Safety of Ramelteon in Elderly Subjects

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT00568789
First received: December 4, 2007
Last updated: February 27, 2012
Last verified: February 2012
  Purpose

The purpose of this study is to investigate the effects of ramelteon in elderly subjects on balance, mobility and memory impairment after awakening in the middle of the night following bedtime dosing.


Condition Intervention Phase
Insomnia
Drug: Ramelteon, zolpidem and placebo
Phase 4

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 Study of the Safety of Ramelteon in Elderly Subjects

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Sensory Organization Test Composite Score. [ Time Frame: Periods 1, 2, and 3 in the evening before sleep and during night when awakened from sleep. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Equilibrium Score (ES) for SOT conditions 5 and 6 (evaluation of the effect of ramelteon on balance). [ Time Frame: Periods 1, 2, and 3 during night when awakened from sleep and in the morning after self-awakening. ] [ Designated as safety issue: No ]
  • Sensory Organization Test derived ratios: Somatosensory, Visual, Vestibular, and Preference (effect on balance). [ Time Frame: Periods 1, 2, and 3 in the evening before sleep and during night when awakened from sleep. ] [ Designated as safety issue: No ]
  • Results of the Step/Quick Turn Test (SQTT), which quantifies turn performance characteristics, were obtained with NeuroCom EquiTest computerized dynamic posturography equipment (effect on mobility and balance). [ Time Frame: Periods 1, 2, and 3 during night when awakened from sleep and in the morning after self-awakening. ] [ Designated as safety issue: No ]
  • Immediate Memory Recall Test. [ Time Frame: Periods 1, 2, and 3 during night when awakened from sleep. ] [ Designated as safety issue: No ]
  • Delayed Recall Test. [ Time Frame: Periods 1, 2, and 3 during night when awakened from sleep. ] [ Designated as safety issue: No ]

Enrollment: 33
Study Start Date: June 2006
Study Completion Date: September 2006
Primary Completion Date: September 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ramelteon 8 mg, zolpidem 10 mg and placebo Drug: Ramelteon, zolpidem and placebo

Ramelteon 8 mg, tablets, orally, one night only during Period 1, 2 or 3

Zolpidem 10 mg, tablets, orally, one night only during Period 1, 2 or 3

Ramelteon/Zolpidem placebo-matching tablets, orally one night only during Period 1, 2 or 3

Other Names:
  • Ambien
  • Rozerem™
  • TAK-375
  • ramelteon

Detailed Description:

Insomnia affects more than half of the US population. Epidemiological data indicate that between 36% and 56% of American adults report occasional insomnia, while 9% to 17% report chronic or severe problems with insomnia. This condition is most prevalent in the elderly. Elderly insomnia sufferers may experience more difficulty staying asleep than younger adults; increasing wakefulness during the sleep period and resulting in the opportunity to get out of bed.

Elderly individuals with insomnia are at risk of falling when they get out of bed during the sleep period. It is not known if this risk merely is the result of being out of bed, or if insomnia or some other physiological processes (eg, postural hypotension) contribute. This risk is significant because falling may result in severe injuries, including hip fractures, for which morbidity and mortality statistics are remarkable. Approximately one-third of those who sustain a hip fracture are placed in long-term care facilities. Of those patients hospitalized due to a hip fracture, 15% die while in the hospital and 33% die within one year of sustaining the fracture.

One important concern regarding the risk of falling in elderly patients with insomnia relates to the commonly accepted pharmacological treatments of insomnia. Although normal control of the sleep-wake cycle is exerted by the suprachiasmatic nucleus via melatonin receptor subtypes 1 and 2 receptors, current pharmacologic treatments for insomnia mainly involve GABAergic (gamma aminobutyric acid) mechanisms: most currently prescribed sleep agents are benzodiazepine receptor agonists, which bind to the benzodiazepine receptor site of the gamma aminobutyric acid receptor complex. Gamma aminobutyric acid is the major inhibitory transmitter in the central nervous system and its receptors are distributed widely throughout the brain. In addition to sleep, benzodiazepine receptor agonists can cause a wide range of ancillary effects not directly related to sleep, depending on the precise subset of gamma aminobutyric acid receptors activated. These include sedative, anxiolytic, muscle-relaxant, and amnesic effects. Drugs that act at this receptor complex, specifically the benzodiazepines, have deleterious effects on body sway.

