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Long-Term Efficacy of Ramelteon on Endocrine Function in Adult Subjects With Chronic Insomnia

Information source: Takeda
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Insomnia

Intervention: Ramelteon (Drug); Placebo (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Takeda

Official(s) and/or principal investigator(s):
VP Clinical Science, Study Director, Affiliation: Takeda


The purpose of this study is to determine the long-term effects of Ramelteon, once daily (QD), on endocrine function values.

Clinical Details

Official title: A Phase III Safety Study to Evaluate the Long-term Effects of TAK-375 on Endocrine Function in Adult Subjects With Chronic Insomnia

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

Primary outcome: Change from baseline in Total Serum Thyroxine.

Secondary outcome:

Change from baseline in free thyroxine.

Change from baseline in thyroid stimulating hormone.

Change from baseline in triiodothyronine.

Change from baseline in total testosterone (men only).

Change from baseline in free testosterone (men only).

Change from baseline in estradiol (women only).

Change from baseline in prolactin.

Change from baseline in follicle stimulating hormone (women only).

Change from baseline in luteinizing hormone (women only).

Change from baseline in luteinizing hormone surge (women only)

Change from baseline in adrenocorticotropic hormone.

Change from baseline in cortisol (AM).

Change from baseline in adrenocorticotropic hormone stimulation test.

Detailed description: Insomnia is characterized by a complaint of either 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. This study has been designed to determine the long-term (6 month) effects of Ramelteon on endocrine function values. Study participation is anticipated to be about 7 months.


Minimum age: 18 Years. Maximum age: 45 Years. Gender(s): Both.


Inclusion Criteria

- Females of childbearing potential who are sexually active must agree to use adequate

contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.

- Has had primary insomnia as defined by the Diagnostic and Statistical Manual of

Mental Disorders, Text Revision for at least 3 months and a history of daytime complaint(s) associated with disturbed sleep.

- Has a subjective sleep latency (sSL) greater than or equal to 45 minutes and a

subjective total sleep time less than or equal to 6. 5 hours for at least 3 nights out of one week.

- Habitual bedtime is between 8: 30PM and 12: 00AM.

- Habitual awakening time is between 5: 00 AM and 10: 00 AM.

- Male and female subjects must have serum prolactin, luteinizing hormone, follicle

stimulating hormone, adrenocorticotropic hormone, thyroid stimulating hormone, triiodothyronine and thyroxine within normal range. Normal ranges for luteinizing hormone and follicle stimulating hormone for female subjects will be defined as the lowest value among the menstrual phases to the highest value among the menstrual phases.

- Body mass index between 18 and 34, inclusive.

- Male subjects must have serum testosterone values of greater than or equal to 150 ng

per dL.

- Female subjects must have serum estradiol values within normal range.

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, whichever is longer.

- Sleep schedule changes required by employment (eg, shift worker) within three months

prior to Day 1, 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.

- 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 (including anxiety or depression) within the past 12


- History of drug addiction or drug abuse within the past 12 months.

- History of alcohol abuse within the past 12 months, as defined in Diagnostic and

Statistical Manual of Mental Disorders, Text Revision and/or regularly consumes 4 or more alcoholic drinks per day.

- Current significant neurological (including psychiatric and cognitive 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.

- Uses tobacco products during nightly awakenings.

- Used melatonin, or other drugs or supplements known to affect sleep/wake function

within 1week (or 5 half lives of the drug, whichever is longer) prior to Day 1.

- Used any central nervous system medication within 1 week (or 5 half lives of the

drug, whichever is longer) prior to Day 1. 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..

- Any significant endocrine pathology based on borderline laboratory results.

- Any additional condition(s) that in the Investigator's opinion would:

- affect endocrine function (eg, hyperthyroidism, diabetes)

- prohibit the subject from completing the study, or

- not be in the best interest of the subject to participate in the study.

- Morning serum cortisol at the Screening visit of less than 7. 0 μg per dl.

- 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:

- 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

- narcotic analgesics

- beta blockers

- St. John's Wort

- kava-kava

- gingko biloba

- melatonin

- other drugs or supplements known to affect sleep/wake function.

Locations and Contacts

Birmingham, Alabama, United States

Jasper, Alabama, United States

Mesa, Arizona, United States

Peoria, Arizona, United States

La Palma, California, United States

Los Angeles, California, United States

Riverside, California, United States

San Diego, California, United States

Denver, Colorado, United States

Fort Lauderdale, Florida, United States

West Palm Beach, Florida, United States

Austell, Georgia, United States

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Des Moines, Iowa, United States

Overland Park, Kansas, United States

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Florence, Kentucky, United States

Wentzville, Missouri, United States

Kenilworth, New Jersey, United States

South Plainfield, New Jersey, United States

Cincinnati, Ohio, United States

Columbus, Ohio, United States

Portland, Oregon, United States

Ninety Six, South Carolina, United States

Sioux Falls, South Dakota, United States

Austin, Texas, United States

Fort Worth, Texas, United States

San Angelo, Texas, United States

Wichita Falls, Texas, United States

Additional Information

Rozerem Package Insert

FDA Safety Alerts and Recalls

Starting date: January 2003
Last updated: February 27, 2012

Page last updated: August 23, 2015

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