Trial Outcomes & Findings for A Phase II/III Study of SEP-190 (Eszopiclone) in Patients With Primary Insomnia (Study 190-126) (NCT NCT00770510)
NCT ID: NCT00770510
Last Updated: 2013-02-04
Results Overview
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.
COMPLETED
PHASE2/PHASE3
192 participants
10 days (5 intervals of two consecutive nights)
2013-02-04
Participant Flow
This study was recruited at 21 centers in Japan.
Of the 192 participants who entered the screening period, 72 were randomized to study medication (excluding 119 ineligible participants; one withdrawal of consent).
Participant milestones
| Measure |
Entire Study Population
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 Study
STARTED
|
72
|
|
Overall Study
COMPLETED
|
67
|
|
Overall Study
NOT COMPLETED
|
5
|
Reasons for withdrawal
| Measure |
Entire Study Population
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 Study
Lost to Follow-up
|
2
|
|
Overall Study
Pregnancy
|
1
|
|
Overall Study
Withdrawal by Subject
|
2
|
Baseline Characteristics
A Phase II/III Study of SEP-190 (Eszopiclone) in Patients With Primary Insomnia (Study 190-126)
Baseline characteristics by cohort
| Measure |
Entire Study Population
n=72 Participants
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
|
|---|---|
|
Age Continuous
|
39.4 years
STANDARD_DEVIATION 11.9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
29 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
43 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 10 days (5 intervals of two consecutive nights)Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=71 Participants
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
n=70 Participants
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
n=69 Participants
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
n=68 Participants
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
n=70 Participants
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.
|
|---|---|---|---|---|---|
|
Latency To Persistent Sleep (LPS)
|
37.5 Minutes
Standard Deviation 37.8
|
24.4 Minutes
Standard Deviation 22.7
|
20.9 Minutes
Standard Deviation 24.3
|
12.8 Minutes
Standard Deviation 11.2
|
14.3 Minutes
Standard Deviation 22.6
|
PRIMARY outcome
Timeframe: 10 days (5 intervals of two consecutive nights)Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=71 Participants
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
n=70 Participants
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
n=69 Participants
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
n=68 Participants
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
n=70 Participants
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.
|
|---|---|---|---|---|---|
|
Sleep Latency (SL)
|
62.0 Minutes
Standard Deviation 47.8
|
45.5 Minutes
Standard Deviation 36.7
|
32.6 Minutes
Standard Deviation 26.4
|
28.4 Minutes
Standard Deviation 23.8
|
28.0 Minutes
Standard Deviation 24.6
|
SECONDARY outcome
Timeframe: 10 days (5 intervals of two consecutive nights)Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=71 Participants
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
n=70 Participants
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
n=69 Participants
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
n=68 Participants
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
n=70 Participants
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.
|
|---|---|---|---|---|---|
|
Total Sleep Time (Objective & Subjective)
Objective Total Sleep Time
|
414.0 Minutes
Interval 279.3 to 470.3
|
438.3 Minutes
Interval 292.3 to 468.5
|
452.5 Minutes
Interval 227.5 to 475.8
|
453.4 Minutes
Interval 313.5 to 474.5
|
448.6 Minutes
Interval 338.8 to 476.3
|
|
Total Sleep Time (Objective & Subjective)
Subjective Total Sleep Time
|
360.0 Minutes
Interval 90.0 to 452.5
|
390.0 Minutes
Interval 225.0 to 460.0
|
397.5 Minutes
Interval 225.0 to 478.5
|
420.0 Minutes
Interval 225.0 to 480.0
|
411.3 Minutes
Interval 195.0 to 480.0
|
SECONDARY outcome
Timeframe: 10 days (5 intervals of two consecutive nights)Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=71 Participants
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
n=70 Participants
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
n=69 Participants
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
n=68 Participants
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
n=70 Participants
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.
|
|---|---|---|---|---|---|
|
Sleep Efficiency
|
86.3 Percentage of time asleep of 8 hours
Interval 58.2 to 98.0
|
91.3 Percentage of time asleep of 8 hours
Interval 60.9 to 97.6
|
94.3 Percentage of time asleep of 8 hours
Interval 47.4 to 99.2
|
94.5 Percentage of time asleep of 8 hours
Interval 65.3 to 98.9
|
93.5 Percentage of time asleep of 8 hours
Interval 70.6 to 99.3
|
SECONDARY outcome
Timeframe: 10 days (5 intervals of two consecutive nights)Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=71 Participants
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
n=70 Participants
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
n=69 Participants
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
n=68 Participants
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
n=70 Participants
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.
|
|---|---|---|---|---|---|
|
Wake Time After Sleep Onset (WASO)- Objective & Subjective
Objective Wake Time After Sleep Onset
|
26.3 Minutes
Interval 1.5 to 164.3
|
22.5 Minutes
Interval 1.0 to 144.8
|
17.8 Minutes
Interval 0.5 to 176.0
|
18.8 Minutes
Interval 0.8 to 165.5
|
20.0 Minutes
Interval 1.5 to 139.5
|
|
Wake Time After Sleep Onset (WASO)- Objective & Subjective
Subjective Wake Time After Sleep Onset
|
75.0 Minutes
Interval 3.0 to 300.0
|
60.0 Minutes
Interval 0.5 to 285.0
|
37.5 Minutes
Interval 0.0 to 255.0
|
40.0 Minutes
Interval 0.0 to 227.5
|
50.0 Minutes
Interval 0.0 to 285.0
|
SECONDARY outcome
Timeframe: 10 days (5 intervals of two consecutive nights)Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=71 Participants
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
n=70 Participants
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
n=69 Participants
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
n=68 Participants
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
n=70 Participants
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.
