Sleep Initiation and Maintenance Disorder; ElderlyPhase 3JadeNCT00561574
A Long-Term Safety Study of Org 50081 (Esmirtazapine) in Elderly Outpatients With Chronic Primary Insomnia (176005/P05697/MK-8265-001)
A Phase 3 study testing Esmirtazapine in people with Sleep Initiation and Maintenance Disorder; Elderly and Mental Disorder, run by Merck Sharp & Dohme LLC.
Trial summary
The current study is a 52-week safety study in elderly outpatients with chronic primary insomnia randomized to treatment with 1.5 mg or 3.0 mg of esmirtazapine (Org 50081, SCH 900265, MK-8265) to investigate the safety and tolerability of long-term treatment with esmirtazapine in elderly patients. Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Sleep Initiation and Maintenance Disorder; Elderly, Mental Disorder, Dyssomnias
- What is being tested?
- Esmirtazapine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 259 participants
- Where
- No sites listed yet
- Study dates
- 9 Jan 2008to 14 Feb 2010
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- are at least 65 years of age at screening;
- sign written informed consent after the scope and nature of the investigation have been explained to them, before screening evaluations;
- are able to speak, read and understand the language of the investigator, study staff (including raters) and the informed consent form, and possess the ability to respond to questions, follow instructions and complete questionnaires;
- have demonstrated capability to independently complete the LogPad questionnaires in the week preceding randomization;
- normal bedtime should be within the 21:00 - 01:00 hour range, with no more variation than 2 hours for 5 nights out of 7;
- have a documented diagnosis of chronic primary insomnia, defined as fulfillment of the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV-TR) criteria for primary insomnia [DSM-IV-TR 307.42]) with a duration of >= 1 month;
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- fulfill the following criteria based on medical or sleep history. Each of these criteria should be present for at least 3 nights per week for at least one month;
- TST <= 6.5 hours
- WASO >= 60 minutes
- Sleep Latency (SL) >= 30 minutes
Who cannot join
- have other sleep disorders (DSM-IV-TR) e.g. rapid eye movement (REM) behavioral disorders, sleep related breathing disorders, periodic leg movement disorder, restless leg syndrome, narcolepsy, circadian sleep wake rhythm disorders, or any parasomnia;
- have any significant medical or DSM-IV-TR psychiatric illness causing the sleep disturbances;
- currently meet diagnostic criteria for DSM-IV-TR depression (Major Depressive Disorder [MDD]) or have been diagnosed and treated for MDD within the last 2 years;
- have signs of dementia or other serious cognitive impairment, defined by a score of less than 26 on the Mini-Mental State Examination (MMSE);
- have a history of bipolar disorder, a history of suicide attempt or a family history of suicide; A family history of suicide is defined as any history of suicide in the first and second degree family (parents, siblings, grandparents, or offspring), or a pattern of completed suicides (more than one) in the third degree family (aunts, uncles, nieces, and nephews);
- are night workers or rotating shift workers;
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- are traveling, or have plans to travel, through more than three time zones during the trial, from the screening visit onwards;
- have a significant, unstable medical illness e.g. acute or chronic pain, hepatic, renal, metabolic or cardiac disease;
- have clinically relevant electrocardiogram (ECG) abnormalities at screening, as judged by the investigator;
- have clinically relevant abnormal hematology or biochemistry values at screening, as judged by the investigator;
- have DSM-IV-TR substance abuse or DSM-IV-TR addiction within the last year;
- drink more than 2 alcoholic drinks in a day. One drink is approximately equal to: 12 oz or 360 mL of beer (regular or light), or 4 oz or 120 mL of red or white wine, or 2 oz or 60 mL of desert wine (e.g. port, sherry), or 12 oz or 360 mL of wine cooler (regular or light), or 1 oz or 30 mL or spirits (80 to 100 proof, e.g. whiskey, vodka);
- had serious head injury or stroke within the past year, or a history of (non-febrile) seizures;
- use psychotropic drugs affecting sleep within 2 weeks prior to randomization (fluoxetine: 5 weeks);
- use concomitant medication affecting sleep (see Protocol Section 3.4, Concomitant medication);
- smoke > 15 cigarettes per day and/or can not abstain from smoking during the night;
- drink excessive amounts of caffeinated beverages (more than 500 mg caffeine per day);
- have a positive urine drug screen at screening;
- are routinely sleeping during daytime (napping) for more than 60 minutes per day, 3 times/ week;
- have a body mass index (BMI) >= 36;
- have a known hypersensitivity to mirtazapine or to any of the excipients;
- participated in another clinical trial within the last 30 days prior to screening;
- participated in another clinical trial using esmirtazapine (Org 50081) at any time.
