, midazolam, SD: Time to maximum observed midazolam plasma concentration without etavopivat, with a single dose of etavopivat, and with etavopivat at steady state | Measured as hours. | Day 1 after midazolam administration |
| CL/Fmidazolam, SD: Apparent plasma clearance of midazolam without etavopivat, with a single dose of etavopivat and with etavopivat at steady state | Measured as L/h. | Day 1 after midazolam administration |
| Vz/Fmidazolam, SD: Apparent volume of distribution of midazolam without etavopivat, with a single dose of etavopivat and with etavopivat at steady state | Measured as L. | Day 1 after midazolam administration |
| AUC0-inf, 1-hydroxymidazolam, SD: Area under the midazolam plasma concentration-time curve from 0 hours and extrapolated to infinity without etavopivat, with a single dose of etavopivat, and with etavopivat at steady state | Measured as h*pg/mL. | Day 1 after midazolam administration |
| Cmax, 1-hydroxymidazolam, SD: Maximum observed midazolam plasma concentration without etavopivat, with a single dose of etavopivat, and with etavopivat at steady state | Measured as pg/mL. | Day 1 after midazolam administration |
| AUC0-last, 1-hydroxymidazolam, SD: Area under the midazolam plasma concentration-time curve from 0 hours to the last quantifiable concentration without etavopivat, with a single dose of etavopivat, and with etavopivat at steady state | Measured as h*pg/mL. | Day 1 after midazolam administration |
| t1/2, 1-hydroxymidazolam: Terminal half-life for 1-hydroxymidazolam without etavopivat, with a single dose of etavopivat, and with etavopivat at steady state | Measured as hours. | Day 1 after midazolam administration |
| tmax, 1-hydroxymidazolam: Time to maximum observed 1-hydroxymidazolam plasma concentration without etavopivat, with a single dose of etavopivat, and with etavopivat at steady state | Measured as hours. | Day 1 after midazolam administration |
| CL/F1-hydroxymidazolam: Apparent plasma clearance of 1-hydroxymidazolam without etavopivat, with a single dose of etavopivat, and with etavopivat at steady state | Measured as L/h. | Day 1 after midazolam administration |
| Vz/F1-hydroxymidazolam: Apparent volume of distribution of 1-hydroxymidazolam based on plasma concentration values without etavopivat, with a single dose of etavopivat, and with etavopivat at steady state | Measured as L. | Day 1 after midazolam administration |
| AUC0-last, pitavastatin, SD: Area under the pitavastatin plasma concentration-time curve from 0 hours to the last quantifiable concentration with and without etavopivat at steady state | Measured as h*ng/mL. | Day 1 and day 3 after pitavastatin administration |
| t1/2, pitavastatin, SD: Terminal half-life for pitavastatin with and without etavopivat at steady state | Measured as hours. | Day 1 and day 3 after pitavastatin administration |
| tmax, pitavastatin, SD: Time to maximum observed pitavastatin plasma concentration with and without etavopivat at steady state | Measured as hours. | Day 1 and day 3 after pitavastatin administration |
| CL/Fpitavastatin, SD: Apparent plasma clearance of pitavastatin with and without etavopivat at steady state | Measured as L/h. | Day 1 and day 3 after pitavastatin administration |
| Vz/Fpitavastatin, SD: Apparent volume of distribution of pitavastatin with and without etavopivat at steady state based on plasma concentration values | Measured as L. | Day 1 and day 3 after pitavastatin administration |
| AUC0-last, metformin, SD: Area under the metformin plasma concentration-time curve from 0 hours to the last quantifiable concentration with and without etavopivat at steady state | Measured as h*ng/mL. | Day 1 and day 3 after metformin administration |
| t1/2, metformin, SD: Terminal half-life for metformin with and without etavopivat at steady state | Measured as hours. | Day 1 and day 3 after metformin administration |
| tmax, metformin, SD: Time to maximum observed metformin plasma concentration with and without etavopivat at steady state | Measured as hours. | Day 1 and day 3 after metformin administration |
| CL/Fmetformin, SD: Apparent plasma clearance of metformin with and without etavopivat at steady state | Measured as L/h. | Day 1 and day 3 after metformin administration |
| Vz/Fmetformin, SD: Apparent volume of distribution of metformin with and without etavopivat at steady state based on plasma concentration values | Measured as L. | Day 1 and day 3 after metformin administration |
| Aelast, metformin, SD%: Percentage of the metformin excreted into urine from the time of dosing to the collection time of the last measurable concentration with and without etavopivat at steady state | Measured as percentage (%) of the metformin excreted into urine. | Day 1 and day 3 after metformin administration |
| CLR, metformin, SD: Renal clearance of metformin | Measured as L/h. | Day 1 and day 3 after metformin administration |
| AUC0-tau, etavopivat: Area under the etavopivat plasma concentration-time curve during one dosing interval at single dose and at steady state | Measured as h*ng/mL. | Day 1 and day 3 after etavopivat administration |
| AUC0-last etavopivat: Area under the etavopivat plasma concentration-time curve from 0 hours to the last quantifiable concentration at single dose and at steady state | Measured as h*ng/mL. | Day 1 and day 3 after etavopivat administration |
| Cmax, etavopivat: Maximum observed etavopivat plasma concentration at single dose and at steady state | Measured as ng/mL. | Day 1 and day 3 after etavopivat administration |
| t1/2, etavopivat: Terminal half-life for etavopivat at single dose and at steady state | Measured as hours. | Day 1 and day 3 after etavopivat administration |
| tmax, etavopivat: Time to maximum observed etavopivat plasma concentration at single dose and at steady state | Measured as hours. | Day 1 and day 3 after etavopivat administration |
| V/Fetavopivat: Apparent volume of distribution of etavopivat based on plasma concentration values at single dose and at steady state | Measured as L. | Day 1 and day 3 after etavopivat administration |
| CL/Fetavopivat: Apparent plasma clearance of etavopivat at single dose and at steady state | Measured as L/h. | Day 1 and day 3 after etavopivat administration |
| C, etavopivat: Observed etavopivat plasma concentration after single and multiple doses | Measured as ng/mL. | From day 1 to day 4 after administration of etavopivat |
| Number of adverse events (AEs) | Measured as count of events. | From first dose (day 1) until end of study (day 32) |
| D006425 |
| Hemic and Lymphatic Diseases |
| D006453 | Hemoglobinopathies |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D013256 |
| Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D013449 | Sulfonamides |
| D000577 | Amides |
| D005464 | Fluorobenzenes |
| D006845 | Hydrocarbons, Fluorinated |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |