Primary Insomnia
Conditions
Brief 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.
Interventions
DRUGSuvorexant
oral tablet taken before bedtime
Dose-matched placebo to suvorexant taken before bedtime (oral tablet)
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
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
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| LS Mean Sleep Efficiency (SE) During Periods 1 and 2 | Night 1 and end of Week 4 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| LS Mean Wake After Persistent Sleep Onset (WASO) During Periods 1 and 2 | Night 1 and end of Week 4 | 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. |
| LS Mean Latency to the Onset of Persistent Sleep (LPS) During Periods 1 and 2 | Night 1 and end of Week 4 | LPS is defined as the duration of time measured in minutes from lights off to persistent sleep onset. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Treated Participants All randomized participants who received at least one dose of study treatment. | 254 |
| Total | 254 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Treatment Period 1 | Adverse Event | 0 | 1 | 0 | 1 | 0 | 1 | 1 | 0 |
| Treatment Period 1 | Lack of Efficacy | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Treatment Period 1 | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Treatment Period 1 | Physician Decision | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 |
| Treatment Period 1 | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Treatment Period 1 | Withdrawal by Subject | 1 | 0 | 1 | 2 | 0 | 2 | 1 | 0 |
| Treatment Period 2 | Lack of Efficacy | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Treatment Period 2 | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Treatment Period 2 | Pregnancy | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Treatment Period 2 | Withdrawal by Subject | 1 | 1 | 0 | 2 | 1 | 0 | 0 | 2 |
| Washout | Adverse Event | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Washout | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | All Treated Participants |
|---|---|
| Age, Continuous | 44.4 years STANDARD_DEVIATION 11.5 |
| Sex: Female, Male Female | 148 Participants |
| Sex: Female, Male Male | 106 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 9 / 249 | 1 / 62 | 4 / 61 | 11 / 59 | 11 / 61 |
| serious Total, serious adverse events | 0 / 249 | 0 / 62 | 0 / 61 | 0 / 59 | 0 / 61 |
Outcome results
Primary
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
Population: Full Analysis Set (FAS) population; subset of all randomized participants who received at least one dose of study medication and had any post-randomization efficacy assessment data. The FAS population may have varied across endpoints due to the degree of missing data for each endpoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | LS Mean Sleep Efficiency (SE) During Periods 1 and 2 | Night 1 (n=249, 62, 61, 59, 61) | 75.8 percent of time in bed | Standard Error 0.93 |
| Placebo | LS Mean Sleep Efficiency (SE) During Periods 1 and 2 | Week 4 (n=232, 59, 57, 57, 55) | 76.6 percent of time in bed | Standard Error 0.94 |
| Suvorexant 10 mg | LS Mean Sleep Efficiency (SE) During Periods 1 and 2 | Night 1 (n=249, 62, 61, 59, 61) | 81.0 percent of time in bed | Standard Error 1.75 |
| Suvorexant 10 mg | LS Mean Sleep Efficiency (SE) During Periods 1 and 2 | Week 4 (n=232, 59, 57, 57, 55) | 81.3 percent of time in bed | Standard Error 1.66 |
| Suvorexant 20 mg | LS Mean Sleep Efficiency (SE) During Periods 1 and 2 | Night 1 (n=249, 62, 61, 59, 61) | 83.4 percent of time in bed | Standard Error 1.75 |
| Suvorexant 20 mg | LS Mean Sleep Efficiency (SE) During Periods 1 and 2 | Week 4 (n=232, 59, 57, 57, 55) | 87.0 percent of time in bed | Standard Error 1.68 |
