Trial Outcomes & Findings for A Study to Evaluate Next-Dose Transition From Zolpidem to Lemborexant (LEM) for the Treatment of Insomnia (NCT NCT04009577)

Last Updated: 2021-04-12

Results Overview

Transition to LEM was defined as participant who remained on LEM at the end of the 2-week titration period and either 1) entered the extension phase, or 2) chooses to not enter the extension phase for reasons not related to LEM (including, but not limited to, time commitment related to the study, study-related travel expenses or preference to continue insomnia management with another health care provider).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

53 participants

Primary outcome timeframe

Up to 2 Weeks

Results posted on

2021-04-12

Participant Flow

Participants took part in the study at 17 investigative sites in the United States from 15 July 2019 to 26 June 2020. This study included 2 parts: Core study (Pretreatment phase and Treatment Phase) and Extension Phase.

A total of 99 participants were screened, of which 46 were screen failures and 53 participants were enrolled and randomized into the Core study. Out of 53 randomized and treated participants in the Core Study, 43 participants entered Extension Phase and 41 participants received study drug.

Participant milestones

Participant milestones
Measure	Cohort 1A: LEM 5 or LEM 10 (Intermittent ZOL Use) Participants who took zolpidem tartrate (ZOL) at least 3 nights but fewer than 5 nights per week, for the last 2 weeks of the 3-week Screening Period, initially received lemborexant 5 milligram (mg) (LEM5) or 10 mg (LEM10) tablet up titrated (in case previous dose was ineffective), orally, once at night for up to 2 weeks in Titration Period of Core Study and continued to receive LEM5 or LEM10 tablet up titrated (in case previous dose was ineffective), orally, once at night for up to 12 weeks in the Extension Phase.	Cohort 1B: LEM 5 or LEM 10 (Mixed ZOL Use) Participants who met both criteria for intermittent and frequent ZOL use for 1 week each of the last 2 weeks of the 3-week Screening Period, initially received LEM5 or LEM10 tablet up titrated (in case previous dose was ineffective), orally, once at night for up to 2 weeks in Titration Period of Core Study and continued to receive LEM5 or LEM10 tablet up titrated (in case previous dose was ineffective), orally, once at night for up to 12 weeks in the Extension Phase.	Cohort 2A: LEM 5 or LEM 10 (Frequent ZOL Use) Participants who took ZOL at least 5 nights per week, for the last 2 weeks of the 3-week Screening Period, initially received LEM5 or LEM10 tablet up titrated (in case previous dose was ineffective), orally, once at night for up to 2 weeks in Titration Period of Core Study and continued to receive LEM5 or LEM10 tablet up titrated (in case previous dose was ineffective), orally, once at night for up to 12 weeks in the Extension Phase.	Cohort 2B: LEM 10 or LEM 5 (Frequent ZOL Use) Participants who took ZOL at least 5 nights per week, for the last 2 weeks of the 3-week Screening Period, initially received LEM10 or LEM5 tablet down titrated (due to tolerability), orally, once at night for up to 2 weeks in Titration Period of Core Study and continued to receive LEM10 or LEM5 tablet down titrated (due to tolerability), orally, once at night for up to 12 weeks in the Extension Phase.
Core Study STARTED	7	3	21	22
Core Study LEM5	7	3	21	5
Core Study LEM10	3	2	10	22
Core Study COMPLETED	6	3	17	17
Core Study NOT COMPLETED	1	0	4	5
Extension Phase STARTED	6	3	17	17
Extension Phase Treated	6	3	15	17
Extension Phase LEM5	6	3	15	8
Extension Phase LEM10	5	3	12	17
Extension Phase COMPLETED	6	3	13	16
Extension Phase NOT COMPLETED	0	0	4	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1A: LEM 5 or LEM 10 (Intermittent ZOL Use) Participants who took zolpidem tartrate (ZOL) at least 3 nights but fewer than 5 nights per week, for the last 2 weeks of the 3-week Screening Period, initially received lemborexant 5 milligram (mg) (LEM5) or 10 mg (LEM10) tablet up titrated (in case previous dose was ineffective), orally, once at night for up to 2 weeks in Titration Period of Core Study and continued to receive LEM5 or LEM10 tablet up titrated (in case previous dose was ineffective), orally, once at night for up to 12 weeks in the Extension Phase.	Cohort 2A: LEM 5 or LEM 10 (Frequent ZOL Use) Participants who took ZOL at least 5 nights per week, for the last 2 weeks of the 3-week Screening Period, initially received LEM5 or LEM10 tablet up titrated (in case previous dose was ineffective), orally, once at night for up to 2 weeks in Titration Period of Core Study and continued to receive LEM5 or LEM10 tablet up titrated (in case previous dose was ineffective), orally, once at night for up to 12 weeks in the Extension Phase.	Cohort 2B: LEM 10 or LEM 5 (Frequent ZOL Use) Participants who took ZOL at least 5 nights per week, for the last 2 weeks of the 3-week Screening Period, initially received LEM10 or LEM5 tablet down titrated (due to tolerability), orally, once at night for up to 2 weeks in Titration Period of Core Study and continued to receive LEM10 or LEM5 tablet down titrated (due to tolerability), orally, once at night for up to 12 weeks in the Extension Phase.
Core Study Adverse Event	1	2	4
Core Study Withdrawal by Subject	0	2	0
Core Study Other	0	0	1
Extension Phase Adverse Event	0	0	1
Extension Phase Inadequate therapeutic effect	0	1	0
Extension Phase Withdrawal by Subject	0	1	0
Extension Phase Not Treated	0	2	0

Baseline Characteristics

A Study to Evaluate Next-Dose Transition From Zolpidem to Lemborexant (LEM) for the Treatment of Insomnia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1A: LEM 5 or LEM 10 (Intermittent ZOL Use) n=7 Participants Participants who took ZOL at least 3 nights but fewer than 5 nights per week, for the last 2 weeks of the 3-week Screening Period, initially received LEM5 or LEM10 tablet up titrated (in case previous dose was ineffective), orally, once at night for up to 2 weeks in Titration Period of Core Study and continued to receive LEM5 or LEM10 tablet up titrated (in case previous dose was ineffective), orally, once at night for up to 12 weeks in the Extension Phase.	Cohort 1B: LEM 5 or LEM 10 (Mixed ZOL Use) n=3 Participants Participants who met both criteria for intermittent and frequent ZOL use for 1 week each of the last 2 weeks of the 3-week Screening Period, initially received LEM5 or LEM10 tablet up titrated (in case previous dose was ineffective), orally, once at night for up to 2 weeks in Titration Period of Core Study and continued to receive LEM5 or LEM10 tablet up titrated (in case previous dose was ineffective), orally, once at night for up to 12 weeks in the Extension Phase.	Cohort 2A: LEM 5 or LEM 10 (Frequent ZOL Use) n=21 Participants Participants who took ZOL at least 5 nights per week, for the last 2 weeks of the 3-week Screening Period, initially received LEM5 or LEM10 tablet up titrated (in case previous dose was ineffective), orally, once at night for up to 2 weeks in Titration Period of Core Study and continued to receive LEM5 or LEM10 tablet up titrated (in case previous dose was ineffective), orally, once at night for up to 12 weeks in the Extension Phase.	Cohort 2B: LEM 10 or LEM 5 (Frequent ZOL Use) n=22 Participants Participants who took ZOL at least 5 nights per week, for the last 2 weeks of the 3-week Screening Period, initially received LEM10 or LEM5 tablet down titrated (due to tolerability), orally, once at night for up to 2 weeks in Titration Period of Core Study and continued to receive LEM10 or LEM5 tablet down titrated (due to tolerability), orally, once at night for up to 12 weeks in the Extension Phase.	Total n=53 Participants Total of all reporting groups
Age, Continuous	63.1 years STANDARD_DEVIATION 6.12 • n=5 Participants	60.0 years STANDARD_DEVIATION 8.72 • n=7 Participants	52.7 years STANDARD_DEVIATION 13.57 • n=5 Participants	63.5 years STANDARD_DEVIATION 10.44 • n=4 Participants	59.0 years STANDARD_DEVIATION 12.21 • n=21 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	3 Participants n=7 Participants	14 Participants n=5 Participants	14 Participants n=4 Participants	35 Participants n=21 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	0 Participants n=7 Participants	7 Participants n=5 Participants	8 Participants n=4 Participants	18 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants	5 Participants n=4 Participants	13 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants	2 Participants n=7 Participants	15 Participants n=5 Participants	17 Participants n=4 Participants	40 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants	3 Participants n=4 Participants	10 Participants n=21 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants	2 Participants n=7 Participants	15 Participants n=5 Participants	18 Participants n=4 Participants	41 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants

PRIMARY outcome

Timeframe: Up to 2 Weeks

Population: The FAS included participants who received at least 1 dose of lemborexant.

Outcome measures

Outcome measures
Measure	Overall Cohort n=53 Participants Participants who took ZOL at least 3 but fewer than 5 nights per week, for the last 2 weeks of the 3-week Screening Period or who met both criteria for intermittent and frequent ZOL use for 1 week each of the last 2 weeks of the 3-week Screening or who took ZOL at least 5 nights per week, for the last 2 weeks of the 3-week Screening Period, received LEM5 or LEM10 tablet (as per titration schedule), orally once at night for up to 2 weeks in Titration Period of Core Study. Eligible participants who completed 2 weeks in Titration Period of Core Study continued to receive LEM5 or LEM10 (as per titration schedule) tablet, orally, once at night for up to 12 weeks in the Extension Phase.	Cohort 1B: LEM 5 or LEM 10 (Mixed ZOL Use) Participants who met both criteria for intermittent and frequent ZOL use for 1 week each of the last 2 weeks of the 3-week Screening Period, initially received LEM5 or LEM10 tablet up titrated (in case previous dose was ineffective), orally, once at night for up to 2 weeks in Titration Period of Core Study and continued to receive LEM5 or LEM10 tablet up titrated (in case previous dose was ineffective), orally, once at night for up to 12 weeks in the Extension Phase.	Cohort 2A: LEM 5 or LEM 10 (Frequent ZOL Use) Participants who took ZOL at least 5 nights per week, for the last 2 weeks of the 3-week Screening Period, initially received LEM5 or LEM10 tablet up titrated (in case previous dose was ineffective), orally, once at night for up to 2 weeks in Titration Period of Core Study and continued to receive LEM5 or LEM10 tablet up titrated (in case previous dose was ineffective), orally, once at night for up to 12 weeks in the Extension Phase.	Cohort 2B: LEM 10 or LEM 5 (Frequent ZOL Use) Participants who took ZOL at least 5 nights per week, for the last 2 weeks of the 3-week Screening Period, initially received LEM10 or LEM5 tablet down titrated (due to tolerability), orally, once at night for up to 2 weeks in Titration Period of Core Study and continued to receive LEM10 or LEM5 tablet down titrated (due to tolerability), orally, once at night for up to 12 weeks in the Extension Phase.	Overall Cohort Participants who took ZOL at least 3 but fewer than 5 nights per week, for the last 2 weeks of the 3-week Screening Period or who met both criteria for intermittent and frequent ZOL use for 1 week each of the last 2 weeks of the 3-week Screening or who took ZOL at least 5 nights per week, for the last 2 weeks of the 3-week Screening Period, received LEM5 or LEM10 tablet (as per titration schedule), orally once at night for up to 2 weeks in Titration Period of Core Study. Eligible participants who completed 2 weeks in Titration Period of Core Study continued to receive LEM5 or LEM10 (as per titration schedule) tablet, orally, once at night for up to 12 weeks in the Extension Phase.
Percentage of Overall Participants Who Transitioned to LEM at the End of the Titration Period of Core Study	81.1 percentage of participants	—	—	—	—

SECONDARY outcome

Timeframe: Up to 2 Weeks

Population: The FAS included participants who received at least 1 dose of lemborexant.

