A Phase II/III Study of SEP-190 (Eszopiclone) in Patients With Primary Insomnia (Study 190-126)

• ClinicalTrials.gov Identifier: NCT00770510
• Recruitment Status: Completed
• First Posted: October 10, 2008
• Results First Posted: February 4, 2013
• Last Update Posted: February 4, 2013
• Sponsor: Eisai Co., Ltd.
• Information provided by (Responsible Party): Eisai Inc. ( Eisai Co., Ltd. )

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Primary Insomnia
• Interventions: Drug: Eszopiclone 1 mg; Drug: Eszopiclone 2 mg; Drug: Eszopiclone 3 mg; Drug: Placebo; Drug: Zolpidem Tartrate 10 mg
• Enrollment: 192

Participant Flow

Recruitment Details	This study was recruited at 21 centers in Japan.
Pre-assignment Details	Of the 192 participants who entered the screening period, 72 were randomized to study medication (excluding 119 ineligible participants; one withdrawal of consent).

Arm/Group Title	Entire Study Population
Arm/Group Description	Includes groups randomized to receive one of 10 prespecified treatment sequence patterns which included receiving: Eszopiclone 1 mg first, Eszopiclone 2 mg first, Eszopiclone 3 mg first, Placebo first, and Zolpidem Tartrate 10 mg first. Group 1: ABECD (n=7) Group 2: BCADE (n=7) Group 3: CDBEA (n=7) Group 4: DECAB (n=8) Group 5: EADBC (n=7) Group 6: DCEBA (n=8) Group 7: EDACB (n=7) Group 8: AEBDC (n=7) Group 9: BACED (n=7) Group 10: CBDAE (n=7) A= Eszopiclone 3 mg; B= Eszopiclone 2 mg; C= Eszopiclone 1mg; D= Placebo; E: Zolpidem 10 mg
Period Title: Overall Study
Started	72
Completed	67
Not Completed	5
Reason Not Completed
Lost to Follow-up	2
Pregnancy	1
Withdrawal by Subject	2

Baseline Characteristics

Arm/Group Title		Entire Study Population
Arm/Group Description		Includes groups randomized to receive one of 10 prespecified treatment sequence patterns which included receiving: Eszopiclone 1 mg first, Eszopiclone 2 mg first, Eszopiclone 3 mg first, Placebo first, and Zolpidem Tartrate 10 mg first. Group 1: ABECD (n=7) Group 2: BCADE (n=7) Group 3: CDBEA (n=7) Group 4: DECAB (n=8) Group 5: EADBC (n=7) Group 6: DCEBA (n=8) Group 7: EDACB (n=7) Group 8: AEBDC (n=7) Group 9: BACED (n=7) Group 10: CBDAE (n=7) A= Eszopiclone 3 mg; B= Eszopiclone 2 mg; C= Eszopiclone 1mg; D= Placebo; E: Zolpidem 10 mg
Overall Number of Baseline Participants		72
Baseline Analysis Population Description		[Not Specified]
Age Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	72 participants
		39.4 (11.9)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	72 participants
	Female	29 40.3%
	Male	43 59.7%

Outcome Measures

1. Primary Outcome

Title	Latency To Persistent Sleep (LPS)
Description	The objective measure, LPS, defined as the amount of time measured in minutes it takes to fall asleep was based on polysomnography (PSG) objective assessments of sleep disturbance. PSG recording was performed according to a manual for overnight PSG. The start time for PSG recording was individualized and scheduled within +/- 30 minutes of the participant's median bedtime as recorded in the sleep diary. During the screening period, participants were provided a diary in which they recorded the time of lights out before bedtime for 1 week pror to PSG evaluations. PSG recording duration for scoring was 8 hours. PSG data recorded during treatment were centrally scored by a trained expert.
Time Frame	10 days (5 intervals of two consecutive nights)

Outcome Measure Data

Analysis Population Description

Full analysis set: includes randomized participants who were administered >= 1 dose of study medication and had evaluable data for the primary efficacy assessments from any of the 5 treatment intervals.

Arm/Group Title	Placebo	Eszopiclone 1 mg	Eszopiclone 2 mg	Eszopiclone 3 mg	Zolpidem Tartrate 10 mg
Arm/Group Description:	Placebo tablet taken orally at bedtime for 2 consecutive nights in one of 5 cross-over intervals in each of 10 prespecified treatment sequence patterns.	Eszopiclone 1 mg tablet taken orally at bedtime for 2 consecutive nights in one of 5 cross-over intervals in each of 10 prespecified treatment sequence patterns.	Eszopiclone 2 mg tablet taken orally at bedtime for 2 consecutive nights in one of 5 cross-over intervals in each of 10 prespecified treatment sequence patterns.	Eszopiclone 3 mg tablet taken orally at bedtime for 2 consecutive nights in one of 5 cross-over intervals in each of 10 prespecified treatment sequence patterns.	Zolpidem Tartrate 10 mg tablet taken orally at bedtime for 2 consecutive nights in one of 5 cross-over intervals in each of 10 prespecified treatment sequence patterns.
Overall Number of Participants Analyzed	71	70	69	68	70
Mean (Standard Deviation); Unit of Measure: Minutes
	37.5 (37.8)	24.4 (22.7)	20.9 (24.3)	12.8 (11.2)	14.3 (22.6)

2. Primary Outcome

Title	Sleep Latency (SL)
Description	The subjective measure, SL, defined as the amount of time measured in minutes it takes to fall asleep was based on participant-reported subjective assessments of sleep disturbance and was obtained from participants' responses to morning questionnaires. Questionnaires were administered during each visit during the treatment period.
Time Frame	10 days (5 intervals of two consecutive nights)

Outcome Measure Data

Analysis Population Description

Full analysis set: includes randomized participants who were administered >= 1 dose of study medication and had evaluable data for the primary efficacy assessments from any of the 5 treatment intervals.

Arm/Group Title	Placebo	Eszopiclone 1 mg	Eszopiclone 2 mg	Eszopiclone 3 mg	Zolpidem Tartrate 10 mg
Arm/Group Description:	Placebo tablet taken orally at bedtime for 2 consecutive nights in one of 5 cross-over intervals in each of 10 prespecified treatment sequence patterns.	Eszopiclone 1 mg tablet taken orally at bedtime for 2 consecutive nights in one of 5 cross-over intervals in each of 10 prespecified treatment sequence patterns.	Eszopiclone 2 mg tablet taken orally at bedtime for 2 consecutive nights in one of 5 cross-over intervals in each of 10 prespecified treatment sequence patterns.	Eszopiclone 3 mg tablet taken orally at bedtime for 2 consecutive nights in one of 5 cross-over intervals in each of 10 prespecified treatment sequence patterns.	Zolpidem Tartrate 10 mg tablet taken orally at bedtime for 2 consecutive nights in one of 5 cross-over intervals in each of 10 prespecified treatment sequence patterns.
Overall Number of Participants Analyzed	71	70	69	68	70
Mean (Standard Deviation); Unit of Measure: Minutes
	62.0 (47.8)	45.5 (36.7)	32.6 (26.4)	28.4 (23.8)	28.0 (24.6)

3. Secondary Outcome

Title	Total Sleep Time (Objective & Subjective)
Description	Total sleep time defined as total sleeping time from bedtime to final awakening (measured in minutes) was objectively determined by polysomnography and subjectively determined based on participant-reported measures following treatment. The objective total sleep time was based on PSG-based assessments. PSG recording was performed according to a manual for overnight PSG. The start time for PSG recording was individualized and scheduled within +/- 30 minutes of the participant's median bedtime as recorded in the sleep diary. PSG recording duration for scoring was 8 hours. PSG data recorded during treatment were centrally scored by a trained expert. The subjective measure was based on participant-reported subjective assessments of sleep disturbance and were obtained from participants' responses to morning questionnaires. Questionnaires were administered during each visit during the treatment period.
Time Frame	10 days (5 intervals of two consecutive nights)

Outcome Measure Data

Analysis Population Description

Full analysis set: includes randomized participants who were administered >= 1 dose of study medication and had evaluable data for the primary efficacy assessments from any of the 5 treatment intervals.

Arm/Group Title	Placebo	Eszopiclone 1 mg	Eszopiclone 2 mg	Eszopiclone 3 mg	Zolpidem Tartrate 10 mg
Arm/Group Description:	Placebo tablet taken orally at bedtime for 2 consecutive nights in one of 5 cross-over intervals in each of 10 prespecified treatment sequence patterns.	Eszopiclone 1 mg tablet taken orally at bedtime for 2 consecutive nights in one of 5 cross-over intervals in each of 10 prespecified treatment sequence patterns.	Eszopiclone 2 mg tablet taken orally at bedtime for 2 consecutive nights in one of 5 cross-over intervals in each of 10 prespecified treatment sequence patterns.	Eszopiclone 3 mg tablet taken orally at bedtime for 2 consecutive nights in one of 5 cross-over intervals in each of 10 prespecified treatment sequence patterns.	Zolpidem Tartrate 10 mg tablet taken orally at bedtime for 2 consecutive nights in one of 5 cross-over intervals in each of 10 prespecified treatment sequence patterns.
Overall Number of Participants Analyzed	71	70	69	68	70
Median (Full Range); Unit of Measure: Minutes
Objective Total Sleep Time	414.0; (279.3 to 470.3)	438.3; (292.3 to 468.5)	452.5; (227.5 to 475.8)	453.4; (313.5 to 474.5)	448.6; (338.8 to 476.3)
Subjective Total Sleep Time	360.0; (90.0 to 452.5)	390.0; (225.0 to 460.0)	397.5; (225.0 to 478.5)	420.0; (225.0 to 480.0)	411.3; (195.0 to 480.0)

4. Secondary Outcome

Title	Sleep Efficiency
Description	Sleep efficiency (SE) was an assessment obtained from PSG during the treatment period and was defined as the ratio of total sleep time to the total time in bed of 8 hours * 100, expressed as a percent. PSG recording was performed according to a manual for overnight PSG. The start time for PSG recording was individualized and scheduled within +/- 30 minutes of the patient's median bedtime as recorded in the sleep diary. During the screening period, participants were provided a diary in which they recorded the time of lights out before bedtime for 1 week pror to PSG evaluations. PSG recording duration for scoring was 8 hours. PSG data recorded during treatment were centrally scored by a trained expert.
Time Frame	10 days (5 intervals of two consecutive nights)

Outcome Measure Data

Analysis Population Description

Full analysis set: includes randomized participants who were administered >= 1 dose of study medication and had evaluable data for the primary efficacy assessments from any of the 5 treatment intervals.

Arm/Group Title	Placebo	Eszopiclone 1 mg	Eszopiclone 2 mg	Eszopiclone 3 mg	Zolpidem Tartrate 10 mg
Arm/Group Description:	Placebo tablet taken orally at bedtime for 2 consecutive nights in one of 5 cross-over intervals in each of 10 prespecified treatment sequence patterns.	Eszopiclone 1 mg tablet taken orally at bedtime for 2 consecutive nights in one of 5 cross-over intervals in each of 10 prespecified treatment sequence patterns.	Eszopiclone 2 mg tablet taken orally at bedtime for 2 consecutive nights in one of 5 cross-over intervals in each of 10 prespecified treatment sequence patterns.	Eszopiclone 3 mg tablet taken orally at bedtime for 2 consecutive nights in one of 5 cross-over intervals in each of 10 prespecified treatment sequence patterns.	Zolpidem Tartrate 10 mg tablet taken orally at bedtime for 2 consecutive nights in one of 5 cross-over intervals in each of 10 prespecified treatment sequence patterns.
Overall Number of Participants Analyzed	71	70	69	68	70
Median (Full Range); Unit of Measure: Percentage of time asleep of 8 hours
	86.3; (58.2 to 98.0)	91.3; (60.9 to 97.6)	94.3; (47.4 to 99.2)	94.5; (65.3 to 98.9)	93.5; (70.6 to 99.3)

5. Secondary Outcome

Title	Wake Time After Sleep Onset (WASO)- Objective & Subjective
Description	Wake Time After Sleep Onset (WASO) defined as total awakening time from falling asleep to final awakening was objectively determined by polysomnography and subjectively determined based on participant-reported measures following treatment. The objective WASO was based on PSG assessments. PSG recording was performed according to a manual for overnight PSG. The start time for PSG recording was individualized and scheduled within +/- 30 minutes of the participant's median bedtime as recorded in the sleep diary. PSG recording duration for scoring was 8 hours. PSG data recorded during treatment were centrally scored by a trained expert. The subjective measure was based on participant-reported subjective assessments and were obtained from participants' responses to morning questionnaires. Questionnaires were administered during each visit during the treatment period.
Time Frame	10 days (5 intervals of two consecutive nights)

Outcome Measure Data

Analysis Population Description

Full analysis set: includes randomized participants who were administered >= 1 dose of study medication and had evaluable data for the primary efficacy assessments from any of the 5 treatment intervals.

Arm/Group Title	Placebo	Eszopiclone 1 mg	Eszopiclone 2 mg	Eszopiclone 3 mg	Zolpidem Tartrate 10 mg
Arm/Group Description:	Placebo tablet taken orally at bedtime for 2 consecutive nights in one of 5 cross-over intervals in each of 10 prespecified treatment sequence patterns.	Eszopiclone 1 mg tablet taken orally at bedtime for 2 consecutive nights in one of 5 cross-over intervals in each of 10 prespecified treatment sequence patterns.	Eszopiclone 2 mg tablet taken orally at bedtime for 2 consecutive nights in one of 5 cross-over intervals in each of 10 prespecified treatment sequence patterns.	Eszopiclone 3 mg tablet taken orally at bedtime for 2 consecutive nights in one of 5 cross-over intervals in each of 10 prespecified treatment sequence patterns.	Zolpidem Tartrate 10 mg tablet taken orally at bedtime for 2 consecutive nights in one of 5 cross-over intervals in each of 10 prespecified treatment sequence patterns.
Overall Number of Participants Analyzed	71	70	69	68	70
Median (Full Range); Unit of Measure: Minutes
Objective Wake Time After Sleep Onset	26.3; (1.5 to 164.3)	22.5; (1.0 to 144.8)	17.8; (0.5 to 176.0)	18.8; (0.8 to 165.5)	20.0; (1.5 to 139.5)
Subjective Wake Time After Sleep Onset	75.0; (3.0 to 300.0)	60.0; (0.5 to 285.0)	37.5; (0.0 to 255.0)	40.0; (0.0 to 227.5)	50.0; (0.0 to 285.0)

6. Secondary Outcome

Title	Number of Awakenings (Objective & Subjective)
Description	Number of awakenings defined as the total number of spontaneous awakenings from falling asleep to final awakening was objectively determined by polysomnography and subjectively determined based on participant-reported measures following treatment. The objective number of awakenings was based on PSG assessments. PSG recording was performed according to a manual for overnight PSG. The start time for PSG recording was individualized and scheduled within +/- 30 minutes of the participant's median bedtime as recorded in the sleep diary. PSG recording duration for scoring was 8 hours. PSG data recorded during treatment were centrally scored by a trained expert. The subjective measure was based on participant-reported subjective assessments and were obtained from participants' responses to morning questionnaires. Questionnaires were administered during each visit during the treatment period.
Time Frame	10 days (5 intervals of two consecutive nights)

Outcome Measure Data

Analysis Population Description

Full analysis set: includes randomized participants who were administered >= 1 dose of study medication and had evaluable data for the primary efficacy assessments from any of the 5 treatment intervals.

Arm/Group Title	Placebo	Eszopiclone 1 mg	Eszopiclone 2 mg	Eszopiclone 3 mg	Zolpidem Tartrate 10 mg
Arm/Group Description:	Placebo tablet taken orally at bedtime for 2 consecutive nights in one of 5 cross-over intervals in each of 10 prespecified treatment sequence patterns.	Eszopiclone 1 mg tablet taken orally at bedtime for 2 consecutive nights in one of 5 cross-over intervals in each of 10 prespecified treatment sequence patterns.	Eszopiclone 2 mg tablet taken orally at bedtime for 2 consecutive nights in one of 5 cross-over intervals in each of 10 prespecified treatment sequence patterns.	Eszopiclone 3 mg tablet taken orally at bedtime for 2 consecutive nights in one of 5 cross-over intervals in each of 10 prespecified treatment sequence patterns.	Zolpidem Tartrate 10 mg tablet taken orally at bedtime for 2 consecutive nights in one of 5 cross-over intervals in each of 10 prespecified treatment sequence patterns.
Overall Number of Participants Analyzed	71	70	69	68	70
Median (Full Range); Unit of Measure: Number of awakenings
Objective Number of Awakenings	4.0; (0.5 to 18.0)	4.0; (0.0 to 11.0)	3.5; (0.0 to 10.0)	2.8; (0.0 to 10.0)	3.5; (0.5 to 14.0)
Subjective Number of Awakenings	3.0; (0.0 to 11.0)	3.0; (0.5 to 8.0)	2.5; (0.0 to 6.5)	2.0; (0.0 to 8.0)	2.0; (0.0 to 6.0)

