A Novel TASK Channel Antagonist Improves Pharyngeal Collapsibility in People with Severe OSA
Authors List
Amal M Osman1*, Sutapa Mukherjee1,3, Thomas J Altree1, Martina Delbeck2, Thomas Muller2, Gerrit Weimann2 and Danny J Eckert1
1 Adelaide Institute for Sleep Health and FHMRI Sleep Health, College of Medicine and Public Health, Flinders University, Adelaide, Australia
2 Bayer AG, Research & Development, Pharmaceuticals, Wuppertal, Germany
3 Respiratory and Sleep Service, Southern Adelaide Local Health Network, SA Health, South Australia, Australia
Introduction
Blocking K+ channels to increase upper airway dilator muscle activity has been identified as a potential pharmacotherapy target for obstructive sleep apnoea (OSA). This study aimed to determine the effects of a novel, potent, K+ channel antagonist on pharyngeal collapsibility during sleep.
Methods
12 people (6 females) with OSA (AHI=55±28 events/h, BMI=36±5kg/m2, 58±12y (mean±SD)) were studied. Pharyngeal collapsibility (Pcrit) was measured during non-REM sleep after a novel TASK-1/3 K+ channel antagonist (BAY 2586116) or placebo nasal spray (160µg) just prior to sleep according to a double-blind, randomised, crossover (~1-week washout) design (NCT04236440). 10 participants returned for two more Pcrit studies: 1) nasal drops (160µg BAY2586116) and 2) half dose nasal spray (80µg BAY2586116) (investigator remained blinded). 8 participants returned for a final Pcrit visit for direct endoscopic application (160µg BAY2586116). At each visit, participants were instrumented with polysomnography equipment to monitor sleep, an epiglottic pressure catheter, pneumotachograph and nasal mask. A modified continuous positive airway pressure (CPAP) machine was used to deliver therapeutic CPAP to maintain airway patency and deliver multiple transient reductions in pressure during stable non-REM sleep to quantify Pcrit.
Results
Compared to placebo, nasal application of 160µg BAY2586116 improved Pcrit (2.1±1.8 vs. 0.1±4.4 cmH2O, p=0.04). There was similar benefit from the 160µg nasal drop application (Δ-1.4±1.7 cmH2O, p=0.04), 80µg nasal spray application (Δ-2.3±1.6 cmH2O, p<0.001) and endoscope application of 160µg BAY2586116 (Δ-2.0±2.2 cmH2O p=0.05).
Conclusions
BAY 2586116 improves upper airway collapsibility during sleep in people with OSA. While these findings highlight the therapeutic potential for this novel pharmacotherapy approach, how these physiological changes relate to improvements in clinical OSA severity remain to be determined and are under investigation (NCT05527457).
Research Funding Source: This work was supported by Bayer (sponsor)
Amal M Osman1*, Sutapa Mukherjee1,3, Thomas J Altree1, Martina Delbeck2, Thomas Muller2, Gerrit Weimann2 and Danny J Eckert1
1 Adelaide Institute for Sleep Health and FHMRI Sleep Health, College of Medicine and Public Health, Flinders University, Adelaide, Australia
2 Bayer AG, Research & Development, Pharmaceuticals, Wuppertal, Germany
3 Respiratory and Sleep Service, Southern Adelaide Local Health Network, SA Health, South Australia, Australia
Introduction
Blocking K+ channels to increase upper airway dilator muscle activity has been identified as a potential pharmacotherapy target for obstructive sleep apnoea (OSA). This study aimed to determine the effects of a novel, potent, K+ channel antagonist on pharyngeal collapsibility during sleep.
Methods
12 people (6 females) with OSA (AHI=55±28 events/h, BMI=36±5kg/m2, 58±12y (mean±SD)) were studied. Pharyngeal collapsibility (Pcrit) was measured during non-REM sleep after a novel TASK-1/3 K+ channel antagonist (BAY 2586116) or placebo nasal spray (160µg) just prior to sleep according to a double-blind, randomised, crossover (~1-week washout) design (NCT04236440). 10 participants returned for two more Pcrit studies: 1) nasal drops (160µg BAY2586116) and 2) half dose nasal spray (80µg BAY2586116) (investigator remained blinded). 8 participants returned for a final Pcrit visit for direct endoscopic application (160µg BAY2586116). At each visit, participants were instrumented with polysomnography equipment to monitor sleep, an epiglottic pressure catheter, pneumotachograph and nasal mask. A modified continuous positive airway pressure (CPAP) machine was used to deliver therapeutic CPAP to maintain airway patency and deliver multiple transient reductions in pressure during stable non-REM sleep to quantify Pcrit.
Results
Compared to placebo, nasal application of 160µg BAY2586116 improved Pcrit (2.1±1.8 vs. 0.1±4.4 cmH2O, p=0.04). There was similar benefit from the 160µg nasal drop application (Δ-1.4±1.7 cmH2O, p=0.04), 80µg nasal spray application (Δ-2.3±1.6 cmH2O, p<0.001) and endoscope application of 160µg BAY2586116 (Δ-2.0±2.2 cmH2O p=0.05).
Conclusions
BAY 2586116 improves upper airway collapsibility during sleep in people with OSA. While these findings highlight the therapeutic potential for this novel pharmacotherapy approach, how these physiological changes relate to improvements in clinical OSA severity remain to be determined and are under investigation (NCT05527457).
Research Funding Source: This work was supported by Bayer (sponsor)