Outcome measures

Outcome measures
Measure	Overall Cohort n=7 Participants Participants who took ZOL at least 3 but fewer than 5 nights per week, for the last 2 weeks of the 3-week Screening Period or who met both criteria for intermittent and frequent ZOL use for 1 week each of the last 2 weeks of the 3-week Screening or who took ZOL at least 5 nights per week, for the last 2 weeks of the 3-week Screening Period, received LEM5 or LEM10 tablet (as per titration schedule), orally once at night for up to 2 weeks in Titration Period of Core Study. Eligible participants who completed 2 weeks in Titration Period of Core Study continued to receive LEM5 or LEM10 (as per titration schedule) tablet, orally, once at night for up to 12 weeks in the Extension Phase.	Cohort 1B: LEM 5 or LEM 10 (Mixed ZOL Use) n=3 Participants Participants who met both criteria for intermittent and frequent ZOL use for 1 week each of the last 2 weeks of the 3-week Screening Period, initially received LEM5 or LEM10 tablet up titrated (in case previous dose was ineffective), orally, once at night for up to 2 weeks in Titration Period of Core Study and continued to receive LEM5 or LEM10 tablet up titrated (in case previous dose was ineffective), orally, once at night for up to 12 weeks in the Extension Phase.	Cohort 2A: LEM 5 or LEM 10 (Frequent ZOL Use) n=21 Participants Participants who took ZOL at least 5 nights per week, for the last 2 weeks of the 3-week Screening Period, initially received LEM5 or LEM10 tablet up titrated (in case previous dose was ineffective), orally, once at night for up to 2 weeks in Titration Period of Core Study and continued to receive LEM5 or LEM10 tablet up titrated (in case previous dose was ineffective), orally, once at night for up to 12 weeks in the Extension Phase.	Cohort 2B: LEM 10 or LEM 5 (Frequent ZOL Use) n=22 Participants Participants who took ZOL at least 5 nights per week, for the last 2 weeks of the 3-week Screening Period, initially received LEM10 or LEM5 tablet down titrated (due to tolerability), orally, once at night for up to 2 weeks in Titration Period of Core Study and continued to receive LEM10 or LEM5 tablet down titrated (due to tolerability), orally, once at night for up to 12 weeks in the Extension Phase.	Overall Cohort Participants who took ZOL at least 3 but fewer than 5 nights per week, for the last 2 weeks of the 3-week Screening Period or who met both criteria for intermittent and frequent ZOL use for 1 week each of the last 2 weeks of the 3-week Screening or who took ZOL at least 5 nights per week, for the last 2 weeks of the 3-week Screening Period, received LEM5 or LEM10 tablet (as per titration schedule), orally once at night for up to 2 weeks in Titration Period of Core Study. Eligible participants who completed 2 weeks in Titration Period of Core Study continued to receive LEM5 or LEM10 (as per titration schedule) tablet, orally, once at night for up to 12 weeks in the Extension Phase.
Percentage of Participants Who Transitioned to LEM at the End of the 2-Week Titration Period of Core Study Within Each Cohort	85.7 percentage of participants	100 percentage of participants	81.0 percentage of participants	77.3 percentage of participants	—

SECONDARY outcome

Timeframe: Up to 2 Weeks

Population: The safety analysis set was the group of participants who received at least 1 dose of study drug and had at least 1 postdose safety assessment.

This outcome measure was planned for Cohort 1A, 1B and 2A. As there was no dose increase happened in Cohort 2B, this Outcome Measure is not applicable for Cohort 2B.

Outcome measures

Outcome measures
Measure	Overall Cohort n=7 Participants Participants who took ZOL at least 3 but fewer than 5 nights per week, for the last 2 weeks of the 3-week Screening Period or who met both criteria for intermittent and frequent ZOL use for 1 week each of the last 2 weeks of the 3-week Screening or who took ZOL at least 5 nights per week, for the last 2 weeks of the 3-week Screening Period, received LEM5 or LEM10 tablet (as per titration schedule), orally once at night for up to 2 weeks in Titration Period of Core Study. Eligible participants who completed 2 weeks in Titration Period of Core Study continued to receive LEM5 or LEM10 (as per titration schedule) tablet, orally, once at night for up to 12 weeks in the Extension Phase.	Cohort 1B: LEM 5 or LEM 10 (Mixed ZOL Use) n=3 Participants Participants who met both criteria for intermittent and frequent ZOL use for 1 week each of the last 2 weeks of the 3-week Screening Period, initially received LEM5 or LEM10 tablet up titrated (in case previous dose was ineffective), orally, once at night for up to 2 weeks in Titration Period of Core Study and continued to receive LEM5 or LEM10 tablet up titrated (in case previous dose was ineffective), orally, once at night for up to 12 weeks in the Extension Phase.	Cohort 2A: LEM 5 or LEM 10 (Frequent ZOL Use) n=21 Participants Participants who took ZOL at least 5 nights per week, for the last 2 weeks of the 3-week Screening Period, initially received LEM5 or LEM10 tablet up titrated (in case previous dose was ineffective), orally, once at night for up to 2 weeks in Titration Period of Core Study and continued to receive LEM5 or LEM10 tablet up titrated (in case previous dose was ineffective), orally, once at night for up to 12 weeks in the Extension Phase.	Cohort 2B: LEM 10 or LEM 5 (Frequent ZOL Use) n=31 Participants Participants who took ZOL at least 5 nights per week, for the last 2 weeks of the 3-week Screening Period, initially received LEM10 or LEM5 tablet down titrated (due to tolerability), orally, once at night for up to 2 weeks in Titration Period of Core Study and continued to receive LEM10 or LEM5 tablet down titrated (due to tolerability), orally, once at night for up to 12 weeks in the Extension Phase.	Overall Cohort Participants who took ZOL at least 3 but fewer than 5 nights per week, for the last 2 weeks of the 3-week Screening Period or who met both criteria for intermittent and frequent ZOL use for 1 week each of the last 2 weeks of the 3-week Screening or who took ZOL at least 5 nights per week, for the last 2 weeks of the 3-week Screening Period, received LEM5 or LEM10 tablet (as per titration schedule), orally once at night for up to 2 weeks in Titration Period of Core Study. Eligible participants who completed 2 weeks in Titration Period of Core Study continued to receive LEM5 or LEM10 (as per titration schedule) tablet, orally, once at night for up to 12 weeks in the Extension Phase.
Percentage of Participants in the LEM5 Treatment Groups With Dose Increasing to LEM10 at the End of the Titration Period of Core Study by Cohort and Overall	42.9 percentage of participant	66.7 percentage of participant	47.6 percentage of participant	48.4 percentage of participant	—

SECONDARY outcome

Timeframe: Up to 2 Weeks

Population: The FAS included participants who received at least 1 dose of lemborexant.

This outcome measure was planned for Cohort 2B. As dose decrease happened in Cohort 2B only, this Outcome Measure is not applicable for Cohort 1A, 1B and 2A.

Outcome measures

Outcome measures
Measure	Overall Cohort n=22 Participants Participants who took ZOL at least 3 but fewer than 5 nights per week, for the last 2 weeks of the 3-week Screening Period or who met both criteria for intermittent and frequent ZOL use for 1 week each of the last 2 weeks of the 3-week Screening or who took ZOL at least 5 nights per week, for the last 2 weeks of the 3-week Screening Period, received LEM5 or LEM10 tablet (as per titration schedule), orally once at night for up to 2 weeks in Titration Period of Core Study. Eligible participants who completed 2 weeks in Titration Period of Core Study continued to receive LEM5 or LEM10 (as per titration schedule) tablet, orally, once at night for up to 12 weeks in the Extension Phase.	Cohort 1B: LEM 5 or LEM 10 (Mixed ZOL Use) Participants who met both criteria for intermittent and frequent ZOL use for 1 week each of the last 2 weeks of the 3-week Screening Period, initially received LEM5 or LEM10 tablet up titrated (in case previous dose was ineffective), orally, once at night for up to 2 weeks in Titration Period of Core Study and continued to receive LEM5 or LEM10 tablet up titrated (in case previous dose was ineffective), orally, once at night for up to 12 weeks in the Extension Phase.	Cohort 2A: LEM 5 or LEM 10 (Frequent ZOL Use) Participants who took ZOL at least 5 nights per week, for the last 2 weeks of the 3-week Screening Period, initially received LEM5 or LEM10 tablet up titrated (in case previous dose was ineffective), orally, once at night for up to 2 weeks in Titration Period of Core Study and continued to receive LEM5 or LEM10 tablet up titrated (in case previous dose was ineffective), orally, once at night for up to 12 weeks in the Extension Phase.	Cohort 2B: LEM 10 or LEM 5 (Frequent ZOL Use) Participants who took ZOL at least 5 nights per week, for the last 2 weeks of the 3-week Screening Period, initially received LEM10 or LEM5 tablet down titrated (due to tolerability), orally, once at night for up to 2 weeks in Titration Period of Core Study and continued to receive LEM10 or LEM5 tablet down titrated (due to tolerability), orally, once at night for up to 12 weeks in the Extension Phase.	Overall Cohort Participants who took ZOL at least 3 but fewer than 5 nights per week, for the last 2 weeks of the 3-week Screening Period or who met both criteria for intermittent and frequent ZOL use for 1 week each of the last 2 weeks of the 3-week Screening or who took ZOL at least 5 nights per week, for the last 2 weeks of the 3-week Screening Period, received LEM5 or LEM10 tablet (as per titration schedule), orally once at night for up to 2 weeks in Titration Period of Core Study. Eligible participants who completed 2 weeks in Titration Period of Core Study continued to receive LEM5 or LEM10 (as per titration schedule) tablet, orally, once at night for up to 12 weeks in the Extension Phase.
Percentage of Participants in LEM10 Treatment Group With Dose Decreasing to LEM5 at the End of the Titration Period of Core Study in Cohort 2	22.7 percentage of participants	—	—	—	—

SECONDARY outcome

Timeframe: Up to 2 Weeks

Population: The FAS included participants who received at least 1 dose of lemborexant.

The PGI-I was a self-report assessment of participant perception of the effects of a medication on their sleep. The PGI-I had 3 items related to study medication effects (a) helped/worsened sleep, (b) decreased/increased time to fall asleep, (c) increased/decreased total sleep time, and 1 item related to perceived appropriateness of study medication strength. The first 3 items were answered on a 3-point scale (1=positive medication effect, 2=neutral medication effect, 3=negative medication effect) and the last item on a different 3 point scale (medication: 1=too strong, 2=just right, 3=too weak), only 'positive medication effects' and 'just right' are reported here.

Outcome measures

Outcome measures
Measure	Overall Cohort n=7 Participants Participants who took ZOL at least 3 but fewer than 5 nights per week, for the last 2 weeks of the 3-week Screening Period or who met both criteria for intermittent and frequent ZOL use for 1 week each of the last 2 weeks of the 3-week Screening or who took ZOL at least 5 nights per week, for the last 2 weeks of the 3-week Screening Period, received LEM5 or LEM10 tablet (as per titration schedule), orally once at night for up to 2 weeks in Titration Period of Core Study. Eligible participants who completed 2 weeks in Titration Period of Core Study continued to receive LEM5 or LEM10 (as per titration schedule) tablet, orally, once at night for up to 12 weeks in the Extension Phase.	Cohort 1B: LEM 5 or LEM 10 (Mixed ZOL Use) n=3 Participants Participants who met both criteria for intermittent and frequent ZOL use for 1 week each of the last 2 weeks of the 3-week Screening Period, initially received LEM5 or LEM10 tablet up titrated (in case previous dose was ineffective), orally, once at night for up to 2 weeks in Titration Period of Core Study and continued to receive LEM5 or LEM10 tablet up titrated (in case previous dose was ineffective), orally, once at night for up to 12 weeks in the Extension Phase.	Cohort 2A: LEM 5 or LEM 10 (Frequent ZOL Use) n=21 Participants Participants who took ZOL at least 5 nights per week, for the last 2 weeks of the 3-week Screening Period, initially received LEM5 or LEM10 tablet up titrated (in case previous dose was ineffective), orally, once at night for up to 2 weeks in Titration Period of Core Study and continued to receive LEM5 or LEM10 tablet up titrated (in case previous dose was ineffective), orally, once at night for up to 12 weeks in the Extension Phase.	Cohort 2B: LEM 10 or LEM 5 (Frequent ZOL Use) n=22 Participants Participants who took ZOL at least 5 nights per week, for the last 2 weeks of the 3-week Screening Period, initially received LEM10 or LEM5 tablet down titrated (due to tolerability), orally, once at night for up to 2 weeks in Titration Period of Core Study and continued to receive LEM10 or LEM5 tablet down titrated (due to tolerability), orally, once at night for up to 12 weeks in the Extension Phase.	Overall Cohort n=53 Participants Participants who took ZOL at least 3 but fewer than 5 nights per week, for the last 2 weeks of the 3-week Screening Period or who met both criteria for intermittent and frequent ZOL use for 1 week each of the last 2 weeks of the 3-week Screening or who took ZOL at least 5 nights per week, for the last 2 weeks of the 3-week Screening Period, received LEM5 or LEM10 tablet (as per titration schedule), orally once at night for up to 2 weeks in Titration Period of Core Study. Eligible participants who completed 2 weeks in Titration Period of Core Study continued to receive LEM5 or LEM10 (as per titration schedule) tablet, orally, once at night for up to 12 weeks in the Extension Phase.
Percentage of Participants With Positive Medication Effect Rating on Each Patient Global Impression of Insomnia (PGI-I) Item at the End of the 2-Week Titration Period of Core Study by Cohort and Overall Using End of the Titration Period Treatment Positive medication effect: on Sleep	42.9 percentage of participants	66.7 percentage of participants	33.3 percentage of participants	54.5 percentage of participants	43.4 percentage of participants
Percentage of Participants With Positive Medication Effect Rating on Each Patient Global Impression of Insomnia (PGI-I) Item at the End of the 2-Week Titration Period of Core Study by Cohort and Overall Using End of the Titration Period Treatment Positive medication effect: Time to fall asleep	85.7 percentage of participants	66.7 percentage of participants	47.6 percentage of participants	54.5 percentage of participants	50.9 percentage of participants
Percentage of Participants With Positive Medication Effect Rating on Each Patient Global Impression of Insomnia (PGI-I) Item at the End of the 2-Week Titration Period of Core Study by Cohort and Overall Using End of the Titration Period Treatment Positive medication effect: Total sleep time	42.9 percentage of participants	66.7 percentage of participants	28.6 percentage of participants	45.5 percentage of participants	39.6 percentage of participants
Percentage of Participants With Positive Medication Effect Rating on Each Patient Global Impression of Insomnia (PGI-I) Item at the End of the 2-Week Titration Period of Core Study by Cohort and Overall Using End of the Titration Period Treatment Appropriateness of Medication Strength: Just Right	71.4 percentage of participants	100 percentage of participants	38.1 percentage of participants	50.0 percentage of participants	54.7 percentage of participants

