Clinical trial NCT00671255: Safety and Efficacy of Ramelteon in Elderly Subjects With Chronic Insomnia
Official title: A Phase III, Randomized, Double-Blind, Placebo-Controlled, Outpatient, Safety and Efficacy Study of TAK-375 in Elderly Subjects With Chronic Insomnia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Insomnia
Keywords: Chronic Insomnia
Drug Therapy
Elderly
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2008-05-05
Enrollment: 829
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This purpose of this study is to evaluate the safety and effectiveness of Ramelteon, once daily (QD), in elderly participants with chronic insomnia.

Detailed description: Insomnia is characterized by a complaint of initiating and maintaining sleep or complaints of nonrestorative and non-refreshing sleep. Transient insomnia affects approximately one-third to one-half of the US population, based on the results of 2 surveys of representative samples of the adult US population conducted by the Gallup Organization in which respondents were asked if they had "ever had difficulty sleeping." Based on reports of "regular" or "frequent" sleep difficulty, results from the same studies suggest that approximately one-tenth of the US population experiences chronic insomnia. The ideal treatment for insomnia would reduce the latency to onset of sleep and increase total sleep time, without a negative impact on sleep architecture and without safety concerns or next-day effects.

Ramelteon is a selective melatonin-1 receptor agonist under development by Takeda Chemical Industries, Ltd., for the treatment of transient and chronic insomnia and for the treatment of Circadian Rhythm Sleep Disorders.

Ramelteon is the first candidate in a novel class of drugs based on this mechanism. Based on non-clinical and clinical studies completed to date, TAK-375 has the potential to offer unique advantages relative to approved hypnotics in terms of its pharmacological profile and its selectivity to the melatonin-1 receptor.

This study is designed to determine the safety and efficacy of 35-day treatment of chronic insomnia with ramelteon. Participation in this study is anticipated to be approximately 2 months.

Eligibility criteria: Inclusion Criteria

* Subject is a male or a post-menopausal female.
* Primary insomnia as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Revised for at least 3 months and a history of daytime complaint(s) associated with disturbed sleep.
* Subjective sleep latency greater than or equal to 45 minutes and a subjective total sleep time less than or equal to 6.5 hours per night for at least 3 nights during the week of the lead-in period.
* Habitual bedtime is between 8:30 PM and 12:00 AM.
* Body mass index between 18 and 34, inclusive.

Exclusion Criteria

* Known hypersensitivity to ramelteon or related compounds, including melatonin.
* Previously participated in a study involving ramelteon.
* Participated in any other investigational study, and/or took any investigational drug within 30 days or five half-lives prior to the first day of single-blind study medication, whichever is longer.
* Sleep schedule changes required by employment (eg, shift worker) within three months prior to the first day of single-blind study medication, or has flown across greater than three time zones within seven days prior to screening.
* Participated in a weight loss program or substantially altered exercise routine within 30 days prior to the first day of single blind study medication.
* Has ever had a history of seizures, sleep apnea, chronic obstructive pulmonary disease, restless leg syndrome, schizophrenia, bipolar disorder, mental retardation, or cognitive disorder.
* History of psychiatric disorder within the past 12 months.
* History of drug addiction or drug abuse within the past 12 months.
* History of alcohol abuse within the past 12 months, as defined in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Revised and/or regularly consumes 4 or more alcoholic drinks per day.
* Current significant neurological, hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, hematologic or metabolic disease, unless currently controlled and stable with protocol-allowed medication.
* Uses tobacco products during nightly awakenings.
* Any clinically important abnormal finding as determined by a medical history, physical examination, electrocardiogram, or clinical laboratory tests, as determined by the investigator.
* Positive hepatitis panel.
* Any additional condition(s) that in the Investigator's opinion would:

  * affect sleep-wake function
  * prohibit the subject from completing the study
  * not be in the best interest of the subject.
* Is required to take or continues taking any disallowed medication, prescription medication, herbal treatment or over-the counter medication, including:

  * Anxiolytics
  * Hypnotics
  * Antidepressants
  * Anticonvulsants
  * Sedating H1 antihistamines
  * Systemic steroids
  * Respiratory stimulants
  * Decongestants
  * Over-the-counter and prescription stimulants
  * Over-the-counter and prescription diet aids
  * Central nervous system active drugs
  * Narcotic analgesics
  * All beta blockers
  * Melatonin
  * St. John's Wort
  * Kava-kava
  * Gingko biloba

