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

Sponsor

Perosphere Pharmaceuticals Inc, a wholly owned subsidiary of AMAG Pharmaceuticals, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT02206087

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

2.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: PER977 Drug: Placebo Drug: Heparin Sodium	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Masking:

Single (Participant)

Primary Purpose:

Other

Official Title:

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

Study Start Date :

Jun 1, 2014

Actual Primary Completion Date :

Mar 1, 2016

Actual Study Completion Date :

Mar 1, 2016

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Effect of PER977 on reversal of heparin anticoagulation [Single day dosing]
To identify a dose of PER977 that reverses the effects of heparin as measured by whole blood clotting time

Secondary Outcome Measures

Safety and tolerability of PER977 administered following heparin [Single day dosing]
Number of participants with adverse events following the administration of PER977

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Adults age 18 to 65 years, inclusive
Laboratory values have no clinically significant abnormalities as judged by the Investigator.
No clinically significant findings on 12-lead electrocardiogram
Body mass index (BMI) 18 to ≤ 27 kg/m2, inclusive
Male subjects agree to use appropriate contraception .
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.
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:

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).
History of unexplained syncope
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
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 or bleeding from hemorrhoids within six months prior to screening
History of minor bleeding episodes such as epistaxis, 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 personal history of heparin-induced thrombocytopenia
Females with a history of dysfunctional uterine bleeding who have not undergone hysterectomy, including history of 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 dosing.
Taking any type of medication for more than 14 consecutive days within the 4 weeks prior to study entry
Positive serologic test for HIV, hepatitis C antibody, or hepatitis B surface antigen
Donation of blood or blood products within 56 days prior to screening
History of randomization in any prior study of PER977
Randomization in any study with an investigational compound or device within 30 days prior to signing informed consent
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