Safety and Efficacy of Ramelteon in Elderly Subjects With Chronic Insomnia.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT00671294
First received: May 1, 2008
Last updated: February 27, 2012
Last verified: February 2012
  Purpose

This purpose of this study is to assess the efficacy and safety of Ramelteon, once daily (QD), in elderly subjects with chronic insomnia.


Condition Intervention Phase
Chronic Insomnia
Drug: Ramelteon and Placebo (9 possible combinations total)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase III, Randomized, Double-Blind, Placebo-Controlled, Crossover Study to Determine the Safety and Efficacy of TAK-375 in Elderly Subjects With Chronic Insomnia.

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Mean latency to persistent sleep of 2-night per polysomnogram recordings, from nights 1 and 2 of each Treatment Period. [ Time Frame: Crossover Periods 1, 2, and 3 on Nights 1 and 2 or Final Visit. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Total Sleep Time. [ Time Frame: Crossover Periods 1, 2, and 3 on Nights 1 and 2 or Final Visit. ] [ Designated as safety issue: No ]
  • Sleep Efficiency. [ Time Frame: Crossover Periods 1, 2, and 3 on Nights 1 and 2 or Final Visit. ] [ Designated as safety issue: No ]
  • Wake Time after Sleep Onset. [ Time Frame: Crossover Periods 1, 2, and 3 on Nights 1 and 2 or Final Visit. ] [ Designated as safety issue: Yes ]
  • Number of Awakenings after Persistent Sleep Onset. [ Time Frame: Crossover Periods 1, 2, and 3 on Nights 1 and 2 or Final Visit. ] [ Designated as safety issue: No ]
  • Subjective Sleep Latency. [ Time Frame: Crossover Periods 1, 2, and 3 on Mornings 2 and 3 or Final Visit. ] [ Designated as safety issue: No ]
  • Subjective Total Sleep Time. [ Time Frame: Crossover Periods 1, 2, and 3 on Mornings 2 and 3 or Final Visit. ] [ Designated as safety issue: No ]
  • Subjective Wake Time after Sleep Onset. [ Time Frame: Crossover Periods 1, 2, and 3 on Mornings 2 and 3 or Final Visit. ] [ Designated as safety issue: No ]
  • Subjective Number of Awakenings. [ Time Frame: Crossover Periods 1, 2, and 3 on Mornings 2 and 3 or Final Visit. ] [ Designated as safety issue: No ]
  • Subjective Ease of Falling Back to Sleep after Awakening. [ Time Frame: Crossover Periods 1, 2, and 3 on Mornings 2 and 3 or Final Visit. ] [ Designated as safety issue: No ]
  • Subjective Sleep Quality. [ Time Frame: Crossover Periods 1, 2, and 3 on Mornings 2 and 3 or Final Visit. ] [ Designated as safety issue: No ]

Enrollment: 100
Study Start Date: October 2002
Study Completion Date: July 2003
Primary Completion Date: July 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ramelteon and Placebo QD (9 possible combinations total) Drug: Ramelteon and Placebo (9 possible combinations total)

Randomized sequence over two consecutive nights for a total of three treatment periods to include the following:

Ramelteon 4 mg, tablets, orally over two nights

Ramelteon 8 mg, tablets, orally over two nights

Ramelteon placebo-matching tablets, orally over two nights

Other Names:
  • Ramelteon
  • Rozerem
  • TAK-375

Detailed Description:

Insomnia is characterized by a complaint of difficulties initiating and maintaining sleep or 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 melatonin-1 receptor agonist under global development by Takeda Chemical Industries, Ltd., Osaka, Japan, for the treatment of transient and chronic insomnia and for the treatment of Circadian Rhythm Sleep Disorders.

Participation in this study is anticipated to be about 2 months.

  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • Male or a post-menopausal female.
  • Primary insomnia as defined by the Diagnostic and Statistical Manual of Mental Disorders, Text Revision for at least 3 months and as defined by subjective sleep latency greater than or equal to 30 minutes, subjective total sleep time less than or equal to 6.5 hours per night, and daytime complaint(s) associated with disturbed sleep.
  • Mean latency of greater than or equal to 20 minutes per polysomnography on two consecutive screening nights with neither night less than 15 minutes. Also, a mean of 60 minutes of wake time during the 480 minutes in bed across two nights with no night less than 45 minutes.
  • Habitual bedtime is between 8:30 p.m. and 12:00 a.m.
  • 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 taken any investigational drug within 30 days or five half-lives prior to Day 1 of single-blind study medication, whichever is longer.
  • Sleep schedule changes required by employment (eg, shift worker) within three months prior to Day 1 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 has substantially altered their exercise routine within 30 days prior to Day 1 of single-blind study medication.
  • Ever had a history of seizures, sleep apnea, chronic obstructive pulmonary disease, schizophrenia, bipolar disorder, mental retardation, or cognitive disorder.
  • History of psychiatric disorder (including anxiety or depression) 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.
  • Had an acute clinically significant illness, as determined by the investigator, within 30 days prior to Day 1 of single-blind study medication.
  • Current significant neurological (including cognitive and psychiatric disorders), hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, hematologic, or metabolic disease, unless currently controlled and stable with protocol-allowed medication 30 days prior to Day 1 of single-blind study medication.
  • Used tobacco products within 90 days prior to Day 1 of single-blind study medication.
  • Used melatonin, or other drugs or supplements known to affect sleep/wake function, or has consumed grapefruit or grapefruit juice within 5 days (or 5 half lives, whichever is longer) prior to Day 1 of single-blind study medication.
  • Used any central nervous system medication within 3 weeks (or 5 half lives of the drug, whichever is longer) prior to Day 1 of singleblind study medication. These medications must not have been used to treat psychiatric disorders.
  • 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 including anti-hepatitis A virus (only immunoglobulin M is exclusionary), anti- hepatitis B surface (except in subjects who have received hepatitis B virus vaccination), hepatitis B surface antigen, anti- hepatitis B core (only immunoglobulin M is exclusionary), or anti-hepatitis C virus.
  • Positive urine drug screen including alcohol at screening and each check-in or a positive breathalyzer test at each check-in.
  • Apnea hypopnea index (per hour of sleep) greater than 15 as seen on polysonography, on the first night of the polysonography screening.
  • Periodic leg movement with arousal index (per hour of sleep) greater than 20 as seen on polysonography, on the first night of polysonography screening.
  • Any additional condition(s) that in the Investigator.s opinion would: a) affect sleep/wake function, b) prohibit the subject from completing the study, or c) not be in the best interest of the subject to participate in the study.
  • Is required to take or continues taking any disallowed medication, prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including:

    • Within 3 weeks prior to Day 1 of single-blind study medication and during the study:

      • anxiolytics
      • hypnotics
      • antidepressants
      • anticonvulsants
      • sedating H1 antihistamines
      • systemic steroids
      • respiratory stimulants (eg, theophylline) and decongestants
      • over-the counter and prescription stimulants
      • over-the counter and prescription diet aids
      • central nervous system active drugs (including herbal preparations with central nervous system effects)
      • narcotic analgesics
      • beta blockers
      • St. John.s wort
      • kava-kava
      • gingko biloba, any other supplements
    • Within 5 days prior to Day 1 of single-blind study medication and during the study:

      • melatonin, or other drugs or supplements known to affect sleep/wake function.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00671294

Locations
United States, Arkansas
Hot Springs,, Arkansas, United States
United States, California
Irvine, California, United States
Palm Springs, California, United States
San Diego, California, United States
United States, Florida
Brandon, Florida, United States
Miami, Florida, United States
Naples, Florida, United States
Pembroke Pines, Florida, United States
St. Petersburg, Florida, United States
United States, Georgia
Atlanta, Georgia, United States
United States, Kansas
Overland Park, Kansas, United States
United States, Kentucky
Crestview Hills, Kentucky, United States
United States, Michigan
Troy, Michigan, United States
United States, Missouri
St. Louis, Missouri, United States
United States, North Carolina
Winston-Salem, North Carolina, United States
United States, Ohio
Cincinnati, Ohio, United States
Toledo, Ohio, United States
United States, Texas
Houston, Texas, United States
Sponsors and Collaborators
Takeda
Investigators
Study Director: VP Clinical Science Takeda
  More Information

Additional Information:
Publications:
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT00671294     History of Changes
Other Study ID Numbers: 01-02-TL-375-017, U1111-1114-8272
Study First Received: May 1, 2008
Last Updated: February 27, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Takeda:
Insomnia

Additional relevant MeSH terms:
Sleep Initiation and Maintenance Disorders
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Disorders
Nervous System Diseases
Mental Disorders

ClinicalTrials.gov processed this record on July 28, 2014