BAY2586116 Nasal Spray and OSA Severity

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

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.

Study Overview

• Status: Completed
• Conditions: Sleep Apnea, Obstructive
• Intervention / Treatment: Drug: Placebo; Drug: BAY2586116

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Bedford Park, South Australia, Australia, 5042
      • Flinders University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Flinders University
• Collaborators: Bayer

Publications and helpful links

General Publications

• Gaisl T, Turnbull CD, Weimann G, Unger S, Finger R, Xing C, Cistulli PA, West S, Chiang AKI, Eckert DJ, Stradling JR, Kohler M. BAY 2253651 for the treatment of obstructive sleep apnoea: a multicentre, double-blind, randomised controlled trial (SANDMAN). Eur Respir J. 2021 Nov 18;58(5):2101937. doi: 10.1183/13993003.01937-2021. Print 2021 Nov.

Helpful Links

• Clinical trial registry for main KOALA study protocol (Parts A-C)

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2022
• Primary Completion (Actual): December 20, 2022
• Study Completion (Actual): December 20, 2022

Study Registration Dates

• First Submitted: August 29, 2022
• First Submitted That Met QC Criteria: September 1, 2022
• First Posted (Actual): September 2, 2022

Study Record Updates

• Last Update Posted (Actual): February 15, 2023
• Last Update Submitted That Met QC Criteria: February 13, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Sleep Apnea Syndromes; Sleep Apnea, Obstructive
• Other Study ID Numbers: 5468

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual data will be included in the study publication.
• IPD Sharing Time Frame: Upon publication
• IPD Sharing Access Criteria: Available in the publication.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No