| Suvorexant 40 mg | LS Mean Sleep Efficiency (SE) During Periods 1 and 2 | Week 4 (n=232, 59, 57, 57, 55) | 84.4 percent of time in bed | Standard Error 1.68 |
| Suvorexant 40 mg | LS Mean Sleep Efficiency (SE) During Periods 1 and 2 | Night 1 (n=249, 62, 61, 59, 61) | 86.6 percent of time in bed | Standard Error 1.77 |
| Suvorexant 80 mg | LS Mean Sleep Efficiency (SE) During Periods 1 and 2 | Night 1 (n=249, 62, 61, 59, 61) | 88.7 percent of time in bed | Standard Error 1.77 |
| Suvorexant 80 mg | LS Mean Sleep Efficiency (SE) During Periods 1 and 2 | Week 4 (n=232, 59, 57, 57, 55) | 84.2 percent of time in bed | Standard Error 1.7 |
Comparison: A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.p-value: <0.00195% CI: [9.5, 16.3]Mixed Models Analysis
Comparison: A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.p-value: <0.00195% CI: [4.4, 10.9]Mixed Models Analysis
Comparison: A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.p-value: <0.00195% CI: [7.4, 14.2]Mixed Models Analysis
Comparison: A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.p-value: <0.00195% CI: [4.6, 10.9]Mixed Models Analysis
Comparison: A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.p-value: <0.00195% CI: [4.2, 11]Mixed Models Analysis
Comparison: A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.p-value: <0.00195% CI: [7.2, 13.6]Mixed Models Analysis
Comparison: A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.p-value: 0.00295% CI: [1.9, 8.6]Mixed Models Analysis
Comparison: A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.p-value: 0.00395% CI: [1.6, 7.8]Mixed Models Analysis
Secondary
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
Population: Full Analysis Set (FAS) population; subset of all randomized participants who received at least one dose of study medication and had any post-randomization efficacy assessment data. The FAS population may have varied across endpoints due to the degree of missing data for each endpoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | LS Mean Latency to the Onset of Persistent Sleep (LPS) During Periods 1 and 2 | Week 4 (n=232, 59, 57, 57, 55) | 41.7 minutes | Standard Error 2.75 |
| Placebo | LS Mean Latency to the Onset of Persistent Sleep (LPS) During Periods 1 and 2 | Night 1 (n=249, 62, 61, 59, 61) | 49.8 minutes | Standard Error 2.91 |
| Suvorexant 10 mg | LS Mean Latency to the Onset of Persistent Sleep (LPS) During Periods 1 and 2 | Night 1 (n=249, 62, 61, 59, 61) | 46.4 minutes | Standard Error 6.08 |
| Suvorexant 10 mg | LS Mean Latency to the Onset of Persistent Sleep (LPS) During Periods 1 and 2 | Week 4 (n=232, 59, 57, 57, 55) | 39.4 minutes | Standard Error 5.12 |
| Suvorexant 20 mg | LS Mean Latency to the Onset of Persistent Sleep (LPS) During Periods 1 and 2 | Week 4 (n=232, 59, 57, 57, 55) | 19.4 minutes | Standard Error 5.17 |
| Suvorexant 20 mg | LS Mean Latency to the Onset of Persistent Sleep (LPS) During Periods 1 and 2 | Night 1 (n=249, 62, 61, 59, 61) | 40.4 minutes | Standard Error 6.08 |
| Suvorexant 40 mg | LS Mean Latency to the Onset of Persistent Sleep (LPS) During Periods 1 and 2 | Night 1 (n=249, 62, 61, 59, 61) | 26.7 minutes | Standard Error 6.13 |
| Suvorexant 40 mg | LS Mean Latency to the Onset of Persistent Sleep (LPS) During Periods 1 and 2 | Week 4 (n=232, 59, 57, 57, 55) | 37.9 minutes | Standard Error 5.19 |
| Suvorexant 80 mg | LS Mean Latency to the Onset of Persistent Sleep (LPS) During Periods 1 and 2 | Night 1 (n=249, 62, 61, 59, 61) | 24.4 minutes | Standard Error 6.13 |
| Suvorexant 80 mg | LS Mean Latency to the Onset of Persistent Sleep (LPS) During Periods 1 and 2 | Week 4 (n=232, 59, 57, 57, 55) | 32.2 minutes | Standard Error 5.28 |
Comparison: A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.p-value: <0.00195% CI: [-37.7, -13.1]Mixed Models Analysis
