Abstract | PURPOSE: MATERIALS AND METHODS: In this multicenter, open-label, single-dose, dose-escalation study, 20 patients with worsening symptoms of lower extremity ischemia within 6 months of enrollment were treated with alfimeprase in five escalating dose cohorts (0.025 mg/kg, 0.05 mg/kg, 0.1 mg/kg, 0.3 mg/kg, and 0.5 mg/kg) by means of intraarterial and sometimes intrathrombic pulsed infusion. The primary endpoint was safety assessed by adverse event rates. Additional safety assessments included vital sign monitoring, serum chemistry testing, hematologic testing, and coagulation testing for 28 days after the procedure, as well as alpha2-macroglobulin and antialfimeprase antibody testing for as long as 3 months after treatment. Pharmacokinetic parameters were evaluated with use of an assay that measures free and alpha2-macroglobulin-bound (ie, total) alfimeprase. RESULTS: No patient experienced a hemorrhagic adverse event. Mean plasminogen and fibrinogen concentrations were not substantially altered by treatment. Three transient treatment-related adverse events were reported in the same patient: one incidence each of increased blood fibrinogen level, skin rash, and headache. All three adverse events were graded as mild. The pharmacokinetic profile of alfimeprase suggested that the half-life for total alfimeprase ranges from 11 to 54 minutes (median, 25 min) in patients with PAO. The serum alpha2-macroglobulin concentrations decreased transiently in a dose response-like manner between 12 and 24 hours and returned to within normal limits approximately 14 days after alfimeprase exposure. CONCLUSIONS:
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Authors | Kenneth Ouriel, Jacob Cynamon, Fred A Weaver, Herbert Dardik, Donald Akers, John Blebea, Laura Gruneiro, Christopher F Toombs, Fong Wang-Clow, Margie Mohler, Luis Pena, Ching-Yi Wan, Steven R Deitcher |
Journal | Journal of vascular and interventional radiology : JVIR
(J Vasc Interv Radiol)
Vol. 16
Issue 8
Pg. 1075-83
(Aug 2005)
ISSN: 1051-0443 [Print] United States |
PMID | 16105919
(Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study)
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Chemical References |
- Blood Coagulation Factors
- Fibrinolytic Agents
- Hemoglobins
- alpha-Macroglobulins
- Metalloendopeptidases
- alfimeprase
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Topics |
- Adult
- Aged
- Angiography
- Blood Coagulation Factors
(analysis)
- Female
- Fibrinolytic Agents
(administration & dosage, adverse effects, pharmacokinetics)
- Hematocrit
- Hemoglobins
(analysis)
- Humans
- Leg
(blood supply)
- Male
- Metalloendopeptidases
(administration & dosage, adverse effects, pharmacokinetics)
- Middle Aged
- Peripheral Vascular Diseases
(blood, diagnostic imaging, drug therapy)
- Thrombolytic Therapy
- Thrombosis
(blood, drug therapy)
- alpha-Macroglobulins
(analysis)
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