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

BACKGROUND: Delivery 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 preclinic...

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Autores principales: Santos-Morales, Orestes, Díaz-Machado, Alina, Jiménez-Rodríguez, Daise, Pomares-Iturralde, Yaisel, Festary-Casanovas, Tatiana, González-Delgado, Carlos A., Pérez-Rodríguez, Sonia, Alfonso-Muñoz, Eulalia, Viada-González, Carmen, Piedra-Sierra, Patricia, García-García, Idrian, Amaro-González, Daniel, García-Rodríguez, Julio César, Sosa-Testé, Iliana, Lagarto-Parra, Alicia, Barrero-Viera, Laura, David-Baldo, Marlene, Tamayo-Rodríguez, Maura, Rivero-Vázquez, Ivonne, González-Gamiz, Gricel, Martín-Trujillo, Alis, Rodríguez-Fernández, Yasmila, Ledo-de la Luz, Ana Alfa, Álvarez-Delgado, Maylén, Howland-Álvarez, Ivón, Cruz-Gómez, Yolanda
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5496637/
https://www.ncbi.nlm.nih.gov/pubmed/28676085
http://dx.doi.org/10.1186/s12883-017-0908-0
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author Santos-Morales, Orestes
Díaz-Machado, Alina
Jiménez-Rodríguez, Daise
Pomares-Iturralde, Yaisel
Festary-Casanovas, Tatiana
González-Delgado, Carlos A.
Pérez-Rodríguez, Sonia
Alfonso-Muñoz, Eulalia
Viada-González, Carmen
Piedra-Sierra, Patricia
García-García, Idrian
Amaro-González, Daniel
García-Rodríguez, Julio César
Sosa-Testé, Iliana
Lagarto-Parra, Alicia
Barrero-Viera, Laura
David-Baldo, Marlene
Tamayo-Rodríguez, Maura
Rivero-Vázquez, Ivonne
González-Gamiz, Gricel
Martín-Trujillo, Alis
Rodríguez-Fernández, Yasmila
Ledo-de la Luz, Ana Alfa
Álvarez-Delgado, Maylén
Howland-Álvarez, Ivón
Cruz-Gómez, Yolanda
author_facet Santos-Morales, Orestes
Díaz-Machado, Alina
Jiménez-Rodríguez, Daise
Pomares-Iturralde, Yaisel
Festary-Casanovas, Tatiana
González-Delgado, Carlos A.
Pérez-Rodríguez, Sonia
Alfonso-Muñoz, Eulalia
Viada-González, Carmen
Piedra-Sierra, Patricia
García-García, Idrian
Amaro-González, Daniel
García-Rodríguez, Julio César
Sosa-Testé, Iliana
Lagarto-Parra, Alicia
Barrero-Viera, Laura
David-Baldo, Marlene
Tamayo-Rodríguez, Maura
Rivero-Vázquez, Ivonne
González-Gamiz, Gricel
Martín-Trujillo, Alis
Rodríguez-Fernández, Yasmila
Ledo-de la Luz, Ana Alfa
Álvarez-Delgado, Maylén
Howland-Álvarez, Ivón
Cruz-Gómez, Yolanda
author_sort Santos-Morales, Orestes
collection PubMed
description BACKGROUND: Delivery 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. METHODS: A 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. RESULTS: Twenty-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. CONCLUSIONS: NeuroEPO was a safe product, well tolerated at the nasal mucosa level and did not stimulate erythropoiesis in healthy volunteers. TRIAL REGISTRATION: Cuban Public Registry of Clinical Trials RPCEC00000157, June 10, 2013.
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spelling pubmed-54966372017-07-07 Nasal administration of the neuroprotective candidate NeuroEPO to healthy volunteers: a randomized, parallel, open-label safety study Santos-Morales, Orestes Díaz-Machado, Alina Jiménez-Rodríguez, Daise Pomares-Iturralde, Yaisel Festary-Casanovas, Tatiana González-Delgado, Carlos A. Pérez-Rodríguez, Sonia Alfonso-Muñoz, Eulalia Viada-González, Carmen Piedra-Sierra, Patricia García-García, Idrian Amaro-González, Daniel García-Rodríguez, Julio César Sosa-Testé, Iliana Lagarto-Parra, Alicia Barrero-Viera, Laura David-Baldo, Marlene Tamayo-Rodríguez, Maura Rivero-Vázquez, Ivonne González-Gamiz, Gricel Martín-Trujillo, Alis Rodríguez-Fernández, Yasmila Ledo-de la Luz, Ana Alfa Álvarez-Delgado, Maylén Howland-Álvarez, Ivón Cruz-Gómez, Yolanda BMC Neurol Research Article BACKGROUND: Delivery 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. METHODS: A 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. RESULTS: Twenty-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. CONCLUSIONS: NeuroEPO was a safe product, well tolerated at the nasal mucosa level and did not stimulate erythropoiesis in healthy volunteers. TRIAL REGISTRATION: Cuban Public Registry of Clinical Trials RPCEC00000157, June 10, 2013. BioMed Central 2017-07-04 /pmc/articles/PMC5496637/ /pubmed/28676085 http://dx.doi.org/10.1186/s12883-017-0908-0 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Santos-Morales, Orestes
Díaz-Machado, Alina
Jiménez-Rodríguez, Daise
Pomares-Iturralde, Yaisel
Festary-Casanovas, Tatiana
González-Delgado, Carlos A.
Pérez-Rodríguez, Sonia
Alfonso-Muñoz, Eulalia
Viada-González, Carmen
Piedra-Sierra, Patricia
García-García, Idrian
Amaro-González, Daniel
García-Rodríguez, Julio César
Sosa-Testé, Iliana
Lagarto-Parra, Alicia
Barrero-Viera, Laura
David-Baldo, Marlene
Tamayo-Rodríguez, Maura
Rivero-Vázquez, Ivonne
González-Gamiz, Gricel
Martín-Trujillo, Alis
Rodríguez-Fernández, Yasmila
Ledo-de la Luz, Ana Alfa
Álvarez-Delgado, Maylén
Howland-Álvarez, Ivón
Cruz-Gómez, Yolanda
Nasal administration of the neuroprotective candidate NeuroEPO to healthy volunteers: a randomized, parallel, open-label safety study
title Nasal administration of the neuroprotective candidate NeuroEPO to healthy volunteers: a randomized, parallel, open-label safety study
title_full Nasal administration of the neuroprotective candidate NeuroEPO to healthy volunteers: a randomized, parallel, open-label safety study
title_fullStr Nasal administration of the neuroprotective candidate NeuroEPO to healthy volunteers: a randomized, parallel, open-label safety study
title_full_unstemmed Nasal administration of the neuroprotective candidate NeuroEPO to healthy volunteers: a randomized, parallel, open-label safety study
title_short Nasal administration of the neuroprotective candidate NeuroEPO to healthy volunteers: a randomized, parallel, open-label safety study
title_sort nasal administration of the neuroprotective candidate neuroepo to healthy volunteers: a randomized, parallel, open-label safety study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5496637/
https://www.ncbi.nlm.nih.gov/pubmed/28676085
http://dx.doi.org/10.1186/s12883-017-0908-0
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