Safety and Efficacy of Ramelteon and Doxepin in Subjects With Chronic Insomnia

NCT00755495 | Completed Phase 2

• 2 other identifiers: 01-05-TL-375-067U1111-1114-2536
• Study Type: interventional
• Target: 472
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to determine the efficacy of ramelteon, once daily (QD), combined with doxepin in treating subjects with insomnia.

Conditions

Sleep Initiation and Maintenance Disorders

Keywords

Chronic Insomnia; DIMS (Disorders of Initiating and Maintaining Sleep); Disorders of Initiating and Maintaining Sleep; Insomnia Disorder Sleep Initiation Dysfunction; Transient Insomnia; Drug Therapy; Sleep Disorders, Intrinsic

Outcome Measures

Primary Outcomes (1)

• Mean wake time after persistent sleep onset during the double-blind Treatment Period, as measured by polysomnography

  Weeks 1, 3, and 5 or Final Visit

Secondary Outcomes (10)

• Number of awakenings after persistent sleep determined by polysomnography.

  Weeks 1, 3, and 5 or Final Visit

• Latency to Persistent Sleep determined by polysomnography.

  Weeks 1, 3, and 5 or Final Visit

• Total Sleep Time determined by polysomnography.

  Weeks 1, 3, and 5 or Final Visit

• Subjective wake time after persistent sleep onset in the sleep lab and at home, as determined by post-sleep questionnaire completed by subject via IVRS.

  Weeks 1, 2, 3, 4, and 5 or Final Visit.

• Subjective number of awakenings in the sleep lab and at home, as determined by post-sleep questionnaire completed by subject via IVRS.

  Weeks 1, 2, 3, 4, and 5 or Final Visit.

Study Arms (4)

Ramelteon 8 mg QD and Doxepin 3 mg QD

EXPERIMENTAL

Drug: Ramelteon and doxepin

Ramelteon 8 mg QD and Doxepin Placebo QD

EXPERIMENTAL

Drug: Ramelteon

Ramelteon Placebo QD and Doxepin 3 mg QD

ACTIVE COMPARATOR

Drug: Doxepin

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Ramelteon and doxepin DRUG

Ramelteon 8 mg, tablets, orally, once daily and doxepin 3 mg, liquid, orally, once daily for up to five weeks.

Also known as: Rozerem™, TAK-375, Sinequan®, ramelteon

Ramelteon 8 mg QD and Doxepin 3 mg QD

Ramelteon DRUG

Ramelteon 8 mg, tablets, orally, once daily and doxepin placebo-matching liquid, orally, once daily for up to five weeks.

Also known as: Rozerem™, TAK-375

Ramelteon 8 mg QD and Doxepin Placebo QD

Doxepin DRUG

Ramelteon placebo-matching tablets, orally, once daily and doxepin 3 mg, liquid, orally, once daily for up to five weeks.

Also known as: Sinequan®

Ramelteon Placebo QD and Doxepin 3 mg QD

Placebo DRUG

Ramelteon placebo-matching tablets, orally, once daily and doxepin placebo-matching liquid, orally, once daily for up to five weeks.

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Based on sleep history, the subject has had primary insomnia as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Revised (DSM-IV-TR™) for at least 3 months.
• Female patients of childbearing potential must be nonpregnant and nonlactating, and utilizing an acceptable method of contraception.
• Has a body mass index between 18 and 34 inclusive (weight/height2).
• Based on sleep history, the subject reports subjective sleep latency greater than or equal to 45 minutes and reports wake time after persistent sleep onset of greater than or equal to 45 minutes.
• The subject has an average wake time after persistent sleep onset of at least 60 minutes as determined by polysomnography during Screening (Day -7 PM through Day -5 AM). Wake time after persistent sleep onset must be greater than or equal to 30 minutes each night of polysomnography Screening.
• In addition to meeting the criteria for wake time after persistent sleep onset, must have an average latency to persistent sleep of at least 20 minutes as determined by polysomnography during Screening (Day -7 PM through Day -5 AM). Latency to persistent sleep must be greater than or equal to 15 minutes each night of polysomnography Screening.
• Based on sleep history, the subject's habitual bedtime is between 9:00 PM and 1:00 AM.
• Is willing to have a fixed bedtime and agrees to go to bed within +/-30 minutes of the habitual bedtime during the entire study.
• Is willing to remain in bed for at least 8 hours each night during the entire study.
• Based on sleep history, the subject either has not been using pharmacological assistance to sleep or uses pharmacological assistance no more than 4 times per week during the 3 months prior to Initial Screening. Subjects must agree to discontinue the use of all pharmacological sleep aids beginning 1 week prior to polysomnography Screening and throughout the entire duration of the study.
• Has consistent access to a touch-tone phone and are willing to complete telephone questionnaires during participation in the study.

You may not qualify if:

• Has a known hypersensitivity to doxepin or related compounds (tricyclic antidepressants), or ramelteon or related compounds, including melatonin, and 5-hydroxytryptophan.
• Has participated in any other investigational study and/or taken any investigational drug within 30 days prior to the first dose of single-blind study medication.
• Has sleep schedule changes required by employment (eg, shift worker) within 3 months prior to the first dose of single-blind study medication.
• Has flown across greater than 3 time zones within 7 days prior to Initial Screening, or will travel across 2 or more time zones during the course of the study.
• Has participated in a weight loss program or has substantially altered their exercise routine within 30 days prior to the first dose of single-blind study medication.
• Is required to take or intends to continue taking any disallowed medication or any prescription medication or over-the counter medication that is known to affect the sleep/wake function or otherwise interfere with evaluation of the study medication, including:
• Anxiolytics central nervous system active drugs (including herbal).
• Hypnotics Narcotic analgesics.
• Antidepressants Beta blockers.
• Anticonvulsants St. John's Wort.
• Sedating H1 antihistamines Kava-kava.
• Systemic steroids Ginkgo-biloba.
• Respiratory stimulants over-the-counter and prescription stimulants.
• Sedating decongestants over-the-counter and prescription diet aids.
• Antipsychotics over-the-counter sleep aids.

Sponsors & Collaborators

• Takeda: lead

Related Links

• Rozerem Package Insert.

MeSH Terms

Conditions

Sleep Initiation and Maintenance Disorders; Sleep Disorders, Intrinsic

Interventions

ramelteon; Doxepin

Condition Hierarchy (Ancestors)

Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders

Intervention Hierarchy (Ancestors)

Oxepins; Ethers, Cyclic; Ethers; Organic Chemicals; Dibenzoxepins; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Medical Director Clinical Science

  Takeda

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2008
• First Posted: September 19, 2008
• Study Start: July 1, 2006
• Primary Completion: March 1, 2007
• Study Completion: March 1, 2007
• Last Updated: February 28, 2012

Record last verified: 2012-02