Anticoagulant ReversalPhase 1PER977-P1NCT01826266
Effects of a Double-Blind, Single Dose of PER977 Administered Alone, and Following a Single Dose of Edoxaban
A Phase 1 study of Anticoagulant Reversal and Reversal of Edoxaban Induced Anticoagulation, run by Perosphere Pharmaceuticals Inc, a wholly owned subsidiary of AMAG Pharmaceuticals, Inc. at 1 site in United States.
Trial summary
PER977 monotherapy and co-administration following 60 mg edoxaban will have an acceptable safety and tolerability profile with no impact on pro-coagulant biomarkers. A dose of PER977 that reverses the effects of edoxaban on the pharmacodynamic (PD) biomarkers (point of care prothrombin time [PoC-PT]), and/or secondary… Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Anticoagulant Reversal, Reversal of Edoxaban Induced Anticoagulation
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 83 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2013to Dec 2013
- Phase
- Phase 1
- 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 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Adults age 18 to 45 years, inclusive
- Laboratory values (chemistry, complete blood count coagulation assessments) and urinalysis performed during screening up to 21 days prior to administration of study treatment are within normal limits.
- No clinically significant findings on 12-lead electrocardiogram (ECG) performed during screening.
- Body mass index (BMI) 18 to ≤32 kg/m2, inclusive
- Male subjects agree to use appropriate contraception (i.e., double barrier contraception such as a latex condom with spermicide with a female partner of child-bearing potential (a non-menopausal female who has not had one of the following: a) a hysterectomy (with or without oophorectomy), b) a bilateral oophorectomy without hysterectomy, or c) a medically documented ovarian failure) using a diaphragm or cervical cap or single barrier contraception if the female partner is using an intrauterine device or hormonal contraceptives or is sterilized; no barrier is required if the female partner has had a hysterectomy) when engaging in sexual activity during the course of the study. Moreover, male subjects should not donate sperm or attempt to impregnate a partner during the course of the study and for a period of 12 weeks following discharge from the study.
- Female subjects of non-childbearing potential (a menopausal female with the above 3 definitions for menopause) agree to use two forms of non-hormonal contraceptive (e.g. barrier methods [condom or diaphragm]) or intrauterine device for the duration of the study and for 30 days following the completion of the study. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.
- Nonsmokers or nonusers of nicotine containing products within 3 months of dosing (occasional use of tobacco products within 30 days of dosing will be considered on a case-by-case basis)
- Subjects must understand and agree to comply with the requirements of the study and they must be willing to sign the informed consent form indicating voluntary consent to participate in the study prior to initiation of screening or study related activities.
Who cannot join
- History or current evidence of clinically significant cardiac, hepatic, renal, pulmonary, endocrine, neurologic, infectious, gastrointestinal, hematologic, or oncologic disease as determined by screening history, physical examination, laboratory test results or 12-lead ECG. History or current evidence of liver function tests greater than the upper limit of normal. History or current evidence of QTc Fridericia (QTcF) greater than normal (430±10 msec for males or 450±10 msec for females; average of three measurements).
- History of unexplained syncope
- Use of any drugs or substances known to be strong inhibitors or strong inducers of CYP3A4/5 transporters of p-glycoprotein within 28 days prior to the first dosing
- 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 hematemesis, melena, rectal bleeding) or bleeding from hemorrhoids within six months prior to screening
- History of minor bleeding episodes such as epistaxis, rectal or hemorrhoidal bleeding (spots of blood on toilet paper) or gingival bleeding within 3 months prior to screening
Show all 17Show fewer
- 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, anticoagulants or platelet inhibitors
- Females with a history of dysfunctional uterine bleeding, including history of menorrhagia (heavy menstrual bleeding), metrorrhagia or polymenorrhea or current use of hormonal contraceptives.
- Pregnant or breast-feeding
- Male subjects with a history of hormone therapy within the 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
- Positive serologic test for human immunodeficiency virus (HIV), Hepatitis C virus (HCV), or Hepatitis B surface antigen (HBsa)
- Use of any of the following medications in the 4 weeks prior to study entry: rifampin, dronedarone, ketoconazole, verapamil, amiodarone, quinidine, clopidogrel, oral anticoagulants, or other agent known to interact with edoxaban
- Donation of blood or blood products within 56 days prior to enrollment
- Participation in any study with an investigational compound or device within 30 days prior to signing informed consent
- Active drug, alcohol or nicotine use or dependence 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.
United States1 site
Duke Clinical Research, Unit 200
Durham, North Carolina, 27705
About this study
Official title: Phase I Evaluation of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Effects of a Double-Blind, Single Dose of PER977 Administered Alone, and Following a Single Dose of Edoxaban
PER977 monotherapy and co-administration following 60 mg edoxaban will have an acceptable safety and tolerability profile with no impact on pro-coagulant biomarkers. A dose of PER977 that reverses the effects of edoxaban on the pharmacodynamic (PD) biomarkers (point of care prothrombin time [PoC-PT]), and/or secondary biomarkers (thromboelastography reaction time [TEG-R]) will be identified.
