0474 Long-Term Efficacy and Safety of Lemborexant in Elderly Adults with Insomnia Disorder: Results from SUNRISE-2

Abstract Introduction In SUNRISE-2 (NCT02952820; E2006-G000-303), the dual orexin receptor antagonist lemborexant (LEM) demonstrated significant benefit versus placebo (PBO) on subjective sleep endpoints over 6mo in subjects age ≥18y; benefits were sustained over 12mo. Here we present 12mo efficacy and safety data for LEM from the elderly (≥65y) subgroup. Methods SUNRISE-2 was a 12mo, randomized, double-blind, PBO-controlled (first 6mo [Period 1]), global phase 3 study. During Period 1, subjects were randomized to PBO or LEM (5mg, [LEM5]; 10mg, [LEM10]). During Period 2 (second 6mo), LEM subjects continued their assigned dose while PBO subjects were rerandomized to LEM5 or LEM10 (not reported here). Patient-reported (subjective) sleep endpoints were assessed from sleep diary data (sleep onset latency [sSOL]; sleep efficiency [sSE]; wake after sleep onset [sWASO]). Results Of the 949 subjects in the Full Analysis Set, 262 were age ≥65y. At 6mo, in subjects ≥65y, median sSOL significantly decreased from baseline for LEM5 (−21.7) and LEM10 (−26.0) versus PBO (−10.8; P<0.0001, P<0.01, respectively). At 12mo, LEM5 and LEM10 subjects maintained decreases in median sSOL (−29.3, −34.3, respectively). At 6mo, the mean (SD) increase from baseline in sSE was significantly larger versus PBO (8.5[13.3]) for LEM5 (16.9[13.6]; P<0.001) and LEM10 (14.9[15.9]; P<0.01). At 12mo, mean (SD) increase in sSE was maintained for LEM5 (18.1[12.5]) and LEM10 (18.0[16.8]). At 6mo, mean (SD) change from baseline in sWASO was significantly decreased versus PBO (−26.5 [52.9]) for LEM5 and LEM10 (−54.8[64.4], P<0.01; −51.4[69.3], P<0.05, respectively). At 12mo, mean (SD) decrease in sWASO was maintained for LEM5 (−58.6[46.0]) and LEM10 (−60.9[80.4]). Over 12mo, the most common (>10% either group) treatment emergent adverse events with LEM5 and LEM10, respectively, were somnolence (9.3%, 19.0%), nasopharyngitis (9.3%, 10.7%), and headache (10.5%, 6.0%). Conclusion In elderly subjects, LEM demonstrated efficacy at 6mo, which persisted at 12mo; LEM was well tolerated. Support Eisai Inc.

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164 Pooled Analyses of Patient-Reported Sleep Onset and Maintenance from Two Phase 3 Studies of Lemborexant

CNS Spectrums ◽

10.1017/s1092852920000802 ◽

2020 ◽

Vol 25 (2) ◽

pp. 304-305 ◽

Cited By ~ 1

Author(s):

Russell Rosenberg ◽

Gary Zammit ◽

Jane Yardley ◽

Kate Pinner ◽

Carlos Perdomo ◽

...

Keyword(s):