About this study
Official title: A Randomized Long-Term Safety Study of Org 50081 in Elderly Outpatients With Chronic Primary Insomnia Examining the Effects of 1.5 mg or 3.0 mg of Org 50081
The current study is a 52-week safety study in elderly outpatients with chronic primary insomnia randomized to treatment with 1.5 mg or 3.0 mg of esmirtazapine (Org 50081, SCH 900265, MK-8265) to investigate the safety and tolerability of long-term treatment with esmirtazapine in elderly patients.
Read the detailed description
Insomnia is a common complaint or disorder throughout the world. About one third of the population in the industrial countries reports difficulty initiating or maintaining sleep, resulting in a non-refreshing or non-restorative sleep. The majority of the insomniacs suffer chronically from their complaints.
The maleic acid salt of Org 4420, code name Org 50081 (esmirtazapine), was selected for development in the treatment of insomnia. The first clinical trial with esmirtazapine was a proof-of-concept trial with a four-way cross-over design. All 3 esmirtazapine dose groups showed a statistically significant positive effect on Total Sleep Time (TST) (objective and subjective) and Wake Time After Sleep Onset (WASO), as compared to placebo.
The current study is a 52-week safety study in elderly outpatients with chronic primary insomnia randomized to treatment with 1.5 mg or 3.0 mg of esmirtazapine to investigate the safety and tolerability of long-term treatment with esmirtazapine in elderly patients.
- Conditions
- Sleep Initiation and Maintenance Disorder; Elderly, Mental Disorder, Dyssomnias, Sleep Disorders, Sleep Disorder, Intrinsic
- Being tested
- Esmirtazapine
- Keywords
- elderly, randomized, double blind
- Medical subject headings
- Mental Disorders, Dyssomnias, Sleep Wake Disorders, Sleep Disorders, Intrinsic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EsmirtazapineDrug
One tablet daily
| Study group | Role | What they receive |
|---|---|---|
| Esmirtazapine 1.5 mg | Experimental | Participants receive esmirtazapine 1.5 mg tablets, one tablet administered orally once daily for up to 52 weeks Receives: Drug: Esmirtazapine |
| Esmirtazapine 3.0 mg | Experimental | Participants receive esmirtazapine 3.0 mg tablets, one tablet administered orally once daily for up to 52 weeks Receives: Drug: Esmirtazapine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Who Experience at Least One Adverse Event (AE)
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not related to the study drug.
Measured: Up to 53 weeks
Number of Participants Who Discontinue Study Drug Due to an AE
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not related to the study drug.
Measured: Up to 52 weeks
Change From Baseline in Alertness at Awakening
Alertness at awakening was assessed by participants using a 0-100 mm visual analog scale (VAS) in response to Weekly Sleep Diary question 6 "How did you feel upon awakening over the past 7 days?". Scores could range from 0=Tired to 100=Alert. Baseline was defined as the Day 1 assessment of Days -7 to 1 before any study drug was taken. Change from Baseline was calculated using an observed cases (OC) approach.
Measured: Baseline and Week 52
Change From Baseline in Feeling Full of Energy
Feeling full of energy was assessed by participants using a 0-100 mm visual analog scale (VAS) in response to Weekly Sleep Diary question 7 "How full of energy have you felt over the past 7 days?". Scores could range from 0=Terribly tired to 100=Full of energy. Baseline was defined as the Day 1 assessment of Days -7 to 1 before any study drug was taken. Change from Baseline was calculated using an OC approach.
Measured: Baseline and Week 52
Change From Baseline in Ability to Work/Function
Ability to work/function was assessed by participants using a 0-100 mm visual analog scale (VAS) in response to Weekly Sleep Diary question 8 "How were you able to work or function over the past 7 days?". Scores could range from 0=Not at all to 100=Very well. Baseline was defined as the Day 1 assessment of Days -7 to 1 before any study drug was taken. Change from Baseline was calculated using an OC approach.
Measured: Baseline and Week 52
Change From Baseline in Total Nap Time
Total nap time was assessed by participants in response to Weekly Sleep Diary question 9a "How much time per day did you nap, on average?". Baseline was defined as the Day 1 assessment of Days -7 to 1 before any study drug was taken. Change from Baseline was calculated using an OC approach.
Measured: Baseline and Week 52
Secondary outcomes (4)
Change From Baseline in Total Sleep Time (TST)
TST was defined as the time recorded by participants in response to Weekly Sleep Diary question 4 "During the past 7 nights, how much time did you actually spend sleeping, on average?". Baseline was defined as the Day 1 assessment of Days -7 to 1 before any study drug was taken. Change from Baseline was calculated using a last observation carried forward (LOCF) approach.
