Clinical trial NCT02206100: PK and PD of Single, Escalating Doses of PER977 Following Enoxaparin
Official title: Phase I/II Evaluation of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Effects of Single, Hourly-Repeating, Escalating Doses of PER977 Following a Single Subcutaneous Dose of Enoxaparin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Healthy
Keywords: PER977
enoxaparin
anticoagulation reversal
whole blood clotting time
Lead sponsor: AMAG Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2014-08-01
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: OTHER

Brief summary: PER977 administration following a single dose of enoxaparin

Detailed description: Single escalating doses of PER977 from 100 to 300 mg, of 25 mg PER977 x 4 doses will be administered following administration of enoxaparin. Serial pharmacokinetic and pharmacodynamic assessments ( whole blood clotting time) will be performed. Adverse events will be monitored.

Eligibility criteria: Inclusion Criteria

1. Adults age 18 to 65 years, inclusive
2. Laboratory values have no clinically significant abnormalities
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 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 enoxaparin sodium, thrombocytopenia with a positive in vitro test to anti-platelet antibody in the presence of enoxaparin sodium, hypersensitivity to heparin or porcine products or any other contraindication to enoxaparin
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

Primary outcomes:
measure: Number of adverse events
timeFrame: 1 day
Secondary outcomes:
measure: Reversal of enoxaparin anticoagulation
timeFrame: 1 day
measure: Pharmacokinetics of enoxaparin
timeFrame: 1 day
measure: Pharmacokinetics of PER977 and its metabolite
timeFrame: 2 days
Other outcomes:
Locations:
city: Overland Park
country: United States
facility: Quintiles
state: Kansas
Study officials:
affiliation: Quintiles, Inc.
name: Scott Rasmussen, MD
role: PRINCIPAL_INVESTIGATOR
References: