Safety and Efficacy of Ramelteon in Elderly Subjects With Chronic Insomnia

Chronic Insomnia Clinical Trial

Official title:

A Phase III, Randomized, Double-Blind, Placebo-Controlled, Outpatient, Safety and Efficacy Study of TAK-375 in Elderly Subjects With Chronic Insomnia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00671255
• Other study ID #: 01-02-TL-375-025
• Secondary ID: U1111-1114-1190
• Status: Completed
• Phase: Phase 3
• First received: May 1, 2008
• Last updated: February 27, 2012
• Start date: December 2002
• Est. completion date: January 2004

Study information

• Verified date: February 2012
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 829
• Est. completion date: January 2004
• Est. primary completion date: January 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 65 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Insomnia
• Sleep Initiation and Maintenance Disorders

Intervention

Drug:
• Ramelteon
Ramelteon 4 mg, tablets, orally, once daily for up to 5 weeks.
• Ramelteon
Ramelteon 8 mg, tablets, orally, once daily for up to 5 weeks.
• Placebo
Ramelteon placebo-matching, tablets, orally, each night for up to 35 consecutive days.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (2)

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. — View 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. Epub 2006 May 18. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Subjective Sleep Latency per subject diary, from Nights 1 through 7 of double-blind Treatment		Weeks 1, 2, 3, 4 and 5 or Final Visit.	No
Secondary	Subjective Total Sleep Time.		Weeks 1, 2, 3, 4 and 5 or Final Visit.	No
Secondary	Subjective Number of Awakenings.		Weeks 1, 2, 3, 4 and 5 or Final Visit.	No
Secondary	Subjective Ease of Falling Back to Sleep after Awakening.		Weeks 1, 2, 3, 4 and 5 or Final Visit.	No
Secondary	Subjective Sleep Quality.		Weeks 1, 2, 3, 4 and 5 or Final Visit.	No
Secondary	Clinical Global Impression Change of Condition.		Weeks 1, 2, 3, 4 and 5 or Final Visit.	No
Secondary	Clinical Global Impression Severity of Illness.		Weeks 1, 2, 3, 4 and 5 or Final Visit.	No
Secondary	Clinical Global Impression Therapeutic Effect.		Weeks 1, 2, 3, 4 and 5 or Final Visit.	No
Secondary	Clinical Global Impression Side Effects.		Weeks 1, 2, 3, 4 and 5 or Final Visit.	No
Secondary	Average Subjective Sleep Latency over the week preceding the Day 15, Day 22, Day 29, and Day 36 Visits.		Weeks 2, 3, 4 and 5 or Final Visit.	No

External Links

•   FDA Safety Alerts and Recalls
•   Rozerem Package Insert