OSA - Obstructive Sleep ApneaPhase 2ELOSANCT06928766
Effects of Eszopiclone and Lemborexant in People With OSA With a Low Arousal Threshold Who Have Difficulty Sleeping
A Phase 2 study testing Eszopiclone 3 mg and Lemborexant 10mg in people with OSA - Obstructive Sleep Apnea, run by Flinders University at 1 site in Australia.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- OSA - Obstructive Sleep Apnea
- What is being tested?
- Eszopiclone 3 mg and Lemborexant 10mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 1 siteAustralia
- Study dates
- 31 Oct 2025to 30 Jun 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Australia1 site, 1 recruiting
- Recruiting
Flinders University, Adelaide Institute for Sleep Health
Bedford Park, South Australia, 5042
Reem Laboratory Manager, +61 8 8201 7781, aish.sleeplab@flinders.edu.au
Charmaine O'Reilly, +61 8 8201 3177, charmaine.oreilly@flinders.edu.au
About this study
Official title: 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).
Read the 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).
- Conditions
- OSA - Obstructive Sleep Apnea
- Being tested
- Eszopiclone 3 mg, Placebo, Lemborexant 10mg
- Keywords
- sleep disordered breathing, arousal, COMISA
- Medical subject headings
- Sleep Apnea, Obstructive, Sleep Apnea Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Eszopiclone 3 mgDrug
Also called Lunesta
Both eszopiclone and lemborexant taken together at bedtime for one night
PlaceboDrug
Also called Sugar pill
Placebo sugar pills that looks like the eszopiclone and lemborexant capsules taken at bedtime for one night.
Lemborexant 10mgDrug
Also called Dayvigo
Both eszopiclone and lemborexant taken together at bedtime for one night
| Study group | Role | What they receive |
|---|---|---|
| Eszopiclone 3mg and lemborexant 10mg | Experimental | Both Eszopiclone 3mg and Lemborexant 10mg in the form of capsules taken before bedtime. Dosages is taken on one instance for one night only. Receives: Drug: Eszopiclone 3 mg; Drug: Lemborexant 10mg |
| Placebo | Placebo comparator | Placebo capsules that look exactly like the study drugs, taken before bedtime. Dosage is taken on one instance for one night only. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in OSA severity (eszopiclone and lemborexant night vs. placebo night)
OSA severity as measured by the apnoea hypopnea index (units: number of respiratory events/h sleep) during overnight in-laboratory polysomnography.
Measured: Two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.
Secondary outcomes (14)
Change in nadir overnight hypoxemia (eszopiclone and lemborexant night vs. placebo night)
Nadir overnight oxygen saturation during sleep (units: %) measured via pulse oximetry during overnight in-laboratory polysomnography.
Measured: 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)
Mean overnight oxygen saturation during sleep (units: %) measured via pulse oximetry during overnight in-laboratory polysomnography.
Measured: Two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.
Change in time below 90% blood arterial oxygen saturation (eszopiclone and lemborexant night vs. placebo night)
Percent time asleep spent below an arterial oxygen saturation of 90% measured via pulse oximetry during overnight in-laboratory polysomnography.
Measured: 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)
Percent time spent asleep divided by the recording time from lights out to lights on during overnight in-laboratory polysomnography
Measured: 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)
Number of cortical arousals per hour of sleep during overnight in-laboratory polysomnography.
Measured: 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)
Loop gain and the ventilatory response to arousal (units: % eupnea) during overnight in-laboratory polysomnography.
Measured: 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)
Threshold to arousal (units: % eupnea) during overnight in-laboratory polysomnography.
Measured: 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)
Vpassive (units: % eupnea) during overnight in-laboratory polysomnography.
Measured: 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)
Vcompensation (units: % eupnea) during overnight in-laboratory polysomnography.
Measured: 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
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)
Measured: Baseline sleep study
Change in next morning balance (eszopiclone and lemborexant night vs. placebo night)
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)
Measured: Next morning following 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)
Next day perceived sleepiness assessed via the Karolinska Sleepiness Scale (10 point scale where 1=extremely alert and 10=extremely sleepy)
Measured: 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)
Next day alertness as measured via the Australian-developed (AusEd) driving simulator performance task (units: SD of steering deviation from median line).
Measured: 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)
Next day alertness as measured via the psychomotor vigilance test (PVT) (units m/s) higher values indicate worse performance.
Measured: Next morning following two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2025
- Study start31 Oct 2025
- Primary completion1 May 2027 (estimated)
- Study completion30 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (29)Papers the sponsor has linked to this study.
