BAY2586116 Nasal Spray and OSA Severity

Study Overview
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Brief Summary
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This investigator-initiated study aims to determine the effects of BAY2586116 (a novel TASK channel blocker nasal spray) on sleep apnoea severity and the potential influence of route of breathing.

Official Title
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Effects of BAY2586116 on Obstructive Sleep Apnoea (OSA) Severity Informed by Upper Airway Physiology and the Role of Route of Breathing

Conditions
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Sleep Apnea, Obstructive

Intervention / Treatment
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* Drug: BAY2586116
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female participants aged 18 years or older at screening Must have completed Part A of the KOALA study (NCT04236440) Must be willing to sleep three nights in the sleep lab without OSA therapy (This includes continuous positive airway pressure therapy (CPAP) and/or a mandibular advancement device (MAD)) Must be willing to refrain from drinking alcohol on the study days. Must be willing to limit consumption of tobacco to four cigarettes or one cigar a day and not smoke while at the sleep laboratory. This might be up to 12 hours. Must be willing to limit caffeinated beverage intake (coffee, tea, cola, and other soft drinks) to 400 mg / day or less of caffeine and not to be used within 4 hours of bedtime on study days. Contraceptive use required by men or women according to the methods of contraception for those participating in clinical studies Exclusion Criteria: Any medications or herbal supplements that may interfere or be contraindicated with the study drug as determined by the investigator Severely impaired breathing within two days prior to randomization (e.g., acute nasal congestion during upper airway infection). known allergies or hypersensitivities to the study drugs (active substances or excipients of the preparations). Any other condition which at the discretion of the investigator would make the participant unsuitable for participation in the study and will not allow participation for the full planned study period (e.g., active malignancy or other condition limiting life expectancy to less than 12 months)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo (saline) nasal spray, taken before bedtime. Dosage is taken on one instance for one night only. | Drug: Placebo<br>* Placebo (saline) nasal spray application<br>|
| Experimental: BAY2586116 (oro-nasal breathing night)<br>BAY2586116 nasal spray, taken before bedtime. Dosage is taken on one instance for one night only for the oro-nasal breathing night. | Drug: BAY2586116<br>* 160 μg BAY2586116 nasal spray application<br>|
| Experimental: BAY2586116 (nasal breathing only night)<br>BAY2586116 nasal spray, taken before bedtime. Dosage is taken on one instance for one night only for the nasal only breathing night. | Drug: BAY2586116<br>* 160 μg BAY2586116 nasal spray application<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Individual comparison between physiology changes in Pcrit during KOALA part A (NCT04236440) between BAY2586116 vs. placebo and change in AHI with BAY2586116 vs. placebo (nasal breathing) during current study | Individual changes in the critical closing pressure of the upper airway during sleep (Pcrit- measured in cmH2O) in KOALA part A (NCT04236440) will be compared to changes in the apnoea/hypopnoea index (AHI- measured as # of apnoeas and hypopneas per hour of sleep) between BAY2586116 (nasal breathing night) vs. placebo night | Two non-consecutive single night sleep studies (BAY2586116 nasal only breathing night vs. placebo night) conducted approximately 1 week apart | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in OSA severity (BAY2586116 nasal only breathing night vs. placebo night) | OSA severity as measured by the AHI (apnoea hypopnea index measured as # events/h sleep) during overnight in-laboratory polysomnography. | Two non-consecutive single night sleep studies (BAY2586116 nasal only breathing night vs. placebo night) conducted approximately 1 week apart | 
| Change in OSA severity (BAY2586116 oro-nasal breathing night vs. placebo night) | OSA severity as measured by the AHI (apnoea hypopnea index measured as # events/h sleep) during overnight in-laboratory polysomnography. | Two non-consecutive single night sleep studies (BAY2586116 oro-nasal breathing night vs. placebo night) conducted approximately 1 week apart | 
| Change in OSA severity (BAY2586116 oro-nasal breathing night vs. BAY2586116 nasal only breathing night) | OSA severity as measured by the AHI (apnoea hypopnea index measured as # events/h sleep) during overnight in-laboratory polysomnography. | Two non-consecutive single night sleep studies (BAY2586116 oro-nasal breathing night vs. BAY2586116 nasal only breathing night) conducted approximately 1 week apart | 
| Change in nadir overnight hypoxemia (BAY2586116 nights vs. placebo night) | Nadir overnight oxygen saturation during sleep (%) measured via pulse oximetry during overnight in-laboratory polysomnography. | Three non-consecutive single night sleep studies (BAY2586116 nasal only breathing night, BAY2586116 oro-nasal breathing night and placebo night) conducted approximately 1 week apart | 
| Change in sleep efficiency (BAY2586116 nights vs. placebo night) | Percent time spent asleep divided by the recording time from lights out to lights on during overnight in-laboratory polysomnography. | Three non-consecutive single night sleep studies (BAY2586116 nasal only breathing night, BAY2586116 oro-nasal breathing night and placebo night) conducted approximately 1 week apart | 
| Change in arousal index (BAY2586116 nights vs. placebo night) | Number of cortical arousals per hour of sleep during overnight in-laboratory polysomnography. | Three non-consecutive single night sleep studies (BAY2586116 nasal only breathing night, BAY2586116 oro-nasal breathing night and placebo night) conducted approximately 1 week apart | 
| Change in sleep architecture (BAY2586116 nights vs. placebo night) | Proportion of sleep stages (% total sleep time) during overnight in-laboratory polysomnography. | Three non-consecutive single night sleep studies (BAY2586116 nasal only breathing night, BAY2586116 oro-nasal breathing night and placebo night) conducted approximately 1 week apart | 
| Change in respiratory control (BAY2586116 nights vs. placebo night) | Loop gain and the ventilatory response to arousal (% eupnea) during overnight in-laboratory polysomnography. | Three non-consecutive single night sleep studies (BAY2586116 nasal only breathing night, BAY2586116 oro-nasal breathing night and placebo night) conducted approximately 1 week apart | 
| Change in the respiratory arousal threshold (BAY2586116 nights vs. placebo night) | Threshold to arousal (% eupnea) during overnight in-laboratory polysomnography. | Three non-consecutive single night sleep studies (BAY2586116 nasal only breathing night, BAY2586116 oro-nasal breathing night and placebo night) conducted approximately 1 week apart | 
| Change in airway collapsibility (BAY2586116 nights vs. placebo night) | Vpassive (% eupnea) during overnight in-laboratory polysomnography. | Three non-consecutive single night sleep studies (BAY2586116 nasal only breathing night, BAY2586116 oro-nasal breathing night and placebo night) conducted approximately 1 week apart | 
| Placebo OSA endotypes (outcomes 8-11) and whether they are associated with changes in OSA severity (BAY2586116 nights vs. placebo night) | Exploratory analysis to determine if OSA endotypes (outcomes 8-11) are associated with changes in OSA severity (BAY2586116 nights vs. placebo night) | Three non-consecutive single night sleep studies (BAY2586116 nasal only breathing night, BAY2586116 oro-nasal breathing night and placebo night) conducted approximately 1 week apart | 
| Change in hypoxic burden (BAY2586116 nights vs. placebo night) | Hypoxic burden during sleep (%min/h) measured via pulse oximetry during overnight in-laboratory polysomnography. | Three non-consecutive single night sleep studies (BAY2586116 nasal only breathing night, BAY2586116 oro-nasal breathing night and placebo night) conducted approximately 1 week apart |