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Pitavastatin-Incorporated Nanoparticles for Chronic Limb Threatening Ischemia: A Phase I/IIa Clinical Trial

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...

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Detalles Bibliográficos
Autores principales: Matsumoto, Takuya, Yoshino, Shinichiro, Furuyama, Tadashi, Morisaki, Koichi, Nakano, Kaku, Koga, Jun-ichiro, Maehara, Yoshihiko, Komori, Kimihiro, Mori, Masaki, Egashira, Kensuke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Japan Atherosclerosis Society 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9135659/
https://www.ncbi.nlm.nih.gov/pubmed/33907060
http://dx.doi.org/10.5551/jat.58941
Descripción
Sumario: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.