Anticoagulation ReversalPhase 2NCT02207257
Study of PER977 Administered to Subjects With Steady State Edoxaban Dosing and Re-anticoagulation With Edoxaban
A Phase 2 study testing PER977 and Edoxaban in people with Anticoagulation Reversal, run by Perosphere Pharmaceuticals Inc, a wholly owned subsidiary of AMAG Pharmaceuticals, Inc. at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Anticoagulation Reversal
- What is being tested?
- PER977 and Edoxaban
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 65 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2014to Nov 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Adults age 18 to 65 years, inclusive
- Laboratory values are not clinically significant
- No clinically significant findings on 12-lead electrocardiogram
- Body mass index (BMI) 18 to ≤ 32 kg/m2, inclusive
- Male subjects agree to use appropriate contraception .
- Female subjects may be post-menopausal or, if of child-bearing potential, must have a negative serum pregnancy test prior to enrollment, and must agree to use two forms of acceptable contraception for the duration of the study and for a minimum of one complete menstrual cycle or 28 days following discharge from the study.
- Subjects must sign informed consent
Who cannot join
- History or current evidence of clinically significant disease, liver function tests greater than the upper limit of normal (presence of Gilbert's syndrome is acceptable), QTcF > normal (440±10 msec for males or 460±10 msec for females).
- History of unexplained syncope
- History of major bleeding, trauma, surgical procedure of any type, or vaginal delivery within six months prior to screening
- History of peptic ulcer, gastrointestinal bleeding, including the mouth, within six months prior to screening
- History of minor bleeding episodes such as epistaxis, rectal or hemorrhoidal bleeding or gingival bleeding within 1 month prior to screening
- Personal or family history of clotting disorder or abnormality, excessive bleeding, thrombovascular disease or any hematologic disorder involving platelets or clotting abnormalities or any condition requiring treatment with transfusions, or history of heparin-induced thrombocytopenia
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- Females with a history of dysfunctional uterine bleeding, menorrhagia , metrorrhagia or polymenorrhea
- Pregnant or breast-feeding
- Males with a history of hormone therapy within 3 months prior to screening
- Administration of any blood product or anticoagulant within 3 months prior to study entry or any non steroidal anti-inflammatory drug or cyclooxygenase inhibitor within 2 weeks prior to screening
- Taking any type of chronic medication within the 4 weeks prior to study entry (use of hormonal contraceptives is acceptable)
- Positive serologic test for HIV, HCV-Ab, or HBsAG
- Donation of blood or blood products within 56 days prior to screening
- Smokers or use of tobacco and/or nicotine containing products within 3 months prior to dosing as determined by the subject's verbal history
- Participation in any study with an investigational compound or device within 30 days prior to signing informed consent
- History of participation in any prior study of PER977 or edoxaban
- Active drug or alcohol dependence within the prior 12 months or any condition that, in the opinion of the Investigator, would interfere with adherence to study protocol
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II Randomized, Sequential Group, Evaluation of Ascending Reversal Doses of PER977 Administered to Subjects With Steady State Edoxaban Dosing and Re-anticoagulation With Edoxaban Following PER977 Reversal
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.
Read the detailed description
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.
- Conditions
- Anticoagulation Reversal
- Being tested
- PER977, Placebo, Edoxaban
- Keywords
- PER977, anticoagulation reversal, pharmacokinetics, edoxaban, whole blood clotting time, D-dimer, prothrombin fragments 1 and 2, tissue factor pathway inhibitor, prothrombin time
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PER977Drug
Reversal of edoxaban-induced anticoagulation
PlaceboDrug
Reversal of edoxaban-induced anticoagulation
EdoxabanDrug
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Drug: PER977; Drug: Placebo; Drug: Edoxaban |
| 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). Receives: Drug: PER977; Drug: Placebo; Drug: Edoxaban |
| 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). Receives: Drug: PER977; Drug: Placebo; Drug: Edoxaban |
| 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). Receives: Drug: PER977; Drug: Placebo; Drug: Edoxaban |
| 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. Receives: Drug: PER977; Drug: Placebo; Drug: Edoxaban |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 5 days
Secondary outcomes (4)
Pharmacokinetic profile of PER977
To assess the maximal concentration, half-life and plasma and urinary clearance of PER977 and its metabolite following intravenous administration
Measured: 5 days
Pharmacokinetic profile of edoxaban
To evaluate the maximal concentration, half-life, and clearance of edoxaban and its metabolite when administered with PER977
Measured: 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
Measured: 5 days
Safety and tolerability
To determine if adverse events occurred in healthy volunteers who received PER977 after edoxaban
Measured: 5 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2014 (estimated)
- Study startMar 2014
- Primary completionSep 2015
- Study completionNov 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Anticoagulation ReversalStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- Perosphere Pharmaceuticals Inc, a wholly owned subsidiary of AMAG Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Quintiles, Inc.
