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CompletedNCT00792298Updated Nov 6, 2018Results posted

Phase IIB 2-Period Crossover Polysomnography Study in Participants With Primary Insomnia (MK-4305-006)

A Phase 2 interventional study of Suvorexant and Dose-matched Placebo to Suvorexant in Primary Insomnia, sponsored by Merck Sharp & Dohme LLC. Completed. Open to participants aged 18 Years to 64 Years. Per ClinicalTrials.gov, last updated 2018-11-06.

Sponsored by Merck Sharp & Dohme LLC · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
254
Allocation
Randomized
Ages
18 Years to 64 Years
Sex
All
01

Study summary

A cross-over, polysomnography study to test the safety, tolerability and effectiveness of different doses of suvorexant (MK-4305) in the treatment of patients with primary insomnia.

02

Conditions studied

  • Primary Insomnia
03

In context

Sleep Initiation and Maintenance Disorders

1,856 studies on the registry are indexed under Sleep Initiation and Maintenance Disorders; 594 are open to participants now.

This study's enrollment of 254 is above the median of 73 across 1,631 interventional studies indexed under Sleep Initiation and Maintenance Disorders.

Browse Sleep Initiation and Maintenance Disorders studies →

Lead sponsor

Merck Sharp & Dohme LLC is the lead sponsor of 2,114 studies on the registry; 133 are open to participants now.

Of its 489 completed or terminated interventional studies of FDA-regulated products, 362 (74%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 64 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Has a diagnosis of Primary Insomnia based on sleep history and the investigator's judgment
  • Must be willing to stay overnight at a sleep laboratory
  • Must be willing to stay in bed for at least 8 hours each night while at the sleep laboratory
  • Regular bedtime is between 9 PM and 12 AM (midnight)

Exclusion criteria

Exclusion Criteria:

  • Breast feeding, pregnant or planning to become pregnant during the study
  • Within the past 6 months before starting the study you have a history of significant cardiovascular disorder such as unstable angina, congestive heart - failure or acute coronary syndrome
  • Currently participating or have participated in a study with an investigational compound or device within the last 30 days
  • Has traveled across 3 or more time zones in the last 2 weeks or plans on traveling across 3 or more time zones at any time during the study
  • Has done shift work within the past 2 weeks
  • Has donated blood products within the last 8 weeks
  • Has difficulty sleeping due to a medical condition
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Double (Participant, Investigator)
Enrollment
254 participants (actual)

Study arms

  • Experimental
    Suvorexant 10 mg → Placebo

    After an \~1- to 2-week single-blind placebo run-in period, participants received 10 mg suvorexant daily prior to bedtime for 4 weeks during Treatment Period 1, followed by a 1-week single-blind placebo washout period, followed by dose-matched placebo to suvorexant daily prior to bedtime during Treatment Period 2.

    Drug: Suvorexant · Drug: Dose-matched Placebo to Suvorexant

  • Experimental
    Placebo → Suvorexant 10 mg

    After an \~1- to 2-week single-blind placebo run-in period, participants received dose-matched placebo to suvorexant daily prior to bedtime for 4 weeks during Treatment Period 1, followed by a 1-week single-blind placebo washout period, followed by 10 mg suvorexant daily prior to bedtime during Treatment Period 2.

    Drug: Suvorexant · Drug: Dose-matched Placebo to Suvorexant

  • Experimental
    Suvorexant 20 mg → Placebo

    After an \~1- to 2-week single-blind placebo run-in period, participants received 20 mg suvorexant daily prior to bedtime for 4 weeks during Treatment Period 1, followed by a 1-week single-blind placebo washout period, followed by dose-matched placebo to suvorexant daily prior to bedtime during Treatment Period 2.

    Drug: Suvorexant · Drug: Dose-matched Placebo to Suvorexant

  • Experimental
    Placebo → Suvorexant 20 mg

    After an \~1- to 2-week single-blind placebo run-in period, participants received dose-matched placebo to suvorexant daily prior to bedtime for 4 weeks during Treatment Period 1, followed by a 1-week single-blind placebo washout period, followed by 20 mg suvorexant daily prior to bedtime during Treatment Period 2.

    Drug: Suvorexant · Drug: Dose-matched Placebo to Suvorexant

  • Experimental
    Suvorexant 40 mg → Placebo

    After an \~1- to 2-week single-blind placebo run-in period, participants received 40 mg suvorexant daily prior to bedtime for 4 weeks during Treatment Period 1, followed by a 1-week single-blind placebo washout period, followed by dose-matched placebo to suvorexant daily prior to bedtime during Treatment Period 2.

    Drug: Suvorexant · Drug: Dose-matched Placebo to Suvorexant

  • Experimental
    Placebo → Suvorexant 40 mg

    After an \~1- to 2-week single-blind placebo run-in period, participants received dose-matched placebo to suvorexant daily prior to bedtime for 4 weeks during Treatment Period 1, followed by a 1-week single-blind placebo washout period, followed by 40 mg suvorexant daily prior to bedtime during Treatment Period 2.

    Drug: Suvorexant · Drug: Dose-matched Placebo to Suvorexant

  • Experimental
    Suvorexant 80 mg → Placebo

    After an \~1- to 2-week single-blind placebo run-in period, participants received 80 mg suvorexant daily prior to bedtime for 4 weeks during Treatment Period 1, followed by a 1-week single-blind placebo washout period, followed by dose-matched placebo to suvorexant daily prior to bedtime during Treatment Period 2.

    Drug: Suvorexant · Drug: Dose-matched Placebo to Suvorexant

  • Experimental
    Placebo → Suvorexant 80 mg

    After an \~1- to 2-week single-blind placebo run-in period, participants received dose-matched placebo to suvorexant daily prior to bedtime for 4 weeks during Treatment Period 1, followed by a 1-week single-blind placebo washout period, followed by 80 mg suvorexant daily prior to bedtime during Treatment Period 2.

    Drug: Suvorexant · Drug: Dose-matched Placebo to Suvorexant

Interventions

  • DrugSuvorexant

    oral tablet taken before bedtime

    Also known as: MK-4305

  • DrugDose-matched Placebo to Suvorexant

    Dose-matched placebo to suvorexant taken before bedtime (oral tablet)

06

What researchers measure

Primary outcomes

  1. LS Mean Sleep Efficiency (SE) During Periods 1 and 2

    SE was defined as total sleep time (TST) in minutes divided by time in bed (measured from lights off to lights on; fixed at 8 hours on each Polysomnography \[PSG\] night) in minutes, multiplied by 100, where TST is defined as the total time (minutes) in Stages 1, 2, 3, 4 and Rapid Eye Movement (REM). SE= (total sleep time/time in bed) x 100

    Time frame: Night 1 and end of Week 4

Secondary outcomes

  1. LS Mean Wake After Persistent Sleep Onset (WASO) During Periods 1 and 2

    WASO was defined as the duration of wakefulness measured in minutes (any epoch of Stage 0) from persistent sleep onset (first epoch of the first twenty consecutive epochs of non-wake) to lights on.

    Time frame: Night 1 and end of Week 4

  2. LS Mean Latency to the Onset of Persistent Sleep (LPS) During Periods 1 and 2

    LPS is defined as the duration of time measured in minutes from lights off to persistent sleep onset.

    Time frame: Night 1 and end of Week 4

07

Results

Posted Nov 14, 2014

Participant flow

Treatment Period 1
Participant flow — Treatment Period 1
MilestoneSuvorexant 10 mg → PlaceboPlacebo → Suvorexant 10 mgSuvorexant 20 mg → PlaceboPlacebo → Suvorexant 20 mgSuvorexant 40 mg → PlaceboPlacebo → Suvorexant 40 mgSuvorexant 80 mg → PlaceboPlacebo → Suvorexant 80 mg
Started3132333232323131
Completed3031312832292730
Not completed11240341
Withdrew: Adverse event01010110
Withdrew: Lack of efficacy00100000
Withdrew: Withdrawal by subject10120210
Withdrew: Lost to follow-up00000010
Withdrew: Physician decision00010010
Withdrew: Protocol violation00000001
Washout
Participant flow — Washout
MilestoneSuvorexant 10 mg → PlaceboPlacebo → Suvorexant 10 mgSuvorexant 20 mg → PlaceboPlacebo → Suvorexant 20 mgSuvorexant 40 mg → PlaceboPlacebo → Suvorexant 40 mgSuvorexant 80 mg → PlaceboPlacebo → Suvorexant 80 mg
Started3031322832292930
Completed3031312832272930
Not completed00100200
Withdrew: Adverse event00000100
Withdrew: Withdrawal by subject00100100
Treatment Period 2
Participant flow — Treatment Period 2
MilestoneSuvorexant 10 mg → PlaceboPlacebo → Suvorexant 10 mgSuvorexant 20 mg → PlaceboPlacebo → Suvorexant 20 mgSuvorexant 40 mg → PlaceboPlacebo → Suvorexant 40 mgSuvorexant 80 mg → PlaceboPlacebo → Suvorexant 80 mg
Started3031312832272930
Completed2930302630272828
Not completed11122012
Withdrew: Lack of efficacy00001000
Withdrew: Physician decision00000010
Withdrew: Pregnancy00100000
Withdrew: Withdrawal by subject11021002