- Other trials for OSA - Obstructive Sleep ApneaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Oral capsules (Eszopiclone 3mg and lemborexant 10mg) taken together or placebo equivalent , order is randomized. After at least a week washout the opposite agent will be given.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Flinders University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Professor Danny Eckert, Flinders University
- Investigators
- Danny J Eckert, PhD, Principal investigator, Flinders University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06928766
- Sponsor's protocol ID
- 7849
- Other IDs
- 1196261
- Acronym
- ELOSA
- Status last verified
- Sep 2026
- First submitted
- 7 Apr 2025
- Last updated
- 2 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: 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.
Publications
Murphy P, Moline M, Mayleben D, Rosenberg R, Zammit G, Pinner K, Dhadda S, Hong Q, Giorgi L, Satlin A. Lemborexant, A Dual Orexin Receptor Antagonist (DORA) for the Treatment of Insomnia Disorder: Results From a Bayesian, Adaptive, Randomized, Double-Blind, Placebo-Controlled Study. J Clin Sleep Med. 2017 Nov 15;13(11):1289-1299. doi: 10.5664/jcsm.6800.
PubMed 29065953Terauchi M, Cheng JY, Yardley J, Pinner K, Moline M, Malhotra M, Inabe K, Nishida M, Pappadopulos E. Efficacy and safety of lemborexant in midlife women with insomnia disorder. Menopause. 2023 Aug 1;30(8):839-848. doi: 10.1097/GME.0000000000002209. Epub 2023 Jun 20.
PubMed 37339396Xue T, Wu X, Li J, Chen S, Wang Z, Tan X, Wang Z, Zhang J. Different doses of dual orexin receptor antagonists in primary insomnia: a Bayesian network analysis. Front Pharmacol. 2023 May 16;14:1175372. doi: 10.3389/fphar.2023.1175372. eCollection 2023.
PubMed 37261282Habiba U, Waseem R, Shaikh TG, Waseem S, Ahmed SH, Asghar MS. Correction to: Comparative efficacy and safety of lemborexant 5 mg versus 10 mg for the treatment of insomnia: a systematic review. Neurol Sci. 2023 May;44(5):1833. doi: 10.1007/s10072-023-06626-x. No abstract available.
PubMed 36650297Habiba U, Waseem R, Shaikh TG, Waseem S, Ahmed SH, Asghar MS. Comparative efficacy and safety of lemborexant 5 mg versus 10 mg for the treatment of insomnia: a systematic review. Neurol Sci. 2023 May;44(5):1533-1541. doi: 10.1007/s10072-023-06601-6. Epub 2023 Jan 12.
PubMed 36633778Cheng JY, Lorch D, Lowe AD, Uchimura N, Hall N, Shah D, Moline M. A randomized, double-blind, placebo-controlled, crossover study of respiratory safety of lemborexant in moderate to severe obstructive sleep apnea. J Clin Sleep Med. 2024 Jan 1;20(1):57-65. doi: 10.5664/jcsm.10788.
PubMed 37677076Cheng JY, Filippov G, Moline M, Zammit GK, Bsharat M, Hall N. Respiratory safety of lemborexant in healthy adult and elderly subjects with mild obstructive sleep apnea: A randomized, double-blind, placebo-controlled, crossover study. J Sleep Res. 2020 Aug;29(4):e13021. doi: 10.1111/jsr.13021. Epub 2020 Mar 18.
PubMed 32187781Eckert DJ, Malhotra A, Wellman A, White DP. Trazodone increases the respiratory arousal threshold in patients with obstructive sleep apnea and a low arousal threshold. Sleep. 2014 Apr 1;37(4):811-9. doi: 10.5665/sleep.3596.
PubMed 24899767Eckert DJ, Owens RL, Kehlmann GB, Wellman A, Rahangdale S, Yim-Yeh S, White DP, Malhotra A. Eszopiclone increases the respiratory arousal threshold and lowers the apnoea/hypopnoea index in obstructive sleep apnoea patients with a low arousal threshold. Clin Sci (Lond). 2011 Jun;120(12):505-14. doi: 10.1042/CS20100588.
PubMed 21269278Messineo L, Eckert DJ, Lim R, Chiang A, Azarbarzin A, Carter SG, Carberry JC. Zolpidem increases sleep efficiency and the respiratory arousal threshold without changing sleep apnoea severity and pharyngeal muscle activity. J Physiol. 2020 Oct;598(20):4681-4692. doi: 10.1113/JP280173. Epub 2020 Aug 30.