Sleep Onset ◽

Pooled Analysis ◽

Elderly Subjects ◽

Sleep Onset Latency ◽

Phase 3 ◽

Double Blind ◽

Subjective Sleep ◽

Sleep Maintenance ◽

Insomnia Disorder ◽

Patient Reported

Abstract:Study Objective(s):The dual orexin receptor antagonist, lemborexant (LEM), is being investigated for the treatment of insomnia disorder. Drugs targeting the orexin system, like LEM, may decrease wakefulness and promote sleep with fewer potential adverse effects (AEs) than some currently available pharmacological insomnia therapies. LEM has been studied in 2 pivotal phase 3 trials for insomnia disorder, SUNRISE-1 (NCT02783729; E2006-G000-304) and SUNRISE-2 (NCT02952820; E2006-G000-303). Analyses presented here are derived from patient-reported (subjective) efficacy data pooled from SUNRISE-1 and SUNRISE-2 during 1-month of treatment in adult and elderly (age ≥65y) subjects with DSM-5 insomnia disorder.Method:SUNRISE-1 was a 1-month, double-blind, randomized, placebo (PBO)- and active-controlled (zolpidem tartrate extended-release 6.25mg [ZOL; not reported), parallel-group study in 1006 subjects (age ≥55y). SUNRISE-2 was a 12-month (6-month PBO-controlled, 6-month active treatment), double-blind study in 949 subjects (age ≥18y). In both studies, subjects were randomized to PBO, LEM5, or LEM10 (SUNRISE-1 subjects could also be randomized to ZOL; not included in pooled analysis) following a 2-week PBO run-in. Changes from baseline (BL) in subjective sleep onset latency (sSOL), subjective sleep efficiency (sSE), and subjective wake after sleep onset (sWASO) were analyzed using mixed effect model repeated measurement analysis. Sleep onset and sleep maintenance responders were analyzed via Cochran–Mantel–Haenszel test stratified by study, region and age group.Results:The pooled analysis set comprised 1693 subjects (PBO, n=527; LEM5, n=582; LEM10, n=584). Reductions from BL in sSOL were significantly greater for LEM5 and LEM10 vs PBO during the first 7 days of treatment and at the end of Month 1 (all comparisons P<0.0001). Both doses of LEM significantly increased sSE from BL (P<0.001 both time points) more than PBO and reduced sWASO from BL (P<0.0001 first 7 days [both doses]; P<0.05 [LEM5] and P<0.001 [LEM10] at Month 1) more than PBO. After the first 7 days and at the end of Month 1, the proportion of sSOL responders (≤20 min if BL >30 min) was statistically significantly larger for LEM5 and LEM10 vs PBO (first 7 days: both P<0.0001; last 7 days of Month 1: both P<0.001) and the proportion of sWASO responders (≤60 minutes and a reduction from BL by >10 min, if BL >60 min) was statistically significantly larger for LEM5 and LEM10 vs PBO (first 7 days: both P<0.01; last 7 days of Month 1: both P<0.05). LEM was well tolerated. Most AEs were mild to moderate in severity, and rates of severe or serious AEs were low.Conclusions:LEM improved sleep onset and sleep maintenance in adult and elderly subjects with insomnia disorder, and was well tolerated. Average values on sleep maintenance endpoints showed that subjects treated with LEM obtained >1 hour of additional sleep per night vs subjects who received PBO.Funding Acknowledgements:Supported by Eisai Inc.

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0480 Efficacy and Safety of Lemborexant in Female Subjects of Perimenopausal Age with Insomnia Disorder

SLEEP ◽

10.1093/sleep/zsaa056.477 ◽

2020 ◽

Vol 43 (Supplement_1) ◽

pp. A184-A184

Author(s):

J Cheng ◽

J Yardley ◽

K Pinner ◽

M Moline

Keyword(s):

Sleep Onset ◽

Safety Data ◽

Sleep Diary ◽

Sleep Onset Latency ◽

Efficacy And Safety ◽

Subjective Sleep ◽

Perimenopausal Women ◽

Sleep Parameters ◽

Age Range ◽

Female Subjects

Abstract Introduction Insomnia is common in women in the perimenopausal age range. We present 12-month efficacy and safety data for the subgroup of female subjects in the age range associated with perimenopause (age 40-58y) from SUNRISE-2 (NCT02952820; E2006-G000-303). Methods SUNRISE-2 was a 12-month, randomized, double-blind, placebo (PBO)-controlled (first 6mo [Period 1]), global phase 3 study. During Period 1, subjects received PBO or lemborexant (LEM: 5mg, [LEM5]; 10mg, [LEM10]). During Period 2 (second 6mo), LEM subjects continued their assigned dose. PBO subjects were rerandomized to LEM5 or LEM10 (not reported here). Changes from baseline in subjective sleep parameters: subjective sleep onset latency (sSOL), sleep efficiency (sSE), wake after sleep onset (sWASO) were assessed from sleep diary data. Results The perimenopausal subgroup comprised 280 subjects (Period 1: PBO, n=90; LEM5, n=82; LEM10, n=108). Baseline median sSOL (min) was 57.5, 51.1, and 54.0 for PBO, LEM5, and LEM10. Greater median decreases from baseline in sSOL (min) occurred at 6mo with LEM vs PBO (PBO, −17.9; LEM5, −20.7; LEM10, −30.4); improvements persisted at 12mo (LEM 5, −27.7; LEM10, −33.9). Baseline mean[SD] sSE was 59.9%[16.6%], 60.7%[20.0%], and 61.2%[17.5%] for PBO, LEM5, and LEM10. Greater mean[SD] increases from baseline in sSE (%) occurred at 6mo with LEM vs PBO (PBO, 12.5%[15.0%]; LEM5, 15.9%[17.0%]; LEM10, 17.2%[14.7%]); improvement persisted at 12mo (LEM5,17.6%[18.2%]; LEM10, 19.1%[14.8%]). Baseline mean[SD] sWASO (min) was 134.9[70.8], 142.4[86.5], and 136.5[84.4]. Greater mean[SD] decreases from baseline in sWASO (min) occurred at 6mo with LEM vs PBO (PBO, −37.0[59.6]; LEM5, −50.1[74.5]; LEM10 −54.5[65.4]); improvement persisted at 12mo (LEM5, −59.1[76.7]; LEM10, −66.2[64.9]). Most treatment emergent adverse events (TEAEs) were mild/moderate. Conclusion Consistent with previously reported data from the total population, subjective sleep parameters improved, and improvement was sustained over time in perimenopausal women. LEM was well tolerated, supporting LEM as a potential treatment option for perimenopausal women with insomnia. Support Eisai Inc.