Outcome measures

PrimaryLS Mean Sleep Efficiency (SE) During Periods 1 and 2

SE was defined as total sleep time (TST) in minutes divided by time in bed (measured from lights off to lights on; fixed at 8 hours on each Polysomnography \[PSG\] night) in minutes, multiplied by 100, where TST is defined as the total time (minutes) in Stages 1, 2, 3, 4 and Rapid Eye Movement (REM). SE= (total sleep time/time in bed) x 100

Time frame:
Night 1 and end of Week 4
Reported as:
Least squares mean · percent of time in bed
LS Mean Sleep Efficiency (SE) During Periods 1 and 2
percent of time in bedPlaceboSuvorexant 10 mgSuvorexant 20 mgSuvorexant 40 mgSuvorexant 80 mg
Night 1 (n=249, 62, 61, 59, 61)75.8 ± 0.9381.0 ± 1.7583.4 ± 1.7586.6 ± 1.7788.7 ± 1.77
Week 4 (n=232, 59, 57, 57, 55)76.6 ± 0.9481.3 ± 1.6687.0 ± 1.6884.4 ± 1.6884.2 ± 1.70
Statistical analysis
  • Placebo vs Suvorexant 80 mg · Mixed Models Analysis · p = <0.001 · Ls mean difference: night 1: 12.9 · 95% CI 9.5 to 16.3
  • Placebo vs Suvorexant 80 mg · Mixed Models Analysis · p = <0.001 · Ls mean difference: week 4: 7.6 · 95% CI 4.4 to 10.9
  • Placebo vs Suvorexant 40 mg · Mixed Models Analysis · p = <0.001 · Ls mean difference: night 1: 10.8 · 95% CI 7.4 to 14.2
  • Placebo vs Suvorexant 40 mg · Mixed Models Analysis · p = <0.001 · Ls mean difference: week 4: 7.8 · 95% CI 4.6 to 10.9
  • Placebo vs Suvorexant 20 mg · Mixed Models Analysis · p = <0.001 · Ls mean difference: night 1: 7.6 · 95% CI 4.2 to 11.0
  • Placebo vs Suvorexant 20 mg · Mixed Models Analysis · p = <0.001 · Ls mean difference: week 4: 10.4 · 95% CI 7.2 to 13.6
  • Placebo vs Suvorexant 10 mg · Mixed Models Analysis · p = 0.002 · Ls mean difference: night 1: 5.2 · 95% CI 1.9 to 8.6
  • Placebo vs Suvorexant 20 mg · Mixed Models Analysis · p = 0.003 · Ls mean difference: week 4: 4.7 · 95% CI 1.6 to 7.8
SecondaryLS Mean Wake After Persistent Sleep Onset (WASO) During Periods 1 and 2

WASO was defined as the duration of wakefulness measured in minutes (any epoch of Stage 0) from persistent sleep onset (first epoch of the first twenty consecutive epochs of non-wake) to lights on.

