Safety and Dosing Evaluation of REG1 Anticoagulation System

• Status: Completed
• Trial end date: 2005-10-01
• Target enrollment: 0
• Participant gender: All

Summary

This 1-week study will test the safety and dosing of an anticoagulation system called REG1 that is designed to improve control of "blood thinning." Patients with heart attack and other conditions require treatment with an anticoagulant (blood thinner) to prevent the formation of blood clots. However, anticoagulation therapy can increase the risk of bleeding. The REG1 system is designed to minimize this risk. One part of the system stops the activity of factor IX (a protein that helps blood clot) while the other part of the system (the antidote) inactivates the drug and stops the thinning process. This study will examine in normal healthy subjects how the REG1 system works in the body and how it leaves the body.

Healthy normal volunteers between 12 and 65 years of age who weigh 50-120 kilograms (110-264 pounds) and have no history of bleeding problems or significant bleeding may be eligible for this study. Candidates are screened with a medical history, physical examination, and blood tests.

Participants must avoid foods that may alter the blood's clotting ability and must not take any medications the week of the study. They undergo the following tests and procedures:

Day 1

Subjects are admitted to the NIH Clinical Center for an overnight stay. Two catheters (plastic tubes) are placed in the subject's arm veins, one for drawing blood samples and the other for injecting one of the following: REG1 drug, REG1 antidote, REG1 drug and antidote, or placebo. Two injections of study medication are given, spaced 3 hours apart, each over a 1-minute period. After each injection, blood is collected at specific times to measure levels of the drug or antidote in the body and the blood's ability to clot. Subjects also provide a 24-hour urine collection and stool sample.

Day 2

A blood sample is drawn 24 hours after the drug or antidote injection from the previous day. If the blood test result is normal, subjects are discharged home with instructions to follow. They return to the Clinical Center at 36 hours and 48 hours for additional blood samples.

Days 3 and 7

A blood sample is collected at the end of day 3 and day 7. Urine and stool samples are also collected.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Criteria

INCLUSION CRITERIA:

• Participants are eligible if they meet the following criteria:

• Age is greater than or equal to 21 years to 65 years

• Ability to give written informed consent

• Weight between 50 Kg and 120 Kg

EXCLUSION CRITERIA:

• Participants are NOT eligible under the following conditions:

• Age is less than 21 years

• Subject weight is less than 50 Kg of greater than 120 Kg

• Females - Pregnant or lactating

• Females - active menstruation on day of injection (Females may be randomized if they are not actively menstruating on day of injection or they can be randomized as soon as menstruation ceases)

• Any medical condition (other than a self-limited illness) that requires ongoing and current medical attention

• Any prescription medication (including oral or patch or injectable contraceptives)

• Any use of NSAIDS or aspirin in the prior 7 days

• Any known individual or family history of a bleeding diathesis or coagulopathy

• Any history of thrombocytopenia, or baseline platelet count less than 150,000

• Any history of thrombocytosis or baseline platelet count greater than 600,000

• Endoscopic peptic ulcer disease in the past 3 years or GI bleeding in the past 3 months

• Genitourinary bleeding within the past 3 months

• Severe trauma, fracture, major surgery, or biopsy of a parenchymal organ within the past 3 months

• Any evidence or history of intracranial bleeding or aneurysm

• Any history of thrombotic or hemorrhagic stroke

• Severe persistent hypertension (systolic pressure greater than 180 mm Hg or diastolic greater than 110 mm Hg)

• Baseline Hgb less than 12.0 g/dL, PT greater than ULN, or APTT greater than ULN

• Baseline liver dysfunction (ALT, AST, bilirubin, or alkaline phosphatase greater than ULN)

• Baseline renal dysfunction (serum creatinine or BUN greater than ULN)

• Use of an investigational drug within the past 30 days

• Any factor that might influence ability to return for follow-up visits

• Illicit drug or alcohol abuse

• Inability to comply with the study protocol