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

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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:
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
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
Hide 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
Arm/Group Title Entire Study Population
Hide 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
Hide 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%
1.Primary Outcome
Title Latency To Persistent Sleep (LPS)
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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)
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
Hide 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   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide 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%) 
Show Other (Not Including Serious) Adverse Events Hide 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%) 
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
Layout table for Results Point of Contact information
Name/Title: Atsushi Kamijo, Study Director
Organization: Eisai Co., Ltd.
Phone: +81-3-3817-5245
EMail: a-kamijo@hhc.eisai.co.jp
Layout table for additonal information
Responsible Party: Eisai Inc. ( Eisai Co., Ltd. )
ClinicalTrials.gov Identifier: NCT00770510     History of Changes
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