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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2017
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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. |
format | Online Article Text |
id | pubmed-5496637 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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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