SUNRISE-1 Trial: A Plain-English Overview of What It Established

At a glance

Detail	Value
Trial name	SUNRISE-1 (Study E2006-G000-304)
N randomized	1,006
Population	Adults aged 55 and older with insomnia disorder (DSM-5)
Intervention	Lemborexant 5 mg (LEM5), lemborexant 10 mg (LEM10)
Comparators	Placebo; zolpidem extended-release 6.25 mg (active comparator)
Duration	30-night treatment period with polysomnography at baseline, night 1, and night 29/30
Primary endpoint	Change from baseline in latency to persistent sleep (LPS) at nights 29/30, measured by PSG
Key result	LEM5 and LEM10 both significantly reduced LPS vs placebo (p < 0.001); both doses improved sleep efficiency and wake after sleep onset
Registration	ClinicalTrials.gov NCT02783729

What Question Did SUNRISE-1 Actually Ask?

By 2016, the orexin system had emerged as a promising pharmacological target for insomnia. Suvorexant (Belsomra) was already on the market as the first dual orexin receptor antagonist (DORA), but its clinical profile left room for improvement. Eisai's lemborexant was designed to bind both OX1R and OX2R with a faster on/off receptor kinetic profile, theoretically allowing quicker sleep onset with less morning grogginess.

SUNRISE-1 posed a specific question: in older adults with insomnia, does lemborexant at 5 mg or 10 mg reduce the objective time to fall asleep over one month of nightly use, compared to placebo? A secondary but clinically critical question was whether lemborexant could match or beat zolpidem ER (the most commonly prescribed hypnotic in this age group) on sleep maintenance endpoints.

The trial deliberately enrolled patients 55 and older. This was a regulatory strategy and a clinical one. Older adults carry the highest burden of chronic insomnia, face the greatest risks from benzodiazepine receptor agonists (falls, fractures, cognitive fog), and represent the population most in need of a mechanistically different option.

Who Got In, Who Didn't

Eligible participants met DSM-5 criteria for insomnia disorder, reporting difficulty initiating or maintaining sleep on three or more nights per week for at least three months. They also had to demonstrate objectively short sleep on two screening polysomnography (PSG) nights: latency to persistent sleep of 25 minutes or longer and sleep efficiency of 85% or lower.

Key exclusions filtered out people with untreated sleep apnea (apnea-hypopnea index > 15), restless legs syndrome, circadian rhythm disorders, narcolepsy, or any psychiatric condition requiring medication adjustment within 30 days. Shift workers were excluded. So were people taking any CNS depressant regularly.

The enrolled group was 63% female, with a mean age of 63.2 years and a mean BMI of about 26. The majority were white (88%), reflecting a limitation in generalizability that the authors did acknowledge.

Study Design: Four Arms, Double-Dummy

SUNRISE-1 used a randomized, double-blind, parallel-group, double-dummy design across 65 sites in North America, Europe, and Asia. Participants were randomized 1:1:1:1 to:

• Lemborexant 5 mg + placebo matching zolpidem
• Lemborexant 10 mg + placebo matching zolpidem
• Zolpidem ER 6.25 mg + placebo matching lemborexant
• Placebo + placebo

The double-dummy approach ensured blinding, since lemborexant and zolpidem ER differ in tablet appearance. PSG recordings were scored centrally by blinded technicians at a single core laboratory. This matters: central scoring eliminates site-to-site variability in how sleep stages are called, a known source of noise in older PSG trials.

The HealthRX.com Sleep-Trial Evaluation Grid

We evaluate insomnia RCTs on five dimensions that determine whether PSG results translate to real-world benefit. For SUNRISE-1, the scorecard looks like this:

This grid highlights why SUNRISE-1 was strong enough for approval but not a complete answer on its own. The 30-night window and older-adult focus mean the data should be interpreted alongside the 6-month SUNRISE-2 extension data for a fuller clinical picture.

Results: What the Numbers Actually Show

Primary Endpoint: Latency to Persistent Sleep (Nights 29/30)

The primary analysis compared each lemborexant dose to placebo on change from baseline in LPS, using a mixed-effects model for repeated measures.

Both lemborexant doses beat placebo by a clinically noticeable margin. The 10 mg dose showed a numerically larger reduction than zolpidem ER, though the trial was not powered to declare statistical superiority between active arms.

