Safety and pharmacokinetics of mosliciguat, a new, inhaled soluble guanylate cyclase activator, in healthy adult subjects
6 affiliations
- 1Research & Development, Pharmaceuticals Bayer AG Wuppertal Germany
- 2Clinical Statistics 1, Pharmaceuticals Bayer AG Wuppertal Germany
- 3Research and Clinical Development, Pharmaceuticals Bayer AG Wuppertal Germany
- 4Research and Development, Clinical Development, Bayer AG Berlin Germany
- 5CRS Clinical Research Services Wuppertal GmbH Wuppertal Germany
- 6NUVISAN GmbH Neu‐Ulm Germany
Abstract
Aim: Mosliciguat (BAY 1237592), the first soluble guanylate cyclase (sGC) activator in a dry powder inhaler (DPI), could potentially treat pulmonary hypertension with a more targeted delivery than systemic sGC stimulators. We report safety and tolerability of mosliciguat in healthy men.
Methods: Three randomized, single‐blinded, placebo‐controlled Phase 1 studies of mosliciguat DPI: a single‐dose escalation study (SDES) of mosliciguat 60–4000 μg (n = 78), a multiple‐dose escalation study (MDES) of seven once‐daily doses of 480–2000 μg over 8 days (n = 36) and a multiple‐dose study (MDS) of mosliciguat 1000 μg for 14 days (n = 21).
Results: Most adverse events (AEs) were mild, with no serious AEs or AEs leading to discontinuation. No clinically relevant lung function impairment or change in oxygen saturation was observed. In the MDES, body plethysmography indicated reduced airway resistance 6 h after dosing. Generally, no clinically relevant effect on blood pressure was seen; however, a few events of mild‐to‐moderate orthostatic hypotension occurred with higher doses in the SDES and MDS. In the SDES, there was a small, dose‐dependent heart rate increase with mosliciguat. Increased plasma cyclic guanosine monophosphate levels confirmed target engagement by mosliciguat. Overall, the PK profile of mosliciguat was appropriate for an inhaled therapy, with low systemic exposures and an effect on airway resistance consistent with targeted inhaled lung‐selective delivery.
Conclusion: Mosliciguat DPI was well tolerated in healthy subjects, without AEs related to bronchospasm or airway irritation, with a pharmacodynamic response indicating sGC activation and a bronchodilating action.
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BibTeX
@article{nagelschmitz2026safety,
title = {{Safety and pharmacokinetics of mosliciguat, a new, inhaled soluble guanylate cyclase activator, in healthy adult subjects}},
author = {Johannes Nagelschmitz and Soundos Saleh and Sandra Ligges and Melanie Seidel‐Greven and Eva Becker‐Pelster and Sylvia M. Nikkho and Stefanie Boxnick and Wolfgang Timmer},
journal = {British Journal of Clinical Pharmacology},
year = {2026},
month = jul,
doi = {10.1002/bcp.70668},
url = {https://doi.org/10.1002/bcp.70668},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Safety and pharmacokinetics of mosliciguat, a new, inhaled soluble guanylate cyclase activator, in healthy adult subjects
AU - Johannes Nagelschmitz
AU - Soundos Saleh
AU - Sandra Ligges
AU - Melanie Seidel‐Greven
AU - Eva Becker‐Pelster
AU - Sylvia M. Nikkho
AU - Stefanie Boxnick
AU - Wolfgang Timmer
PY - 2026
DA - 2026/07/23
JO - British Journal of Clinical Pharmacology
DO - 10.1002/bcp.70668
UR - https://doi.org/10.1002/bcp.70668
AB - Aim: Mosliciguat (BAY 1237592), the first soluble guanylate cyclase (sGC) activator in a dry powder inhaler (DPI), could potentially treat pulmonary hypertension with a more targeted delivery than systemic sGC stimulators. We report safety and tolerability of mosliciguat in healthy men. Methods: Three randomized, single‐blinded, placebo‐controlled Phase 1 studies of mosliciguat DPI: a single‐dose escalation study (SDES) of mosliciguat 60–4000 μg (n = 78), a multiple‐dose escalation study (MDES) of seven once‐daily doses of 480–2000 μg over 8 days (n = 36) and a multiple‐dose study (MDS) of mosliciguat 1000 μg for 14 days (n = 21). Results: Most adverse events (AEs) were mild, with no serious AEs or AEs leading to discontinuation. No clinically relevant lung function impairment or change in oxygen saturation was observed. In the MDES, body plethysmography indicated reduced airway resistance 6 h after dosing. Generally, no clinically relevant effect on blood pressure was seen; however, a few events of mild‐to‐moderate orthostatic hypotension occurred with higher doses in the SDES and MDS. In the SDES, there was a small, dose‐dependent heart rate increase with mosliciguat. Increased plasma cyclic guanosine monophosphate levels confirmed target engagement by mosliciguat. Overall, the PK profile of mosliciguat was appropriate for an inhaled therapy, with low systemic exposures and an effect on airway resistance consistent with targeted inhaled lung‐selective delivery. Conclusion: Mosliciguat DPI was well tolerated in healthy subjects, without AEs related to bronchospasm or airway irritation, with a pharmacodynamic response indicating sGC activation and a bronchodilating action.
SN - 0306-5251
SN - 1365-2125
ER -