Nasal administration of the neuroprotective candidate NeuroEPO to healthy volunteers: a randomized, parallel, open-label safety studyReportar como inadecuado




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BMC Neurology

, 17:129

Cerebrovascular disease and stroke

Abstract

BackgroundDelivery of therapeutic agents as erythropoietin EPO into Central Nervous System through intranasal route could benefit patients with neurological disorders. A new nasal formulation containing a non-hematopoietic recombinant EPO NeuroEPO has shown neuroprotective actions in preclinical models. In the current study, the safety of NeuroEPO was evaluated for the first time in humans.

MethodsA phase I, randomized, parallel, open-label study was carried out in healthy volunteers. They received, intranasally, 1 mg of NeuroEPO every 8 h during 4 days Group A or 0.5 mg of NeuroEPO Group B with the same schedule. The working hypothesis was that intranasal NeuroEPO produce <10% of severe adverse reactions in the evaluated groups. Therefore, a rigorous assessment of possible adverse events was carried out, which included tolerance of the nasal mucosa and the effect on hematopoietic activity. Clinical safety evaluation was daily during treatment and laboratory tests were done before and on days 5 and 14 after starting treatment.

ResultsTwenty-five volunteers, 56% women, with a mean age of 27 yrs. were included. Twelve of them received the highest NeuroEPO dose. Twenty types of adverse events occurred, with headache 20% and increase of hepatic enzymes 20% as the most reported ones. Nasopharyngeal itching was the most common local event but only observed in four patients 16%, all of them from the lowest dose group. About half of the events were very probably or probably caused by the studied product. Most of the events were mild 95.5%, did not require treatment 88.6% and were completely resolved 81.8%. No severe adverse events were reported. During the study the hematopoietic variables were kept within reference values.

ConclusionsNeuroEPO was a safe product, well tolerated at the nasal mucosa level and did not stimulate erythropoiesis in healthy volunteers.

Trial registrationCuban Public Registry of Clinical Trials RPCEC00000157, June 10, 2013.

KeywordsNon-hematopoietic recombinant erythropoietin NeuroEPO Stroke Neurodegenerative diseases Healthy volunteers Safety Hematopoietic activity AbbreviationsALTAlanine aminotransferase

ASTAspartate aminotransferase

BBBBlood-brain barrier

CHOChinese hamster ovary

CNSCentral Nervous System

EDTAEthylenediaminetetraacetic acid

GGTGamma-glutamyltransferase

HgbHemoglobin

HPMCHydroxypropyl methylcellulose

MSSDMaximum safe starting dose

NaCLSodium chloride

rHu-EPORecombinant human erythropoietin

WHOWorld Health Organization

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Autor: Orestes Santos-Morales - Alina Díaz-Machado - Daise Jiménez-Rodríguez - Yaisel Pomares-Iturralde - Tatiana Festary-Casanov

Fuente: https://link.springer.com/



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