Safety and Efficacy of Ramelteon in Adults With Chronic Insomnia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT00237497
First received: October 11, 2005
Last updated: January 31, 2012
Last verified: January 2012
  Purpose

The purpose of the study is to evaluate the safety and efficacy of Ramelteon, once daily (QD), compared to placebo with Zopiclone in adults with chronic insomnia


Condition Intervention Phase
Balance
Drug: Ramelteon
Drug: Zopiclone
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-Blind, Double-Dummy, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Ramelteon Compared to Placebo With Zopiclone as a Reference Arm in Adults With Chronic Insomnia

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Calculated Area of Center of Pressure (COP) in cm2 recorded on the AccuSway® balance platform during Night 14 with Eyes Open [ Time Frame: 1.5 to 2 hours Postdose on Night 14. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Calculated Area of Center of Pressure (COP) in cm2 recorded on the AccuSway® balance platform during Night 14 with Eyes Closed. [ Time Frame: 1.5 to 2 hours Postdose on Night 14. ] [ Designated as safety issue: Yes ]
  • Latency to Persistent Sleep Over a 2-night Average Measured by Polysomnography (Nights 1-2). [ Time Frame: Nights 1 and 2. ] [ Designated as safety issue: No ]
  • Latency to Persistent Sleep Over a 2-night Average Measured by Polysomnography (Nights 27-28). [ Time Frame: Nights 27 and 28. ] [ Designated as safety issue: No ]
  • Subjective Sleep Latency Measured by a Post-sleep Questionnaire (Nights 1-2). [ Time Frame: Nights 1 and 2. ] [ Designated as safety issue: No ]
  • Subjective sleep latency Measured by a Post-sleep Questionnaire (Nights 27-28). [ Time Frame: Nights 27 and 28. ] [ Designated as safety issue: No ]
  • Subjective Total Sleep Time Measured by a Post-sleep Questionnaire (Nights 1-2). [ Time Frame: Nights 1 and 2. ] [ Designated as safety issue: No ]
  • Subjective Total Sleep Time Measured by a Post-sleep Questionnaire (Nights 27-28). [ Time Frame: Nights 27 and 28. ] [ Designated as safety issue: No ]
  • Subjective Wake Time After Sleep Onset Measured by a Post-sleep Questionnaire (Nights 1-2). [ Time Frame: Nights 1 and 2. ] [ Designated as safety issue: No ]
  • Subjective Wake Time After Sleep Onset Measured by a Post-sleep Questionnaire (Nights 27-28). [ Time Frame: Nights 27 and 28. ] [ Designated as safety issue: No ]
  • Subjective Number of Awakenings Measured by a Post-sleep Questionnaire (Nights 1-2). [ Time Frame: Nights 1 and 2. ] [ Designated as safety issue: No ]
  • Subjective Number of Awakenings Measured by a Post-sleep Questionnaire (Nights 27-28). [ Time Frame: Nights 27 and 28. ] [ Designated as safety issue: No ]
  • Subjective Sleep Quality Measured by a Post-sleep Questionnaire (Nights 1-2). [ Time Frame: Nights 1 and 2. ] [ Designated as safety issue: No ]
  • Subjective Sleep Quality Measured by a Post-sleep Questionnaire (Nights 27-28). [ Time Frame: Nights 27 and 28. ] [ Designated as safety issue: No ]
  • Restorative Nature of Sleep Measured by a Post-sleep Questionnaire (Nights 1-2). [ Time Frame: Nights 1 and 2. ] [ Designated as safety issue: No ]
  • Restorative nature of sleep Measured by a Post-sleep Questionnaire (Nights 27-28). [ Time Frame: Nights 27 and 28. ] [ Designated as safety issue: No ]
  • Morning Alertness Measured by a Post-sleep Questionnaire (Nights 1-2). [ Time Frame: Nights 1 and 2 ] [ Designated as safety issue: No ]
  • Morning Alertness Measured by a Post-sleep Questionnaire (Nights 27-28). [ Time Frame: Nights 27 and 28 ] [ Designated as safety issue: No ]
  • Morning Ability to Concentrate Measured by a Post-sleep Questionnaire (Nights 1-2). [ Time Frame: Nights 1 and 2 ] [ Designated as safety issue: No ]
  • Morning Ability to Concentrate Measured by a Post-sleep Questionnaire (Nights 27-28). [ Time Frame: Nights 27 and 28 ] [ Designated as safety issue: No ]

Enrollment: 275
Study Start Date: July 2005
Study Completion Date: October 2006
Primary Completion Date: October 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ramelteon 8 mg QD Drug: Ramelteon
Ramelteon 8 mg, tablets, orally, once daily for up to 28 nights.
Other Names:
  • Rozerem
  • TAK-375
Active Comparator: Zopiclone 7.5 mg QD Drug: Zopiclone
Zopiclone 7.5 mg, tablets, orally, once daily for up to 28 nights.
Other Names:
  • Zimovane
  • Imovane
  • Rovane
Placebo Comparator: Placebo QD Drug: Placebo
Placebo-matching tablets, orally, once daily for up to 28 nights.

Detailed Description:

A vast majority of people are affected by chronic insomnia in the western world. Several studies have looked at this and have estimated that 30% to 48% of the general population is affected at some time in their life with a form of insomnia that goes on for several months, and about one third of those are described as severely affected. Daytime symptoms of insomnia include tiredness, lack of energy, difficulty concentrating, and irritability. Recent epidemiologic research focusing on the quality of life has identified significant insomnia-related conditions that relate to work productivity, health care utilization, and risk of depression. Insomnia is associated with diminished work output, absenteeism, and greater rates of accidents.

This study will examine the effect of ramelteon on balance/postural stability on Night 14 at peak plasma concentration levels, compared with placebo and using zopiclone as the reference arm.

