Efficacy and Safety of Ramelteon on Chronic Insomnia

A Double-Blind, Dose-Response, Cross-Over Study of TAK-375 With Chronic Insomnia (Phase II Study) -- Polysomnographic Evaluation

The purpose of this study is to determine the dose response of Ramelteon, once daily (QD), in Japanese subjects with Chronic Insomnia

Study Overview

• Status: Completed
• Conditions: Chronic Insomnia
• Intervention / Treatment: Drug: Ramelteon and Placebo (25 possible combinations total)

Detailed Description

Complaints of sleep disorder are increasing with today's aging society and changing lifestyle. Sleep disorders not only impact one's activities of daily living, but also impede one's social life, leading to reduced productivity and sometimes accidents through carelessness.

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.

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Has primary chronic insomnia for at least 3 months.
• Has a mean latency of greater than or equal to 20 minutes on 2 consecutive polysomnography screening nights with no night less than 15 minutes, and has a mean of at least 60 minutes of wake time across 2 nights with no night less than 45 minutes.
• Has a habitual bedtime between 8:30 PM and 12:00 AM.
• Has a body mass index that is not less than 17, but less than 34.
• Females of childbearing potential who are sexually active must agree to use a medically accepted means of contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.

Exclusion Criteria:

• Has a history of psychiatric disorder (including depression and anxiety), seizures, drug addiction, sleep apnea, nocturnal myoclonus and/or mental retardation as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition.
• Has a history of alcohol abuse within the previous 2 years.
• Has a hepatic disease, and a significant neurological, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, hematological or metabolic disease.
• Has a known hypersensitivity to ramelteon or related compounds, including melatonin.
• Has a positive hepatitis panel including hepatitis A, hepatitis B or hepatitis C.
• Has any clinically abnormal findings as determined by a medical history, physical examination, electrocardiogram or clinical laboratory tests by the investigator or sub investigator.
• Has experienced 3 hours or more of jet lag within 7 days preceding the polysomnography screening.
• Has an apnea-hypopnea index (per hour of sleep) greater than or equal to 10 as seen on the first night of polysomnography screening.
• Has periodic limb movement with arousal index (per hour o sleep) greater than or equal to 10 as seen on the first night of polysomnography screening.
• Has participated in an excessive weight loss program that may have given influence on the evaluation of this study, or altered the participant's exercise routine within 30 days prior to double-blind study medication administration.
• Has had a clinically significant illness within 30 days prior to double-blind study medication administration.
• Has had sleep schedule changes required by employment (e.g., shift worker) within 3 months prior to double-blind study medication administration.
• The investigator or sub investigator judges the study subject inappropriate for participation because it is considered difficult to complete the study, or participating in the study will not be in the best interest of the subject.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Ramelteon QD and Placebo QD (25 possible combinations total)

Drug: Ramelteon and Placebo (25 possible combinations total); Randomized sequence over two consecutive nights for a total of five treatment periods to include the following: Ramelteon 4 mg, tablets, orally over two nights Ramelteon 8 mg, tablets, orally over two nights Ramelteon 16 mg, tablets, orally over two nights Ramelteon 32 mg, tablets, orally over two nights Ramelteon placebo-matching tablets, orally over two nights; Other Names: Rozerem; TAK-375; Ramelteon

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mean Latency to Persistent Sleep	Mean of Nights 1 and 2.

Secondary Outcome Measures

Outcome Measure	Time Frame
Mean Total Sleep Time	Mean of Nights 1 and 2.
Sleep Efficiency	Mean of Nights 1 and 2
Awake Time after Persistent Sleep	Mean of Nights 1 and 2.
Percent of Total Sleep Time in NREM sleep Stage 1	Mean of Nights 1 and 2.
Percent of Total Sleep Time in NREM sleep Stage 2	Mean of Nights 1 and 2.
Percent of Total Sleep Time in NREM sleep Stage 3/4	Mean of Nights 1 and 2.
Percent of Total Sleep Time in REM sleep Stage	Mean of Nights 1 and 2.
Latency to REM sleep stage	Mean of Nights 1 and 2.
Subjective Sleep Latency	Mean of Nights 1 and 2.
Subjective Total Sleep Time	Mean of Nights 1 and 2.
Subjective Sleep Quality	Mean of Nights 1 and 2.

Collaborators and Investigators

• Sponsor: Takeda

Study record dates

Study Major Dates

• Study Start: May 1, 2002
• Primary Completion (ACTUAL): December 1, 2003
• Study Completion (ACTUAL): December 1, 2003

Study Registration Dates

• First Submitted: June 3, 2009
• First Submitted That Met QC Criteria: June 3, 2009
• First Posted (ESTIMATE): June 5, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): June 2, 2010
• Last Update Submitted That Met QC Criteria: May 31, 2010
• Last Verified: May 1, 2010

More Information

Terms related to this study

• Keywords: Drug Therapy; Insomnia; Sleep Initiation and Maintenance Disorders
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Sleep Initiation and Maintenance Disorders
• Other Study ID Numbers: TAK-375-CCT-001; U1111-1115-2062 (REGISTRY: WHO)