Sleep Initiation and Maintenance DisordersPhase 2NCT00755508
Efficacy and Safety of Ramelteon Combined With Gabapentin in Treating Patients With Insomnia
A Phase 2 study testing Ramelteon and gabapentin, Ramelteon and Gabapentin in people with Sleep Initiation and Maintenance Disorders, run by Takeda.
Trial summary
The purpose of this study is to determine the efficacy and safety of ramelteon, once daily (QD), taken in combination with Gabapentin for treating insomnia. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Sleep Initiation and Maintenance Disorders
- What is being tested?
- Ramelteon and gabapentin, Ramelteon and Gabapentin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 378 participants
- Where
- No sites listed yet
- Study dates
- Nov 2005to Sep 2006
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female patients of childbearing potential must be nonpregnant and nonlactating, and utilizing an acceptable method of contraception.
- Based on sleep history, the subject has had primary insomnia as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Revised (DSM-IV-TR™) for at least 3 months.
- Based on sleep history, reports a subjective sleep latency greater than or equal to 45 minutes and reports wake time after persistent sleep onset of greater than or equal to 45 minutes.
- Has an average wake time after persistent sleep onset of at least 60 minutes as determined by polysomnography during Screening (Day minus 7 PM through Day minus 5 AM). Wake time after persistent sleep onset must be greater than or equal to 30 minutes each night of polysomnography Screening.
- Reports wake time after persistent sleep onset values of at least 60 minutes on at least 3 of the 7 nights during the single-blind screening period (Day minus 6 AM through Day 1 AM) as determined by post-sleep questionnaire.
- Has an average latency to persistent sleep of at least 20 minutes as determined by polysomnography during Screening (Day minus 7 PM through Day minus 5 AM).
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- Based on sleep history, has an habitual bedtime between 9:00 PM and 1:00 AM.
- The subject is willing to have a fixed bedtime and agrees to go to bed within plus or minus 30 minutes of the habitual bedtime during the entire study and agrees to remain in bed for at least 8 hours each night.
- Based on sleep history, has not been using pharmacological assistance to sleep or uses pharmacological assistance no more than 4 times per week during the 3 months prior to Initial Screening.
- Has consistent access to a touch-tone phone and are willing to complete telephone questionnaires twice daily during participation in the study.
Who cannot join
- Has a known hypersensitivity to gabapentin or its ingredients, ramelteon or related compounds, including melatonin, and 5-hydroxytryptophan.
- Has participated in any other investigational study and/or taken any investigational drug within 30 days prior to the first dose of single-blind study medication.
- Has sleep schedule changes required by employment (eg, shift worker) within 3 months prior to the first dose of single-blind study medication.
- Has flown across greater than 3 time zones within 7 days prior to Initial Screening, or will travel across 2 or more time zones during the course of the study.
- Has participated in a weight loss program or has substantially altered their exercise routine within 30 days prior to the first dose of single-blind study medication.
- Has ever had a history of seizures, sleep apnea, and/or chronic obstructive pulmonary disease.
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- Has a history of psychiatric disorder (including anxiety, depression, mental retardation, cognitive disorder, bipolar illness and schizophrenia) within the past 6 months of Initial Screening.
- Has a history of fibromyalgia.
- Has a history of drug addiction or drug abuse within the past 12 months of Initial Screening.
- Has a history of alcohol abuse within the past 12 months, as defined in DSM-IV-TR™ and/or regularly consumes more than 2 alcoholic drinks per day.
- Has a current significant hepatic, endocrine, cardiovascular, gastrointestinal, pulmonary, hematological, metabolic or neurological disorders, unless currently controlled and stable with protocol-allowed medication, within 30 days prior to the first dose of single-blind study medication.
- Has any diagnosed renal impairment within 30 days prior to the first dose of single-blind study medication.
- Has a previous history of cancer, other than basal cell carcinoma, that has not been in remission for at least 5 years prior to the first dose of single-blind study drug.
- Uses tobacco products or any other products that may interfere with the sleep wake cycle during nightly awakenings.
- Is required to take or 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, including:
- Anxiolytics central nervous system active drugs (including herbal)
- Hypnotics 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
- Sedating decongestants over-the counter and prescription diet aids
- Antipsychotics over-the counter sleep aids
- Muscle relaxants Antacids
- Melatonin and all other drugs or supplements known to affect sleep/wake function.
- Has a positive hepatitis panel including anti- hepatitis A virus, hepatitis B surface antigen or anti-hepatitis C virus.
- Has a positive urine drug screen including alcohol at Initial Screening or a positive breathalyzer test at each polysomnography Screening check-in.
