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. )

Tracking Information

• First Submitted Date: October 9, 2008
• First Posted Date: October 10, 2008
• Results First Submitted Date: December 28, 2012
• Results First Posted Date: February 4, 2013
• Last Update Posted Date: February 4, 2013
• Study Start Date: September 2008
• Actual Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 28, 2012)

• Latency To Persistent Sleep (LPS) [ Time Frame: 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) [ Time Frame: 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.

• Original Primary Outcome Measures (submitted: October 9, 2008): Latency to persistent sleep and sleep latency (co-primary measures) [ Time Frame: 2 consecutive nights of each term; number of terms = 5. ]

Current Secondary Outcome Measures (submitted: December 28, 2012)

• Total Sleep Time (Objective & Subjective) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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.

• Original Secondary Outcome Measures (submitted: October 9, 2008): Objective total sleep time, sleep efficiency and subjective evaluation by questionnaires [ Time Frame: 2 consecutive nights of each term; number of terms = 5. ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase II/III Study of SEP-190 (Eszopiclone) in Patients With Primary Insomnia (Study 190-126)
• Official Title: A Phase II/III Study of SEP-190 (Eszopiclone) in Patients With 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.
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Primary Insomnia

Intervention

• 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 Name: SEP-190
• 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 Name: SEP-190
• 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 Name: SEP-190
• 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.
• 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.

Study Arms

• Experimental: Eszopiclone 1 mg
  Intervention: Drug: Eszopiclone 1 mg
• Experimental: Eszopiclone 2 mg
  Intervention: Drug: Eszopiclone 2 mg
• Experimental: Eszopiclone 3 mg
  Intervention: Drug: Eszopiclone 3 mg
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo
• Active Comparator: Zolpidem Tartrate 10 mg
  Intervention: Drug: Zolpidem Tartrate 10 mg

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 28, 2012): 192
• Original Estimated Enrollment (submitted: October 9, 2008): 70
• Actual Study Completion Date: May 2010
• Actual Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 21 Years to 64 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT00770510
• Other Study ID Numbers: 190-126
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Eisai Inc. ( Eisai Co., Ltd. )
• Original Responsible Party: Customer Information Services Department. CRC and QA, Eisai Company Limited
• Current Study Sponsor: Eisai Co., Ltd.
• Original Study Sponsor: Eisai Limited
• Collaborators: Not Provided

Investigators

• Study Director: Atsushi Kamijo; New Product Development Department, Clinical Research Center

• PRS Account: Eisai Inc.
• Verification Date: December 2012