Evaluation of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Effects of PER977 Following Heparin

Phase I/II Evaluation of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Effects of a Single Escalating Dose of PER977 Following Administration of Unfractionated Heparin

Normal subjects will receive unfractionated heparin followed by a single dose of PER977 with dose escalation by cohort. Ten subjects enrolled in Cohort 4 will receive a single dose of PER977 followed by a one-week washout and then will receive unfractionated heparin followed by a single dose of PER977. The study will provide some insight into the doses that may be required to reverse anticoagulation induced by heparin.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: PER977; Drug: Placebo; Drug: Heparin Sodium

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Overland Park, Kansas, United States, 66211
      • Quintiles

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adults age 18 to 65 years, inclusive
2. Laboratory values have no clinically significant abnormalities as judged by the Investigator.
3. No clinically significant findings on 12-lead electrocardiogram
4. Body mass index (BMI) 18 to ≤ 27 kg/m2, inclusive
5. Male subjects agree to use appropriate contraception .
6. Female subjects may be surgically sterile or 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 cycles or 28 days following discharge from the study.
7. 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.

Exclusion Criteria:

1. History or current evidence of clinically significant disease Current evidence of liver function tests or renal function tests (serum creatinine) greater than the upper limit of normal. The presence of Gilbert's Syndrome is acceptable. Current evidence of QTcF >normal (450±10 msec for males or 470±10 msec for females).
2. History of unexplained syncope
3. Hypersensitivity to unfractionated heparin, thrombocytopenia with a positive in vitro test to anti-platelet antibody in the presence of unfractionated heparin, hypersensitivity to heparin or porcine products or any other contraindication to unfractionated heparin
4. History of major bleeding, trauma, surgical procedure of any type, or vaginal delivery within six months prior to screening
5. History of peptic ulcer, gastrointestinal bleeding or bleeding from hemorrhoids within six months prior to screening
6. History of minor bleeding episodes such as epistaxis, or gingival bleeding within 1 month prior to screening
7. 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 personal history of heparin-induced thrombocytopenia
8. Females with a history of dysfunctional uterine bleeding who have not undergone hysterectomy, including history of menorrhagia, metrorrhagia or polymenorrhea
9. Pregnant or breast-feeding
10. Males with a history of hormone therapy within 3 months prior to screening
11. 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 dosing.
12. Taking any type of medication for more than 14 consecutive days within the 4 weeks prior to study entry
13. Positive serologic test for HIV, hepatitis C antibody, or hepatitis B surface antigen
14. Donation of blood or blood products within 56 days prior to screening
15. History of randomization in any prior study of PER977
16. Randomization in any study with an investigational compound or device within 30 days prior to signing informed consent
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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: SINGLE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; 100 mg PER977 or placebo administered following heparin sodium	Drug: PER977; Reversal of heparin-induced anticoagulation; Drug: Placebo; Reversal of heparin-induced anticoagulation; Drug: Heparin Sodium
Experimental: Cohort 2; 200 mg PER977 or placebo administered following heparin sodium	Drug: PER977; Reversal of heparin-induced anticoagulation; Drug: Placebo; Reversal of heparin-induced anticoagulation; Drug: Heparin Sodium
Experimental: Cohort 3; 300 mg PER977 or placebo administered following heparin sodium	Drug: PER977; Reversal of heparin-induced anticoagulation; Drug: Placebo; Reversal of heparin-induced anticoagulation; Drug: Heparin Sodium
Experimental: Cohort 4; 400 mg PER977 or placebo administered as a single agent followed by 3-day wash-out. A second dose of 400 mg PER977 or placebo will be administered following heparin sodium injection	Drug: PER977; Reversal of heparin-induced anticoagulation; Drug: Placebo; Reversal of heparin-induced anticoagulation; Drug: Heparin Sodium
Experimental: Cohort 5; 500 mg PER977 or placebo will be administered following heparin sodium injection	Drug: PER977; Reversal of heparin-induced anticoagulation; Drug: Placebo; Reversal of heparin-induced anticoagulation; Drug: Heparin Sodium
Experimental: Cohort 6; 600 mg PER977 or placebo will be administered following heparin sodium injection	Drug: PER977; Reversal of heparin-induced anticoagulation; Drug: Placebo; Reversal of heparin-induced anticoagulation; Drug: Heparin Sodium

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of PER977 on reversal of heparin anticoagulation	To identify a dose of PER977 that reverses the effects of heparin as measured by whole blood clotting time	Single day dosing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of PER977 administered following heparin	Number of participants with adverse events following the administration of PER977	Single day dosing

Collaborators and Investigators

• Sponsor: Perosphere Pharmaceuticals Inc, a wholly owned subsidiary of AMAG Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Barbara Lomeli, MD, Quintiles, Inc.

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: June 2, 2014
• First Submitted That Met QC Criteria: July 30, 2014
• First Posted (Estimate): August 1, 2014

Study Record Updates

• Last Update Posted (Actual): May 21, 2020
• Last Update Submitted That Met QC Criteria: May 19, 2020
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: heparin; whole blood clotting time; PER977; anticoagulation reversal
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin; Calcium heparin
• Other Study ID Numbers: PER977-01-002