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0479 Sleep Onset and Sleep Maintenance Responder Profiles Over 12 Months of Treatment with Lemborexant: Results from SUNRISE-2

SLEEP ◽

10.1093/sleep/zsaa056.476 ◽

2020 ◽

Vol 43 (Supplement_1) ◽

pp. A184-A184

Author(s):

G Zammit ◽

J Yardley ◽

K Pinner ◽

M Moline

Keyword(s):

Treatment Success ◽

Sleep Onset ◽

Sleep Diary ◽

Sleep Onset Latency ◽

Double Blind ◽

Subjective Sleep ◽

Sleep Maintenance ◽

Insomnia Disorder ◽

Patient Reported

Abstract Introduction In addition to analyzing treatment response by comparing change from baseline (CFB) between active treatment and placebo (PBO), it is also informative to evaluate the percent of patients with a given magnitude of response. This can help establish the expected degree of improvement for patients, thereby helping to determine treatment success. Methods SUNRISE-2 (NCT02952820; E2006-G000-303) was a randomized, double-blind, global phase 3 study of lemborexant (LEM) in adults (≥18y) with insomnia disorder. Subjects received PBO or LEM (5mg [LEM5]; 10mg [LEM10]) for 6mo. LEM subjects continued their original dose, while PBO subjects were rerandomized to LEM for another 6mo (not reported here). Responder profiles were constructed separately for patient-reported, sleep diary-based subjective sleep onset and sleep maintenance based on the cumulative proportion of subjects with CFBs in 10-minute increments for subjective sleep onset latency (sSOL) or subjective wake after sleep onset (sWASO), respectively. The proportion was based on number of subjects with baseline data (denominator) and data available at time of visit; study dropouts were considered nonresponders. Results Baseline values were similar (median sSOL [min]: PBO, 55.9; LEM5, 53.6; LEM10, 55.7; mean[SD] sWASO [min]: PBO, 132.5[80.2]; LEM5, 132.8[82.5]; LEM10, 136.8[87.4]). At 6mo, a higher percentage of subjects with CFB of ≥20min in sSOL was observed with LEM versus PBO (PBO, 30.4%; LEM5, 45.5%; LEM10, 44.9%). At 12mo, a similar percentage of responders with a ≥20min CFB in sSOL was observed for LEM (LEM5, 40.4%; LEM10, 43.3%). A higher percentage of subjects with a CFB in sWASO of ≥60min was observed for LEM versus PBO at 6mo (PBO, 24.2%; LEM5, 27.8%: LEM10, 30.2%); similar percentages were observed at 12mo with LEM (LEM5, 27.8%; LEM10, 27.7%). The majority of treatment-emergent adverse events were mild/moderate. Conclusion LEM treatment provided important levels of sustained efficacy over the long term. LEM was well tolerated. Support Eisai Inc.

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0486 Impact of Intrinsic Factors on Efficacy of Lemborexant: Subgroup Analyses of SUNRISE-2

SLEEP ◽

10.1093/sleep/zsaa056.483 ◽

2020 ◽

Vol 43 (Supplement_1) ◽

pp. A186-A187

Author(s):

M Moline ◽

Y Inoue ◽

N Kubota ◽

K Pinner ◽

C Perdomo ◽

...