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cohort 1A (Core Study): LEM 5 n=7 participants at risk Participants who took ZOL at least 3 but fewer than 5 nights per week, for the last 2 weeks of the 3-week Screening Period, received LEM5 tablet, orally, once at night for up to 2 weeks in Titration Period of Core Study.	Cohort 1A (Core Study): LEM 10 n=3 participants at risk Participants who took ZOL at least 3 but fewer than 5 nights per week, for the last 2 weeks of the 3-week Screening Period, initially received LEM5 and later up titrated to LEM10 tablet, orally, once at night for up to 2 weeks in Titration Period of Core Study.	Cohort 1B (Core Study): LEM 5 n=3 participants at risk Participants who met both criteria for intermittent and frequent ZOL use for 1 week each of the last 2 weeks of the 3-week Screening Period, received LEM5 tablet, orally, once at night for up to 2 weeks in Titration Period of Core Study.	Cohort 1B (Core Study): LEM 10 n=2 participants at risk Participants who met both criteria for intermittent and frequent ZOL use for 1 week each of the last 2 weeks of the 3-week Screening Period, initially received LEM5 and later up titrated to LEM10 tablet, orally, once at night for up to 2 weeks in Titration Period of Core Study.	Cohort 2A (Core Study): LEM 5 n=21 participants at risk Participants who took ZOL at least 5 nights per week, for the last 2 weeks of the 3-week Screening Period, received LEM5 tablet, orally, once at night for up to 2 weeks in Titration Period of Core Study.	Cohort 2A (Core Study): LEM 10 n=10 participants at risk Participants who took ZOL at least 5 nights per week, for the last 2 weeks of the 3-week Screening Period, initially received LEM5 and later up titrated to LEM10 tablet, orally, once at night for up to 2 weeks in Titration Period of Core Study.	Cohort 2B (Core Study) : LEM 5 n=5 participants at risk Participants who took ZOL at least 5 nights per week, for the last 2 weeks of the 3-week Screening Period, initially received LEM10 and later down titrated to LEM5 tablet, orally, once at night for up to 2 weeks in Titration Period of Core Study.	Cohort 2B (Core Study): LEM 10 n=22 participants at risk Participants who took ZOL at least 5 nights per week, for the last 2 weeks of the 3-week Screening Period, received LEM10 tablet, orally, once at night for up to 2 weeks in Titration Period of Core Study.	Cohort 1A (Extension Phase): LEM 5 n=6 participants at risk Participants who took ZOL at least 3 but fewer than 5 nights per week, for the last 2 weeks of the 3-week Screening Period, received LEM5 tablet, orally, once at night for up to 2 weeks in Titration Period of Core Study. Eligible participants who completed Titration Period of Core Study entered Extension Phase and continued to receive LEM5 tablet, orally, once at night for up to 12 weeks in the Extension Phase.	Cohort 1A (Extension Phase): LEM 10 n=5 participants at risk Participants who took ZOL at least 3 but fewer than 5 nights per week, for the last 2 weeks of the 3-week Screening Period, initially received LEM5 and later up titrated to LEM10 tablet, orally, once at night for up to 2 weeks in Titration Period of Core Study. Eligible participants who completed Titration Period of Core Study entered Extension Phase and continued to receive LEM10 tablet, orally, once at night for up to 12 weeks in the Extension Phase.	Cohort 1B (Extension Phase): LEM 5 n=3 participants at risk Participants who met both criteria for intermittent and frequent ZOL use for 1 week each of the last 2 weeks of the 3-week Screening Period, received LEM5 tablet, orally, once at night for up to 2 weeks in Titration Period of Core Study. Eligible participants who completed Titration Period of Core Study entered Extension Phase and continued to receive LEM5 tablet, orally, once at night for up to 12 weeks in the Extension Phase.	Cohort 1B (Extension Phase): LEM 10 n=3 participants at risk Participants who met both criteria for intermittent and frequent ZOL use for 1 week each of the last 2 weeks of the 3-week Screening Period, initially received LEM5 and later up titrated to LEM10 tablet, orally, once at night for up to 2 weeks in Titration Period of Core Study. Eligible participants who completed Titration Period of Core Study entered Extension Phase and continued to receive LEM10 tablet, orally, once at night for up to 12 weeks in the Extension Phase.	Cohort 2A (Extension Phase): LEM 5 n=15 participants at risk Participants who took ZOL at least 5 nights per week, for the last 2 weeks of the 3-week Screening Period, received LEM5 tablet, orally, once at night for up to 2 weeks in Titration Period of Core Study. Eligible participants who completed Titration Period of Core Study entered Extension Phase and continued to receive LEM5 tablet, orally, once at night for up to 12 weeks in the Extension Phase.	Cohort 2A (Extension Phase): LEM 10 n=12 participants at risk Participants who took ZOL at least 5 nights per week, for the last 2 weeks of the 3-week Screening Period, initially received LEM5 and later up titrated to LEM10 tablet, orally, once at night for up to 2 weeks in Titration Period of Core Study. Eligible participants who completed Titration Period of Core Study entered Extension Phase and continued to receive LEM10 tablet, orally, once at night for up to 12 weeks in the Extension Phase.	Cohort 2B (Extension Phase): LEM 5 n=8 participants at risk Participants who took ZOL at least 5 nights per week, for the last 2 weeks of the 3-week Screening Period, initially received LEM10 and later down titrated to LEM5 tablet, orally, once at night for up to 2 weeks in Titration Period of Core Study. Eligible participants who completed Titration Period of Core Study entered Extension Phase and continued to receive initially LEM10 and later down titrated to LEM5 tablet, orally, once at night for up to 12 weeks in the Extension Phase.	Cohort 2B (Extension Phase): LEM 10 n=17 participants at risk Participants who took ZOL at least 5 nights per week, for the last 2 weeks of the 3-week Screening Period, received LEM10 tablet, orally, once at night for up to 2 weeks in Titration Period of Core Study. Eligible participants who completed Titration Period of Core Study entered Extension Phase and continued to receive LEM10 tablet, orally, once at night for up to 12 weeks in the Extension Phase.
Infections and infestations Pneumonia	0.00% 0/7 • From the first dose of study drug up to 22 weeks	0.00% 0/3 • From the first dose of study drug up to 22 weeks	0.00% 0/3 • From the first dose of study drug up to 22 weeks	0.00% 0/2 • From the first dose of study drug up to 22 weeks	0.00% 0/21 • From the first dose of study drug up to 22 weeks	0.00% 0/10 • From the first dose of study drug up to 22 weeks	0.00% 0/5 • From the first dose of study drug up to 22 weeks	0.00% 0/22 • From the first dose of study drug up to 22 weeks	0.00% 0/6 • From the first dose of study drug up to 22 weeks	0.00% 0/5 • From the first dose of study drug up to 22 weeks	0.00% 0/3 • From the first dose of study drug up to 22 weeks	0.00% 0/3 • From the first dose of study drug up to 22 weeks	0.00% 0/15 • From the first dose of study drug up to 22 weeks	0.00% 0/12 • From the first dose of study drug up to 22 weeks	0.00% 0/8 • From the first dose of study drug up to 22 weeks	5.9% 1/17 • From the first dose of study drug up to 22 weeks
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/7 • From the first dose of study drug up to 22 weeks	0.00% 0/3 • From the first dose of study drug up to 22 weeks	0.00% 0/3 • From the first dose of study drug up to 22 weeks	0.00% 0/2 • From the first dose of study drug up to 22 weeks	0.00% 0/21 • From the first dose of study drug up to 22 weeks	0.00% 0/10 • From the first dose of study drug up to 22 weeks	0.00% 0/5 • From the first dose of study drug up to 22 weeks	0.00% 0/22 • From the first dose of study drug up to 22 weeks	0.00% 0/6 • From the first dose of study drug up to 22 weeks	0.00% 0/5 • From the first dose of study drug up to 22 weeks	0.00% 0/3 • From the first dose of study drug up to 22 weeks	0.00% 0/3 • From the first dose of study drug up to 22 weeks	0.00% 0/15 • From the first dose of study drug up to 22 weeks	0.00% 0/12 • From the first dose of study drug up to 22 weeks	0.00% 0/8 • From the first dose of study drug up to 22 weeks	5.9% 1/17 • From the first dose of study drug up to 22 weeks