Ramelteon is marketed in the United States as Rozerem for the treatment of insomnia characterized by difficulty with sleep initiation. It's mechanism of action is based on the agonism of melatonin receptor subtype 1 and 2.

This study will investigate the effects of ramelteon on balance, mobility and memory impairment awakening in the middle of the night following bedtime dosing. Participation in this study is anticipated to be about 1 to 1.5 months.

  Eligibility

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

Inclusion Criteria

  • Self-reported sleep latency of 30 minutes or greater on at least 3 nights per week during the last 3 months.
  • Body mass index between 18 and 34, inclusive
  • Habitual bedtime between 9 pm and 1 am.

Exclusion Criteria

  • Performance outside of normal limits on the EquiTest Motor Control Test at the Screening Visit.
  • Average score on the EquiTest Sensory Organization Test #5 of less than 40 at the Screening Visit.
  • Average score on the EquiTest Sensory Organization Test #6 of less than 40 at the Screening Visit.
  • History of sleep apnea, restless leg syndrome, period limb movement syndrome, or other known disorders which affect sleep with the exception of insomnia.
  • Current vestibular system disorder or inner ear disease.
  • Recent history of clinically significant head injury.
  • Significant visual acuity or field abnormalities that are not improved with the use of corrective lenses.
  • History of balance disturbance or frequent falling.
  • History of seizures, strokes, degenerative neurological disease, fibromyalgia, diabetic neuropathy, thyroid dysfunction, hypotension, clinically significant arthritis or musculoskeletal disorder.
  • History of cancer, other than basal cell carcinoma, that has not been in remission for at least five years prior to the first dose of study drug.
  • Current significant neurological, hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, hematologic, or metabolic disease, unless currently controlled and stable.
  • Acute clinically significant illness within two weeks or has been hospitalized within four weeks prior to the Screening Visit.
  • History of treatment for a psychiatric disorder (including anxiety, depression, mental retardation, cognitive disorder, bipolar illness and schizophrenia) within the past six months.
  • History of drug addiction or drug abuse within the past 12 months, as defined in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Revised.
  • History of alcohol abuse within the past 12 months.
  • Any clinically important abnormal finding, as determined by medical history, physical examination, electrocardiogram or clinical laboratory tests, as determined by the investigator.
  • Positive hepatitis panel.
  • Positive urine drug screen for drugs known to alter sleep.
  • Participated in any other investigational study and/or taken any investigational drug within 30 days or five half-lives prior to the first dose of single-blind study medication, whichever is longer.
  • Any additional condition 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 that may interfere with evaluation of the study medication, including:

    • Melatonin and all other drugs or supplements known to affect sleep/wake function
    • Anxiolytics
    • Sedatives
    • Hypnotics
    • Central nervous system active drugs (including herbal)
    • Antidepressants
    • Narcotic analgesics
    • Anticonvulsants
    • Beta blockers
    • Sedating H1 antihistamines
    • St. John's Wort
    • Systemic steroids
    • Kava-kava
    • Respiratory stimulants
    • Ginkgo-biloba
    • Decongestants
    • Over-the-counter and prescription stimulants
    • Antipsychotics
    • Over-the-counter and prescription diet aids
    • Muscle relaxants
  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: NCT00568789

Locations
United States, California
Costa Mesa, California, United States
San Diego, California, United States
United States, Florida
Miami, Florida, United States
Miramar, Florida, United States
Orlando, Florida, United States
United States, New York
New York, New York, United States
Sponsors and Collaborators
Takeda
Investigators
Study Director: Medical Director Takeda
  More Information

Additional Information:
Publications:
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT00568789     History of Changes
Other Study ID Numbers: 01-05-TL-375-060, U1111-1115-1906
Study First Received: December 4, 2007
Last Updated: February 27, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Takeda:
Insomnia
Aged
Postural Balance
Drug Therapy

Additional relevant MeSH terms:
Zolpidem
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
GABA-A Receptor Agonists
GABA Agonists
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 19, 2014