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| Name | Class |
|---|---|
| Quintiles, Inc. | INDUSTRY |
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This study will evaluate the establishment of anticoagulation ("re-anticoagulation") of subjects with edoxaban following reversal by PER977 and will identify a dose regimen of PER977 that reverses the effects of edoxaban for up to 21 hours.
This is a randomized, single-blind, sequential group, ascending PER977 reversal dose study in healthy volunteers. Subjects will be randomized in a 4:1 ratio to receive either PER977 or placebo. All subjects will receive a single dose of edoxaban 60 mg on Days 1-4. On Days 3 and 4, study drug will be administered 3 hours following edoxaban. Beginning with Cohort 2, study drug will be administered only to those subjects with a minimum increase in whole blood clotting time >25% above baseline.
Pharmacokinetic assessment of PER977 and tis metabolite, and edoxaban and its metabolite will be performed. Pharmacodynamic assessment of WBCT and Point of Care prothrombin time will be performed. Safety will be assessed throughout the study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 | Experimental | Subjects will receive 60 mg edoxaban in the morning on Days 1-2. On Day 3 and 4, they will receive a single dose of 60 mg edoxaban, followed 3 hours later by a single dose of 25 mg PER977 or placebo (n=10). |
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| Cohort 2 | Experimental | Subjects will receive 60 mg edoxaban in the morning on Days 1-2. On Day 3 and 4, they will receive a single dose of 60 mg edoxaban, followed 3 hours later by a single dose of 50 mg PER977 or placebo (n=10). |
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| Cohort 3 | Experimental | Subjects will receive 60 mg edoxaban in the morning on Days 1-2. On Day 3 and 4, they will receive a single dose of 60 mg edoxaban, followed 3 hours later by a single dose of 100 mg PER977 or placebo (n=10). |
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| Cohort 4 | Experimental | Subjects will receive 60 mg edoxaban in the morning on Days 1-2. On Day 3 and 4, they will receive a single dose of 60 mg edoxaban, followed 3 hours later by a single dose of 300 mg PER977 or placebo (n=10). Study amendments expanded the cohort to include an additional 7 subjects (randomized 1:6 PER977:placebo) and up to an additional 4 placebo and 8 active subjects (ongoing). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PER977 | Drug | Reversal of edoxaban-induced anticoagulation |
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| Measure | Description | Time Frame |
|---|---|---|
| Whole blood clotting time as a measure of edoxaban anticoagulation reversal by PER977 | To evaluate the safety, tolerability and effect on whole blood clotting time of escalating intravenous doses of PER977 (25, 50, 100, 300 mg, and 600 mg) administered after 60 mg edoxaban as a "rescue" medication in healthy volunteers and repeated for a second day to investigate any effects of PER977 on the re-anticoagulation with edoxaban and second reversal with PER977. | 5 days |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetic profile of PER977 | To assess the maximal concentration, half-life and plasma and urinary clearance of PER977 and its metabolite following intravenous administration | 5 days |
| Pharmacokinetic profile of edoxaban |
| Measure | Description | Time Frame |
|---|---|---|
| Analytical measurement range (AMR), reproducibility, and precision of WBCT measurements | To determine to normal range, variability, and reproducibility of WBCT in blood collected from healthy volunteers | 5 days |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Scott Rasmussen, MD | Quintiles, Inc. | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Quintiles | Overland Park | Kansas | 66212 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26843482 | Derived | Sciascia S, Lopez-Pedrera C, Cecchi I, Pecoraro C, Roccatello D, Cuadrado MJ. Non-vitamin K antagonist oral anticoagulants and antiphospholipid syndrome. Rheumatology (Oxford). 2016 Oct;55(10):1726-35. doi: 10.1093/rheumatology/kev445. Epub 2016 Feb 3. |
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| Cohort 5 | Experimental | Subjects will receive 60 mg edoxaban in the morning on Days 1-2. On Day 3 and 4, they will receive a single dose of 60 mg edoxaban, followed 3 hours later by a single dose of 600 mg PER977 or placebo (n=10). A protocol amendment expanded the cohort to include an additional 2 placebo and up to an additional 4 active subject. |
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| Placebo | Drug | Reversal of edoxaban-induced anticoagulation |
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| Edoxaban | Drug |
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To evaluate the maximal concentration, half-life, and clearance of edoxaban and its metabolite when administered with PER977
| 5 days |
| Safety coagulation measures | To evaluate changes in point of care prothrombin time, d-dimer, prothrombin factors 1 and 2, tissue factor pathway inhibitor, and possibly other biomarkers following escalating intravenous doses of PER977 administered after edoxaban in healthy volunteers | 5 days |
| Safety and tolerability | To determine if adverse events occurred in healthy volunteers who received PER977 after edoxaban | 5 days |
| ID | Term |
|---|---|
| C000593571 | PER977 |
| C552171 | edoxaban |
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