Study of PER977 Administered to Subjects With Steady State Edoxaban Dosing and Re-anticoagulation With Edoxaban

NCT02207257 | Completed Phase 2 DMC

• 1 other identifier: PER977-02-001
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Anticoagulation Reversal

Keywords

PER977; anticoagulation reversal; pharmacokinetics; edoxaban; whole blood clotting time; D-dimer; prothrombin fragments 1 and 2; tissue factor pathway inhibitor; prothrombin time

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (4)

• Pharmacokinetic profile of PER977

  5 days

• Pharmacokinetic profile of edoxaban

  5 days

• Safety coagulation measures

  5 days

• Safety and tolerability

  5 days

Other Outcomes (1)

• Analytical measurement range (AMR), reproducibility, and precision of WBCT measurements

  5 days

Study Arms (5)

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).

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).

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).

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).

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.

Drug: PER977; Drug: Placebo; Drug: Edoxaban

Interventions

PER977 DRUG

Reversal of edoxaban-induced anticoagulation

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5

Placebo DRUG

Reversal of edoxaban-induced anticoagulation

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5

Edoxaban DRUG

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Perosphere Pharmaceuticals Inc, a wholly owned subsidiary of AMAG Pharmaceuticals, Inc.: lead
• Quintiles, Inc.: collaborator

Study Sites (1)

Quintiles

Overland Park, Kansas, 66212, United States

Location

Related Publications (1)

• 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.

  PMID: 26843482 DERIVED

MeSH Terms

Interventions

PER977; edoxaban

Study Officials

• Scott Rasmussen, MD

  Quintiles, Inc.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2014
• First Posted: August 4, 2014
• Study Start: March 1, 2014
• Primary Completion: September 1, 2015
• Study Completion: November 1, 2015
• Last Updated: May 21, 2020

Record last verified: 2017-11

Locations

US (1)