Here's the actual abstract (as presumably submitted a few months ago):
Antrin photoangioplasty: results of a phase I study in patients undergoing intracoronary stent implantation
Citation: European Heart Journal Volume 22, Abstr. Suppl. September 2001, page 3
D. Kereiakes1, A.M. Syzniszewski2, D. Wahr2, H.C. Herrmann3, D.I. Simon4, C.D.K Rogers4, P.H. Kramer5, W. Shear6, A.C. Yeung7, T. M. Chou8
1University of Cincinnati, The Lindner Center, Cincinnati, United States of America
2Michigan Heart & Vascular Institute, Ann Arbor, United States of America
3University of Pennsylvania, Department of Medicine, Philadelphia, United States of America
4Brigham & Women's Hospital, Department of Medicine, Harvard, Boston, United States of America
5Mid-American Heart Institute, Kansas City, United States of America
6University of Minnesota, Department of Medicine, Minneapolis, United States of America
7Stanford University, Department of Medicine, Palo Alto, United States of America
8Pharmacyclics, Sunnyvale, United States of America
Background: Motexafin lutetium (Antrin") is a photosensitizing expanded porphyrin (texaphyrin) that accumulates preferentially in atheromatous plaque while quickly clearing from plasma. When activated by light corresponding to its absorbance properties, Antrin generates cytotoxic singlet oxygen that has been shown to induce apoptosis in macrophages and smooth muscle cells. The combination of drug and endovascular illumination (photoangioplasty, or PA) has been shown to reduce plaque in animal models.
Methods: The safety, tolerability, and preliminary efficacy of Antrin PA were assessed in a Phase I dose escalating clinical trial in subjects with critical de novo or nonstented restenosis lesions of the native coronary arteries undergoing percutaneous coronary intervention (PCI) with stent implantation. In the absence of dose-limiting toxicities such as evidence of MI or unstable arrhythmia, drug or light doses were increased in successive cohorts of 5 subjects. Drug escalation consisted of Antrin, given IV over 1020 min at 0.05, 0.15, 0.50, 1, 2, 3, or 4 mg/kg, to determine a maximum acceptable dose (MAD). The day after IV Antrin, illumination with laser-generated non-thermal far-red light (732 nm) was performed using an optical fiber with a 3- or 5-cm diffusing tip. Fibers were centered over the target lesion, delivering 100, 200, 400, or 600 J/cm-fiber light over 12 minutes. Pharmacokinetics was assessed; quantitative angiography and intravascular ultrasound of the treatment and illumination sites were performed immediately after PCI and on Day 180.
Results: At the time of abstract submission, 65 subjects were enrolled in the trial and complete follow-up is pending. If no dose-limiting toxicities are encountered, 90 subjects will be enrolled. There have been no major angiographic or biochemical adverse effects from Antrin PA. The drug appears to be well tolerated in all patients except one had a non-dose-related reaction to the infusion, and developed a drug rash requiring antihistamine therapy. A maximum drug dosage of 4.0 mg/kg was determined.
Conclusions: These preliminary results suggest that Antrin PA is a novel, well-tolerated, potential nontraumatic treatment for coronary atherosclerosis. Results of the completed enrollment and 30-day safety evaluation will be presented.
Peter |