Other adverse events

Other adverse events
Measure	Cohort 1A (Core Study): LEM 5 n=7 participants at risk Participants who took ZOL at least 3 but fewer than 5 nights per week, for the last 2 weeks of the 3-week Screening Period, received LEM5 tablet, orally, once at night for up to 2 weeks in Titration Period of Core Study.	Cohort 1A (Core Study): LEM 10 n=3 participants at risk Participants who took ZOL at least 3 but fewer than 5 nights per week, for the last 2 weeks of the 3-week Screening Period, initially received LEM5 and later up titrated to LEM10 tablet, orally, once at night for up to 2 weeks in Titration Period of Core Study.	Cohort 1B (Core Study): LEM 5 n=3 participants at risk Participants who met both criteria for intermittent and frequent ZOL use for 1 week each of the last 2 weeks of the 3-week Screening Period, received LEM5 tablet, orally, once at night for up to 2 weeks in Titration Period of Core Study.	Cohort 1B (Core Study): LEM 10 n=2 participants at risk Participants who met both criteria for intermittent and frequent ZOL use for 1 week each of the last 2 weeks of the 3-week Screening Period, initially received LEM5 and later up titrated to LEM10 tablet, orally, once at night for up to 2 weeks in Titration Period of Core Study.	Cohort 2A (Core Study): LEM 5 n=21 participants at risk Participants who took ZOL at least 5 nights per week, for the last 2 weeks of the 3-week Screening Period, received LEM5 tablet, orally, once at night for up to 2 weeks in Titration Period of Core Study.	Cohort 2A (Core Study): LEM 10 n=10 participants at risk Participants who took ZOL at least 5 nights per week, for the last 2 weeks of the 3-week Screening Period, initially received LEM5 and later up titrated to LEM10 tablet, orally, once at night for up to 2 weeks in Titration Period of Core Study.	Cohort 2B (Core Study) : LEM 5 n=5 participants at risk Participants who took ZOL at least 5 nights per week, for the last 2 weeks of the 3-week Screening Period, initially received LEM10 and later down titrated to LEM5 tablet, orally, once at night for up to 2 weeks in Titration Period of Core Study.	Cohort 2B (Core Study): LEM 10 n=22 participants at risk Participants who took ZOL at least 5 nights per week, for the last 2 weeks of the 3-week Screening Period, received LEM10 tablet, orally, once at night for up to 2 weeks in Titration Period of Core Study.	Cohort 1A (Extension Phase): LEM 5 n=6 participants at risk Participants who took ZOL at least 3 but fewer than 5 nights per week, for the last 2 weeks of the 3-week Screening Period, received LEM5 tablet, orally, once at night for up to 2 weeks in Titration Period of Core Study. Eligible participants who completed Titration Period of Core Study entered Extension Phase and continued to receive LEM5 tablet, orally, once at night for up to 12 weeks in the Extension Phase.	Cohort 1A (Extension Phase): LEM 10 n=5 participants at risk Participants who took ZOL at least 3 but fewer than 5 nights per week, for the last 2 weeks of the 3-week Screening Period, initially received LEM5 and later up titrated to LEM10 tablet, orally, once at night for up to 2 weeks in Titration Period of Core Study. Eligible participants who completed Titration Period of Core Study entered Extension Phase and continued to receive LEM10 tablet, orally, once at night for up to 12 weeks in the Extension Phase.	Cohort 1B (Extension Phase): LEM 5 n=3 participants at risk Participants who met both criteria for intermittent and frequent ZOL use for 1 week each of the last 2 weeks of the 3-week Screening Period, received LEM5 tablet, orally, once at night for up to 2 weeks in Titration Period of Core Study. Eligible participants who completed Titration Period of Core Study entered Extension Phase and continued to receive LEM5 tablet, orally, once at night for up to 12 weeks in the Extension Phase.	Cohort 1B (Extension Phase): LEM 10 n=3 participants at risk Participants who met both criteria for intermittent and frequent ZOL use for 1 week each of the last 2 weeks of the 3-week Screening Period, initially received LEM5 and later up titrated to LEM10 tablet, orally, once at night for up to 2 weeks in Titration Period of Core Study. Eligible participants who completed Titration Period of Core Study entered Extension Phase and continued to receive LEM10 tablet, orally, once at night for up to 12 weeks in the Extension Phase.	Cohort 2A (Extension Phase): LEM 5 n=15 participants at risk Participants who took ZOL at least 5 nights per week, for the last 2 weeks of the 3-week Screening Period, received LEM5 tablet, orally, once at night for up to 2 weeks in Titration Period of Core Study. Eligible participants who completed Titration Period of Core Study entered Extension Phase and continued to receive LEM5 tablet, orally, once at night for up to 12 weeks in the Extension Phase.	