  Eligibility

Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Men or women aged 18 to 64 years, inclusive.
  • Capable of understanding and willing to comply with the protocol and had to fully understand and sign the informed consent document at screening prior to any study-related procedures being performed.

In addition, subjects had to meet the following study-specific criteria:

  • Chronic insomnia as defined by:

    • A complaint of difficulty initiating or maintaining sleep or of nonrestorative sleep that lasted for at least 3 months.
    • The sleep disturbance (or associated daytime fatigue) caused clinically significant distress or impairment in social, occupational, or other important areas of functioning.
    • The disturbance did not occur exclusively during the course of narcolepsy, breathing related sleep disorder, circadian rhythm sleep disorder or a parasomnia.
    • The sleep disturbance did not occur exclusively during the course of another mental disorder (eg, major depressive disorder, generalized anxiety disorder, a delirium).
    • The disturbance was not due to the direct physiological effects of a substance (eg, a drug of abuse, a medication) or a general medical condition.
  • Based on sleep history, a subjective sleep latency (sSL) ≥45 minutes.
  • Based on sleep history, a subjective total sleep time (sTST) ≤6.5 hours.
  • Based on sleep history, a mean LPS of ≥20 minutes on 2 consecutive screening nights with neither night <15 minutes.
  • Based on sleep history, their habitual bedtime was between 10:00 PM and 1:00 AM.
  • Able to stand with eyes closed, arms at side and feet apart at hips width for at least 1 minute with out taking a step.
  • A body mass index (BMI) between 18 and 34, inclusive.
  • Used pharmacological assistance to sleep 0 to 4 times per week in the last 3 months.
  • Agreed to discontinue use of all pharmacological sleep aids 1 week prior to the dose of singleblind study medication and throughout the entire duration of the study.
  • Women of childbearing potential were non-pregnant and non-lactating and had appropriate birth control (barrier methods, hormonal contraceptives, and/or intrauterine devices) for the entire duration of the study (women who were not of childbearing potential were postmenopausal for 1 year or had a history of hysterectomy and/or bilateral oophorectomy).

Exclusion Criteria:

  • A known hypersensitivity to ramelteon, zopiclone or related compounds, including melatonin and melatonin related compounds.
  • Participated in any other investigational study and/or taken any investigational drug within 30 days or 5 half-lives prior to the first night of single-blind study medication (whichever was longer).
  • Had sleep schedule changes required by employment (eg, shift worker) within 3 months prior to the first night of single-blind study medication, or had flown across greater than 3 time zones within 7 days prior to screening.
  • Participated in a weight-loss program or had substantially altered their exercise routine within 30 days prior to the first night of single-blind study medication.
  • A history of, or currently had, conditions that would affect balance such as:

    • Orthostatic hypotension.
    • Dizziness.
    • Vertigo, or benign paroxysmal positional vertigo.
    • A history of seizures, sleep apnea, chronic obstructive pulmonary disease, restless leg syndrome, periodic leg movement syndrome, or fibromyalgia.
  • A history of psychiatric disorder (including anxiety, depression, mental retardation, cognitive disorder, bipolar illness and schizophrenia) within the past 6 months.
  • A history of drug addiction or drug abuse within the past 12 months.
  • A history of alcohol abuse within the past 12 months or regularly consumed more than 14 alcoholic drinks per week or consumed any alcoholic drinks within 24 hours of all polysomnography visits.
  • A current significant neurological (including cognitive and psychiatric disorders), hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, hematological, or metabolic disease, unless currently controlled and stable with protocol-allowed medication 30 days prior to the first night of single-blind study medication.
  • Used tobacco products during nightly awakenings.
  • Used melatonin, or other drugs or supplements known to affect sleep/wake function within 1 week or 5 half-lives of the drug (whichever was longer) prior to the first day of single-blind study medication.
  • Used any central nervous system (CNS) medication within 1 week or 5 half lives of the drug (whichever was longer) prior to the first day of single-blind study medication.
  • Intended to continue taking any disallowed medication or any prescription medication, over the counter (OTC) or herbal medication known to affect the sleep/wake function or otherwise interfere with evaluation of the study medication.
  • Any clinically important abnormal finding as determined by a medical history, physical examination, electrocardiogram (ECG), or clinical laboratory tests.
  • A positive urine drug screen including alcohol at screening or a positive breathalyzer test at each check-in.
  • An apnea hypopnea index (per hour of sleep) >10 as seen on PSG, on the first night of the PSG screening.
  • Periodic leg movement with arousal index (per hour of sleep) >10 as seen on PSG, on the first night of PSG 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.
  • Had lower limb prosthetics.
  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: NCT00237497

Locations
United Kingdom
London, United Kingdom
Sponsors and Collaborators
Takeda
Investigators
Principal Investigator: Medical Director Clinical Science Takeda Global Research & Development Centre (Europe)
  More Information

Additional Information:
No publications provided

Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT00237497     History of Changes
Other Study ID Numbers: TAK-375-EC301, U1111-1114-1542, 2004-004350-91
Study First Received: October 11, 2005
Last Updated: January 31, 2012
Health Authority: Australia: National Health and Medical Research Council
Austria: Ethikkommission
Finland: Finnish Medicines Agency
France: Ministry of Health
Germany: Ministry of Health
Italy: Ministry of Health
Russia: Ministry of Health of the Russian Federation
Switzerland: Federal Office of Public Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Takeda:
Insomnia
Center of Pressure
Postural Sway
Drug Therapy
Balance and Stability

Additional relevant MeSH terms:
Sleep Initiation and Maintenance Disorders
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Disorders
Nervous System Diseases
Mental Disorders
Zopiclone
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 18, 2014