Read the detailed description
Normal subjects will be dosed with PER977 or placebo alone and 1 week later, they will be given a single dose of edoxaban followed in 3 hours by a single IV dose of PER977. The purpose is to show safety and tolerability of PER977 alone and when combined with a NOAC (edoxaban). The study will also provide some insight into the doses that may be required to reverse a steady state edoxaban.
- Being tested
- PER977, Placebo
- Keywords
- PER977, Activated partial thromboplastin time, Assessment, D-dimer, Enrollment, Investigational drug, Investigational treatment, Period, Premature subject withdrawal, Prothrombin time, Randomization number, Study discontinuation, Study drug, Subject number, Study treatment, Thromboelastography-reaction time
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PER977, PlaceboDrug
Also called ciraparantag
| Study group | Role | What they receive |
|---|---|---|
| PER977-Dose 1 | Placebo comparator | Dose titration Receives: Drug: PER977, Placebo |
| PER977-Dose 2 | Placebo comparator | Dose Titration Receives: Drug: PER977, Placebo |
| PER977-Dose 3 | Placebo comparator | Dose Titration Receives: Drug: PER977, Placebo |
| PER977-Dose 4 | Placebo comparator | Dose Titration Receives: Drug: PER977, Placebo |
| PER977-Dose 5 | Placebo comparator | Dose Titration Receives: Drug: PER977, Placebo |
| PER977-Dose 6 | Placebo comparator | Dose Titration Receives: Drug: PER977, Placebo |
| PER977-Dose 7 | Placebo comparator | Dose Titration Receives: Drug: PER977, Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the safety, tolerability, and plasma and urinary pharmacokinetics (PK) of a range of single intravenous (IV) doses of PER977
Measured: 7 months
Secondary outcomes (1)
Pharmacodynamic assessment
To determine the effect of escalating doses of PER977 on the reversal of edoxaban-induced anticoagulation
Measured: 2 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2013 (estimated)
- Study startJul 2013
- Primary completionDec 2013
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Anticoagulant 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 83 participants (actual)
Sponsor and investigators
- Lead sponsor
- Perosphere Pharmaceuticals Inc, a wholly owned subsidiary of AMAG Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Robert Noveck, MD, PhD, Principal investigator, Duke Clinical Research Unit
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01826266
- Sponsor's protocol ID
- PER977-01-001
- Other IDs
- PER977-01-001
- Acronym
- PER977-P1
- Status last verified
- Sep 2017
- First submitted
- 3 Apr 2013
- Last updated
- 28 May 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Ansell JE, Bakhru SH, Laulicht BE, Steiner SS, Grosso MA, Brown K, Dishy V, Lanz HJ, Mercuri MF, Noveck RJ, Costin JC. Single-dose ciraparantag safely and completely reverses anticoagulant effects of edoxaban. Thromb Haemost. 2017 Jan 26;117(2):238-245. doi: 10.1160/TH16-03-0224. Epub 2016 Nov 17.
PubMed 27853809Sciascia 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 26843482Ansell JE, Bakhru SH, Laulicht BE, Steiner SS, Grosso M, Brown K, Dishy V, Noveck RJ, Costin JC. Use of PER977 to reverse the anticoagulant effect of edoxaban. N Engl J Med. 2014 Nov 27;371(22):2141-2. doi: 10.1056/NEJMc1411800. Epub 2014 Nov 5. No abstract available.
PubMed 25371966
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Evaluation of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Effects of a Double-Blind, Single Dose of PER977 Administered Alone, and Following a Single Dose of Edoxaban
- ClinicalTrials.gov ID
- NCT01826266
- Acronym / sponsor ID
- PER977-P1 / PER977-01-001
- Keywords
- PER977, Activated partial thromboplastin time, Assessment, D-dimer, Enrollment, Investigational drug, Investigational treatment, Period
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 83 participants (actual)
- Lead sponsor
- Perosphere Pharmaceuticals Inc, a wholly owned subsidiary of AMAG Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Jul 2013
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 8 Apr 2013 (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.
PER977 monotherapy and co-administration following 60 mg edoxaban will have an acceptable safety and tolerability profile with no impact on pro-coagulant biomarkers. A dose of PER977 that reverses the effects of edoxaban on the pharmacodynamic (PD) biomarkers (point of care prothrombin time [PoC-PT]), and/or secondary biomarkers (thromboelastography reaction time [TEG-R]) will be identified.