PubMed 32864734Messineo L, Carter SG, Taranto-Montemurro L, Chiang A, Vakulin A, Adams RJ, Carberry JC, Eckert DJ. Addition of zolpidem to combination therapy with atomoxetine-oxybutynin increases sleep efficiency and the respiratory arousal threshold in obstructive sleep apnoea: A randomized trial. Respirology. 2021 Sep;26(9):878-886. doi: 10.1111/resp.14110. Epub 2021 Jun 23.
PubMed 34164887Carter SG, Eckert DJ. Effects of hypnotics on obstructive sleep apnea endotypes and severity: Novel insights into pathophysiology and treatment. Sleep Med Rev. 2021 Aug;58:101492. doi: 10.1016/j.smrv.2021.101492. Epub 2021 Apr 22.
PubMed 33965721Carter SG, Carberry JC, Grunstein RR, Eckert DJ. Randomized Trial on the Effects of High-Dose Zopiclone on OSA Severity, Upper Airway Physiology, and Alertness. Chest. 2020 Jul;158(1):374-385. doi: 10.1016/j.chest.2020.02.057. Epub 2020 Mar 18.
PubMed 32197956Carter SG, Carberry JC, Cho G, Fisher LP, Rollo CM, Stevens DJ, D'Rozario AL, McKenzie DK, Grunstein RR, Eckert DJ. Effect of 1 month of zopiclone on obstructive sleep apnoea severity and symptoms: a randomised controlled trial. Eur Respir J. 2018 Jul 19;52(1):1800149. doi: 10.1183/13993003.00149-2018. Print 2018 Jul.
PubMed 29976648Carter SG, Berger MS, Carberry JC, Bilston LE, Butler JE, Tong BK, Martins RT, Fisher LP, McKenzie DK, Grunstein RR, Eckert DJ. Zopiclone Increases the Arousal Threshold without Impairing Genioglossus Activity in Obstructive Sleep Apnea. Sleep. 2016 Apr 1;39(4):757-66. doi: 10.5665/sleep.5622.
PubMed 26715227
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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.
- ClinicalTrials.gov ID
- NCT06928766
- Acronym / sponsor ID
- ELOSA / 7849
- Conditions
- OSA - Obstructive Sleep Apnea
- Keywords
- sleep disordered breathing, arousal, COMISA
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Flinders UniversityUniversity, hospital or other
- Study start
- 31 Oct 2025 (actual)
- Primary completion
- 1 May 2027 (estimated)
- Study completion
- 30 Jun 2027 (estimated)
- First posted
- 15 Apr 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Oral capsules (Eszopiclone 3mg and lemborexant 10mg) taken together or placebo equivalent , order is randomized. After at least a week washout the opposite agent will be given.
| Arm | Type | Receives |
|---|---|---|
| Eszopiclone 3mg and lemborexant 10mg | Experimental | Drug: Eszopiclone 3 mg, Drug: Lemborexant 10mgBoth Eszopiclone 3mg and Lemborexant 10mg in the form of capsules taken before bedtime. Dosages is taken on one instance for one night only. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo capsules that look exactly like the study drugs, taken before bedtime. Dosage is taken on one instance for one night only. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Eszopiclone 3 mgAlso: LunestaBoth eszopiclone and lemborexant taken together at bedtime for one night | Drug | Eszopiclone 3mg and lemborexant 10mg |
| PlaceboAlso: Sugar pillPlacebo sugar pills that looks like the eszopiclone and lemborexant capsules taken at bedtime for one night. | Drug | Placebo |
| Lemborexant 10mgAlso: DayvigoBoth eszopiclone and lemborexant taken together at bedtime for one night | Drug | Eszopiclone 3mg and lemborexant 10mg |
Primary outcome
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.
14 secondary outcomes
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.
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.
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.
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.
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.
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.
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.
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.
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.
Baseline OSA endotype and whether they are associated with changes in OSA severity
Time frame: 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.
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.
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.
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2026.
- Background: PubMed 29065953Murphy P, Moline M, Mayleben D, Rosenberg R, Zammit G, Pinner K, Dhadda S, Hong Q, Giorgi L, Satlin A. Lemborexant, A Dual Orexin Receptor Antagonist (DORA) for the Treatment of Insomnia Disorder: Results From a Bayesian, Adaptive, Randomized, Double-Blind, Placebo-Controlled Study. J Clin Sleep Med. 2017 Nov 15;13(11):1289-1299. doi: 10.5664/jcsm.6800.