Measured: Baseline and Week 52
Change From Baseline in Wake Time After Sleep Onset (WASO)
WASO was defined as the time recorded by participants in response to Weekly Sleep Diary question 4 "During the past 7 nights, how much time were you awake, on average, after falling asleep initially?" Baseline was defined as the Day 1 assessment of Days -7 to 1 before any study drug was taken. Change from Baseline was calculated using a LOCF approach.
Measured: Baseline and Week 52
Change From Baseline in Sleep Latency (SL)
SL was defined as the time recorded by participants in response to Weekly Sleep Diary question 4 "During the past 7 nights, how long did it take you to fall asleep, on average?" Baseline was defined as the Day 1 assessment of Days -7 to 1 before any study drug was taken. Change from Baseline was calculated using a LOCF approach.
Measured: Baseline and Week 52
Change From Baseline in Number of Awakenings (NAW)
NAW was defined as the time recorded by participants in response to Weekly Sleep Diary question 2a "During the past 7 nights, how many times did you wake up, on average?" Baseline was defined as the Day 1 assessment of Days -7 to 1 before any study drug was taken. Change from Baseline was calculated using a LOCF approach.
Measured: Baseline and Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2007 (estimated)
- Study start9 Jan 2008
- Primary completion14 Feb 2010
- Study completion14 Feb 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Sleep Initiation and Maintenance Disorder; ElderlyStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 259 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00561574
- Sponsor's protocol ID
- P05697
- Other IDs
- 176005, 2007-003636-35
- Acronym
- Jade
- Status last verified
- Jan 2021
- First submitted
- 19 Nov 2007
- Last updated
- 27 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
Publications
Ivgy-May N, Chang Q, Pong A, Winokur A. Esmirtazapine for the treatment of chronic primary insomnia: a randomized long-term safety study in elderly outpatients. J Sleep Med. 2020;17(1):19-30. doi: 10.13078/jsm.190032
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Long-Term Safety Study of Org 50081 in Elderly Outpatients With Chronic Primary Insomnia Examining the Effects of 1.5 mg or 3.0 mg of Org 50081
- ClinicalTrials.gov ID
- NCT00561574
- Acronym / sponsor ID
- Jade / P05697
- Conditions
- Sleep Initiation and Maintenance Disorder; Elderly, Mental Disorder, Dyssomnias, Sleep Disorders, Sleep Disorder, Intrinsic
- Keywords
- elderly, randomized, double blind
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 259 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 9 Jan 2008 (actual)
- Primary completion
- 14 Feb 2010 (actual)
- Study completion
- 14 Feb 2010 (actual)
- First posted
- 21 Nov 2007 (estimated)
- Results
- Posted 7 Jul 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The current study is a 52-week safety study in elderly outpatients with chronic primary insomnia randomized to treatment with 1.5 mg or 3.0 mg of esmirtazapine (Org 50081, SCH 900265, MK-8265) to investigate the safety and tolerability of long-term treatment with esmirtazapine in elderly patients.
Detailed description
Insomnia is a common complaint or disorder throughout the world. About one third of the population in the industrial countries reports difficulty initiating or maintaining sleep, resulting in a non-refreshing or non-restorative sleep. The majority of the insomniacs suffer chronically from their complaints.
The maleic acid salt of Org 4420, code name Org 50081 (esmirtazapine), was selected for development in the treatment of insomnia. The first clinical trial with esmirtazapine was a proof-of-concept trial with a four-way cross-over design. All 3 esmirtazapine dose groups showed a statistically significant positive effect on Total Sleep Time (TST) (objective and subjective) and Wake Time After Sleep Onset (WASO), as compared to placebo.