Primary outcomes:
measure: Mean Subjective Sleep Latency per subject diary, from Nights 1 through 7 of double-blind Treatment
timeFrame: Weeks 1, 2, 3, 4 and 5 or Final Visit.
Secondary outcomes:
measure: Subjective Total Sleep Time.
timeFrame: Weeks 1, 2, 3, 4 and 5 or Final Visit.
measure: Subjective Number of Awakenings.
timeFrame: Weeks 1, 2, 3, 4 and 5 or Final Visit.
measure: Subjective Ease of Falling Back to Sleep after Awakening.
timeFrame: Weeks 1, 2, 3, 4 and 5 or Final Visit.
measure: Subjective Sleep Quality.
timeFrame: Weeks 1, 2, 3, 4 and 5 or Final Visit.
measure: Clinical Global Impression Change of Condition.
timeFrame: Weeks 1, 2, 3, 4 and 5 or Final Visit.
measure: Clinical Global Impression Severity of Illness.
timeFrame: Weeks 1, 2, 3, 4 and 5 or Final Visit.
measure: Clinical Global Impression Therapeutic Effect.
timeFrame: Weeks 1, 2, 3, 4 and 5 or Final Visit.
measure: Clinical Global Impression Side Effects.
timeFrame: Weeks 1, 2, 3, 4 and 5 or Final Visit.
measure: Average Subjective Sleep Latency over the week preceding the Day 15, Day 22, Day 29, and Day 36 Visits.
timeFrame: Weeks 2, 3, 4 and 5 or Final Visit.
Other outcomes:
Locations:
city: Columbiana
country: United States
state: Alabama
city: Mobile
country: United States
state: Alabama
city: Muscle Shoals
country: United States
state: Alabama
city: Tallahassee
country: United States
state: Alabama
city: Phoenix
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state: Arizona
city: Scottsdale
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state: Arizona
city: Tempe
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state: Arizona
city: Hot Springs
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state: Arkansas
city: Little Rock
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state: Arkansas
city: Anaheim
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state: California
city: Encinitas
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state: California
city: Irvine
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state: California
city: La Jolla
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state: California
city: La Mesa
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state: California
city: Los Angeles
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state: California
city: Murrieta
country: United States
state: California
city: Northridge
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state: California
city: Oakland
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state: California
city: Redlands
country: United States
state: California
city: Riverside
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state: California
city: Rosemead
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state: California
city: San Diego
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state: California
city: Spring Valley
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state: California
city: Vista
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state: California
city: Colorado Springs
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state: Colorado
city: Denver
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state: Colorado
city: Clearwater
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state: Florida
city: DeLand
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city: Hollywood
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city: Jacksonville
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city: Kissimmee
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city: Longwood
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city: Pembroke Pines
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city: Pinellas Park
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city: Safety Harbor
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state: Florida
city: St. Petersburg
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state: Florida
city: Tampa
country: United States
state: Florida
city: Vero Beach
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state: Florida
city: West Palm Beach
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state: Florida
city: Winter Park
country: United States
state: Florida
city: Atlanta
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state: Georgia
city: Blairsville
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state: Georgia
city: Macon
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state: Georgia
city: Chciago
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state: Illinois
city: Northfield
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state: Illinois
city: Evansville
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state: Indiana
city: Shawnee Mission
country: United States
state: Kansas
city: Wichita
country: United States
state: Kansas
city: Louisville
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state: Kentucky
city: Murray
country: United States
state: Kentucky
city: New Orleans
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state: Louisiana
city: Bethesda
country: United States
state: Maryland
city: Belmont
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state: Massachusetts
city: Brockton
country: United States
state: Massachusetts
city: Newton
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state: Massachusetts
city: Detroit
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state: Michigan
city: Hattiesburg
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state: Mississippi
city: Kansas City
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state: Missouri
city: St. Louis
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state: Missouri
city: Lincoln
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state: Nebraska
city: Las Vegas
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state: Nevada
city: Brick
country: United States
state: New Jersey
city: Edison
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state: New Jersey
city: Toms River
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city: Albuquerque
country: United States
state: New Mexico
city: Great Neck
country: United States
state: New York
city: Manlius
country: United States
state: New York
city: Mineola
country: United States
state: New York
city: Williamsville
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state: New York
city: Cary
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state: North Carolina
city: Greensboro
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state: North Carolina
city: Hickory
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state: North Carolina
city: Raleigh
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state: North Carolina
city: Salisbury
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state: North Carolina
city: Winston-Salem
country: United States
state: North Carolina
city: Beachwood
country: United States
state: Ohio
city: Canfield
country: United States
state: Ohio
city: Cincinnati
country: United States
state: Ohio
city: Toledo
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Tulsa
country: United States
state: Oklahoma
city: Eugene
country: United States
state: Oregon
city: Portland
country: United States
state: Oregon
city: Jenkintown
country: United States
state: Pennsylvania
city: Reading
country: United States
state: Pennsylvania
city: Scotland
country: United States
state: Pennsylvania
city: Warwick
country: United States
state: Rhode Island
city: Anderson
country: United States
state: South Carolina
city: Greer
country: United States
state: South Carolina
city: Mt. Pleasant
country: United States
state: South Carolina
city: Fayetteville
country: United States
state: Tennessee
city: Johnson City
country: United States
state: Tennessee
city: Dallas
country: United States
state: Texas
city: Fort Worth
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Norfolk
country: United States
state: Virginia
city: Bellevue
country: United States
state: Washington
city: Gig Harbor
country: United States
state: Washington
city: Madison
country: United States
state: Wisconsin
city: New Berlin
country: United States
state: Wisconsin
city: Calgary
country: Canada
state: Alberta
city: Edmonton
country: Canada
state: Alberta
city: Medicine Hat
country: Canada
state: Alberta
city: North Vancouver
country: Canada
state: British Columbia
city: Winnipeg
country: Canada
state: Manitoba
city: St. John's
country: Canada
state: Newfoundland and Labrador
city: Corunna
country: Canada
state: Ontario
city: London
country: Canada
state: Ontario
city: North Bay
country: Canada
state: Ontario
city: Sarnia
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Parkdale
country: Canada
state: Prince Edward Island
city: Montreal
country: Canada
state: Quebec
Study officials:
affiliation: Takeda
name: VP Clinical Science
role: STUDY_DIRECTOR
References:
citation: Mini LJ, Wang-Weigand S, Zhang J. Self-reported efficacy and tolerability of ramelteon 8 mg in older adults experiencing severe sleep-onset difficulty. Am J Geriatr Pharmacother. 2007 Sep;5(3):177-84. doi: 10.1016/j.amjopharm.2007.09.004.
citation: Roth T, Seiden D, Sainati S, Wang-Weigand S, Zhang J, Zee P. Effects of ramelteon on patient-reported sleep latency in older adults with chronic insomnia. Sleep Med. 2006 Jun;7(4):312-8. doi: 10.1016/j.sleep.2006.01.003. Epub 2006 May 18.