What was the primary endpoint of SUNRISE-1?

The primary endpoint was change from baseline in latency to persistent sleep (LPS), measured by polysomnography on nights 29 and 30 of treatment. LPS is the time from lights-off to 10 consecutive minutes of non-wake sleep.

How much faster did patients fall asleep on lemborexant?

Patients on lemborexant 5 mg fell asleep approximately 9 minutes faster than placebo, and those on 10 mg fell asleep about 12 minutes faster. Absolute sleep onset latency at the end of treatment was around 21 to 24 minutes.

Was lemborexant compared directly to zolpidem in SUNRISE-1?

Zolpidem ER 6.25 mg was included as an active reference arm, but the trial was not powered for formal superiority testing of lemborexant over zolpidem. Descriptive comparisons showed lemborexant performed better on second-half-of-the-night WASO.

Who was enrolled in the SUNRISE-1 trial?

Adults aged 55 years and older with DSM-5 insomnia disorder. Key exclusions included moderate-to-severe sleep apnea, concurrent CNS depressant use, and unstable psychiatric conditions.

Did SUNRISE-1 lead to FDA approval?

Yes. SUNRISE-1 was the key efficacy trial supporting the FDA's December 2019 approval of lemborexant (Dayvigo) for insomnia with difficulty in sleep onset and/or maintenance.

Is lemborexant safer than zolpidem for older adults?

SUNRISE-1 showed a low rate of adverse events with lemborexant, no study-drug-related falls, and minimal next-morning somnolence at 5 mg. The trial was too short and small to make definitive safety comparisons, but the DORA mechanism avoids GABA-related risks like respiratory depression and complex sleep behaviors.

How long did the treatment period last?

Treatment lasted 30 nights. This is adequate for demonstrating acute efficacy but does not reflect the chronic nature of most insomnia. The companion trial SUNRISE-2 extended treatment to 6 months.

Does insurance cover lemborexant?

Coverage varies. Many formularies require prior authorization or step therapy through generic alternatives (zolpidem, trazodone) before approving lemborexant. As a branded product with no generic as of 2026, out-of-pocket costs can be significant.

Can younger adults use lemborexant based on SUNRISE-1 data?

SUNRISE-1 enrolled only patients 55 and older. The pharmacokinetic profile of lemborexant is similar across age groups, and the FDA label does not restrict use by age, but direct trial evidence in younger adults comes from other studies, not this one.

What is a dual orexin receptor antagonist?

DORAs block both orexin-A and orexin-B receptors, which promote wakefulness. By suppressing the wake-promoting orexin signal rather than broadly enhancing inhibitory GABA signaling, DORAs offer a mechanistically distinct approach to treating insomnia.

What SUNRISE-1 Actually Changes in Clinical Practice

By HealthRX Medical Team

Published May 25, 2026Updated May 25, 2026Last reviewed May 25, 2026

At a glance

| Parameter | Detail | |---|---| | Trial name | SUNRISE-1 (NCT02783729) | | N | 1,006 randomized | | Intervention | Lemborexant 5 mg or 10 mg nightly | | Comparator | Placebo and zolpidem extended-release 6.25 mg (active reference) | | Duration | 30 nights (1-month treatment period) | | Primary endpoint | Change from baseline in latency to persistent sleep (LPS) via polysomnography at nights 29/30 | | Key result | LPS reduced by ~10 min vs placebo for both doses (p < 0.001); sleep efficiency increased by ~4-5 percentage points | | Published | 2019, JAMA Network Open |

Why This Trial Exists

Before SUNRISE-1, clinicians treating insomnia in older adults faced a narrow set of pharmacologic options, each carrying familiar baggage. Benzodiazepines and Z-drugs (zolpidem, eszopiclone) work through GABA-A receptor modulation, which raises well-documented concerns about falls, cognitive impairment, and dependence in patients over 55. Suvorexant, the first approved dual orexin receptor antagonist (DORA), had shown efficacy, but its longer half-life and next-day somnolence left room for a competitor with tighter pharmacokinetics.

Lemborexant was designed to fill that gap. Eisai needed a registration trial that could satisfy the FDA's requirement for objective polysomnographic endpoints while also demonstrating a favorable comparison against an active reference (zolpidem ER). SUNRISE-1 was that trial.

Methodology: What the Abstract Doesn't Tell You

The trial enrolled adults aged 55 years and older meeting DSM-5 criteria for insomnia disorder. This age restriction matters. The FDA and clinical guideline bodies have long wanted better data in older populations specifically because that group absorbs the most harm from sedative-hypnotics.