- Has an apnea hypopnea index (per hour of sleep) >15 as seen on polysomnography, on the first night of the polysomnography screening.
- Has a history of restless leg syndrome.
- The subject has a body mass index of less than 18 or greater than 34 (weight /height2).
- Has 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.
About this study
Official title: A Phase 2, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group, Multicenter, Proof-of-Concept Study to Evaluate the Safety and Efficacy of ROZEREM™ Taken in Combination With Gabapentin for the Treatment of Subjects With Chronic Insomnia
The purpose of this study is to determine the efficacy and safety of ramelteon, once daily (QD), taken in combination with Gabapentin for treating insomnia.
Read the detailed description
Approximately 60 to 70 million adults in the United States alone are affected by insomnia. Daytime symptoms of insomnia include tiredness, lack of energy, difficulty concentrating, and irritability. Recent epidemiologic research focusing on quality of life has identified significant insomnia-related morbidities that relate to work productivity, health care utilization, and risk of depression. Insomnia is also associated with diminished work output, absenteeism, and greater rates of accidents. gamma-aminobutyric acid is the major inhibitory transmitter in the central nervous system and most currently prescribed sleep agents are benzodiazepine receptor agonists, which induce sleep by binding to the benzodiazepine receptor site of the gamma-aminobutyric acid -A receptor complex. In addition to sleep, benzodiazepine receptor agonists can cause a wide range of ancillary effects not directly related to sleep, including sedative, anxiolytic, muscle-relaxant, and amnesic effects, and have risks of tolerance, dependence, and abuse potential.
Gabapentin is a novel anti-epileptic drug, which is currently used in subjects with partial seizures. Some studies have shown that gabapentin also has an effect on sleep architecture. In several studies, which included healthy subjects, epileptic subjects, and subjects with restless leg syndrome, the use of gabapentin been shown to prolong slow-wave sleep, increase total sleep time and sleep efficiency, and decrease number of awakenings.
Ramelteon is a melatonin receptor agonist with affinity for the human melatonin receptor subtype 1, melatonin receptor subtype 2 and selectivity over the melatonin receptor subtype 3 receptor. It also demonstrates agonist activity in vitro relative to melatonin in cells expressing human melatonin receptor subtype 1 or melatonin receptor subtype 2 receptors. The binding of melatonin at these receptors is thought to contribute to maintenance of the circadian rhythm underlying the normal sleep-wake cycle.
The purpose of this trial is to determine if the co-administration of Ramelteon and gabapentin may produce increased sleep efficiency through reduction of wake time after persistent sleep onset, in addition to the reduction in sleep latency and increase in sleep duration. Study participation is anticipated to be about one month.
- Being tested
- Ramelteon and gabapentin, Ramelteon, Gabapentin, Placebo
- Keywords
- Chronic Insomnia, DIMS (Disorders of Initiating and Maintaining Sleep), Disorders of Initiating and Maintaining Sleep, Insomnia Disorder Sleep Initiation Dysfunction, Transient Insomnia, Drug Therapy, Sleep Disorders, Intrinsic
- Medical subject headings
- Sleep Initiation and Maintenance Disorders, Sleep Disorders, Intrinsic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ramelteon and gabapentinDrug
Also called TAK-375, Ramelteon, Neurontin®, Rozerem
Ramelteon 4 mg, tablets, orally, once daily and gabapentin 400 mg, capsules, orally, once daily for up to one week.
Ramelteon and gabapentinDrug
Also called TAK-375, Ramelteon, Neurontin®, Rozerem
Ramelteon 8 mg, tablets, orally, once daily and gabapentin 800 mg, capsules, orally, once daily for up to one week.
RamelteonDrug
Also called TAK-375, Rozerem
Ramelteon 8 mg, tablets, orally, once daily and gabapentin placebo-matching capsules, orally, once daily for up to one week.
GabapentinDrug
Also called Neurontin®, Rozerem
Ramelteon placebo-matching tablets, orally, once daily and gabapentin 800 mg, capsules, orally, once daily for up to one week.
PlaceboDrug
Also called Rozerem
Ramelteon placebo-matching tablets, orally, once daily and gabapentin placebo-matching capsules, orally, once daily for up to one week.
| Study group | Role | What they receive |
|---|---|---|
| Ramelteon 4 mg QD and Gabapentin 400 mg QD | Experimental | Not described Receives: Drug: Ramelteon and gabapentin |
| Ramelteon 8 mg QD and Gabapentin 800 mg QD | Experimental | Not described Receives: Drug: Ramelteon and gabapentin |
| Ramelteon 8 mg QD and Gabapentin Placebo QD | Experimental | Not described Receives: Drug: Ramelteon |
| Gabapentin 800 mg QD | Active comparator | Not described Receives: Drug: Gabapentin |
| Placebo | 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 objective wake time after persistent sleep onset in sleep lab.
Measured: Nights: 1 and 2.
Secondary outcomes (6)
Subjective wake time after persistent sleep onset determined by the post-sleep questionnaire.
Measured: Nights: 1, 2, 3, 4, 5, 6 and 7.
Number of awakenings after persistent sleep polysomnography.
Measured: Nights: 1 and 2
Subjective number of awakenings as determined by post-sleep questionnaire.
Measured: Nights: 1, 2, 3, 4, 5, 6 and 7.
Latency to persistent sleep and total sleep time as determined by polysomnography.
Measured: Nights: 1 and 2
Subjective sleep latency, subjective total sleep time and subjective sleep quality determined by post-sleep questionnaire.
Measured: Nights: 1, 2, 3, 4, 5, 6 and 7.
Daytime functioning determined by pre-sleep questionnaire.
Measured: Nights: 1, 2, 3, 4, 5, 6 and 7.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2008 (estimated)
- Study startNov 2005
- Primary completionSep 2006
- Study completionSep 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sleep Initiation and Maintenance DisordersStudies 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
- 378 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Sr. VP Clinical Science, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00755508
- Sponsor's protocol ID
- 01-05-TL-375-055
- Other IDs
- U1111-1114-3348
- Status last verified
- Feb 2012
- First submitted
- 17 Sep 2008
- Last updated
- 28 Feb 2012
- Results posted
- No
- Data monitoring committee
- No
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, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group, Multicenter, Proof-of-Concept Study to Evaluate the Safety and Efficacy of ROZEREM™ Taken in Combination With Gabapentin for the Treatment of Subjects With Chronic Insomnia
- ClinicalTrials.gov ID
- NCT00755508
- Acronym / sponsor ID
- 01-05-TL-375-055
- Keywords
- Chronic Insomnia, DIMS (Disorders of Initiating and Maintaining Sleep), Disorders of Initiating and Maintaining Sleep, Insomnia Disorder Sleep Initiation Dysfunction, Transient Insomnia, Drug Therapy, Sleep Disorders, Intrinsic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 378 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- Nov 2005
- Primary completion
- Sep 2006 (actual)
- Study completion
- Sep 2006 (actual)
- First posted
- 19 Sep 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 efficacy and safety of ramelteon, once daily (QD), taken in combination with Gabapentin for treating insomnia.
Detailed description
Approximately 60 to 70 million adults in the United States alone are affected by insomnia. Daytime symptoms of insomnia include tiredness, lack of energy, difficulty concentrating, and irritability. Recent epidemiologic research focusing on quality of life has identified significant insomnia-related morbidities that relate to work productivity, health care utilization, and risk of depression. Insomnia is also associated with diminished work output, absenteeism, and greater rates of accidents. gamma-aminobutyric acid is the major inhibitory transmitter in the central nervous system and most currently prescribed sleep agents are benzodiazepine receptor agonists, which induce sleep by binding to the benzodiazepine receptor site of the gamma-aminobutyric acid -A receptor complex. In addition to sleep, benzodiazepine receptor agonists can cause a wide range of ancillary effects not directly related to sleep, including sedative, anxiolytic, muscle-relaxant, and amnesic effects, and have risks of tolerance, dependence, and abuse potential.
Gabapentin is a novel anti-epileptic drug, which is currently used in subjects with partial seizures. Some studies have shown that gabapentin also has an effect on sleep architecture. In several studies, which included healthy subjects, epileptic subjects, and subjects with restless leg syndrome, the use of gabapentin been shown to prolong slow-wave sleep, increase total sleep time and sleep efficiency, and decrease number of awakenings.
Ramelteon is a melatonin receptor agonist with affinity for the human melatonin receptor subtype 1, melatonin receptor subtype 2 and selectivity over the melatonin receptor subtype 3 receptor. It also demonstrates agonist activity in vitro relative to melatonin in cells expressing human melatonin receptor subtype 1 or melatonin receptor subtype 2 receptors. The binding of melatonin at these receptors is thought to contribute to maintenance of the circadian rhythm underlying the normal sleep-wake cycle.
The purpose of this trial is to determine if the co-administration of Ramelteon and gabapentin may produce increased sleep efficiency through reduction of wake time after persistent sleep onset, in addition to the reduction in sleep latency and increase in sleep duration. Study participation is anticipated to be about one month.
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 4 mg QD and Gabapentin 400 mg QD | Experimental | Drug: Ramelteon and gabapentin |
| Ramelteon 8 mg QD and Gabapentin 800 mg QD | Experimental | Drug: Ramelteon and gabapentin |
| Ramelteon 8 mg QD and Gabapentin Placebo QD | Experimental | Drug: Ramelteon |
| Gabapentin 800 mg QD | Active comparator | Drug: Gabapentin |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Female patients of childbearing potential must be nonpregnant and nonlactating, and utilizing an acceptable method of contraception.
- Based on sleep history, the subject has had primary insomnia as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Revised (DSM-IV-TR™) for at least 3 months.
- Based on sleep history, reports a subjective sleep latency greater than or equal to 45 minutes and reports wake time after persistent sleep onset of greater than or equal to 45 minutes.
- Has an average wake time after persistent sleep onset of at least 60 minutes as determined by polysomnography during Screening (Day minus 7 PM through Day minus 5 AM). Wake time after persistent sleep onset must be greater than or equal to 30 minutes each night of polysomnography Screening.
- Reports wake time after persistent sleep onset values of at least 60 minutes on at least 3 of the 7 nights during the single-blind screening period (Day minus 6 AM through Day 1 AM) as determined by post-sleep questionnaire.
Key exclusion criteria (35 listed)
- Has a known hypersensitivity to gabapentin or its ingredients, ramelteon or related compounds, including melatonin, and 5-hydroxytryptophan.
- Has participated in any other investigational study and/or taken any investigational drug within 30 days prior to the first dose of single-blind study medication.
- Has sleep schedule changes required by employment (eg, shift worker) within 3 months prior to the first dose of single-blind study medication.
- Has flown across greater than 3 time zones within 7 days prior to Initial Screening, or will travel across 2 or more time zones during the course of the study.
- Has participated in a weight loss program or has substantially altered their exercise routine within 30 days prior to the first dose 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 |
|---|---|---|
| Ramelteon and gabapentinAlso: TAK-375, Ramelteon, Neurontin®, RozeremRamelteon 4 mg, tablets, orally, once daily and gabapentin 400 mg, capsules, orally, once daily for up to one week. | Drug | Ramelteon 4 mg QD and Gabapentin 400 mg QD |
| Ramelteon and gabapentinAlso: TAK-375, Ramelteon, Neurontin®, RozeremRamelteon 8 mg, tablets, orally, once daily and gabapentin 800 mg, capsules, orally, once daily for up to one week. | Drug | Ramelteon 8 mg QD and Gabapentin 800 mg QD |
| RamelteonAlso: TAK-375, RozeremRamelteon 8 mg, tablets, orally, once daily and gabapentin placebo-matching capsules, orally, once daily for up to one week. | Drug | Ramelteon 8 mg QD and Gabapentin Placebo QD |
| GabapentinAlso: Neurontin®, RozeremRamelteon placebo-matching tablets, orally, once daily and gabapentin 800 mg, capsules, orally, once daily for up to one week. | Drug | Gabapentin 800 mg QD |
| PlaceboAlso: RozeremRamelteon placebo-matching tablets, orally, once daily and gabapentin placebo-matching capsules, orally, once daily for up to one week. | Drug | Placebo |
Primary outcome
Mean objective wake time after persistent sleep onset in sleep lab.
Time frame: Nights: 1 and 2.
6 secondary outcomes
Subjective wake time after persistent sleep onset determined by the post-sleep questionnaire.
Time frame: Nights: 1, 2, 3, 4, 5, 6 and 7.
Number of awakenings after persistent sleep polysomnography.
Time frame: Nights: 1 and 2
Subjective number of awakenings as determined by post-sleep questionnaire.
Time frame: Nights: 1, 2, 3, 4, 5, 6 and 7.
Latency to persistent sleep and total sleep time as determined by polysomnography.
Time frame: Nights: 1 and 2
Subjective sleep latency, subjective total sleep time and subjective sleep quality determined by post-sleep questionnaire.
Time frame: Nights: 1, 2, 3, 4, 5, 6 and 7.
Daytime functioning determined by pre-sleep questionnaire.
Time frame: Nights: 1, 2, 3, 4, 5, 6 and 7.
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.
- Rozerem Package Insert.Link 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.
Sr. VP Clinical Science study director
Takeda
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ramelteon and gabapentin, Ramelteon and Gabapentin in people with Sleep Initiation and Maintenance Disorders, run by Takeda.
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 10 inclusion and 35 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.
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?
Mean objective wake time after persistent sleep onset in sleep lab. (time frame: Nights: 1 and 2.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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.