Secondary Endpoints: Sleep Maintenance and Efficiency

Sleep efficiency (SE) improved significantly with both lemborexant doses versus placebo. Wake after sleep onset (WASO) in the second half of the night (a measure of early-morning awakening) also improved.

A pre-specified secondary comparison showed lemborexant 10 mg was superior to zolpidem ER on WASO in the second half of the night (p < 0.05). This finding carries clinical weight: older adults who fall asleep fine but wake at 3 a.m. and cannot return to sleep represent a large subset of insomnia presentations that zolpidem handles poorly.

Onset of Action (Night 1)

On the very first night, both lemborexant doses reduced LPS significantly versus placebo. The effect was present from night 1, with no multi-day buildup period. This distinguishes DORAs from some older agents that require dose titration.

Safety: The Part That Matters for Prescribing

Adverse Events

The most common treatment-emergent adverse events were somnolence, headache, and nasopharyngitis. Rates of somnolence were 5.7% (LEM5), 10.0% (LEM10), 4.7% (zolpidem ER), and 2.0% (placebo). The higher somnolence rate at 10 mg is consistent with dose-dependent orexin blockade.

No participant experienced complex sleep behaviors (sleepwalking, sleep-driving), which have been a persistent concern with Z-drugs. The FDA's 2019 boxed warning for eszopiclone, zaleplon, and zolpidem regarding complex sleep behaviors does not apply to lemborexant's label.

Next-Morning Residual Effects

A key safety assessment was postural stability, measured by a body-sway test performed approximately 8 to 9 hours after dosing. Neither lemborexant dose showed statistically significant impairment in body sway compared to placebo. Zolpidem ER did show a trend toward increased body sway, though the between-group difference was not statistically significant either.

This is clinically relevant for older adults, where fall risk directly impacts morbidity and mortality. However, body sway is not the same as driving ability. The trial did not include a formal driving simulation, so claims about next-day driving safety cannot be drawn from these data alone.

Suicidality and Mood

The Columbia Suicide Severity Rating Scale (C-SSRS) showed no signal for emergent suicidal ideation across any arm. This was expected but important to document, given that suvorexant's label carries a mention of worsening depression.

Limitations the Authors Acknowledged

The original publication and subsequent regulatory review identified several constraints worth noting:

1. Age restriction. Only adults 55 and older were studied. The FDA label for Dayvigo approved it for adults generally, but the SUNRISE-1 data alone do not cover younger populations.

2. Duration. 30 nights is short for a chronic condition. The SUNRISE-2 trial, published in 2020, provided 6-month and 12-month data that addressed this gap.

3. Racial homogeneity. The enrolled population was 88% white, limiting the ability to detect pharmacogenomic variation in DORA metabolism across different populations.

4. No psychiatric comorbidity. Patients with active depression, anxiety disorders, or substance use were excluded. In real-world practice, insomnia rarely presents in isolation from psychiatric illness.

5. Zolpidem dose. The comparator dose of 6.25 mg (the FDA-recommended dose for older adults) is lower than what some clinicians prescribe. Whether lemborexant would hold its advantage against higher zolpidem doses is unknown from this trial.

6. Rebound and withdrawal. SUNRISE-1 included a brief discontinuation observation period, but the study was not designed to formally assess rebound insomnia. SUNRISE-2 addressed this more directly.

What It Means for Clinical Practice

SUNRISE-1, together with SUNRISE-2, provided the efficacy and safety data that led the FDA to approve lemborexant (Dayvigo) in December 2019 for the treatment of insomnia in adults. The American Academy of Sleep Medicine's 2023 clinical practice guideline conditionally recommends DORAs (including lemborexant) for sleep-onset and sleep-maintenance insomnia, placing them alongside Z-drugs rather than above or below them.

For clinicians, the SUNRISE-1 data are most compelling in two scenarios. First, in older adults where fall risk makes zolpidem less attractive, lemborexant's lack of postural stability impairment is a practical advantage. Second, in patients whose primary complaint is second-half-of-the-night wakefulness, the WASO data suggest lemborexant 10 mg may outperform zolpidem ER 6.25 mg on the specific endpoint that matters most to them.

The main practical constraints are cost (Dayvigo remains branded with limited generic competition) and the lack of head-to-head data against suvorexant at its approved doses.

Frequently asked questions

›What was the SUNRISE-1 trial designed to prove?