Randomization was 2:2:2:1 across four arms: lemborexant 5 mg, lemborexant 10 mg, placebo, and zolpidem ER 6.25 mg. The zolpidem arm was included as an active reference, not as a formal superiority comparator for the primary endpoint. This distinction is critical, because marketing materials sometimes blur the line. The primary statistical comparison was lemborexant versus placebo; zolpidem served to contextualize effect sizes and assess secondary measures like wake after sleep onset (WASO) in the second half of the night.

The HealthRX Methodology Scorecard

| Criterion | Assessment | |---|---| | Blinding | Double-blind, double-dummy design (patients took both a capsule and a tablet nightly to mask assignment). Strong. | | Endpoint objectivity | Primary endpoint measured by in-lab polysomnography on two consecutive nights, averaged. Eliminates subjective recall bias. | | Population relevance | Adults ≥55 years. Directly relevant to the highest-risk prescribing group. | | Active comparator | Zolpidem ER included but underpowered for formal superiority testing. Useful for descriptive comparison only. | | Duration | 30 nights. Adequate for acute efficacy, short for real-world use patterns. | | Attrition | Completion rate exceeded 90%. Low dropout reduces bias concern. | | Sponsor | Eisai Inc. funded and designed the trial. Standard for registration studies, but independent replication would strengthen confidence. |

Polysomnography was conducted at screening, baseline (nights 1/2), and at the end of treatment (nights 29/30). The primary endpoint, latency to persistent sleep (LPS), is defined as the time from lights-off to the first 10 consecutive minutes of non-wake sleep. This is a stricter threshold than simple sleep onset, making it a more conservative measure.

Results in Full

Primary Endpoint: Latency to Persistent Sleep

| Group | Baseline LPS (min) | Night 29/30 LPS (min) | LS Mean Change | Difference vs Placebo | p-value | |---|---|---|---|---|---| | Lemborexant 5 mg | ~44 | ~24 | -19.4 | -9.4 | <0.001 | | Lemborexant 10 mg | ~45 | ~21 | -22.4 | -12.4 | <0.001 | | Zolpidem ER 6.25 mg | ~42 | ~26 | -17.5 | -7.6 | (reference) | | Placebo | ~43 | ~33 | -10.0 |, |, |

Both lemborexant doses met the primary endpoint with statistical significance. The 10 mg dose showed a numerically larger reduction, though the clinical difference between 5 mg and 10 mg was modest (about 3 minutes).

Secondary Endpoints

Sleep efficiency improved significantly with both lemborexant doses. Sleep efficiency, the percentage of time in bed actually spent asleep, rose by approximately 4 to 5 percentage points over placebo. For a patient with baseline efficiency around 75%, that translates to roughly 20 to 25 additional minutes of sleep per night.

Wake after sleep onset (WASO) showed a meaningful finding in the second half of the night. Lemborexant reduced second-half WASO significantly versus zolpidem ER, suggesting better maintenance of sleep during the early-morning hours when zolpidem's effect wanes. This was a pre-specified secondary comparison and represents the strongest head-to-head signal in the trial.

| WASO Measure | LEM 5 mg | LEM 10 mg | Zolpidem ER | Placebo | |---|---|---|---|---| | WASO overall (change, min) | -20.2 | -22.4 | -19.0 | -11.3 | | WASO second half (change, min) | -12.5 | -15.4 | -5.3 | -6.7 |

The second-half WASO difference between lemborexant and zolpidem is clinically relevant. Patients who fall asleep but wake at 3 or 4 AM and cannot return to sleep represent a common phenotype in geriatric insomnia. This subgroup may benefit most from the DORA mechanism.

Safety Profile

Adverse events were generally mild. The most common treatment-emergent adverse events with lemborexant were somnolence, headache, and nasopharyngitis. Rates of next-morning residual sleepiness were low and did not differ significantly from placebo at the 5 mg dose.

No falls were adjudicated as related to study drug. This is a small trial for fall detection, but the absence of signal matters given the known fall risk associated with benzodiazepine receptor agonists in older adults.

There were no reports of complex sleep behaviors (sleepwalking, sleep-driving) during the 30-day treatment period, though the trial was not powered to detect rare events.

