Effects of Eszopiclone and Lemborexant in People With OSA With a Low Arousal Threshold Who Have Difficulty Sleeping (ELOSA)

April 15, 2025 updated by: Professor Danny Eckert, Flinders University

Effects of Eszopiclone and Lemborexant in People With Obstructive Sleep Apnoea (OSA) With a Low Arousal Threshold Who Have Difficulty Maintaining or Falling Asleep (ELOSA): A Double-blind, Placebo-controlled, Randomised, Trial.

Insomnia and obstructive sleep apnoea (OSA) are very common conditions, collectively estimated to affect 2 billion people globally, and share many of the same symptoms. It is also common for people to have both insomnia and sleep apnoea (COMISA). Indeed, 30 to 40% of patients with chronic insomnia also fulfil the diagnostic criteria for OSA. These people can be particularly challenging to treat with conventional therapy approaches.

People get OSA for different reasons. One key cause is waking up too easily to minor airway narrowing episodes (a low arousal threshold).

Accordingly, this study aims to increase the arousal threshold using a combination approach with a GABAergic and an orexin agent in appropriately selected individuals (i.e., the clinically relevant group of people with OSA with a low arousal threshold and difficulty maintain or initiating sleep). Sleep, breathing and next day performance will be compared across two monitored overnight sleep studies (placebo vs the study drugs).

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Background:

Insomnia and obstructive sleep apnoea (OSA) are very common conditions, collectively estimated to affect 2 billion people globally, and share many of the same symptoms. It is also common for people to have both insomnia and sleep apnoea (COMISA). Indeed, 30 to 40% of patients with chronic insomnia also fulfil the diagnostic criteria for OSA. These people can be particularly challenging to treat with conventional therapy approaches.

OSA is characterised by repeated narrowing and closure of the upper airway during sleep, desaturation in oxygen levels, and fragmented sleep. OSA is a heterogeneous disease, with anatomical crowding of the upper airway and at least three distinct non-anatomical endotypes. The non-anatomical OSA endotypes include high loop gain (unstable control of breathing), poor upper airway dilator muscle function, and a low arousal threshold (ArTH- waking up too easily to minor airway narrowing events). Each OSA endotype represents a novel therapeutic target. Adding to the complexity of OSA, more than one endotype can contribute to a person's OSA. While the first line treatment for OSA, continuous positive airway pressure (CPAP) is efficacious, long-term compliance is only 40 to 70%. Those with a low ArTH endotype have markedly lower CPAP uptake and compliance.

Indeed, people with a low ArTH endotype experience frequent cortical arousals (awakenings) leading to fragmented and non-restorative sleep. Frequent cortical arousals prevent transitioning into deeper sleep states that are characterised by more stable breathing. Thus, strategies to increase the arousal threshold to stabilise breathing and reduce OSA severity in people who wake up easily (low ArTH) have been investigated as a novel therapeutic target. For example, commonly used hypnotic agents such as eszopiclone and trazodone can increase the arousal threshold and reduce OSA severity in people with a low ArTH. More recently, we have shown that 50mg quetiapine also improves sleep and reduces OSA severity in people with OSA who report difficulty maintaining sleep. However, the extent to which common hypnotic agents increase the arousal threshold in people with OSA is modest at best (~20%). This limits the therapeutic efficacy for people with OSA.

Orexin has been identified as an important sleep wake modulator. Accordingly, new orexin antagonists have been developed as novel sleep promotion aids for the treatment of insomnia. For example, the orexin antagonist, Lemborexant, has been shown to be safe and efficacious for the treatment of insomnia including in the elderly and people with OSA.

Given that current monotherapy approaches to increase the arousal threshold in people with OSA have only modestly increased the threshold for arousal with correspondingly modest reductions in OSA severity, there is a need to investigate the potential role for combination hypnotic therapy. Accordingly, this study aims to target two key sleep/wake mechanisms (the GABAergic and orexin systems) to determine if this combination approach yields greater therapeutic benefit than previous attempts with monotherapy in appropriately selected individuals (i.e., the clinically relevant group of people with OSA with a low ArTH and difficulty maintain or initiating sleep).

Study Type

Interventional

Enrollment (Estimated)

15

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Australia
    • South Australia
      • Bedford Park, South Australia, Australia, 5042

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Moderate or more difficulty "staying or initiating asleep" score on the Insomnia Severity Index questionnaire
  • Obstructive Sleep Apnoea (OSA), Apnoea Hypopnea Index ≥ 10 events/hour
  • Low arousal respiratory threshold OSA endotype
  • BMI ≤35 kg/m2

Exclusion Criteria:

  • Concomitant medications that interact or are contraindicated with eszopiclone, zopiclone, and Lemborexant
  • Concomitant medications known to influence breathing, sleep, arousal, or muscle physiology
  • Current pregnancy or breast-feeding
  • Current or recent other medical conditions likely to affect results or safety

