Takuya Matsumoto1,2, Shinichiro Yoshino2, Tadashi Furuyama2, Koichi Morisaki2, Kaku Nakano3, Jun-Ichiro Koga3,4, Yoshihiko Maehara2, Kimihiro Komori5, Masaki Mori2, Kensuke Egashira3,6. 1. Department of Vascular Surgery, National Hospital Organization Fukuoka-higashi Medical Center. 2. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University. 3. Department of Cardiovascular Research, Development, and Translational Medicine, Center for Disruptive Cardiovascular Innovation, Kyushu University. 4. Department of Cardiovascular Medicine, Kyusyu University Graduate School of Medical Sciences. 5. Division of Vascular Surgery, Department of Surgery, Nagoya University Graduate School of Medicine. 6. Department of Translational Medicine, Kyushu University Graduate School of Pharmaceutical Sciences.
Abstract
AIM: To assess the results of a phase I/IIa open-label dose-escalation clinical trial of 5-day repeated intramuscular administration of pitavastatin-incorporated poly (lactic-co-glycolic acid) nanoparticles (NK-104-NP) in patients with chronic limb threatening ischemia (CLTI). METHODS: NK-104-NP was formulated using an emulsion solvent diffusion method. NK-104-NP at four doses (nanoparticles containing 0.5, 1, 2, and 4 mg of pitavastatin calcium, n=4 patients per dose) was investigated in a dose-escalation manner and administered intramuscularly into the ischemic limbs of 16 patients with CLTI. The safety and therapeutic efficacy of treatment were investigated over a 26-week follow-up period. RESULTS: No cardiovascular or other serious adverse events caused by NK-104-NP were detected during the follow-up period. Improvements in Fontaine and Rutherford classifications were noted in five patients (one, three, and one in the 1-, 2-, and 4-mg dose groups, respectively). Pharmacokinetic parameters including the maximum serum concentration and the area under the blood concentration-time curve increased with pitavastatin treatment in a dose-dependent manner. The area under the curve was slightly increased at day 5 compared with that at day 1 of treatment, although the difference was not statistically significant. CONCLUSIONS: This is the first clinical trial of pitavastatin-incorporated nanoparticles in patients with CLTI. Intramuscular administration of NK-104-NP to the ischemic limbs of patients with CLTI was safe and well tolerated and resulted in improvements in limb function.
AIM: To assess the results of a phase I/IIa open-label dose-escalation clinical trial of 5-day repeated intramuscular administration of pitavastatin-incorporated poly (lactic-co-glycolic acid) nanoparticles (NK-104-NP) in patients with chronic limb threatening ischemia (CLTI). METHODS: NK-104-NP was formulated using an emulsion solvent diffusion method. NK-104-NP at four doses (nanoparticles containing 0.5, 1, 2, and 4 mg of pitavastatin calcium, n=4 patients per dose) was investigated in a dose-escalation manner and administered intramuscularly into the ischemic limbs of 16 patients with CLTI. The safety and therapeutic efficacy of treatment were investigated over a 26-week follow-up period. RESULTS: No cardiovascular or other serious adverse events caused by NK-104-NP were detected during the follow-up period. Improvements in Fontaine and Rutherford classifications were noted in five patients (one, three, and one in the 1-, 2-, and 4-mg dose groups, respectively). Pharmacokinetic parameters including the maximum serum concentration and the area under the blood concentration-time curve increased with pitavastatin treatment in a dose-dependent manner. The area under the curve was slightly increased at day 5 compared with that at day 1 of treatment, although the difference was not statistically significant. CONCLUSIONS: This is the first clinical trial of pitavastatin-incorporated nanoparticles in patients with CLTI. Intramuscular administration of NK-104-NP to the ischemic limbs of patients with CLTI was safe and well tolerated and resulted in improvements in limb function.
Entities:
Keywords:
Angiogenesis; Arteriogenesis; Drug delivery system; Peripheral arterial disease; Statin
Authors: Anthony J Comerota; Richard C Throm; Kathryn A Miller; Timothy Henry; Nicolas Chronos; John Laird; Rafael Sequeira; Craig K Kent; Matthew Bacchetta; Corey Goldman; Juha-Pekka Salenius; Frank A Schmieder; Richard Pilsudski Journal: J Vasc Surg Date: 2002-05 Impact factor: 4.268