What Changed After This Trial

FDA Approval

The FDA approved lemborexant (Dayvigo) in December 2019 for the treatment of insomnia characterized by difficulty with sleep onset and/or sleep maintenance. The prescribing label lists both 5 mg and 10 mg doses, with 5 mg as the recommended starting dose. SUNRISE-1 was the primary efficacy study cited in the approval package, supplemented by SUNRISE-2 (a longer-duration subjective-endpoint trial).

Guideline Updates

The American Academy of Sleep Medicine (AASM) updated its clinical practice guideline in 2023, conditionally recommending DORAs (suvorexant and lemborexant) for sleep onset and sleep maintenance insomnia in adults. This was a notable shift. The 2017 version of the guideline had listed suvorexant alone among orexin antagonists, and the evidence base was thinner. The addition of SUNRISE-1 data strengthened the DORA class recommendation.

The European Sleep Research Society and the British Association for Psychopharmacology have also acknowledged DORAs in updated consensus statements, though European availability of lemborexant has been slower.

Prescribing Pattern Shifts

In practice, the impact has been gradual rather than sudden. Z-drugs remain the most prescribed hypnotics in primary care. But among sleep specialists and geriatricians, DORA prescribing has grown steadily since 2020. The growth is concentrated in exactly the population SUNRISE-1 studied: older adults with comorbid concerns about falls, cognitive decline, or prior adverse reactions to GABA-ergic agents.

Insurance coverage remains a barrier. Lemborexant is a branded product with no generic equivalent as of mid-2026. Many formularies require prior authorization or step therapy through generic zolpidem or trazodone before approving a DORA.

Limitations the Authors Acknowledged

The investigators listed several limitations that deserve closer attention.

Short duration. Thirty nights is enough for registration but does not address chronic use. Insomnia is typically a months-to-years problem. SUNRISE-2 partially addresses this with 6-month data, but even that falls short of the timeline most patients need.

Age restriction. Enrolling only patients 55 and older makes the results directly applicable to that group but limits extrapolation to younger adults. The pharmacokinetics of lemborexant do not change dramatically with age, so efficacy in younger populations is plausible but unproven by this trial.

Active comparator design limitations. Zolpidem ER was included at a single dose (6.25 mg, the geriatric dose) and was not part of the primary hypothesis testing. Claims that lemborexant is "better than zolpidem" based on this trial overstate the evidence. The second-half WASO finding is suggestive, not definitive.

No CBT-I comparison arm. Cognitive behavioral therapy for insomnia is the recommended first-line treatment per every major guideline. SUNRISE-1 compared drugs to drugs and placebo. It cannot answer the question of whether lemborexant adds value on top of, or instead of, behavioral therapy.

Polysomnography setting. In-lab PSG introduces a "first-night effect" and does not replicate the home sleep environment. The trial mitigated this with adaptation nights, but some artificiality remains.

What This Means for Patients Who Differ from the Trial Population

Patients under 55, patients with psychiatric comorbidities (excluded from the trial), patients on concurrent CNS depressants, and patients with obstructive sleep apnea all represent gaps. The Dayvigo prescribing label carries warnings about use with CNS depressants, and moderate-to-severe OSA was an exclusion criterion in SUNRISE-1.

For patients with comorbid depression or anxiety, the orexin mechanism is theoretically neutral to favorable compared with GABA-ergic agents, but trial evidence in this subgroup is sparse. Case series and post-marketing data have not raised red flags, but clinicians should not assume efficacy or safety equivalent to what was shown in the carefully selected SUNRISE-1 population.

Patients taking strong CYP3A4 inhibitors require dose adjustment (avoid the 10 mg dose). This pharmacokinetic interaction is well-characterized but easy to miss in polypharmacy settings common among older adults.

Frequently asked questions

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References

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
U.S. Food and Drug Administration. Dayvigo (lemborexant) prescribing information. December 2019. FDA Label
Sateia MJ, Buysse DJ, Krystal AD, et al. 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
Kärppä M, Yardley J, Pinner K, et al. Long-term efficacy and tolerability of lemborexant compared with placebo in adults with insomnia disorder (SUNRISE-2). J Clin Sleep Med. 2020;16(9):1547-1555. PubMed
Berry SD, Lee Y, Cai S, Dore DD. Nonbenzodiazepine sleep medication use and hip fractures in nursing home residents. JAMA Intern Med. 2013;173(9):754-761. PubMed
Edinger JD, Arnedt JT, Bertisch SM, et al. Behavioral and psychological treatments for chronic insomnia disorder in adults: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2021;17(2):255-262. PubMed