Cohort 2A (Extension Phase): LEM 10 n=12 participants at risk Participants who took ZOL at least 5 nights per week, for the last 2 weeks of the 3-week Screening Period, initially received LEM5 and later up titrated to LEM10 tablet, orally, once at night for up to 2 weeks in Titration Period of Core Study. Eligible participants who completed Titration Period of Core Study entered Extension Phase and continued to receive LEM10 tablet, orally, once at night for up to 12 weeks in the Extension Phase.	Cohort 2B (Extension Phase): LEM 5 n=8 participants at risk Participants who took ZOL at least 5 nights per week, for the last 2 weeks of the 3-week Screening Period, initially received LEM10 and later down titrated to LEM5 tablet, orally, once at night for up to 2 weeks in Titration Period of Core Study. Eligible participants who completed Titration Period of Core Study entered Extension Phase and continued to receive initially LEM10 and later down titrated to LEM5 tablet, orally, once at night for up to 12 weeks in the Extension Phase.	Cohort 2B (Extension Phase): LEM 10 n=17 participants at risk Participants who took ZOL at least 5 nights per week, for the last 2 weeks of the 3-week Screening Period, received LEM10 tablet, orally, once at night for up to 2 weeks in Titration Period of Core Study. Eligible participants who completed Titration Period of Core Study entered Extension Phase and continued to receive LEM10 tablet, orally, once at night for up to 12 weeks in the Extension Phase.
Injury, poisoning and procedural complications Accidental overdose	0.00% 0/7 • From the first dose of study drug up to 22 weeks	0.00% 0/3 • From the first dose of study drug up to 22 weeks	0.00% 0/3 • From the first dose of study drug up to 22 weeks	0.00% 0/2 • From the first dose of study drug up to 22 weeks	9.5% 2/21 • From the first dose of study drug up to 22 weeks	0.00% 0/10 • From the first dose of study drug up to 22 weeks	0.00% 0/5 • From the first dose of study drug up to 22 weeks	0.00% 0/22 • From the first dose of study drug up to 22 weeks	0.00% 0/6 • From the first dose of study drug up to 22 weeks	0.00% 0/5 • From the first dose of study drug up to 22 weeks	0.00% 0/3 • From the first dose of study drug up to 22 weeks	0.00% 0/3 • From the first dose of study drug up to 22 weeks	0.00% 0/15 • From the first dose of study drug up to 22 weeks	0.00% 0/12 • From the first dose of study drug up to 22 weeks	0.00% 0/8 • From the first dose of study drug up to 22 weeks	0.00% 0/17 • From the first dose of study drug up to 22 weeks
Nervous system disorders Somnolence	0.00% 0/7 • From the first dose of study drug up to 22 weeks	0.00% 0/3 • From the first dose of study drug up to 22 weeks	0.00% 0/3 • From the first dose of study drug up to 22 weeks	0.00% 0/2 • From the first dose of study drug up to 22 weeks	4.8% 1/21 • From the first dose of study drug up to 22 weeks	0.00% 0/10 • From the first dose of study drug up to 22 weeks	0.00% 0/5 • From the first dose of study drug up to 22 weeks	13.6% 3/22 • From the first dose of study drug up to 22 weeks	0.00% 0/6 • From the first dose of study drug up to 22 weeks	0.00% 0/5 • From the first dose of study drug up to 22 weeks	0.00% 0/3 • From the first dose of study drug up to 22 weeks	0.00% 0/3 • From the first dose of study drug up to 22 weeks	0.00% 0/15 • From the first dose of study drug up to 22 weeks	0.00% 0/12 • From the first dose of study drug up to 22 weeks	0.00% 0/8 • From the first dose of study drug up to 22 weeks	17.6% 3/17 • From the first dose of study drug up to 22 weeks
Psychiatric disorders Abnormal dreams	0.00% 0/7 • From the first dose of study drug up to 22 weeks	0.00% 0/3 • From the first dose of study drug up to 22 weeks	0.00% 0/3 • From the first dose of study drug up to 22 weeks	0.00% 0/2 • From the first dose of study drug up to 22 weeks	0.00% 0/21 • From the first dose of study drug up to 22 weeks	0.00% 0/10 • From the first dose of study drug up to 22 weeks	0.00% 0/5 • From the first dose of study drug up to 22 weeks	18.2% 4/22 • From the first dose of study drug up to 22 weeks	0.00% 0/6 • From the first dose of study drug up to 22 weeks	0.00% 0/5 • From the first dose of study drug up to 22 weeks	0.00% 0/3 • From the first dose of study drug up to 22 weeks	0.00% 0/3 • From the first dose of study drug up to 22 weeks	0.00% 0/15 • From the first dose of study drug up to 22 weeks	0.00% 0/12 • From the first dose of study drug up to 22 weeks	0.00% 0/8 • From the first dose of study drug up to 22 weeks	11.8% 2/17 • From the first dose of study drug up to 22 weeks

Additional Information

Eisai Medical Information

Eisai Inc.

Phone: +1-888-274-2378

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER