A Phase 2 interventional study of Eszopiclone 3 mg and Placebo in OSA - Obstructive Sleep Apnea, sponsored by Flinders University. Recruiting at 1 site in Australia. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-02.
Sponsored by Flinders University · Phase 2, Interventional, and Treatment
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).
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).
2,240 studies on the registry are indexed under Sleep Apnea, Obstructive; 475 are open to participants now.
This study's planned enrollment of 15 is below the median of 52 across 1,472 interventional studies indexed under Sleep Apnea, Obstructive.
Browse Sleep Apnea, Obstructive studies →Flinders University is the lead sponsor of 13 studies on the registry; 3 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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 · Drug: Lemborexant 10mg
Placebo capsules that look exactly like the study drugs, taken before bedtime. Dosage is taken on one instance for one night only.
Drug: Placebo
Both eszopiclone and lemborexant taken together at bedtime for one night
Also known as: Lunesta
Placebo sugar pills that looks like the eszopiclone and lemborexant capsules taken at bedtime for one night.
Also known as: Sugar pill
Both eszopiclone and lemborexant taken together at bedtime for one night
Also known as: Dayvigo
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.
Time frame: 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)
Nadir overnight oxygen saturation during sleep (units: %) measured via pulse oximetry during overnight in-laboratory polysomnography.
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)
Mean overnight oxygen saturation during sleep (units: %) measured via pulse oximetry during overnight in-laboratory polysomnography.
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)
Percent time asleep spent below an arterial oxygen saturation of 90% measured via pulse oximetry during overnight in-laboratory polysomnography.
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)
Percent time spent asleep divided by the recording time from lights out to lights on during overnight in-laboratory polysomnography
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)
Number of cortical arousals per hour of sleep during overnight in-laboratory polysomnography.
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)
Loop gain and the ventilatory response to arousal (units: % eupnea) during overnight in-laboratory polysomnography.
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)
Threshold to arousal (units: % eupnea) during overnight in-laboratory polysomnography.
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)
Vpassive (units: % eupnea) during overnight in-laboratory polysomnography.
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)
Vcompensation (units: % eupnea) during overnight in-laboratory polysomnography.
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
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)
Time frame: 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)
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)
Next day perceived sleepiness assessed via the Karolinska Sleepiness Scale (10 point scale where 1=extremely alert and 10=extremely sleepy)
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)
Next day alertness as measured via the Australian-developed (AusEd) driving simulator performance task (units: SD of steering deviation from median line).
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)
Next day alertness as measured via the psychomotor vigilance test (PVT) (units m/s) higher values indicate worse performance.
Time frame: Next morning following two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.
Plan to share: 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.
Started Oct 2025 (actual). Primary completion is estimated for May 2027, 18 months after the start.
Of 47 phase 2 interventional studies under Sleep Apnea, Obstructive, half reached primary completion within 26 months of starting (the median), counting those still running; a quarter within 9 and three quarters within 46. This study's planned 18 months is below that.
How these figures are worked out, and which studies are left out of them.
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drugs tested here: Eszopiclone · Lemborexant
Flinders University