Time frame:
Night 1 and end of Week 4
Reported as:
Least squares mean · minutes
LS Mean Wake After Persistent Sleep Onset (WASO) During Periods 1 and 2
minutesPlaceboSuvorexant 10 mgSuvorexant 20 mgSuvorexant 40 mgSuvorexant 80 mg
Night 1 (n=249, 62, 61, 59, 61)72.4 ± 3.3851.3 ± 6.4047.7 ± 6.4138.5 ± 6.4735.6 ± 6.46
Week 4 (n=232, 59, 57, 57, 55)76.7 ± 3.6055.2 ± 6.6548.6 ± 6.7543.4 ± 6.7747.8 ± 6.84
Statistical analysis
  • Placebo vs Suvorexant 80 mg · Mixed Models Analysis · p = <0.001 · Ls mean difference: night 1: -36.8 · 95% CI -49.4 to -24.3
  • Placebo vs Suvorexant 80 mg · Mixed Models Analysis · p = <0.001 · Ls mean difference: week 4: -28.9 · 95% CI -42.1 to -15.7
  • Placebo vs Suvorexant 40 mg · Mixed Models Analysis · p = <0.001 · Ls mean difference: night 1: -33.9 · 95% CI -46.4 to -21.5
  • Placebo vs Suvorexant 40 mg · Mixed Models Analysis · p = <0.001 · Ls mean difference: week 4: -33.2 · 95% CI -46.3 to -20.2
  • Placebo vs Suvorexant 20 mg · Mixed Models Analysis · p = <0.001 · Ls mean difference: night 1: -24.7 · 95% CI -37.1 to -12.3
  • Placebo vs Suvorexant 20 mg · Mixed Models Analysis · p = <0.001 · Ls mean difference: week 4: -28.1 · 95% CI -41.0 to -15.1
  • Placebo vs Suvorexant 10 mg · Mixed Models Analysis · p = <0.001 · Ls mean difference: night 1: -21.2 · 95% CI -33.5 to -8.8
  • Placebo vs Suvorexant 10 mg · Mixed Models Analysis · p = 0.001 · Ls mean difference: week 4: -21.4 · 95% CI -34.2 to -8.7
SecondaryLS Mean Latency to the Onset of Persistent Sleep (LPS) During Periods 1 and 2

LPS is defined as the duration of time measured in minutes from lights off to persistent sleep onset.

Time frame:
Night 1 and end of Week 4
Reported as:
Least squares mean · minutes
LS Mean Latency to the Onset of Persistent Sleep (LPS) During Periods 1 and 2
minutesPlaceboSuvorexant 10 mgSuvorexant 20 mgSuvorexant 40 mgSuvorexant 80 mg
Night 1 (n=249, 62, 61, 59, 61)49.8 ± 2.9146.4 ± 6.0840.4 ± 6.0826.7 ± 6.1324.4 ± 6.13
Week 4 (n=232, 59, 57, 57, 55)41.7 ± 2.7539.4 ± 5.1219.4 ± 5.1737.9 ± 5.1932.2 ± 5.28
Statistical analysis
  • Placebo vs Suvorexant 80 mg · Mixed Models Analysis · p = <0.001 · Ls mean difference: night 1: -25.4 · 95% CI -37.7 to -13.1
  • Placebo vs Suvorexant 80 mg · Mixed Models Analysis · p = 0.068 · Ls mean difference: week 4: -9.5 · 95% CI -19.7 to 0.7
  • Placebo vs Suvorexant 40 mg · Mixed Models Analysis · p = <0.001 · Ls mean difference: night 1: -23.1 · 95% CI -35.3 to -10.9
  • Placebo vs Suvorexant 40 mg · Mixed Models Analysis · p = 0.459 · Ls mean difference: week 4: -3.8 · 95% CI -13.8 to 6.3
  • Placebo vs Suvorexant 20 mg · Mixed Models Analysis · p = 0.130 · Ls mean difference: night 1: -9.4 · 95% CI -21.5 to 2.8
  • Placebo vs Suvorexant 20 mg · Mixed Models Analysis · p = <0.001 · Ls mean difference: week 4: -22.3 · 95% CI -32.3 to -12.3
  • Placebo vs Suvorexant 10 mg · Mixed Models Analysis · p = 0.577 · Ls mean difference: night 1: -3.4 · 95% CI -15.6 to 8.7
  • Placebo vs Suvorexant 10 mg · Mixed Models Analysis · p = 0.644 · Ls mean difference: week 4: -2.3 · 95% CI -12.2 to 7.5
Post-hocLS Mean Latency to the Onset of Persistent Sleep (LPS) During Period 1 (To Exclude Carryover Effect)

LPS is defined as the duration of time measured in minutes from lights off to persistent sleep onset. In order to evaluate the efficacy of suvorexant on LPS excluding the influence of a carryover effect from Period 1 to Period 2, an ad hoc analysis of LPS restricted to Period 1 data was also performed.

Time frame:
Night 1 (Period 1 only) and end of Week 4 (Period 1 only)
Reported as:
Least squares mean · minutes
LS Mean Latency to the Onset of Persistent Sleep (LPS) During Period 1 (To Exclude Carryover Effect)
minutesPlaceboSuvorexant 10 mgSuvorexant 20 mgSuvorexant 40 mgSuvorexant 80 mg
Night 1 (n=127, 31, 33, 32, 31)57.0 ± 4.2938.0 ± 7.6739.6 ± 7.4126.0 ± 7.5634.7 ± 7.67
Week 4 (n=116, 29, 31, 30, 28)52.4 ± 4.4332.2 ± 7.9727.7 ± 7.7136.6 ± 7.8832.8 ± 8.07
Statistical analysis
  • Placebo vs Suvorexant 80 mg · Mixed Models Analysis · p = 0.007 · Ls mean difference: night 1: -22.3 · 95% CI -38.3 to -6.2
  • Placebo vs Suvorexant 80 mg · Mixed Models Analysis · p = 0.024 · Ls mean difference: week 4: -19.6 · 95% CI -36.6 to -2.6
  • Placebo vs Suvorexant 40 mg · Mixed Models Analysis · p = <0.001 · Ls mean difference: night 1: -31.0 · 95% CI -46.9 to -15.2
  • Placebo vs Suvorexant 40 mg · Mixed Models Analysis · p = 0.063 · Ls mean difference: week 4: -15.7 · 95% CI -32.3 to 0.8
  • Placebo vs Suvorexant 20 mg · Mixed Models Analysis · p = 0.030 · Ls mean difference: night 1: -17.4 · 95% CI -33.1 to -1.7
  • Placebo vs Suvorexant 20 mg · Mixed Models Analysis · p = 0.003 · Ls mean difference: week 4: -24.6 · 95% CI -41.0 to -8.3
  • Placebo vs Suvorexant 10 mg · Mixed Models Analysis · p = 0.020 · Ls mean difference: night 1: -19.1 · 95% CI -35.1 to -3.0
  • Placebo vs Suvorexant 10 mg · Mixed Models Analysis · p = 0.019 · Ls mean difference: week 4: -20.2 · 95% CI -37.0 to -3.4

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo—0/249 (0%)9/249 (3.6%)
Suvorexant 10 mg—0/62 (0%)1/62 (1.6%)
Suvorexant 20 mg—0/61 (0%)4/61 (6.6%)
Suvorexant 40 mg—0/59 (0%)11/59 (18.6%)
Suvorexant 80 mg—0/61 (0%)11/61 (18%)
Most frequent other events
Most frequent other events
EventPlaceboSuvorexant 10 mgSuvorexant 20 mgSuvorexant 40 mgSuvorexant 80 mg
SomnolenceNervous system disorders1/2491/623/617/597/61
Urinary tract infectionInfections and infestations2/2490/620/613/592/61
HeadacheNervous system disorders6/2490/621/613/593/61

Baseline characteristics

Age, Continuous
Age, Continuous(years)All Treated Participants
Mean44.4 ± 11.5
Sex: Female, Male
Sex: Female, Male(Participants)All Treated Participants
Female148
Male106
08

Study locations

No study locations are listed for this record.

09

References and documents

Publications

  • Herring WJ, Snyder E, Budd K, Hutzelmann J, Snavely D, Liu K, Lines C, Roth T, Michelson D. Orexin receptor antagonism for treatment of insomnia: a randomized clinical trial of suvorexant. Neurology. 2012 Dec 4;79(23):2265-74. doi: 10.1212/WNL.0b013e31827688ee. Epub 2012 Nov 28. PubMed 23197752 ↗

Individual participant data

Plan to share: Yes — https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Nov 6, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00792298
Lead sponsor
Merck Sharp & Dohme LLC
Responsible party
Sponsor
First posted
Nov 17, 2008
Start date
Nov 5, 2008
Primary completion
Dec 26, 2009
Completion
Dec 26, 2009
Results posted
Nov 14, 2014
Last update
Nov 6, 2018

Study contacts

Medical Monitor
study director · Merck Sharp & Dohme LLC
View the source record on ClinicalTrials.gov ↗

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