Safety and Dosing Evaluation of REG1 Anticoagulation System

NCT00113997 | Completed Phase 1

• 2 other identifiers: 05016405-H-0164
• Study Type: interventional
• Target: 106
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Healthy

Keywords

Anticoagulant; Antidote; Pharmacokinetics; Pharmacodynamics; Healthy Volunteer; HV

Interventions

REG1 DRUG

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

National Heart, Lung and Blood Institute (NHLBI)

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Al Suwaidi J, Reddan DN, Williams K, Pieper KS, Harrington RA, Califf RM, Granger CB, Ohman EM, Holmes DR Jr; GUSTO-IIb, GUSTO-III, PURSUIT. Global Use of Strategies to Open Occluded Coronary Arteries. Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy; PARAGON-A Investigators. Platelet IIb/IIIa Antagonism for the Reduction of Acute coronary syndrome events in a Global Organization Network. Prognostic implications of abnormalities in renal function in patients with acute coronary syndromes. Circulation. 2002 Aug 20;106(8):974-80. doi: 10.1161/01.cir.0000027560.41358.b3.

  PMID: 12186803 BACKGROUND

• Benedict CR, Ryan J, Wolitzky B, Ramos R, Gerlach M, Tijburg P, Stern D. Active site-blocked factor IXa prevents intravascular thrombus formation in the coronary vasculature without inhibiting extravascular coagulation in a canine thrombosis model. J Clin Invest. 1991 Nov;88(5):1760-5. doi: 10.1172/JCI115495.

  PMID: 1939660 BACKGROUND

• Bracey AW, Radovancevic R, Riggs SA, Houston S, Cozart H, Vaughn WK, Radovancevic B, McAllister HA Jr, Cooley DA. Lowering the hemoglobin threshold for transfusion in coronary artery bypass procedures: effect on patient outcome. Transfusion. 1999 Oct;39(10):1070-7. doi: 10.1046/j.1537-2995.1999.39101070.x.

  PMID: 10532600 BACKGROUND

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: June 11, 2005
• First Posted: June 13, 2005
• Study Start: June 1, 2005
• Study Completion: October 1, 2005
• Last Updated: March 4, 2008

Record last verified: 2005-10

Locations

US (1)