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

Orestes Santos-Morales, Alina Díaz-Machado, Daise Jiménez-Rodríguez, Yaisel Pomares-Iturralde, Tatiana Festary-Casanovas, Carlos A. González-Delgado, Sonia Pérez-Rodríguez, Eulalia Alfonso-Muñoz, Carmen Viada-González, Patricia Piedra-Sierra, Idrian García-García, Daniel Amaro-González, for the NeuroEPO Study Group, Julio César García-Rodríguez, Iliana Sosa-Testé, Alicia Lagarto-Parra, Laura Barrero-Viera, Marlene David-Baldo, Maura Tamayo-Rodríguez, Ivonne Rivero-Vázquez, Gricel González-Gamiz, Alis Martín-Trujillo, Yasmila Rodríguez-Fernández, Ana Alfa Ledo-de la Luz, Maylén Álvarez-Delgado, Ivón Howland-Álvarez, Yolanda Cruz-Gómez

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. 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. 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. NeuroEPO was a safe product, well tolerated at the nasal mucosa level and did not stimulate erythropoiesis in healthy volunteers. Cuban Public Registry of Clinical Trials RPCEC00000157 , June 10, 2013.