Detailed description
Normal subjects will be dosed with PER977 or placebo alone and 1 week later, they will be given a single dose of edoxaban followed in 3 hours by a single IV dose of PER977. The purpose is to show safety and tolerability of PER977 alone and when combined with a NOAC (edoxaban). The study will also provide some insight into the doses that may be required to reverse a steady state edoxaban.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Single blind (participant)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| PER977-Dose 1 | Placebo comparator | Drug: PER977, PlaceboDose titration |
| PER977-Dose 2 | Placebo comparator | Drug: PER977, PlaceboDose Titration |
| PER977-Dose 3 | Placebo comparator | Drug: PER977, PlaceboDose Titration |
| PER977-Dose 4 | Placebo comparator | Drug: PER977, PlaceboDose Titration |
| PER977-Dose 5 | Placebo comparator | Drug: PER977, PlaceboDose Titration |
| PER977-Dose 6 | Placebo comparator | Drug: PER977, PlaceboDose Titration |
| PER977-Dose 7 | Placebo comparator | Drug: PER977, PlaceboDose Titration |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Adults age 18 to 45 years, inclusive
- Laboratory values (chemistry, complete blood count coagulation assessments) and urinalysis performed during screening up to 21 days prior to administration of study treatment are within normal limits.
- No clinically significant findings on 12-lead electrocardiogram (ECG) performed during screening.
- Body mass index (BMI) 18 to ≤32 kg/m2, inclusive
- Male subjects agree to use appropriate contraception (i.e., double barrier contraception such as a latex condom with spermicide with a female partner of child-bearing potential (a non-menopausal female who has not had one of the following: a) a hysterectomy (with or without oophorectomy), b) a bilateral oophorectomy without hysterectomy, or c) a medically documented ovarian failure) using a diaphragm or cervical cap or single barrier contraception if the female partner is using an intrauterine device or hormonal contraceptives or is sterilized; no barrier is required if the female partner has had a hysterectomy) when engaging in sexual activity during the course of the study. Moreover, male subjects should not donate sperm or attempt to impregnate a partner during the course of the study and for a period of 12 weeks following discharge from the study.
Key exclusion criteria (17 listed)
- History or current evidence of clinically significant cardiac, hepatic, renal, pulmonary, endocrine, neurologic, infectious, gastrointestinal, hematologic, or oncologic disease as determined by screening history, physical examination, laboratory test results or 12-lead ECG. History or current evidence of liver function tests greater than the upper limit of normal. History or current evidence of QTc Fridericia (QTcF) greater than normal (430±10 msec for males or 450±10 msec for females; average of three measurements).
- History of unexplained syncope
- Use of any drugs or substances known to be strong inhibitors or strong inducers of CYP3A4/5 transporters of p-glycoprotein within 28 days prior to the first dosing
- 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 hematemesis, melena, rectal bleeding) or bleeding from hemorrhoids within six months 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 |
|---|---|---|
| PER977, PlaceboAlso: ciraparantag | Drug | PER977-Dose 1, PER977-Dose 2, PER977-Dose 3, PER977-Dose 4, PER977-Dose 5, PER977-Dose 6, PER977-Dose 7 |
Primary outcome
To evaluate the safety, tolerability, and plasma and urinary pharmacokinetics (PK) of a range of single intravenous (IV) doses of PER977
Time frame: 7 months
1 secondary outcome
Pharmacodynamic assessment
Time frame: 2 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 28 May 2020.
- Derived from this study: PubMed 27853809Ansell JE, Bakhru SH, Laulicht BE, Steiner SS, Grosso MA, Brown K, Dishy V, Lanz HJ, Mercuri MF, Noveck RJ, Costin JC. Single-dose ciraparantag safely and completely reverses anticoagulant effects of edoxaban. Thromb Haemost. 2017 Jan 26;117(2):238-245. doi: 10.1160/TH16-03-0224. Epub 2016 Nov 17.
- 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.
- Derived from this study: PubMed 25371966Ansell JE, Bakhru SH, Laulicht BE, Steiner SS, Grosso M, Brown K, Dishy V, Noveck RJ, Costin JC. Use of PER977 to reverse the anticoagulant effect of edoxaban. N Engl J Med. 2014 Nov 27;371(22):2141-2. doi: 10.1056/NEJMc1411800. Epub 2014 Nov 5. No abstract available.
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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.
Robert Noveck, MD, PhD principal investigator
Duke Clinical Research Unit
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study of Anticoagulant Reversal and Reversal of Edoxaban Induced Anticoagulation, 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 8 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 28 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. Some participants in this study may receive a placebo. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
To evaluate the safety, tolerability, and plasma and urinary pharmacokinetics (PK) of a range of single intravenous (IV) doses of PER977 (time frame: 7 months). 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 NCT01826266, which also lists 3 linked publications.
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 28 May 2020.