The current study is a 52-week safety study in elderly outpatients with chronic primary insomnia randomized to treatment with 1.5 mg or 3.0 mg of esmirtazapine to investigate the safety and tolerability of long-term treatment with esmirtazapine in elderly patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Esmirtazapine 1.5 mg | Experimental | Drug: EsmirtazapineParticipants receive esmirtazapine 1.5 mg tablets, one tablet administered orally once daily for up to 52 weeks |
| Esmirtazapine 3.0 mg | Experimental | Drug: EsmirtazapineParticipants receive esmirtazapine 3.0 mg tablets, one tablet administered orally once daily for up to 52 weeks |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (10 listed)
- are at least 65 years of age at screening;
- sign written informed consent after the scope and nature of the investigation have been explained to them, before screening evaluations;
- are able to speak, read and understand the language of the investigator, study staff (including raters) and the informed consent form, and possess the ability to respond to questions, follow instructions and complete questionnaires;
- have demonstrated capability to independently complete the LogPad questionnaires in the week preceding randomization;
- normal bedtime should be within the 21:00 - 01:00 hour range, with no more variation than 2 hours for 5 nights out of 7;
Key exclusion criteria (23 listed)
- have other sleep disorders (DSM-IV-TR) e.g. rapid eye movement (REM) behavioral disorders, sleep related breathing disorders, periodic leg movement disorder, restless leg syndrome, narcolepsy, circadian sleep wake rhythm disorders, or any parasomnia;
- have any significant medical or DSM-IV-TR psychiatric illness causing the sleep disturbances;
- currently meet diagnostic criteria for DSM-IV-TR depression (Major Depressive Disorder [MDD]) or have been diagnosed and treated for MDD within the last 2 years;
- have signs of dementia or other serious cognitive impairment, defined by a score of less than 26 on the Mini-Mental State Examination (MMSE);
- have a history of bipolar disorder, a history of suicide attempt or a family history of suicide; A family history of suicide is defined as any history of suicide in the first and second degree family (parents, siblings, grandparents, or offspring), or a pattern of completed suicides (more than one) in the third degree family (aunts, uncles, nieces, and nephews);
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 |
|---|---|---|
| EsmirtazapineOne tablet daily | Drug | Esmirtazapine 1.5 mg, Esmirtazapine 3.0 mg |
Primary outcome
Number of Participants Who Experience at Least One Adverse Event (AE)
Time frame: Up to 53 weeks
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not related to the study drug.
Number of Participants Who Discontinue Study Drug Due to an AE
Time frame: Up to 52 weeks
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not related to the study drug.
Change From Baseline in Alertness at Awakening
Time frame: Baseline and Week 52
Alertness at awakening was assessed by participants using a 0-100 mm visual analog scale (VAS) in response to Weekly Sleep Diary question 6 "How did you feel upon awakening over the past 7 days?". Scores could range from 0=Tired to 100=Alert. Baseline was defined as the Day 1 assessment of Days -7 to 1 before any study drug was taken. Change from Baseline was calculated using an observed cases (OC) approach.
Change From Baseline in Feeling Full of Energy
Time frame: Baseline and Week 52
Feeling full of energy was assessed by participants using a 0-100 mm visual analog scale (VAS) in response to Weekly Sleep Diary question 7 "How full of energy have you felt over the past 7 days?". Scores could range from 0=Terribly tired to 100=Full of energy. Baseline was defined as the Day 1 assessment of Days -7 to 1 before any study drug was taken. Change from Baseline was calculated using an OC approach.
Change From Baseline in Ability to Work/Function
Time frame: Baseline and Week 52
Ability to work/function was assessed by participants using a 0-100 mm visual analog scale (VAS) in response to Weekly Sleep Diary question 8 "How were you able to work or function over the past 7 days?". Scores could range from 0=Not at all to 100=Very well. Baseline was defined as the Day 1 assessment of Days -7 to 1 before any study drug was taken. Change from Baseline was calculated using an OC approach.
Change From Baseline in Total Nap Time
Time frame: Baseline and Week 52
Total nap time was assessed by participants in response to Weekly Sleep Diary question 9a "How much time per day did you nap, on average?". Baseline was defined as the Day 1 assessment of Days -7 to 1 before any study drug was taken. Change from Baseline was calculated using an OC approach.
4 secondary outcomes
Change From Baseline in Total Sleep Time (TST)
Time frame: Baseline and Week 52
Change From Baseline in Wake Time After Sleep Onset (WASO)
Time frame: Baseline and Week 52
Change From Baseline in Sleep Latency (SL)
Time frame: Baseline and Week 52
Change From Baseline in Number of Awakenings (NAW)
Time frame: Baseline and Week 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publicationIvgy-May N, Chang Q, Pong A, Winokur A. Esmirtazapine for the treatment of chronic primary insomnia: a randomized long-term safety study in elderly outpatients. J Sleep Med. 2020;17(1):19-30. doi: 10.13078/jsm.190032
- Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
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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 study director
Merck Sharp & Dohme LLC
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Esmirtazapine in people with Sleep Initiation and Maintenance Disorder; Elderly and Mental Disorder, run by Merck Sharp & Dohme LLC.
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 23 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 27 Jan 2021. 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. 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?
Yes. Results are posted in the registry (first posted 7 Jul 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants Who Experience at Least One Adverse Event (AE) (time frame: Up to 53 weeks). The study lists 6 primary outcomes in all. 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 NCT00561574, 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 27 Jan 2021.