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	Safety population included randomized participants who were administered >= 1 dose of study medication and had any evaluable safety data.
Arm/Group Title	Placebo	Eszopiclone 1 mg	Eszopiclone 2 mg	Eszopiclone 3 mg	Zolpidem Tartrate 10 mg
Arm/Group Description	Placebo tablet taken orally at bedtime for 2 consecutive nights in one of 5 cross-over intervals in each of 10 prespecified treatment sequence patterns.	Eszopiclone 1 mg tablet taken orally at bedtime for 2 consecutive nights in one of 5 cross-over intervals in each of 10 prespecified treatment sequence patterns.	Eszopiclone 2 mg tablet taken orally at bedtime for 2 consecutive nights in one of 5 cross-over intervals in each of 10 prespecified treatment sequence patterns.	Eszopiclone 3 mg tablet taken orally at bedtime for 2 consecutive nights in one of 5 cross-over intervals in each of 10 prespecified treatment sequence patterns.	Zolpidem Tartrate 10 mg tablet taken orally at bedtime for 2 consecutive nights in one of 5 cross-over intervals in each of 10 prespecified treatment sequence patterns.
All-Cause Mortality
	Placebo	Eszopiclone 1 mg	Eszopiclone 2 mg	Eszopiclone 3 mg	Zolpidem Tartrate 10 mg
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--	--/--	--/--
Serious Adverse Events
	Placebo	Eszopiclone 1 mg	Eszopiclone 2 mg	Eszopiclone 3 mg	Zolpidem Tartrate 10 mg
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/71 (0.00%)	0/70 (0.00%)	0/69 (0.00%)	0/68 (0.00%)	0/70 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	2%
	Placebo	Eszopiclone 1 mg	Eszopiclone 2 mg	Eszopiclone 3 mg	Zolpidem Tartrate 10 mg
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	5/71 (7.04%)	10/70 (14.29%)	10/69 (14.49%)	17/68 (25.00%)	8/70 (11.43%)
General disorders
Feeling Abnormal	0/71 (0.00%)	3/70 (4.29%)	0/69 (0.00%)	0/68 (0.00%)	0/70 (0.00%)
Nervous system disorders
Dysgeusia	1/71 (1.41%)	4/70 (5.71%)	6/69 (8.70%)	11/68 (16.18%)	1/70 (1.43%)
Somnolence	2/71 (2.82%)	1/70 (1.43%)	3/69 (4.35%)	4/68 (5.88%)	3/70 (4.29%)
Dizziness	0/71 (0.00%)	0/70 (0.00%)	0/69 (0.00%)	2/68 (2.94%)	3/70 (4.29%)
Skin and subcutaneous tissue disorders
Dermatitis Contact	2/71 (2.82%)	2/70 (2.86%)	1/69 (1.45%)	0/68 (0.00%)	1/70 (1.43%)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Atsushi Kamijo, Study Director
• Organization: Eisai Co., Ltd.
• Phone: +81-3-3817-5245
• EMail: a-kamijo@hhc.eisai.co.jp

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Uchimura N, Kamijo A, Kuwahara H, Uchiyama M, Shimizu T, Chiba S, Inoue Y. A randomized placebo-controlled polysomnographic study of eszopiclone in Japanese patients with primary insomnia. Sleep Med. 2012 Dec;13(10):1247-53. doi: 10.1016/j.sleep.2012.08.015. Epub 2012 Oct 11.

• Responsible Party: Eisai Inc. ( Eisai Co., Ltd. )
• ClinicalTrials.gov Identifier: NCT00770510
• Other Study ID Numbers: 190-126
• First Submitted: October 9, 2008
• First Posted: October 10, 2008
• Results First Submitted: December 28, 2012
• Results First Posted: February 4, 2013
• Last Update Posted: February 4, 2013