Keyword(s):

Sleep Onset ◽

Sleep Diary ◽

Sleep Onset Latency ◽

Double Blind ◽

Intrinsic Factors ◽

Insomnia Disorder ◽

Patient Reported ◽

Full Analysis ◽

The Impact ◽

Patient Subgroups

Abstract Introduction Lemborexant (LEM), a dual orexin receptor antagonist, demonstrated significant benefits vs placebo on patient-reported sleep outcomes in adults age ≥18y in SUNRISE-2 (NCT02952820; E2006-G000-303). The impact of intrinsic factors (sex, race, and region) on LEM efficacy outcomes was assessed. Methods SUNRISE-2 was a randomized, double-blind, global phase 3 study in adults age ≥18y with insomnia disorder (Full Analysis Set, n=949). Subjects received placebo (n=318) or LEM (5mg [LEM5], n=316; 10mg [LEM10]; n=315) for 6 months. At 6 months, placebo subjects were rerandomized to LEM for another 6 months (not reported here); LEM subjects remained on their assigned dose. Sleep diary-based (subjective) sleep onset latency (sSOL) and wake after sleep onset (sWASO) were assessed for prespecified patient subgroups including: sex (male [n=302], female [n=647]), race (white [n=679], black [n=76], Asian [n=178]), and region (North America [n=302], Europe/New Zealand [n=483], Asia [n=164]). Analyses were not controlled for multiplicity. Results LEM5 and LEM10 provided numerically greater median reductions (improvement) from baseline in sSOL vs placebo at 6 months in across all subgroups examined. Also, LEM5 and LEM10 led to mean reductions (improvement) from baseline at 6 months in sWASO for all subgroups. While several subgroups had small numbers of subjects, changes from baseline in sSOL and sWASO were in the direction of improvement in the majority of subgroups. Pharmacokinetic analyses showed no important differences in exposure by these factors. Conclusion LEM treatment demonstrated efficacy in improving sSOL and sWASO across patient subgroups, supporting common dosing instructions for both sexes and all races. Support Eisai Inc.

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0473 Effectiveness and Safety of Lemborexant in Subjects Previously Treated with Placebo for 6 Months in SUNRISE-2

SLEEP ◽

10.1093/sleep/zsaa056.470 ◽

2020 ◽

Vol 43 (Supplement_1) ◽

pp. A181-A182

Author(s):

J Yardley ◽

Y Inoue ◽

K Pinner ◽

C Perdomo ◽

G Filippov ◽

...

Keyword(s):

Adverse Events ◽

Sleep Onset ◽

Sleep Diary ◽

Sleep Onset Latency ◽

Double Blind ◽

Subjective Sleep ◽

Insomnia Disorder ◽

Previously Treated ◽

Treatment Changes ◽

Additional Improvement

Abstract Introduction In SUNRISE-2 (NCT02952820; E2006-G000-303), while lemborexant (LEM) provided significant benefit versus placebo (PBO) on sleep-diary measurements over 6mo, some improvement was noted in PBO subjects. We report outcomes from PBO subjects rerandomized to LEM during the last 6mo of SUNRISE-2. Methods SUNRISE-2 was a randomized, double-blind, global phase 3 study in adults (≥18y) with insomnia disorder. Subjects received PBO or LEM (5mg [LEM5]; 10mg [LEM10]) for 6mo. PBO subjects were rerandomized to LEM for another 6mo; LEM subjects continued assigned treatment. Changes from 6mo baseline (calculated after PBO completion) in subjective sleep onset latency (sSOL), subjective sleep efficiency (sSE), and subjective wake after sleep onset (sWASO) are reported for rerandomized subjects. Results At study baseline for PBO subjects (n=318), median sSOL (min) was 55.9, mean (SD) sSE (%) and sWASO (min) were 61.3 (17.8) and 132.5 (80.2), respectively. The 6mo baseline values for rerandomized PBO-LEM5 (n=133) and PBO-LEM10 (n=125) subjects, respectively, were: median sSOL, 31.2, 34.3; mean (SD) sSE, 70.5 (20.2), 71.1 (18.0); mean (SD) sWASO, 105.1 (80.6), 100.1 (84.6). Median sSOL decreased from the 6mo baseline after 1mo (PBO-LEM5, −3.2; PBO-LEM10, −2.9) and 6mo (PBO-LEM5, −2.7; PBO-LEM10, −5.0). Mean (SD) sSE increased from the 6mo baseline after 1mo (PBO-LEM5, 3.9 [12.1]; PBO-LEM10, 3.5 [8.1]) and 6mo (PBO-LEM5, 3.9 [13.6]; PBO-LEM10, 4.5 [13.0]). Mean (SD) sWASO decreased after 1mo (PBO-LEM5, −8.5 [49.4]; PBO-LEM10, −5.7 [36.1]) and 6mo (PBO-LEM5, −8.2 [49.0]; PBO-LEM10, −10.0 [58.8]). Treatment-emergent adverse events incidence was similar during PBO (62.7%) and LEM treatment (PBO-LEM5, 54.9%; PBO-LEM10, 57.7%). Adverse events were consistent with those seen in the initial 6mo of treatment for patients originally randomized to LEM. Conclusion Rerandomization to LEM was associated with additional improvement in sleep outcomes following the PBO-related response. LEM benefit was evident after 1mo and was sustained throughout treatment. LEM was well tolerated. Support Eisai Inc.

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Mindfulness and Behaviour Therapy for Insomnia: An Assessment of Treatment Effect in a Sleep Disorders Clinic Population with Insomnia

Behaviour Change ◽

10.1017/bec.2020.18 ◽

2020 ◽

pp. 1-15

Author(s):

Allie Peters ◽

John Reece ◽

Hailey Meaklim ◽

Moira Junge ◽

David Cunnington ◽

...

Keyword(s):

Sleep Disorders ◽

Treatment Effect ◽

Sleep Onset ◽

Sleep Efficiency ◽

Health Concern ◽

Sleep Diary ◽

Sleep Onset Latency ◽

Subjective Sleep ◽

Sleep Parameters

Abstract Insomnia is a common major health concern, which causes significant distress and disruption in a person's life. The objective of this paper was to evaluate a 6-week version of Mindfulness-Based Therapy for Insomnia (MBTI) in a sample of people attending a sleep disorders clinic with insomnia, including those with comorbidities. Thirty participants who met the DSM-IV-TR diagnosis of insomnia participated in a 6-week group intervention. Outcome measures were a daily sleep diary and actigraphy during pre-treatment and follow-up, along with subjective sleep outcomes collected at baseline, end-of-treatment, and 3-month follow-up. Trend analyses showed that MBTI was associated with a large decrease in insomnia severity (p < .001), with indications of maintenance of treatment effect. There were significant improvements in objective sleep parameters, including sleep onset latency (p = .005), sleep efficiency (p = .033), and wake after sleep onset (p = .018). Significant improvements in subjective sleep parameters were also observed for sleep efficiency (p = .005) and wake after sleep onset (p < .001). Overall, this study indicated that MBTI can be successfully delivered in a sleep disorders clinic environment, with evidence of treatment effect for both objective and subjective measures of sleep.

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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 ◽

10.1093/sleep/zsaa123 ◽

2020 ◽

Vol 43 (9) ◽

Cited By ~ 2

Author(s):

Mikko Kärppä ◽

Jane Yardley ◽

Kate Pinner ◽

Gleb Filippov ◽

Gary Zammit ◽

...

Keyword(s):

Clinical Trial ◽

Sleep Onset ◽

Sleep Onset Latency ◽

Phase 3 ◽

Subjective Sleep ◽

Term Efficacy ◽

Sleep Maintenance ◽

Insomnia Disorder ◽

Patient Reported

Abstract Study Objectives To assess long-term efficacy and safety of lemborexant (LEM), a novel dual orexin receptor antagonist, versus placebo in adults with insomnia disorder. Methods This was a 12-month, global, multicenter, randomized, double-blind, parallel-group phase 3 study comprising a 6-month placebo-controlled period (reported here) followed by a 6-month active-treatment-only period (reported separately). A total of 949 participants with insomnia (age ≥18 years) were randomized, received treatment with an oral dose of placebo or LEM (5 mg [LEM5] or 10 mg [LEM10]) and were analyzed. Sleep onset and sleep maintenance endpoints were analyzed from daily electronic sleep diary data. Treatment-emergent adverse events (TEAEs) were monitored throughout the study. Results Decreases from baseline in patient-reported (subjective) sleep onset latency and subjective wake after sleep onset, and increases from baseline in subjective sleep efficiency, were significantly greater with LEM5 and LEM10 versus placebo. Significant benefits over placebo were observed at the end of month 6, and at most time points assessed over the 6-month period, indicating long-term sustained efficacy of LEM. A significantly greater percentage of sleep onset responders and sleep maintenance responders were observed with LEM treatment versus placebo. Participants treated with LEM reported a significant improvement in quality of sleep after 6 months versus placebo. The majority of TEAEs were mild or moderate. There was a low rate of serious TEAEs and no deaths. Conclusions LEM5 and LEM10 provided significant benefit on sleep onset and sleep maintenance in individuals with insomnia disorder versus placebo, and was well tolerated. Clinical trial registration ClinicalTrials.gov, NCT02952820; ClinicalTrialsRegister.eu, EudraCT Number 2015-001463-39

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Effectiveness of a Multicomponent Group Treatment for Insomnia

Behavioural and Cognitive Psychotherapy ◽

10.1017/s1352465800014375 ◽

1995 ◽

Vol 23 (2) ◽

pp. 109-127 ◽

Cited By ~ 10

Author(s):

Elisabeth Schramm ◽

Fritz Hohagen ◽

Jutta Backhaus ◽

Stefanie Lis ◽

Mathias Berger

Keyword(s):

Sleep Quality ◽

Group Treatment ◽

Psychological Treatment ◽

Sleep Onset ◽

Sleep Diary ◽

Management Problem ◽

Sleep Onset Latency ◽

Subjective Sleep Quality ◽

Significant Treatment ◽

Problem Solving Skills

The present study evaluates a multifaceted cognitive-behavioral group treatment in a routine clinical setting. The program consists of directly sleep related strategies such as sleep education, sleep restriction, stimulus control, relaxation, and cognitive restructuring. Also included are techniques that target illness maintaining factors such as stress-management, problem solving skills, and increase of activities. Twenty-eight physician-referred outpatients with chronic primary insomnia according to DSM-III-R criteria attended 11 weekly therapy-sessions. Results were obtained on a subjective and objective level using a sleep diary, questionnaires, and polysomnography, respectively. Pre- and post-treatment comparisons indicated significant changes on all main sleep diary variables, i.e. total sleep time, sleep efficiency, number of awakenings, sleep onset latency and wake after sleep onset, as well as for the global subjective sleep quality. Maximum improvement was reached after the more directly sleep-related part of the program. In addition, the intervention helped patients to reduce the amount and frequency of sleeping aids over time and improved their daytime-functioning. Subjective therapeutic gains were maintained at 3- and 12-month follow-ups. No significant treatment effects could be obtained on polysomnographic measures, taking into account that the baseline values were already in the normative range. After the intervention the patients were able to give a more realistic evaluation of their sleep. These results suggest that a multicomponent psychological treatment is beneficial for the improvement of sleep quality on a subjective level.

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0484 How Much Improvement in Subject-Reported Sleep Onset Latency is Needed for Patients to Report a Positive Impact of Their Insomnia Medication?

SLEEP ◽

10.1093/sleep/zsaa056.481 ◽

2020 ◽

Vol 43 (Supplement_1) ◽

pp. A185-A186

Author(s):

C Drake ◽

J Yardley ◽

K Pinner ◽

C Perdomo ◽

D Kumar ◽

...

Keyword(s):

