Chronic InsomniaPhase 3NCT00247390
Long-Term Efficacy and Safety of Ramelteon in Adults With Chronic Insomnia.
A Phase 3 study testing Ramelteon in people with Chronic Insomnia, run by Takeda at 48 sites in 9 countries.
Trial summary
The purpose of this study to determine the long-term efficacy and safety of ramelteon, once daily (QD). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Insomnia
- 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
- 451 participants
- Where
- 48 sitesin 9 countries
- Study dates
- Jul 2005to Dec 2006
- Phase
- Phase 3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older 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 of the study.
- Body mass index between 18 and 34, inclusive.
- Based on sleep history, has had chronic insomnia for at least 3 months.
- Based on sleep history, reports a subjective sleep latency greater than or equal to 45 min and a subjective total sleep time less than or equal to 6.5 hours.
- Based on sleep history, habitual bedtime is between 10:00 PM and 1:00 AM.
- Mean latency to persistent sleep of greater than 20 minutes on two consecutive screening nights with neither night less than 15 minutes. Also, a mean of 60 minutes of wake time during the 480 minutes in bed across two nights with no night less than 45 minutes.
- Based on sleep history, normally uses pharmacological assistance to sleep 0 to 4 times per week in the last 3 months.
Who cannot join
- Known hypersensitivity to ramelteon 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 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 7 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.
- Has ever had a history of seizures, sleep apnea, restless leg syndrome, periodic leg movement syndrome, chronic obstructive pulmonary disease or fibromyalgia.
Show all 43Show fewer
- History of psychiatric disorder within the past 6 months.
- History of alcohol abuse within the past 12 months, as defined in Diagnostic \& Statistical Manual of Mental Disorders, 4th Edition Revised, or regularly consumes more than 14 alcoholic drinks per week, or consumed any alcoholic drinks within 24 hours of any polysomnogram visits.
- History of drug abuse within the past 12 months, as defined in Diagnostic \& Statistical Manual of Mental Disorders, 4th Edition Revised.
- Current significant hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, hematologic, neurological, or metabolic disease, unless currently controlled and stable with protocol-allowed medication, within 30 days prior to the first night of single-blind study medication.
- Apnea hypopnea index (per hour of sleep) greater than 10 as seen on the first polysomnogram screening night.
- Periodic Leg Movement Syndrome with arousal index (per hour of sleep) greater than 10 as seen on the first polysomnogram screening night.
- Positive urine drug screen at Screening Visit 1 or any of the polysomnogram assessment visits.
- Positive breathalyzer test on any of the polysomnogram assessment visits.
- Uses tobacco products (including nicotine gum and patch) or any other products that may interfere with the sleep wake cycle during nightly awakenings.
- Used any central nervous system medication or other drugs or supplements known to affect sleep/wake function within 1 week (or 5 half lives of the drug, whichever is longer) prior to the administration of single-blind study medication. These medications must not have been used to treat psychiatric disorders.
- Intends to continue taking any disallowed medication or any prescription medication or over the counter medication that is known to affect the sleep/wake function or otherwise interfere with evaluation of the study medication. The subject must report all prescription and over the counter medications taken in the three weeks prior to screening.
- 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
- Sedatives
- Hypnotics
- CNS active drugs (including herbal)
- Antidepressants
- Narcotic analgesics
- Anticonvulsants
- Beta blockers
- Sedating H1 antihistamines
- St. John's Wort
- Systemic steroids
- Kava-kava
- Respiratory stimulants
- Ginkgo-biloba
- Decongestants
- Over-the-counter and prescription stimulants
- Antipsychotics
- Over-the-counter and prescription diet aids
- Muscle Relaxants
- Melatonin and all other drugs or supplements known to affect sleep/wake function
- Any additional condition(s) that in the Investigator's opinion would
- affect sleep/wake function
- prohibit the subject from completing the study
- indicate that continuation in the study would not be in the best interests of the subject.
- History of hepatitis B or hepatitis C.
Trial locations and contacts
48 sites in 9 countries.
48 sites in 9 countries
United States19 sites
Study site
Atlanta, Georgia
Study site
Austin, Texas
Study site
Birmingham, Alabama
Study site
Chevy Chase, Maryland
Study site
Cincinnati, Ohio
Study site
Columbia, South Carolina
Study site
Hot Springs, Arkansas
Study site
Lincoln, Nebraska
Study site
Los Angeles, California
Study site
Louisville, Kentucky
Study site
Miami, Florida
Study site
Naples, Florida
Study site
New York, New York
Study site
Oakland, California
Study site
Overland Park, Kansas
Study site
San Diego, California
Study site
Santa Monica, California
Study site
Toledo, Ohio
Study site
Winter Park, Florida
Germany6 sites
Study site
Berlin
Study site
Göttingen
Study site
Hamburg
Study site
Münster
Study site
Schwalmstadt
Study site
Schwerin
France5 sites
Study site
Bron
Study site
Clamart
Study site
Garches
Study site
Paris
Study site
Rouffach
Russia5 sites
Study site
Irkutsk
Study site
Moscow
Study site
Saint Petersburg
Study site
Samara
Study site
Yekateringburg
Australia4 sites
Study site
Adelaide
Study site
Camperdown
Study site
Melbourne
Study site
Victoria
Czechia3 sites
Study site
České Budějovice
Study site
Ostrava-Poruba
Study site
Prague
About this study
Official title: A Randomised, Double-blind, Placebo-controlled Study to Determine the Long-term Efficacy and Safety of Ramelteon in Adults With Chronic Insomnia.
The purpose of this study to determine the long-term efficacy and safety of ramelteon, once daily (QD).
Read the 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.
An ideal treatment for chronic insomnia would include administration of therapy for an extended period. Specifically, it should be safe and effective for a period longer than the 7 to 10 days to which use of the current drugs approved for short-term use are limited.
Because of the absence of evidence of residual effects in pre-clinical studies and phase 2 and 3 clinical trials, ramelteon may be a candidate for extended use. As chronic insomnia becomes more prevalent, there is a need to assess the long-term efficacy and safety of nightly dosing with ramelteon in the general population. Study participation is anticipated to be about 8 months and 3 weeks.
- Conditions
- Chronic Insomnia
- Being tested
- Ramelteon, Placebo
- Keywords
- Chronic Insomnia, Sleep Initiation and Maintenance Disorder, Drug Therapy
- Medical subject headings
- Sleep Initiation and Maintenance Disorders
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 8 mg, tablets, orally, once daily for up to 42 weeks.
PlaceboDrug
Ramelteon placebo-matching tablets, orally, once daily for up to 42 weeks.
| Study group | Role | What they receive |
|---|---|---|
| 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.
Mean change in Latency to Persistent Sleep of 2-night polysomnogram.
Measured: Months 3 and 6 or Final Visit
Secondary outcomes (11)
Mean change in Total Sleep Time from polysomnogram, on 2 nights over 6 months.
Measured: Week 1 and Months 1, 3, 5 and 6 or Final Visit
Mean change in Subjective Sleep Latency by postsleep questionnaire on 2 nights over 6 months.
Measured: Week 1 and Months 1, 3, 5 and 6 or Final Visit
Mean change in Subjective Total Sleep Time by postsleep questionnaire on 2 nights over 6 months.
Measured: Week 1 and Months 1, 3, 5 and 6 or Final Visit
Mean change in Subjective Number of Awakenings by postsleep questionnaire.
Measured: Week 1 and Months 1, 3, 5 and 6 or Final Visit
Mean change in Subjective Sleep Quality by postsleep questionnaire.
Measured: Week 1 and Months 1, 3, 5 and 6 or Final Visit
Total Sleep Time in rapid eye movement (REM) sleep as determined by polysomnogram.
Measured: Week 1 and Months 1, 3, 5 and 6 or Final Visit
Total Sleep Time in stage 1 non-rapid eye movement (NREM) sleep as determined by polysomnogram.
Measured: Week 1 and Months 1, 3, 5 and 6 or Final Visit
Total Sleep Time in stage 2 non-rapid eye movement (NREM) sleep as determined by polysomnogram.
Measured: Week 1 and Months 1, 3, 5 and 6 or Final Visit
Total Sleep Time in stage 3/4 non-rapid eye movement (NREM) sleep as determined by polysomnogram.
Measured: Week 1 and Months 1, 3, 5 and 6 or Final Visit
Total Sleep Time in stage 1 sleep as determined by polysomnogram.
Measured: Week 1 and Months 1, 3, 5 and 6 or Final Visit
Latency to Rapid Eye Movement as determined by polysomnogram.
Measured: Week 1 and Months 1, 3, 5 and 6 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 posted1 Nov 2005 (estimated)
- Study startJul 2005
- Primary completionDec 2006
- Study completionDec 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Chronic InsomniaStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 451 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Medical Director Clinical Science, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00247390
- Sponsor's protocol ID
- TAK-375-EC302
- Other IDs
- 2004-004351-20, U1111-1114-3231, 2004
- Status last verified
- Jun 2010
- First submitted
- 28 Oct 2005
- Last updated
- 3 Jun 2010
- Results posted
- No
- Data monitoring committee
- No
Publications
Mayer G, Wang-Weigand S, Roth-Schechter B, Lehmann R, Staner C, Partinen M. Efficacy and safety of 6-month nightly ramelteon administration in adults with chronic primary insomnia. Sleep. 2009 Mar;32(3):351-60. doi: 10.1093/sleep/32.3.351.
PubMed 19294955Wang-Weigand S, McCue M, Ogrinc F, Mini L. Effects of ramelteon 8 mg on objective sleep latency in adults with chronic insomnia on nights 1 and 2: pooled analysis. Curr Med Res Opin. 2009 May;25(5):1209-13. doi: 10.1185/03007990902858527.
PubMed 19327100
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Double-blind, Placebo-controlled Study to Determine the Long-term Efficacy and Safety of Ramelteon in Adults With Chronic Insomnia.
