Trial Outcomes & Findings for Phase IIB 2-Period Crossover Polysomnography Study in Participants With Primary Insomnia (MK-4305-006) (NCT NCT00792298)

Last Updated: 2018-11-06

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

254 participants

Primary outcome timeframe

Night 1 and end of Week 4

Results posted on

2018-11-06

Participant Flow

Participant milestones

Participant milestones
Measure	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.	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.	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.	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.	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.	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.	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.	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.
Treatment Period 1 STARTED	31	32	33	32	32	32	31	31
Treatment Period 1 COMPLETED	30	31	31	28	32	29	27	30
Treatment Period 1 NOT COMPLETED	1	1	2	4	0	3	4	1
Washout STARTED	30	31	32	28	32	29	29	30
Washout COMPLETED	30	31	31	28	32	27	29	30
Washout NOT COMPLETED	0	0	1	0	0	2	0	0
Treatment Period 2 STARTED	30	31	31	28	32	27	29	30
Treatment Period 2 COMPLETED	29	30	30	26	30	27	28	28
Treatment Period 2 NOT COMPLETED	1	1	1	2	2	0	1	2

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.	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.	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.	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.	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.	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.	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.
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 Withdrawal by Subject	1	0	1	2	0	2	1	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
Washout Adverse Event	0	0	0	0	0	1	0	0
Washout Withdrawal by Subject	0	0	1	0	0	1	0	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

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Treated Participants n=254 Participants All randomized participants who received at least one dose of study treatment.
Age, Continuous	44.4 years STANDARD_DEVIATION 11.5 • n=93 Participants
Sex: Female, Male Female	148 Participants n=93 Participants
Sex: Female, Male Male	106 Participants n=93 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=249 Participants Participants received dose-matched placebo to suvorexant daily prior to bedtime over a 4-week treatment period.	Suvorexant 10 mg n=62 Participants Participants received 10 mg suvorexant daily prior to bedtime over a 4-week treatment period.	Suvorexant 20 mg n=61 Participants Participants received 20 mg suvorexant daily prior to bedtime over a 4-week treatment period.	Suvorexant 40 mg n=59 Participants Participants received 40 mg suvorexant daily prior to bedtime over a 4-week treatment period.	Suvorexant 80 mg n=61 Participants Participants received 80 mg suvorexant daily prior to bedtime over a 4-week treatment period.
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 • Interval 74.0 to 77.6	81.0 percent of time in bed Standard Error 1.75 • Interval 77.6 to 84.5	83.4 percent of time in bed Standard Error 1.75 • Interval 79.9 to 86.8	86.6 percent of time in bed Standard Error 1.77 • Interval 83.1 to 90.1	88.7 percent of time in bed Standard Error 1.77 • Interval 85.2 to 92.2
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 • Interval 74.8 to 78.5	81.3 percent of time in bed Standard Error 1.66 • Interval 78.0 to 84.6	87.0 percent of time in bed Standard Error 1.68 • Interval 83.7 to 90.3	84.4 percent of time in bed Standard Error 1.68 • Interval 81.1 to 87.7	84.2 percent of time in bed Standard Error 1.70 • Interval 80.9 to 87.6

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=249 Participants Participants received dose-matched placebo to suvorexant daily prior to bedtime over a 4-week treatment period.	Suvorexant 10 mg n=62 Participants Participants received 10 mg suvorexant daily prior to bedtime over a 4-week treatment period.	Suvorexant 20 mg n=61 Participants Participants received 20 mg suvorexant daily prior to bedtime over a 4-week treatment period.	Suvorexant 40 mg n=59 Participants Participants received 40 mg suvorexant daily prior to bedtime over a 4-week treatment period.	Suvorexant 80 mg n=61 Participants Participants received 80 mg suvorexant daily prior to bedtime over a 4-week treatment period.
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 • Interval 65.8 to 79.1	51.3 minutes Standard Error 6.40	47.7 minutes Standard Error 6.41	38.5 minutes Standard Error 6.47	35.6 minutes Standard Error 6.46
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 3.60 • Interval 69.6 to 83.7	55.2 minutes Standard Error 6.65	48.6 minutes Standard Error 6.75	43.4 minutes Standard Error 6.77	47.8 minutes Standard Error 6.84

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=249 Participants Participants received dose-matched placebo to suvorexant daily prior to bedtime over a 4-week treatment period.	Suvorexant 10 mg n=62 Participants Participants received 10 mg suvorexant daily prior to bedtime over a 4-week treatment period.	Suvorexant 20 mg n=61 Participants Participants received 20 mg suvorexant daily prior to bedtime over a 4-week treatment period.	Suvorexant 40 mg n=59 Participants Participants received 40 mg suvorexant daily prior to bedtime over a 4-week treatment period.	Suvorexant 80 mg n=61 Participants Participants received 80 mg suvorexant daily prior to bedtime over a 4-week treatment period.
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	46.4 minutes Standard Error 6.08	40.4 minutes Standard Error 6.08	26.7 minutes Standard Error 6.13	24.4 minutes Standard Error 6.13
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	39.4 minutes Standard Error 5.12	19.4 minutes Standard Error 5.17	37.9 minutes Standard Error 5.19	32.2 minutes Standard Error 5.28

POST_HOC outcome

Timeframe: Night 1 (Period 1 only) and end of Week 4 (Period 1 only)

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.