- Background: PubMed 37339396Terauchi M, Cheng JY, Yardley J, Pinner K, Moline M, Malhotra M, Inabe K, Nishida M, Pappadopulos E. Efficacy and safety of lemborexant in midlife women with insomnia disorder. Menopause. 2023 Aug 1;30(8):839-848. doi: 10.1097/GME.0000000000002209. Epub 2023 Jun 20.
- Background: PubMed 37261282Xue T, Wu X, Li J, Chen S, Wang Z, Tan X, Wang Z, Zhang J. Different doses of dual orexin receptor antagonists in primary insomnia: a Bayesian network analysis. Front Pharmacol. 2023 May 16;14:1175372. doi: 10.3389/fphar.2023.1175372. eCollection 2023.
- Background: PubMed 36650297Habiba U, Waseem R, Shaikh TG, Waseem S, Ahmed SH, Asghar MS. Correction to: Comparative efficacy and safety of lemborexant 5 mg versus 10 mg for the treatment of insomnia: a systematic review. Neurol Sci. 2023 May;44(5):1833. doi: 10.1007/s10072-023-06626-x. No abstract available.
- Background: PubMed 36633778Habiba U, Waseem R, Shaikh TG, Waseem S, Ahmed SH, Asghar MS. Comparative efficacy and safety of lemborexant 5 mg versus 10 mg for the treatment of insomnia: a systematic review. Neurol Sci. 2023 May;44(5):1533-1541. doi: 10.1007/s10072-023-06601-6. Epub 2023 Jan 12.
- Background: PubMed 37677076Cheng JY, Lorch D, Lowe AD, Uchimura N, Hall N, Shah D, Moline M. A randomized, double-blind, placebo-controlled, crossover study of respiratory safety of lemborexant in moderate to severe obstructive sleep apnea. J Clin Sleep Med. 2024 Jan 1;20(1):57-65. doi: 10.5664/jcsm.10788.
- Background: PubMed 32187781Cheng JY, Filippov G, Moline M, Zammit GK, Bsharat M, Hall N. Respiratory safety of lemborexant in healthy adult and elderly subjects with mild obstructive sleep apnea: A randomized, double-blind, placebo-controlled, crossover study. J Sleep Res. 2020 Aug;29(4):e13021. doi: 10.1111/jsr.13021. Epub 2020 Mar 18.
- Background: PubMed 24899767Eckert DJ, Malhotra A, Wellman A, White DP. Trazodone increases the respiratory arousal threshold in patients with obstructive sleep apnea and a low arousal threshold. Sleep. 2014 Apr 1;37(4):811-9. doi: 10.5665/sleep.3596.
- Background: PubMed 21269278Eckert DJ, Owens RL, Kehlmann GB, Wellman A, Rahangdale S, Yim-Yeh S, White DP, Malhotra A. Eszopiclone increases the respiratory arousal threshold and lowers the apnoea/hypopnoea index in obstructive sleep apnoea patients with a low arousal threshold. Clin Sci (Lond). 2011 Jun;120(12):505-14. doi: 10.1042/CS20100588.
- Background: PubMed 32864734Messineo L, Eckert DJ, Lim R, Chiang A, Azarbarzin A, Carter SG, Carberry JC. Zolpidem increases sleep efficiency and the respiratory arousal threshold without changing sleep apnoea severity and pharyngeal muscle activity. J Physiol. 2020 Oct;598(20):4681-4692. doi: 10.1113/JP280173. Epub 2020 Aug 30.
- Background: PubMed 34164887Messineo L, Carter SG, Taranto-Montemurro L, Chiang A, Vakulin A, Adams RJ, Carberry JC, Eckert DJ. Addition of zolpidem to combination therapy with atomoxetine-oxybutynin increases sleep efficiency and the respiratory arousal threshold in obstructive sleep apnoea: A randomized trial. Respirology. 2021 Sep;26(9):878-886. doi: 10.1111/resp.14110. Epub 2021 Jun 23.
- Background: PubMed 33965721Carter SG, Eckert DJ. Effects of hypnotics on obstructive sleep apnea endotypes and severity: Novel insights into pathophysiology and treatment. Sleep Med Rev. 2021 Aug;58:101492. doi: 10.1016/j.smrv.2021.101492. Epub 2021 Apr 22.
- Individual participant dataSharing planned: Undecided. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Danny J Eckert, PhD principal investigator
Flinders University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Eszopiclone 3 mg and Lemborexant 10mg in people with OSA - Obstructive Sleep Apnea, run by Flinders University at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Danny J Eckert, PhD (+61 8 7421 9780, danny.eckert@flinders.edu.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06928766, which also lists 29 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Sep 2026.