- Responsible party
- Sponsor
- Investigators
- Scott Rasmussen, MD, Principal investigator, Quintiles, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02207257
- Sponsor's protocol ID
- PER977-02-001
- Status last verified
- Nov 2017
- First submitted
- 28 Jul 2014
- Last updated
- 21 May 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 26843482
Study at a glance
From the registry record, last updated by the sponsor on 21 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Randomized, Sequential Group, Evaluation of Ascending Reversal Doses of PER977 Administered to Subjects With Steady State Edoxaban Dosing and Re-anticoagulation With Edoxaban Following PER977 Reversal
- ClinicalTrials.gov ID
- NCT02207257
- Acronym / sponsor ID
- PER977-02-001
- Conditions
- Anticoagulation Reversal
- Keywords
- PER977, anticoagulation reversal, pharmacokinetics, edoxaban, whole blood clotting time, D-dimer, prothrombin fragments 1 and 2, tissue factor pathway inhibitor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 65 participants (actual)
- Lead sponsor
- Perosphere Pharmaceuticals Inc, a wholly owned subsidiary of AMAG Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Quintiles, Inc.
- Study start
- Mar 2014
- Primary completion
- Sep 2015 (actual)
- Study completion
- Nov 2015 (actual)
- First posted
- 4 Aug 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Single blind (participant)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: PER977, Drug: Placebo, Drug: EdoxabanSubjects 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). |
| Cohort 2 | Experimental | Drug: PER977, Drug: Placebo, Drug: EdoxabanSubjects 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). |
| Cohort 3 | Experimental | Drug: PER977, Drug: Placebo, Drug: EdoxabanSubjects 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). |
| Cohort 4 | Experimental | Drug: PER977, Drug: Placebo, Drug: EdoxabanSubjects 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). |
| Cohort 5 | Experimental | Drug: PER977, Drug: Placebo, Drug: EdoxabanSubjects 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Adults age 18 to 65 years, inclusive
- Laboratory values are not clinically significant
- No clinically significant findings on 12-lead electrocardiogram
- Body mass index (BMI) 18 to ≤ 32 kg/m2, inclusive
- Male subjects agree to use appropriate contraception .
Key exclusion criteria (17 listed)
- History or current evidence of clinically significant disease, liver function tests greater than the upper limit of normal (presence of Gilbert's syndrome is acceptable), QTcF > normal (440±10 msec for males or 460±10 msec for females).
- History of unexplained syncope
- History of major bleeding, trauma, surgical procedure of any type, or vaginal delivery within six months prior to screening
- History of peptic ulcer, gastrointestinal bleeding, including the mouth, within six months prior to screening
- History of minor bleeding episodes such as epistaxis, rectal or hemorrhoidal bleeding or gingival bleeding within 1 month prior to screening
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PER977Reversal of edoxaban-induced anticoagulation | Drug | Cohort 1, Cohort 2, Cohort 3, Cohort 4, Cohort 5 |
| PlaceboReversal of edoxaban-induced anticoagulation | Drug | Cohort 1, Cohort 2, Cohort 3, Cohort 4, Cohort 5 |
| Edoxaban | Drug | Cohort 1, Cohort 2, Cohort 3, Cohort 4, Cohort 5 |
Primary outcome
Whole blood clotting time as a measure of edoxaban anticoagulation reversal by PER977
Time frame: 5 days
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.
4 secondary outcomes
Pharmacokinetic profile of PER977
Time frame: 5 days
Pharmacokinetic profile of edoxaban
Time frame: 5 days
Safety coagulation measures
Time frame: 5 days
Safety and tolerability
Time frame: 5 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 May 2020.
- Derived from this study: PubMed 26843482Sciascia 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Scott Rasmussen, MD principal investigator
Quintiles, Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PER977 and Edoxaban in people with Anticoagulation Reversal, run by Perosphere Pharmaceuticals Inc, a wholly owned subsidiary of AMAG Pharmaceuticals, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Whole blood clotting time as a measure of edoxaban anticoagulation reversal by PER977 (time frame: 5 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02207257, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 May 2020.