Effects of common cold and concomitant administration of nasal decongestant on the pharmacokinetics and pharmacodynamics of nasal glucagon in otherwise healthy participants: A randomized clinical trial

Cristina B Guzman, Helene Dulude, Claude Piché, Marianne Rufiange, Aziz A Sadoune, Emmanouil Rampakakis, Dolores Carballo, Myriam Triest, Michelle Xiaotian Zhang, Shuyu Zhang, Maryam Tafreshi, Eric Sicard, Cristina B Guzman, Helene Dulude, Claude Piché, Marianne Rufiange, Aziz A Sadoune, Emmanouil Rampakakis, Dolores Carballo, Myriam Triest, Michelle Xiaotian Zhang, Shuyu Zhang, Maryam Tafreshi, Eric Sicard

Abstract

Aims: Nasal glucagon (NG) is a nasally-administered glucagon powder, absorbed through the nasal mucosa, designed for treatment of severe hypoglycaemia. This study evaluated the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of NG in otherwise healthy participants with common colds and after recovery from cold symptoms, with and without concomitant nasal decongestant.

Materials and methods: This was a single-centre, open-label study. Cohort 1 participants (N = 18) received 2 doses of NG: one while experiencing nasal congestion and another after recovery from cold symptoms. Cohort 2 participants (N = 18), who also had colds with nasal congestion, received a single dose of NG 2 hours after treatment with the decongestant oxymetazoline. Total symptoms score and other safety measures were assessed before and after NG administration.

Results: NG was well tolerated, without serious adverse events. Common adverse events (transient lacrimation, nasal discomfort, rhinorrhea and nausea) were more frequent in both Cohorts 1 and 2 during nasal congestion. Glucagon levels peaked 18 minutes post-dose and glucose levels peaked 30 to 42 minutes post-dose in all groups. Nasal congestion, with or without concomitant nasal decongestant, did not significantly affect PK of NG. Although glucose AUECs0-t was different between Cohort 1 with nasal congestion and Cohort 2, glucose concentrations at 30 minutes appeared similar in all groups.

Conclusions: There were no clinically relevant differences in safety or PK/PD of NG associated with nasal congestion or concomitant administration of nasal decongestant, suggesting that NG can be used to treat severe hypoglycaemia in individuals experiencing nasal congestion.

Keywords: glucagon; hypoglycaemia.

Conflict of interest statement

E. S. is a consultant for Algorithme Pharma Inc. M. R. and A. A. S. are employees of Algorithme Pharma Inc. H. D., M. Tr., C. P. and D. C. are employees and stockholders of Locemia Solutions, which funded the study. M. Ta. and E. R. are employees of JSS Medical Research. M. Z. is an employee of and stockholder in Eli Lilly Canada. C. B. G. and S. Z. are employees of and stockholders in Eli Lilly and Company. Algorithme Pharma Inc. and JSS Medical Research was under contract with Locemia Solutions to perform different portions of this study. The authors report no other conflicts of interest.

© 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Diagram of the nasal passage and sinuses. [For illustrative purposes only.] From Intranasal Drug Administration — An Attractive Delivery Route for Some Drugs by Degenhard Marx, Gerallt Williams and Matthias Birkhoff (http://dx.doi.org/10.5772/59468). Use of the figure does not assert or imply any connection with, sponsorship or endorsement by the Original Authors and is subject to Creative Commons License 3.0 (https://creativecommons.org/licenses/by/3.0/legalcode)
Figure 2
Figure 2
Glucagon and glucose concentrations over time following nasal glucagon administration. A single 3‐mg dose of nasal glucagon was administered at time 0. Glucagon concentrations are shown in Panel A. Glucose concentrations are shown in Panel B. White circles = Cohort 1 NG with nasal congestion. Black circles = Cohort 1 NG without cold symptoms. White squares = Cohort 2 (NG with nasal congestion, treated with decongestant). Values are given as means (adjusted for baseline concentration) ± standard error; NG = nasal glucagon; 1 mmol/L = 18 mg/dL

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