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Pharmacodynamic studies of nasal tetracosactide with salivary glucocorticoids for a noninvasive Short Synacthen Test.

Authors :
Elder CJ
Vilela R
Johnson TN
Taylor RN
Kemp EH
Keevil BG
Cross AS
Ross RJ
Wright NP
Source :
The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2020 Aug 01; Vol. 105 (8).
Publication Year :
2020

Abstract

Context: The Short Synacthen Test (SST) is the gold standard for diagnosing adrenal insufficiency. It requires invasive administration of Synacthen, venous sampling, and is resource-intensive.<br />Objective: To develop a nasally administered SST, with salivary glucocorticoids measurement, to assess the adrenal response.<br />Design: We conducted 5 studies: 4 open-label, sequence-randomized, crossover, pharmacodynamic studies testing 6 doses/formulations and a repeatability study. Additionally, pharmacokinetic analysis was undertaken using our chosen formulation, 500 µg tetracosactide with mucoadhesive chitosan, Nasacthin003, in our pediatric study.<br />Setting: Adult and children's clinical research facilities.<br />Participants: A total of 36 healthy adult males and 24 healthy children.<br />Intervention: We administered all 6 nasal formulations using an European regulator endorsed atomization device. The IV comparators were 250 µg or 1 µg SST.<br />Main Outcome Measures: We analyzed paired blood and saliva samples for plasma cortisol and salivary cortisol and cortisone.<br />Results: The addition of chitosan to tetracosactide and dose escalation increased peak cortisol response (Pā€…=ā€…0.01 and 0.001, respectively). The bioavailability of Nasacthin003 was 14.3%. There was no significant difference in plasma cortisol at 60 minutes between 500 µg Nasacthin003 and 250 µg IV Synacthen (Pā€…=ā€…0.17). The repeatability coefficient at 60 minutes was 105 nmol/L for IV Synacthen and salivary cortisol and cortisone was 10.3 and 21.1 nmol/L, respectively. The glucocorticoid response in children was indistinguishable from that of adults.<br />Conclusions: Nasal administration of Nasacthin003 generates equivalent plasma cortisol values to the 250-µg IV SST and, with measurement at 60 minutes of salivary cortisol or cortisone, provides a noninvasive test for adrenal insufficiency.<br /> (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Details

Language :
English
ISSN :
1945-7197
Volume :
105
Issue :
8
Database :
MEDLINE
Journal :
The Journal of clinical endocrinology and metabolism
Publication Type :
Academic Journal
Accession number :
32593173
Full Text :
https://doi.org/10.1210/clinem/dgaa323