|
|---|---|---|---|---|---|
|
Number of Awakenings (Objective & Subjective)
Objective Number of Awakenings
|
4.0 Number of awakenings
Interval 0.5 to 18.0
|
4.0 Number of awakenings
Interval 0.0 to 11.0
|
3.5 Number of awakenings
Interval 0.0 to 10.0
|
2.8 Number of awakenings
Interval 0.0 to 10.0
|
3.5 Number of awakenings
Interval 0.5 to 14.0
|
|
Number of Awakenings (Objective & Subjective)
Subjective Number of Awakenings
|
3.0 Number of awakenings
Interval 0.0 to 11.0
|
3.0 Number of awakenings
Interval 0.5 to 8.0
|
2.5 Number of awakenings
Interval 0.0 to 6.5
|
2.0 Number of awakenings
Interval 0.0 to 8.0
|
2.0 Number of awakenings
Interval 0.0 to 6.0
|
Adverse Events
Placebo
Eszopiclone 1 mg
Eszopiclone 2 mg
Eszopiclone 3 mg
Zolpidem Tartrate 10 mg
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=71 participants at risk
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
n=70 participants at risk
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
n=69 participants at risk
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
n=68 participants at risk
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
n=70 participants at risk
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.
|
|---|---|---|---|---|---|
|
Nervous system disorders
Dysgeusia
|
1.4%
1/71
Safety population included randomized participants who were administered \>= 1 dose of study medication and had any evaluable safety data.
|
5.7%
4/70
Safety population included randomized participants who were administered \>= 1 dose of study medication and had any evaluable safety data.
|
8.7%
6/69
Safety population included randomized participants who were administered \>= 1 dose of study medication and had any evaluable safety data.
|
16.2%
11/68
Safety population included randomized participants who were administered \>= 1 dose of study medication and had any evaluable safety data.
|
1.4%
1/70
Safety population included randomized participants who were administered \>= 1 dose of study medication and had any evaluable safety data.
|
|
Nervous system disorders
Somnolence
|
2.8%
2/71
Safety population included randomized participants who were administered \>= 1 dose of study medication and had any evaluable safety data.
|
1.4%
1/70
Safety population included randomized participants who were administered \>= 1 dose of study medication and had any evaluable safety data.
|
4.3%
3/69
Safety population included randomized participants who were administered \>= 1 dose of study medication and had any evaluable safety data.
|
5.9%
4/68
Safety population included randomized participants who were administered \>= 1 dose of study medication and had any evaluable safety data.
|
4.3%
3/70
Safety population included randomized participants who were administered \>= 1 dose of study medication and had any evaluable safety data.
|
|
Nervous system disorders
Dizziness
|
0.00%
0/71
Safety population included randomized participants who were administered \>= 1 dose of study medication and had any evaluable safety data.
|
0.00%
0/70
Safety population included randomized participants who were administered \>= 1 dose of study medication and had any evaluable safety data.
|
0.00%
0/69
Safety population included randomized participants who were administered \>= 1 dose of study medication and had any evaluable safety data.
|
2.9%
2/68
Safety population included randomized participants who were administered \>= 1 dose of study medication and had any evaluable safety data.
|
4.3%
3/70
Safety population included randomized participants who were administered \>= 1 dose of study medication and had any evaluable safety data.
|
|
Skin and subcutaneous tissue disorders
Dermatitis Contact
|
2.8%
2/71
Safety population included randomized participants who were administered \>= 1 dose of study medication and had any evaluable safety data.
|
2.9%
2/70
Safety population included randomized participants who were administered \>= 1 dose of study medication and had any evaluable safety data.
|
1.4%
1/69
Safety population included randomized participants who were administered \>= 1 dose of study medication and had any evaluable safety data.
|
0.00%
0/68
Safety population included randomized participants who were administered \>= 1 dose of study medication and had any evaluable safety data.
|
1.4%
1/70
Safety population included randomized participants who were administered \>= 1 dose of study medication and had any evaluable safety data.
|
|
General disorders
Feeling Abnormal
|
0.00%
0/71
Safety population included randomized participants who were administered \>= 1 dose of study medication and had any evaluable safety data.
|
4.3%
3/70
Safety population included randomized participants who were administered \>= 1 dose of study medication and had any evaluable safety data.
|
0.00%
0/69
Safety population included randomized participants who were administered \>= 1 dose of study medication and had any evaluable safety data.
|
0.00%
0/68
Safety population included randomized participants who were administered \>= 1 dose of study medication and had any evaluable safety data.
|
0.00%
0/70
Safety population included randomized participants who were administered \>= 1 dose of study medication and had any evaluable safety data.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place