- ClinicalTrials.gov ID
- NCT00247390
- Acronym / sponsor ID
- TAK-375-EC302
- Conditions
- Chronic Insomnia
- Keywords
- Chronic Insomnia, Sleep Initiation and Maintenance Disorder, Drug Therapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 451 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- Jul 2005
- Primary completion
- Dec 2006 (actual)
- Study completion
- Dec 2006 (actual)
- First posted
- 1 Nov 2005 (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 to determine the long-term efficacy and safety of ramelteon, once daily (QD).
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.
An ideal treatment for chronic insomnia would include administration of therapy for an extended period. Specifically, it should be safe and effective for a period longer than the 7 to 10 days to which use of the current drugs approved for short-term use are limited.
Because of the absence of evidence of residual effects in pre-clinical studies and phase 2 and 3 clinical trials, ramelteon may be a candidate for extended use. As chronic insomnia becomes more prevalent, there is a need to assess the long-term efficacy and safety of nightly dosing with ramelteon in the general population. Study participation is anticipated to be about 8 months and 3 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ramelteon 8 mg QD | Experimental | Drug: Ramelteon |
| Placebo QD | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 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 of the study.
- Body mass index between 18 and 34, inclusive.
- Based on sleep history, has had chronic insomnia for at least 3 months.
- Based on sleep history, reports a subjective sleep latency greater than or equal to 45 min and a subjective total sleep time less than or equal to 6.5 hours.
- Based on sleep history, habitual bedtime is between 10:00 PM and 1:00 AM.
Key exclusion criteria (43 listed)
- Known hypersensitivity to ramelteon 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 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 7 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.
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 8 mg, tablets, orally, once daily for up to 42 weeks. | Drug | Ramelteon 8 mg QD |
| PlaceboRamelteon placebo-matching tablets, orally, once daily for up to 42 weeks. | Drug | Placebo QD |
Primary outcome
Mean change in Latency to Persistent Sleep of 2-night polysomnogram.
Time frame: Months 3 and 6 or Final Visit
11 secondary outcomes
Mean change in Total Sleep Time from polysomnogram, on 2 nights over 6 months.
Time frame: Week 1 and Months 1, 3, 5 and 6 or Final Visit
Mean change in Subjective Sleep Latency by postsleep questionnaire on 2 nights over 6 months.
Time frame: Week 1 and Months 1, 3, 5 and 6 or Final Visit
Mean change in Subjective Total Sleep Time by postsleep questionnaire on 2 nights over 6 months.
Time frame: Week 1 and Months 1, 3, 5 and 6 or Final Visit
Mean change in Subjective Number of Awakenings by postsleep questionnaire.
Time frame: Week 1 and Months 1, 3, 5 and 6 or Final Visit
Mean change in Subjective Sleep Quality by postsleep questionnaire.
Time frame: Week 1 and Months 1, 3, 5 and 6 or Final Visit
Total Sleep Time in rapid eye movement (REM) sleep as determined by polysomnogram.
Time frame: Week 1 and Months 1, 3, 5 and 6 or Final Visit
Total Sleep Time in stage 1 non-rapid eye movement (NREM) sleep as determined by polysomnogram.
Time frame: Week 1 and Months 1, 3, 5 and 6 or Final Visit
Total Sleep Time in stage 2 non-rapid eye movement (NREM) sleep as determined by polysomnogram.
Time frame: Week 1 and Months 1, 3, 5 and 6 or Final Visit
Total Sleep Time in stage 3/4 non-rapid eye movement (NREM) sleep as determined by polysomnogram.
Time frame: Week 1 and Months 1, 3, 5 and 6 or Final Visit
Total Sleep Time in stage 1 sleep as determined by polysomnogram.
Time frame: Week 1 and Months 1, 3, 5 and 6 or Final Visit
Latency to Rapid Eye Movement as determined by polysomnogram.
Time frame: Week 1 and Months 1, 3, 5 and 6 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 3 Jun 2010.
- Results publication: PubMed 19294955Mayer G, Wang-Weigand S, Roth-Schechter B, Lehmann R, Staner C, Partinen M. Efficacy and safety of 6-month nightly ramelteon administration in adults with chronic primary insomnia. Sleep. 2009 Mar;32(3):351-60. doi: 10.1093/sleep/32.3.351.
- Results publication: PubMed 19327100Wang-Weigand S, McCue M, Ogrinc F, Mini L. Effects of ramelteon 8 mg on objective sleep latency in adults with chronic insomnia on nights 1 and 2: pooled analysis. Curr Med Res Opin. 2009 May;25(5):1209-13. doi: 10.1185/03007990902858527.
- 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.
Medical Director Clinical Science study director
Takeda
48 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ramelteon in people with Chronic Insomnia, run by Takeda at 48 sites in 9 countries.
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 7 inclusion and 43 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 3 Jun 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 48 sites in United States, Germany, France, Russia, Australia and 4 more countries. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Mean change in Latency to Persistent Sleep of 2-night polysomnogram. (time frame: Months 3 and 6 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 NCT00247390, which also lists 2 linked publications.
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 3 Jun 2010.