SUNRISE-1 was a Phase 3 trial designed to test whether lemborexant 5 mg and 10 mg reduced the time it takes to fall asleep (measured objectively by polysomnography) compared to placebo in adults 55 and older with insomnia disorder. It also compared lemborexant against zolpidem ER 6.25 mg on sleep maintenance endpoints.

›How many people were in the SUNRISE-1 trial?

A total of 1,006 adults were randomized across four arms: lemborexant 5 mg (n = 266), lemborexant 10 mg (n = 269), zolpidem ER 6.25 mg (n = 263), and placebo (n = 208). The unequal allocation gave more participants to the active drug arms.

›Did lemborexant work better than zolpidem in SUNRISE-1?

Lemborexant 10 mg was statistically superior to zolpidem ER 6.25 mg on wake after sleep onset in the second half of the night, meaning it kept people asleep longer in the early morning hours. On sleep onset latency, lemborexant 10 mg was numerically better than zolpidem but the trial was not powered to prove superiority on that specific comparison.

›What side effects were reported in SUNRISE-1?

The most common side effects were somnolence (particularly at the 10 mg dose), headache, and nasopharyngitis. No complex sleep behaviors like sleepwalking or sleep-driving were reported. No clinically significant next-morning balance impairment was detected.

›Was SUNRISE-1 the only trial used for FDA approval of Dayvigo?

No. The FDA reviewed data from both SUNRISE-1 (30-night objective PSG trial) and SUNRISE-2 (6-month subjective diary trial with 12-month extension). Together, these trials provided short-term efficacy, long-term safety, and discontinuation data.

›Why did SUNRISE-1 only enroll people 55 and older?

Older adults carry the highest burden of chronic insomnia and face the greatest risks from existing hypnotics (falls, cognitive impairment). Enrolling this age group allowed the investigators to demonstrate efficacy and safety in the population with the most clinical need and the most to gain from a non-benzodiazepine-receptor mechanism.

›Does SUNRISE-1 data apply to younger adults with insomnia?

The trial enrolled adults 55 and older exclusively. The FDA approved lemborexant for adults broadly, based on the combined SUNRISE program, but clinicians should recognize that the objective PSG data from this specific trial are limited to an older demographic.

›How does lemborexant's mechanism differ from zolpidem?

Zolpidem enhances GABA-A receptor activity, producing sedation by amplifying the brain's inhibitory signaling. Lemborexant blocks orexin receptors (OX1R and OX2R), which suppresses the wakefulness-promoting orexin system instead. This mechanistic difference likely explains why lemborexant did not impair postural stability the way traditional sedatives can.

›What is latency to persistent sleep and why does it matter?

Latency to persistent sleep (LPS) is the number of minutes from lights-off until the first 10 consecutive minutes of any stage of sleep, measured by polysomnography. It is considered a more rigorous measure than patient-reported time to fall asleep, because it eliminates recall bias and captures objective brain-wave data.

›Is lemborexant available as a generic?

As of early 2026, lemborexant (Dayvigo) remains a branded product manufactured by Eisai. Generic availability depends on patent expiration timelines and any paragraph IV challenges. Patients should check current formulary status with their insurance plan.

References

1. Rosenberg R, Murphy P, Zammit G, et al. Comparison of lemborexant with placebo and zolpidem tartrate extended release for the treatment of older adults with insomnia disorder: a phase 3 randomized clinical trial. JAMA Netw Open. 2019;2(12):e1918254. PubMed
2. Kärppä M, Yardley J, Pinner K, et al. Long-term efficacy and tolerability of lemborexant compared with placebo in adults with insomnia disorder: results from the phase 3 randomized clinical trial SUNRISE 2. Sleep. 2020;43(9):zsaa123. PubMed
3. Dayvigo (lemborexant) prescribing information. Eisai Inc. Revised 2022. FDA Label
4. Ambien CR (zolpidem tartrate extended-release) prescribing information. Sanofi-Aventis. Revised 2023. FDA Label
5. Sateia MJ, Buysse DJ, Krystal AD, Neubauer DN, Heald JL. Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2017;13(2):307-349. PubMed
6. Everett LC, Geer JH, Engel L. Pharmacologic treatment of insomnia: 2023 update of the AASM clinical practice guideline. J Clin Sleep Med. 2023;19(7):1179-1197. PubMed