Sleep DisorderPhase 2NCT00671190
Safety and Efficacy of Ramelteon in Healthy Subjects
A Phase 2 study testing Ramelteon in people with Sleep Disorder, run by Takeda at 13 sites in United States.
Trial summary
The purpose of this study is to determine the phase-advance in circadian rhythms in healthy adults subjects taking ramelteon, once daily (QD). Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Sleep Disorder
- What is being tested?
- Ramelteon
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 75 participants
- Where
- 13 sitesUnited States
- Study dates
- Mar 2005to May 2005
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
- Habitual bedtime is between 10:00 p.m. and 1:00 a.m.
- Body mass index between 18 and 30, inclusive.
- Medial subjective sleep latency of less than 30 minutes and a median subjective total sleep time of greater than 6.5 but less than 9 hours.
Who cannot join
- Known hypersensitivity to ramelteon or related compounds, including melatonin, and melatonin related compounds.
- 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 the first dose of single-blind study medication, whichever is longer.
- Sleep schedule changes required by employment (eg, shift worker) within three months prior to the administration of single-blind study medication.
- Flown across greater than three time zones within 21 days prior to or during screening.
- Participated in a weight loss program or has substantially altered their exercise routine within 30 days prior to the administration of single-blind study medication.
Show all 41Show fewer
- Ever had a history of seizures, sleep apnea, restless leg syndrome, periodic limb movement syndrome, chronic obstructive pulmonary disease, schizophrenia, bipolar disorder, mental retardation, or cognitive disorder.
- History of primary sleep disorders as determined by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Revised within the past 6 months.
- History of psychiatric disorder (including anxiety or depression) within the past 12 months.
- History of alcohol abuse within the past 12 months, as defined in Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Revised, or regularly consumes more than 14 alcoholic drinks per week, or consumes any alcoholic drinks 2 hours prior to bedtime.
- History of drug abuse within the past 12 months.
- Current neurological, hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, hematologic, or metabolic disease.
- Apnea hypopnea index (per hour of sleep) greater than 10.
- Periodic leg movement syndrome with arousal index (per hour of sleep) greater than 10 as seen on the polysomnography screening night.
- Positive urine drug screen.
- Smokes greater than 3 cigarettes per day or uses tobacco products during nightly awakenings.
- Reports high caffeine consumption (greater than 500 mg daily).
- 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.
- Unwilling to remain in the sleep laboratory in dim-light conditions for 5 days and nights or fully cooperate with site personnel.
- 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
- Central nervous system active drugs (including herbal)
- Antipsychotics
- Narcotic analgesics
- Antidepressants
- Beta blockers
- Anticonvulsants
- St. John's Wort
- Sedating H1 antihistamines
- Kava-kava
- Systemic steroids
- Ginkgo-biloba
- Respiratory stimulants
- Over the counter and prescription stimulants
- Decongestants
- Over-the-counter and prescription diet aids
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
United States13 sites
Study site
Atlanta, Georgia
Study site
Chevy Chase, Maryland
Study site
Columbia, South Carolina
Study site
Danville, Indiana
Study site
Dublin, Ohio
Study site
Hot Springs, Arkansas
Study site
Las Vegas, Nevada
Study site
Los Angeles, California
Study site
Macon, Georgia
Study site
Metairie, Louisiana
Study site
Miami, Florida
Study site
Overland Park, Kansas
Study site
San Diego, California
About this study
Official title: A Phase 2 Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Dose-Ranging Study to Evaluate the Phase-Shifting Effects of Repeated Daily Dosing of Ramelteon in Healthy Subjects
The purpose of this study is to determine the phase-advance in circadian rhythms in healthy adults subjects taking ramelteon, once daily (QD).
Read the detailed description
Circadian rhythms are the innate daily fluctuation of physiologic or behavior functions, included sleep-wake states, generally tied to the 24-hour daily dark-light cycle. Circadian Rhythm Sleep Disorders share a common chronophysiologic basis in which the major feature is a misalignment between the patient's sleep pattern and the sleep pattern that is desired or regarded as the societal norm.
Circadian Rhythm Sleep Disorders affect a sizable portion of the United States population, representing a significant underserved need. It has been estimated that 7% of all adolescents suffer from Delayed Sleep Phase Syndrome. Approximately 1% of all middle-aged people have Advanced Sleep Phase Syndrome. There are 21 million people who are shift workers and between 5% to 20% of these workers develop severe symptoms of Shift Work Sleep Disorder soon after starting shift work. Time Zone Change (Jet Lag) Syndrome can affect millions of travelers each year. Most symptoms are a result of sleep deprivation.
Current treatment of these disorders include behavioral therapy, light therapy and use of hypnotics and stimulants. Melatonin has also been used with mixed results.
The effects of melatonin on circadian phase depend on the time at which it is administered, and are generally opposite those of light. Specifically, melatonin given in the evening results in an advance of the circadian system to an earlier hour ("phase advance"). While melatonin appears to be useful in the treatment of sleep disruption in the blind, the phase shifting ability of native melatonin is much less than that of light, limiting its utility in the treatment of circadian dysfunction in sighted individuals.
Ramelteon is under global development as a sleep-promoting agent. Ramelteon demonstrates affinity and selectivity for human melatonin-1 or melatonin-2 receptors. Ramelteon also demonstrates full agonist activity relative to melatonin in cells expressing human melatonin-1 or melatonin-2 receptors.
The purpose of this study is to determine whether ramelteon given over multiple days can produce a phase advance in circadian rhythms as measured in salivary melatonin levels in dim-light conditions. Participation in this study is anticipated to be about 4 weeks.
- Conditions
- Sleep Disorder
- Being tested
- Ramelteon, Placebo
- Keywords
- Sleep Disorder, Circadian Rhythm Sleep Disorder, Drug Therapy
- Medical subject headings
- Sleep Wake Disorders, Sleep Disorders, Circadian Rhythm
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RamelteonDrug
Also called Rozerem™, TAK-375
Ramelteon 1 mg, tablets, orally once daily for up to 5 days
RamelteonDrug
Also called Rozerem™, TAK-375
Ramelteon 2 mg, tablets, orally once daily for up to 5 days
RamelteonDrug
Also called Rozerem™, TAK-375
Ramelteon 4 mg, tablets, orally once daily for up to 5 days
RamelteonDrug
Also called Rozerem™, TAK-375
Ramelteon 8 mg, tablets, orally once daily for up to 5 days
PlaceboDrug
Ramelteon placebo-matching tablets, orally once daily for up to 5 days
| Study group | Role | What they receive |
|---|---|---|
| Ramelteon 1 mg QD | Experimental | Not described Receives: Drug: Ramelteon |
| Ramelteon 2 mg QD | Experimental | Not described Receives: Drug: Ramelteon |
| Ramelteon 4 mg QD | Experimental | Not described Receives: Drug: Ramelteon |
| Ramelteon 8 mg QD | Experimental | Not described Receives: Drug: Ramelteon |
| Placebo QD | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dim Light Melatonin Secretion Offset Time.
Measured: Days 1, 2, 3, and 4 or Final Visit.
Secondary outcomes (1)
Dim-Light Melatonin Onset (DLMOn) time.
Measured: Days 1, 2, 3, and 4 or Final Visit.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 May 2008 (estimated)
- Study startMar 2005
- Primary completionMay 2005
- Study completionMay 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Sleep DisorderStudies of the same condition, open and under way.
- More trials run by TakedaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- VP Clinical Science, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00671190
- Sponsor's protocol ID
- 01-02-TL-375-018
- Other IDs
- U1111-1114-8304
- Status last verified
- Feb 2012
- First submitted
- 1 May 2008
- Last updated
- 28 Feb 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
Richardson GS, Zee PC, Wang-Weigand S, Rodriguez L, Peng X. Circadian phase-shifting effects of repeated ramelteon administration in healthy adults. J Clin Sleep Med. 2008 Oct 15;4(5):456-61.
PubMed 18853704
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Dose-Ranging Study to Evaluate the Phase-Shifting Effects of Repeated Daily Dosing of Ramelteon in Healthy Subjects
- ClinicalTrials.gov ID
- NCT00671190
- Acronym / sponsor ID
- 01-02-TL-375-018
- Conditions
- Sleep Disorder
- Keywords
- Sleep Disorder, Circadian Rhythm Sleep Disorder, Drug Therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- Mar 2005
- Primary completion
- May 2005 (actual)
- Study completion
- May 2005 (actual)
- First posted
- 5 May 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the phase-advance in circadian rhythms in healthy adults subjects taking ramelteon, once daily (QD).
Detailed description
Circadian rhythms are the innate daily fluctuation of physiologic or behavior functions, included sleep-wake states, generally tied to the 24-hour daily dark-light cycle. Circadian Rhythm Sleep Disorders share a common chronophysiologic basis in which the major feature is a misalignment between the patient's sleep pattern and the sleep pattern that is desired or regarded as the societal norm.
Circadian Rhythm Sleep Disorders affect a sizable portion of the United States population, representing a significant underserved need. It has been estimated that 7% of all adolescents suffer from Delayed Sleep Phase Syndrome. Approximately 1% of all middle-aged people have Advanced Sleep Phase Syndrome. There are 21 million people who are shift workers and between 5% to 20% of these workers develop severe symptoms of Shift Work Sleep Disorder soon after starting shift work. Time Zone Change (Jet Lag) Syndrome can affect millions of travelers each year. Most symptoms are a result of sleep deprivation.
Current treatment of these disorders include behavioral therapy, light therapy and use of hypnotics and stimulants. Melatonin has also been used with mixed results.
The effects of melatonin on circadian phase depend on the time at which it is administered, and are generally opposite those of light. Specifically, melatonin given in the evening results in an advance of the circadian system to an earlier hour ("phase advance"). While melatonin appears to be useful in the treatment of sleep disruption in the blind, the phase shifting ability of native melatonin is much less than that of light, limiting its utility in the treatment of circadian dysfunction in sighted individuals.
Ramelteon is under global development as a sleep-promoting agent. Ramelteon demonstrates affinity and selectivity for human melatonin-1 or melatonin-2 receptors. Ramelteon also demonstrates full agonist activity relative to melatonin in cells expressing human melatonin-1 or melatonin-2 receptors.
The purpose of this study is to determine whether ramelteon given over multiple days can produce a phase advance in circadian rhythms as measured in salivary melatonin levels in dim-light conditions. Participation in this study is anticipated to be about 4 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Ramelteon 1 mg QD | Experimental | Drug: Ramelteon |
| Ramelteon 2 mg QD | Experimental | Drug: Ramelteon |
| Ramelteon 4 mg QD | Experimental | Drug: Ramelteon |
| Ramelteon 8 mg QD | Experimental | Drug: Ramelteon |
| Placebo QD | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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
- Habitual bedtime is between 10:00 p.m. and 1:00 a.m.
- Body mass index between 18 and 30, inclusive.
- Medial subjective sleep latency of less than 30 minutes and a median subjective total sleep time of greater than 6.5 but less than 9 hours.
Key exclusion criteria (41 listed)
- Known hypersensitivity to ramelteon or related compounds, including melatonin, and melatonin related compounds.
- 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 the first dose of single-blind study medication, whichever is longer.
- Sleep schedule changes required by employment (eg, shift worker) within three months prior to the administration of single-blind study medication.
- Flown across greater than three time zones within 21 days prior to or during screening.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RamelteonAlso: Rozerem™, TAK-375Ramelteon 1 mg, tablets, orally once daily for up to 5 days | Drug | Ramelteon 1 mg QD |
| RamelteonAlso: Rozerem™, TAK-375Ramelteon 2 mg, tablets, orally once daily for up to 5 days | Drug | Ramelteon 2 mg QD |
| RamelteonAlso: Rozerem™, TAK-375Ramelteon 4 mg, tablets, orally once daily for up to 5 days | Drug | Ramelteon 4 mg QD |
| RamelteonAlso: Rozerem™, TAK-375Ramelteon 8 mg, tablets, orally once daily for up to 5 days | Drug | Ramelteon 8 mg QD |
| PlaceboRamelteon placebo-matching tablets, orally once daily for up to 5 days | Drug | Placebo QD |
Primary outcome
Dim Light Melatonin Secretion Offset Time.
Time frame: Days 1, 2, 3, and 4 or Final Visit.
1 secondary outcome
Dim-Light Melatonin Onset (DLMOn) time.
Time frame: Days 1, 2, 3, and 4 or Final Visit.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2012.
- Results publication: PubMed 18853704Richardson GS, Zee PC, Wang-Weigand S, Rodriguez L, Peng X. Circadian phase-shifting effects of repeated ramelteon administration in healthy adults. J Clin Sleep Med. 2008 Oct 15;4(5):456-61.
- Rozerem Package InsertLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
VP Clinical Science study director
Takeda
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ramelteon in people with Sleep Disorder, run by Takeda at 13 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 41 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Feb 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dim Light Melatonin Secretion Offset Time. (time frame: Days 1, 2, 3, and 4 or Final Visit.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00671190, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2012.