Multiple murine studies demonstrated rhACE2 modulates the RAS pathway, although it is unclear if these effects translate to humans. A clinical study (Safety and Tolerability Study of APN01 [Recombinant Human Angiotensin Converting Enzyme 2]; NCT00886353) that assessed the pharmacokinetics and pharmacodynamics of soluble rhACE2 treatment in healthy volunteers with no known comorbidities showed a decrease in plasma Ang1-8 and increased Ang1-7 and Ang1-5 with no effect on blood pressure and heart rate (54). Common side effects included diarrhea and headache. No antibodies to rhACE2 developed, which suggested there was no elicit immune response to single or repeated dosing (54). Further studies investigating the immunogenicity of rhACE are required.