Comparison: A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.p-value: 0.06895% CI: [-19.7, 0.7]Mixed Models Analysis
Comparison: A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.p-value: <0.00195% CI: [-35.3, -10.9]Mixed Models Analysis
Comparison: A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.p-value: 0.45995% CI: [-13.8, 6.3]Mixed Models Analysis
Comparison: A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.p-value: 0.1395% CI: [-21.5, 2.8]Mixed Models Analysis
Comparison: A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.p-value: <0.00195% CI: [-32.3, -12.3]Mixed Models Analysis
Comparison: A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.p-value: 0.57795% CI: [-15.6, 8.7]Mixed Models Analysis
Comparison: A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.p-value: 0.64495% CI: [-12.2, 7.5]Mixed Models Analysis
Secondary
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
Population: Full Analysis Set (FAS) population; subset of all randomized participants who received at least one dose of study medication and had any post-randomization efficacy assessment data. The FAS population may have varied across endpoints due to the degree of missing data for each endpoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | LS Mean Wake After Persistent Sleep Onset (WASO) During Periods 1 and 2 | Night 1 (n=249, 62, 61, 59, 61) | 72.4 minutes | Standard Error 3.38 |
| Placebo | LS Mean Wake After Persistent Sleep Onset (WASO) During Periods 1 and 2 | Week 4 (n=232, 59, 57, 57, 55) | 76.7 minutes | Standard Error 3.6 |
| Suvorexant 10 mg | LS Mean Wake After Persistent Sleep Onset (WASO) During Periods 1 and 2 | Night 1 (n=249, 62, 61, 59, 61) | 51.3 minutes | Standard Error 6.4 |
| Suvorexant 10 mg | LS Mean Wake After Persistent Sleep Onset (WASO) During Periods 1 and 2 | Week 4 (n=232, 59, 57, 57, 55) | 55.2 minutes | Standard Error 6.65 |
| Suvorexant 20 mg | LS Mean Wake After Persistent Sleep Onset (WASO) During Periods 1 and 2 | Night 1 (n=249, 62, 61, 59, 61) | 47.7 minutes | Standard Error 6.41 |
| Suvorexant 20 mg | LS Mean Wake After Persistent Sleep Onset (WASO) During Periods 1 and 2 | Week 4 (n=232, 59, 57, 57, 55) | 48.6 minutes | Standard Error 6.75 |
| Suvorexant 40 mg | LS Mean Wake After Persistent Sleep Onset (WASO) During Periods 1 and 2 | Week 4 (n=232, 59, 57, 57, 55) | 43.4 minutes | Standard Error 6.77 |
| Suvorexant 40 mg | LS Mean Wake After Persistent Sleep Onset (WASO) During Periods 1 and 2 | Night 1 (n=249, 62, 61, 59, 61) | 38.5 minutes | Standard Error 6.47 |
| Suvorexant 80 mg | LS Mean Wake After Persistent Sleep Onset (WASO) During Periods 1 and 2 | Night 1 (n=249, 62, 61, 59, 61) | 35.6 minutes | Standard Error 6.46 |
| Suvorexant 80 mg | LS Mean Wake After Persistent Sleep Onset (WASO) During Periods 1 and 2 | Week 4 (n=232, 59, 57, 57, 55) | 47.8 minutes | Standard Error 6.84 |
Comparison: A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.p-value: <0.00195% CI: [-49.4, -24.3]Mixed Models Analysis
Comparison: A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.p-value: <0.00195% CI: [-42.1, -15.7]Mixed Models Analysis
Comparison: A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.p-value: <0.00195% CI: [-46.4, -21.5]Mixed Models Analysis
Comparison: A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.p-value: <0.00195% CI: [-46.3, -20.2]Mixed Models Analysis
Comparison: A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.p-value: <0.00195% CI: [-37.1, -12.3]Mixed Models Analysis
Comparison: A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.p-value: <0.00195% CI: [-41, -15.1]Mixed Models Analysis
Comparison: A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.p-value: <0.00195% CI: [-33.5, -8.8]Mixed Models Analysis
