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

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

Status

Completed

Phases

Phase 2Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00770510

Enrollment

192

Registered

2008-10-10

Start date

2008-09-30

Completion date

2010-05-31

Last updated

2013-02-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Primary Insomnia

Keywords

Primary insomnia

Brief summary

The purpose of this study is to investigate and evaluate the efficacy of Eszopiclone in Japanese participants with primary insomnia.

Detailed description

This is a multicenter, randomized, double-blind, placebo-controlled, 5-way cross-over study to investigate and evaluate the efficacy of eszopiclone in Japanese participants with primary insomnia. The treatment period consists of two consecutive days (two nights) as one term. Patients will receive oral eszopiclone (1, 2, 3 mg), zolpidem tartrate (10 mg), or placebo once daily at bedtime for each use. Participants were randomly assigned to one of 10 prespecified treatment sequence patterns.

Interventions

DRUGEszopiclone 1 mg

Eszopiclone 1 mg tablet, taken orally at bed time for 2 consecutive nights. Each participant was assigned to one of 10 prespecified treatment sequence patterns. Each interval (five total intervals) of 2 consecutive nights was separated by a washout of approximately 5 days. A follow-up period consisted of 6 days.

DRUGEszopiclone 2 mg

Eszopiclone 2 mg tablet, taken orally at bed time for 2 consecutive nights. Each participant was assigned to one of 10 prespecified treatment sequence patterns. Each interval (five total intervals) of 2 consecutive nights was separated by a washout of approximately 5 days. A follow-up period consisted of 6 days.

DRUGEszopiclone 3 mg

Eszopiclone 3 mg tablet, taken orally at bed time for 2 consecutive nights. Each participant was assigned to one of 10 prespecified treatment sequence patterns. Each interval (five total intervals) of 2 consecutive nights was separated by a washout of approximately 5 days. A follow-up period consisted of 6 days.

DRUGPlacebo

Placebo tablet, taken orally at bed time for 2 consecutive nights. Each participant was assigned to one of 10 prespecified treatment sequence patterns. Each interval (five total intervals) of 2 consecutive nights was separated by a washout of approximately 5 days. A follow-up period consisted of 6 days.

DRUGZolpidem Tartrate 10 mg

Zolpidem Tartrate 10 mg tablet, taken orally at bed time for 2 consecutive nights. Each participant was assigned to one of 10 prespecified treatment sequence patterns. Each interval (five total intervals) of 2 consecutive nights was separated by a washout of approximately 5 days. A follow-up period consisted of 6 days.

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

21 Years to 64 Years

Healthy volunteers

Inclusion criteria

1. Participants aged greater than or equal to 21 and less than 65 years at the time of obtaining written informed consent 2. Participants diagnosed with primary insomnia based on the Diagnostic and Statistical Manual of Mental Disorders, text revision (DSM-IV-TR) Japanese version and have both of the following conditions which are persistent for more than or equal to 4 weeks before the start of observation period: * Sleep latency of more than or equal to 30 minutes for more than or equal to 3 days a week * Total sleep time of less than or equal to 390 minutes for more than or equal to 3 days a week 3. Participants who meet both of the following based on polysomnogram (PSG) in observation period: * Objective sleep latency of more than or equal to 20 minutes for 2 consecutive PSG days * Objective total sleep time of less than or equal to 420 minutes for 2 consecutive PSG days, or objective wake time during sleep of more than or equal to 20 minutes for 2 consecutive PSG days

Exclusion criteria

1. Participants with comorbid primary sleep disorders (e.g., circadian rhythm disorder, restless limb syndrome, periodic limb movement disorder, sleep apnea syndrome), other than primary insomnia. 2. Participants with insomnia caused by pharmacological actions (drug-induced insomnia). 3. Participants with comorbid sleep disorder associated with other disease(s) such as psychiatric and/or physical disease(s). 4. Participants with a complication of psychiatric disorders in Axis I or personality disorder in Axis II defined in DSM-IV-TR Japanese version. 5. Participants with organic mental disorder.

Design outcomes

Primary

Measure	Time frame	Description
Latency To Persistent Sleep (LPS)	10 days (5 intervals of two consecutive nights)	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.
Sleep Latency (SL)	10 days (5 intervals of two consecutive nights)	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.

Secondary

Measure	Time frame	Description
Total Sleep Time (Objective & Subjective)	10 days (5 intervals of two consecutive nights)	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.
Sleep Efficiency	10 days (5 intervals of two consecutive nights)	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.
Wake Time After Sleep Onset (WASO)- Objective & Subjective	10 days (5 intervals of two consecutive nights)	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.
Number of Awakenings (Objective & Subjective)	10 days (5 intervals of two consecutive nights)	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.

Countries

Japan

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).

Participants by arm

Arm	Count
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	72
Total	72

Arm

Count

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

Total

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Lost to Follow-up	2
Overall Study	Pregnancy	1
Overall Study	Withdrawal by Subject	2

Baseline characteristics

Characteristic	Entire Study Population
Age Continuous	39.4 years STANDARD_DEVIATION 11.9
Sex: Female, Male Female	29 Participants
Sex: Female, Male Male	43 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	5 / 71	10 / 70	10 / 69	17 / 68	8 / 70
serious Total, serious adverse events	0 / 71	0 / 70	0 / 69	0 / 68	0 / 70

Outcome results

Primary

Latency To Persistent Sleep (LPS)

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.