Efficacy and Safety of Eplivanserin Treatment for Sleep Maintenance Insomnia (GEMS)

• Change from baseline of the mean of the FOSQ items 1 and 2 (concentration/memory) [ Time Frame: at week 12 ] [ Designated as safety issue: No ]
• Change from baseline of the mean of the FOSQ items 4 and 10 (hobby/work) [ Time Frame: at week 12 ] [ Designated as safety issue: No ]

• Secondary outcomes
• Main secondary objective:
• - To evaluate patient’s daytime functioning; using the FOSQ
• Other secondary objectives:
• - To evaluate residual effects(using patient’s morning questionnaire)
• - To compare the effect on sleep following abrupt discontinuation (after 12 weeks) *
• - To evaluate the clinical safety and tolerability of eplivanserin 5mg/day compared to placebo
• - To document eplivanserin and the main metabolite SR141342 plasma concentrations of eplivanserin.

The purpose of the study is to assess efficacy and safety of eplivanserin in the population of patients complaining of sleep maintenance insomnia. The patients suffering from that condition frequently wake up during the night, their sleep is nonrestorative and they suffer from a significant distress or impairment in their daily activities consecutive to insomnia.

The study is being conducted world-wide. It consists of 3 segments:

• Segment A: 7-day run-in (screening).
• Segment B: 12-week double blind treatment.
• Segment C: 2-week Run-out period

An IVR system will be used to register patients, report completion of certain phases of the trial, and to discontinue patients. In addition, a daily patient diary will be completed via the IVRS. A central laboratory for processing blood specimens will be used. Patients will be requested to complete questionnaires at each visit, including completion of the FOSQ (Functional Outcome of Sleep Questionnaire) the evening prior to each visit.

• Sleep Initiation and Maintenance Disorders
• Insomnia

• Drug: eplivanserin (SR46349)
  oral administration
• Drug: placebo
  oral administration

• Experimental: 1
  5 mg/day
  Intervention: Drug: eplivanserin (SR46349)
• Placebo Comparator: 2
  Intervention: Drug: placebo

Inclusion Criteria:

• Out patients
• Each patient must have primary insomnia in accordance with DSM-IV-TR-Axis I criteria
• Based on patient's information, the patient must complain of at least one hour of wakefulness after sleep onset for at least 3 nights per week over the preceding month
• Patient must report impact daytime functioning associated with sleep maintenance insomnia as measured by question 3 of Insomnia Severity Index at screening visit and randomization visit.

Exclusion Criteria:

• Females who are lactating or pregnant
• Woman of childbearing potential with a positive serum beta human chorionic gonadotropin pregnancy test at screening and not using an acceptable form of contraception
• Patients presenting with acute or chronic pain resulting in insomnia
• Patients with history of epilepsy or seizures
• Consumption of xanthine containing beverage (i.e. tea, coffee, or cola) comprising more than 5 glasses/day
• Evidence of any clinically significant, severe, or unstable acute or chronically progressive medical or surgical disorder which may affect patient safety
• BMI >32
• Acute or chronic pain resulting in insomnia
• Patients with current psychiatric disorders according to DSM-IV-TR criteria, mental retardation, or dementia
• Clinically significant and abnormal EKG (QTc interval >=500 msec)
• Positive for hepatitis B or C
• Serious head injury or stroke within 1 year
• Use of OTC medications such as valerian root, kava, melatonin, St. John's Wort, or alluna; prescription sleep medications or anxiolytics within 1 week or 5 half-lives
• Participation in another trial within two month before the screening visit
• Use of any substance with psychotropic effects or properties known to affect sleep/wake
• Unable to complete the study questionnaires
• Night shift workers, and individuals who nap 3 or more times per week over the preceding month

• History of:

  • Primary hypersomnia
  • Narcolepsy
  • Breathing-related sleep disorder (such as sleep apnea)
  • Circadian rhythm sleep disorder
  • Parasomnia (somnambulism)
  • Dyssomnia (such as periodic leg movements)