Positive Impact ◽

Sleep Onset ◽

Sleep Diary ◽

Sleep Onset Latency ◽

Onset Latency ◽

Double Blind ◽

Meaningful Improvement ◽

Treatment Groups ◽

Medication Effect ◽

Full Analysis

Abstract Introduction How much improvement would be considered meaningful from the patient perspective is not well defined. In SUNRISE-2 (NCT02952820; E2006-G000-303), using the Patient Global Impression-Insomnia version (PGI-I), subjects rated how treatment impacted subjective (sleep diary-based) sleep onset latency (sSOL; Question2; positive, neutral, and negative) relative to before starting treatment. Meaningful change can thus be determined based on the change from baseline (CFB) in subjects with a positive score. Methods SUNRISE-2 (n=949, full analysis set) was a Phase 3, 12-month, double-blind, global study in subjects age ≥18y with insomnia disorder. Subjects received PBO (N=318), LEM 5mg (LEM5, N=316) or LEM 10mg (LEM10, N=315) for 6 months. At the end of Month 6, PBO subjects were rerandomized to LEM5 or LEM10; LEM5 and LEM10 subjects continued at the same dose for 6 more months. The ranges of median CFB in sSOL (minutes) at 6 months were examined in response to PGI-I Item 2. Results At 6 months, subjects reporting positive medication effect (PBO, n=110; LEM5, n=178; LEM10, n=159) showed median CFB in sSOL from -17.5 to -32.1 minutes across treatment groups. In subjects reporting neutral effect (PBO, n=49; LEM5, n=28; LEM10, n=27), median CFB in sSOL ranged from -10.4 to -25.6 minutes across treatment groups. In subjects reporting negative medication effect (PBO, n=82; LEM5, n=34; LEM10, n=32), median CFB in sSOL ranged from -8.6 to -10.4 minutes across treatment groups. The PBO group provided the smallest numbers for each response category range. Conclusion Subjects reporting positive medication effect on PGI-I Item 2, i.e. decreased time to fall asleep, had corresponding changes from baseline in sSOL ranging from -17.5 to -32.1 minutes. Thus, this range may represent a clinically meaningful improvement as perceived by patient-subjects, and may be useful to clinicians in determining whether a treatment regimen is working for their patients. Support Eisai Inc.

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0481 Impact of Lemborexant on Fatigue Severity in Subjects with Clinically Significant Levels of Fatigue at Baseline

SLEEP ◽

10.1093/sleep/zsaa056.478 ◽

2020 ◽

Vol 43 (Supplement_1) ◽

pp. A184-A185

Author(s):

R Rosenberg ◽

D Kumar ◽

K Pinner ◽

C Perdomo ◽

M Moline

Keyword(s):

Sleep Onset ◽

Sleep Diary ◽

Double Blind Study ◽

Double Blind ◽

Insomnia Disorder ◽

Parallel Group ◽

Patient Reported ◽

Fatigue Severity ◽

Clinically Significant ◽

The Impact

Abstract Introduction In Phase 3 SUNRISE-1 (NCT02783729; E2006-G000-304) and SUNRISE-2 (NCT02952820; E2006-G000-303), lemborexant (LEM) provided significant benefit versus placebo on sleep diary-based sleep onset/maintenance outcomes over 1mo and 6mo, respectively, in subjects with insomnia disorder. The impact of LEM on patient-reported fatigue, assessed using the Fatigue Severity Scale (FSS), in subjects with clinically significant fatigue (CSF) at baseline was examined for each study. Methods SUNRISE-1 was a 1mo, randomized, double-blind, placebo- and active-controlled, parallel-group study in female (≥55y) and male (≥65y) subjects (n=1006); subjects received placebo, LEM 5mg (LEM5), LEM 10mg (LEM10) or zolpidem tartrate extended-release (not reported here). SUNRISE-2 was a 12mo, randomized, double-blind study in subjects age ≥18y (n=949). Subjects received placebo, LEM5, or LEM10 for 6mo. Placebo subjects were rerandomized to LEM5 or LEM10 for another 6mo; LEM subjects continued assigned treatment. CSF was defined as FSS total score (FSSts) ≥36. Results In subjects with baseline CSF, in SUNRISE-1, baseline FSSts was 46.8, 46.5, and 46.6 in placebo (n=117), LEM5 (n=157), and LEM10 (n=153) groups, respectively, and, in SUNRISE-2, was 45.7, 46.4, and 45.8 in placebo (n=169), LEM5 (n=181), and LEM10 (n=173) groups, respectively. At 1mo, mean changes from baseline in FSSts were not significantly different vs placebo for LEM5 in both studies, and for LEM10 in SUNRISE-1. In SUNRISE-2, LEM10 significantly decreased mean [SD] FSSts from baseline vs placebo at 1mo (LEM10, −11.2[13.9] vs placebo, −8.7[10.5]; P=0.03). By 6mo in SUNRISE-2, both LEM5 and LEM10 significantly decreased mean [SD] FSSts from baseline versus placebo (LEM5, −15.4[13.8]; LEM10, −15.0[14.2] vs placebo, −11.2[11.6]; both P<0.05). At 12mo, mean [SD] FSSts improvements were sustained for LEM5 (−20.4[12.8]) and LEM10 (−18.1[14.7]). Conclusion In subjects with CSF, longer treatments (>1mo) may be needed to observe significant FSSts improvements, which were evident at 6mo and sustained at 12mo with continuous LEM treatment. Support Eisai Inc.

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