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Eszopiclone 3mg and lemborexant 10mg
Both Eszopiclone 3mg and Lemborexant 10mg in the form of capsules taken before bedtime. Dosages is taken on one instance for one night only.
Drug: Eszopiclone 3 mg
Both eszopiclone and lemborexant taken together at bedtime for one night
Other Names:
  • Lunesta
Drug: Lemborexant 10mg
Both eszopiclone and lemborexant taken together at bedtime for one night
Other Names:
  • Dayvigo
Placebo Comparator: Placebo
Placebo capsules that look exactly like the study drugs, taken before bedtime. Dosage is taken on one instance for one night only.
Drug: Placebo
Placebo sugar pills that looks like the eszopiclone and lemborexant capsules taken at bedtime for one night.
Other Names:
  • Sugar pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in OSA severity (eszopiclone and lemborexant night vs. placebo night)
Time Frame: Two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.
OSA severity as measured by the apnoea hypopnea index (units: number of respiratory events/h sleep) during overnight in-laboratory polysomnography.
Two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in time below 90% blood arterial oxygen saturation (eszopiclone and lemborexant night vs. placebo night)
Time Frame: Two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.
Percent time asleep spent below an arterial oxygen saturation of 90% measured via pulse oximetry during overnight in-laboratory polysomnography.
Two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.
Change in sleep efficiency (eszopiclone and lemborexant night vs. placebo night)
Time Frame: Two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.
Percent time spent asleep divided by the recording time from lights out to lights on during overnight in-laboratory polysomnography
Two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.
Change in arousal index (eszopiclone and lemborexant night vs. placebo night)
Time Frame: Two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.
Number of cortical arousals per hour of sleep during overnight in-laboratory polysomnography.
Two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.
Change in perceived sleepiness (eszopiclone and lemborexant night vs. placebo night)
Time Frame: Next morning following two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.
Next day perceived sleepiness assessed via the Karolinska Sleepiness Scale (10 point scale where 1=extremely alert and 10=extremely sleepy)
Next morning following two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.
Change in nadir overnight hypoxemia (eszopiclone and lemborexant night vs. placebo night)
Time Frame: Two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.
Nadir overnight oxygen saturation during sleep (units: %) measured via pulse oximetry during overnight in-laboratory polysomnography.
Two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.
Change in mean overnight hypoxemia (eszopiclone and lemborexant night vs. placebo night)
Time Frame: Two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.
Mean overnight oxygen saturation during sleep (units: %) measured via pulse oximetry during overnight in-laboratory polysomnography.
Two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.
Change in respiratory control (eszopiclone and lemborexant night vs. placebo night)
Time Frame: Two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.
Loop gain and the ventilatory response to arousal (units: % eupnea) during overnight in-laboratory polysomnography.
Two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.
Change in the respiratory arousal threshold (eszopiclone and lemborexant night vs. placebo night)
Time Frame: Two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.
Threshold to arousal (units: % eupnea) during overnight in-laboratory polysomnography.
Two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.
Change in airway collapsibility (eszopiclone and lemborexant night vs. placebo night)
Time Frame: Two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.
Vpassive (units: % eupnea) during overnight in-laboratory polysomnography.
Two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.
Change in pharyngeal muscle response (eszopiclone and lemborexant night vs. placebo night)
Time Frame: Two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.
Vcompensation (units: % eupnea) during overnight in-laboratory polysomnography.
Two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.
Baseline OSA endotype and whether they are associated with changes in OSA severity
Time Frame: Baseline sleep study
Exploratory analysis to determine if baseline OSA endotypes as defined above (outcomes 7-10) are associated with changes in OSA severity as measured via the AHI- outcome 1 (eszopiclone and lemborexant night vs. placebo night)
Baseline sleep study
Change in next morning balance (eszopiclone and lemborexant night vs. placebo night)
Time Frame: Next morning following two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.
Stand on AMTI AccuSway Balance Board, eyes open and eyes closed 1 minute each. To evaluate balance in the next morning after eszopiclone and lemborexant night vs. placebo night (units: distance from center in cm)
Next morning following two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.
Change in driving simulator performance (eszopiclone and lemborexant night vs. placebo night)
Time Frame: Next morning following two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.
Next day alertness as measured via the Australian-developed (AusEd) driving simulator performance task (units: SD of steering deviation from median line).
Next morning following two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.
Change in psycho-motor vigilance (eszopiclone and lemborexant night vs. placebo night)
Time Frame: Next morning following two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.
Next day alertness as measured via the psychomotor vigilance test (PVT) (units m/s) higher values indicate worse performance.
Next morning following two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Flinders University

Investigators

  • Principal Investigator: Danny J Eckert, PhD, Flinders University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 1, 2025

Primary Completion (Estimated)

May 1, 2027

Study Completion (Estimated)

June 30, 2027

Study Registration Dates

First Submitted

April 7, 2025

First Submitted That Met QC Criteria

April 7, 2025

First Posted (Actual)

April 15, 2025

Study Record Updates

Last Update Posted (Actual)

April 18, 2025

Last Update Submitted That Met QC Criteria

April 15, 2025

Last Verified

April 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 7849
  • 1196261 (Other Grant/Funding Number: National health and medical research council of Australia)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

Our Participant Information Consent Form (PICF) asks if the participant is happy for their information to be shared with other researchers if it is deidentified. Deidentified individual participant data (IPD) might be made available to other researchers upon reasonable request and subject to ethical approval. Requests must include a methodologically sound proposal and will be reviewed by the Principal Investigator.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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