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

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

Study Overview

• Status: Completed
• Conditions: Primary Insomnia
• Intervention / Treatment: Drug: Eszopiclone 1 mg; Drug: Eszopiclone 2 mg; Drug: Eszopiclone 3 mg; Drug: Placebo; Drug: Zolpidem Tartrate 10 mg

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.

• Study Type: Interventional
• Enrollment (Actual): 192
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Japan
  • Akita, Japan
  • Fukuoka, Japan
  • Gifu, Japan
  • Hiroshima, Japan
  • Kagoshima, Japan
  • Kochi, Japan
  • Kumamoto, Japan
  • Kyoto, Japan
  • Osaka, Japan
  • Aichi
    • Toyohashi, Aichi, Japan
  • Fukuoka
    • Kitakyushu, Fukuoka, Japan
    • Kurume, Fukuoka, Japan
  • Hokkaido
    • Otaru, Hokkaido, Japan
    • Sapporo, Hokkaido, Japan
  • Kanagawa
    • Kawasaki, Kanagawa, Japan
  • Okinawa
    • Urazoe, Okinawa, Japan
  • Osaka
    • Sakai, Osaka, Japan
  • Tokyo
    • Kodaira, Tokyo, Japan
    • Setagaya, Tokyo, Japan
    • Shibuya, Tokyo, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; 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.
Experimental: Eszopiclone 1 mg	Drug: Eszopiclone 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.; Other Names: SEP-190
Experimental: Eszopiclone 2 mg	Drug: Eszopiclone 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.; Other Names: SEP-190
Experimental: Eszopiclone 3 mg	Drug: Eszopiclone 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.; Other Names: SEP-190
Active Comparator: Zolpidem Tartrate 10 mg	Drug: Zolpidem 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	10 days (5 intervals of two consecutive nights)
Sleep Latency (SL)	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.	10 days (5 intervals of two consecutive nights)

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Eisai Co., Ltd.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): May 1, 2010
• Study Completion (Actual): May 1, 2010

Study Registration Dates

• First Submitted: October 9, 2008
• First Submitted That Met QC Criteria: October 9, 2008
• First Posted (Estimate): October 10, 2008

Study Record Updates

• Last Update Posted (Estimate): February 4, 2013
• Last Update Submitted That Met QC Criteria: December 28, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Keywords: Primary insomnia
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Sleep Initiation and Maintenance Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Hypnotics and Sedatives; GABA Agents; Sleep Aids, Pharmaceutical; GABA-A Receptor Agonists; GABA Agonists; Eszopiclone; Zolpidem
• Other Study ID Numbers: 190-126