Comparison: A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.p-value: 0.00195% CI: [-34.2, -8.7]Mixed Models Analysis
Post Hoc
LS 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)
Population: Full Analysis Set (FAS) population; subset of all randomized participants who received at least one dose of study medication and had any post-randomization efficacy assessment data. The FAS population may have varied across endpoints due to the degree of missing data for each endpoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | LS Mean Latency to the Onset of Persistent Sleep (LPS) During Period 1 (To Exclude Carryover Effect) | Night 1 (n=127, 31, 33, 32, 31) | 57.0 minutes | Standard Error 4.29 |
| Placebo | LS Mean Latency to the Onset of Persistent Sleep (LPS) During Period 1 (To Exclude Carryover Effect) | Week 4 (n=116, 29, 31, 30, 28) | 52.4 minutes | Standard Error 4.43 |
| Suvorexant 10 mg | LS Mean Latency to the Onset of Persistent Sleep (LPS) During Period 1 (To Exclude Carryover Effect) | Night 1 (n=127, 31, 33, 32, 31) | 38.0 minutes | Standard Error 7.67 |
| Suvorexant 10 mg | LS Mean Latency to the Onset of Persistent Sleep (LPS) During Period 1 (To Exclude Carryover Effect) | Week 4 (n=116, 29, 31, 30, 28) | 32.2 minutes | Standard Error 7.97 |
| Suvorexant 20 mg | LS Mean Latency to the Onset of Persistent Sleep (LPS) During Period 1 (To Exclude Carryover Effect) | Night 1 (n=127, 31, 33, 32, 31) | 39.6 minutes | Standard Error 7.41 |
| Suvorexant 20 mg | LS Mean Latency to the Onset of Persistent Sleep (LPS) During Period 1 (To Exclude Carryover Effect) | Week 4 (n=116, 29, 31, 30, 28) | 27.7 minutes | Standard Error 7.71 |
| Suvorexant 40 mg | LS Mean Latency to the Onset of Persistent Sleep (LPS) During Period 1 (To Exclude Carryover Effect) | Week 4 (n=116, 29, 31, 30, 28) | 36.6 minutes | Standard Error 7.88 |
| Suvorexant 40 mg | LS Mean Latency to the Onset of Persistent Sleep (LPS) During Period 1 (To Exclude Carryover Effect) | Night 1 (n=127, 31, 33, 32, 31) | 26.0 minutes | Standard Error 7.56 |
| Suvorexant 80 mg | LS Mean Latency to the Onset of Persistent Sleep (LPS) During Period 1 (To Exclude Carryover Effect) | Night 1 (n=127, 31, 33, 32, 31) | 34.7 minutes | Standard Error 7.67 |
| Suvorexant 80 mg | LS Mean Latency to the Onset of Persistent Sleep (LPS) During Period 1 (To Exclude Carryover Effect) | Week 4 (n=116, 29, 31, 30, 28) | 32.8 minutes | Standard Error 8.07 |
Comparison: A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.p-value: 0.00795% CI: [-38.3, -6.2]Mixed Models Analysis
Comparison: A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.p-value: 0.02495% CI: [-36.6, -2.6]Mixed Models Analysis
Comparison: A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.p-value: <0.00195% CI: [-46.9, -15.2]Mixed Models Analysis
Comparison: A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.p-value: 0.06395% CI: [-32.3, 0.8]Mixed Models Analysis
Comparison: A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.p-value: 0.0395% CI: [-33.1, -1.7]Mixed Models Analysis
Comparison: A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.p-value: 0.00395% CI: [-41, -8.3]Mixed Models Analysis
Comparison: A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.p-value: 0.0295% CI: [-35.1, -3]Mixed Models Analysis
Comparison: A fixed sequential testing procedure assessed statistical significance, beginning with the highest dose. The comparison of suvorexant vs placebo had to be significant at α=0.05 at both Night 1 and Week 4 in order to assess statistical significance of the comparison of suvorexant vs placebo for the next highest dose. If a non-significant result was observed at either time point, the differences between suvorexant and placebo for SE was considered nonsignificant for this and all lower doses.p-value: 0.01995% CI: [-37, -3.4]Mixed Models Analysis