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

NCT ID: NCT02207257

Last Updated: 2020-05-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 65 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-31
• Study Completion Date: 2015-11-30

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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: OTHER
• Blinding Strategy: SINGLE

Study Groups

Cohort 1

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).

Group Type: EXPERIMENTAL

PER977

Intervention Type: DRUG

Reversal of edoxaban-induced anticoagulation

Placebo

Intervention Type: DRUG

Reversal of edoxaban-induced anticoagulation

Edoxaban

Intervention Type: DRUG

Cohort 2

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).

Group Type: EXPERIMENTAL

PER977

Intervention Type: DRUG

Reversal of edoxaban-induced anticoagulation

Placebo

Intervention Type: DRUG

Reversal of edoxaban-induced anticoagulation

Edoxaban

Intervention Type: DRUG

Cohort 3

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).

Group Type: EXPERIMENTAL

PER977

Intervention Type: DRUG

Reversal of edoxaban-induced anticoagulation

Placebo

Intervention Type: DRUG

Reversal of edoxaban-induced anticoagulation

Edoxaban

Intervention Type: DRUG

Cohort 4

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).

Group Type: EXPERIMENTAL

PER977

Intervention Type: DRUG

Reversal of edoxaban-induced anticoagulation

Placebo

Intervention Type: DRUG

Reversal of edoxaban-induced anticoagulation

Edoxaban

Intervention Type: DRUG

Cohort 5

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.

Group Type: EXPERIMENTAL

PER977

Intervention Type: DRUG

Reversal of edoxaban-induced anticoagulation

Placebo

Intervention Type: DRUG

Reversal of edoxaban-induced anticoagulation

Edoxaban

Intervention Type: DRUG

Interventions

PER977

Reversal of edoxaban-induced anticoagulation

Intervention Type: DRUG

Placebo

Reversal of edoxaban-induced anticoagulation

Intervention Type: DRUG

Edoxaban

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Adults age 18 to 65 years, inclusive

2. Laboratory values are not clinically significant

3. No clinically significant findings on 12-lead electrocardiogram

4. Body mass index (BMI) 18 to ≤ 32 kg/m2, inclusive

5. Male subjects agree to use appropriate contraception .

6. 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.

7. Subjects must sign informed consent

Exclusion Criteria

1. 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).

2. History of unexplained syncope

3. History of major bleeding, trauma, surgical procedure of any type, or vaginal delivery within six months prior to screening

4. History of peptic ulcer, gastrointestinal bleeding, including the mouth, within six months prior to screening

5. History of minor bleeding episodes such as epistaxis, rectal or hemorrhoidal bleeding or gingival bleeding within 1 month prior to screening

6. 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

7. Females with a history of dysfunctional uterine bleeding, menorrhagia , metrorrhagia or polymenorrhea

8. Pregnant or breast-feeding

9. Males with a history of hormone therapy within 3 months prior to screening

10. 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

11. Taking any type of chronic medication within the 4 weeks prior to study entry (use of hormonal contraceptives is acceptable)

12. Positive serologic test for HIV, HCV-Ab, or HBsAG

13. Donation of blood or blood products within 56 days prior to screening

14. Smokers or use of tobacco and/or nicotine containing products within 3 months prior to dosing as determined by the subject's verbal history

15. Participation in any study with an investigational compound or device within 30 days prior to signing informed consent

16. History of participation in any prior study of PER977 or edoxaban

17. 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Quintiles, Inc.

INDUSTRY

Sponsor Role: collaborator

Perosphere Pharmaceuticals Inc, a wholly owned subsidiary of AMAG Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Scott Rasmussen, MD

Role: PRINCIPAL_INVESTIGATOR

Quintiles, Inc.

Locations

Quintiles

Overland Park, Kansas, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 26843482 (View on PubMed)

Other Identifiers

PER977-02-001

Identifier Type: -

Identifier Source: org_study_id