Sleep Initiation and Maintenance DisordersPhase 3NCT00631657
A 6-Month Efficacy and Safety Study of Org 50081 in Adult Patients With Chronic Primary Insomnia (21106/P05701/MK-8265-002)
A Phase 3 study testing Esmirtazapine in people with Sleep Initiation and Maintenance Disorders and Mental Disorders, run by Merck Sharp & Dohme LLC.
Trial summary
To investigate the long-term efficacy and safety of treatment with esmirtazapine (Org 50081, SCH 900265, MK-8265) compared to placebo, in participants with chronic primary insomnia. Primary efficacy variable is Total Sleep Time (TST). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Sleep Initiation and Maintenance Disorders, Mental Disorders, Dyssomnias
- What is being tested?
- Esmirtazapine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 460 participants
- Where
- No sites listed yet
- Study dates
- 4 Mar 2008to 19 Nov 2009
- 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- are at least 18 and less than 65 years;
- sign written informed consent after the scope and nature of the investigation have been explained;
- have shown capability to complete the LogPad questionnaires;
- have difficulty falling asleep, maintaining sleep or have early morning awakening;
Who cannot join
- Significant medical or psychiatric illness causing sleep disturbances.
- Have a history of bipolar disorder or attempted suicide or have a family (immediate family) history of suicide.
- Have a sleep disorder such as sleep-related breathing disorder, restless leg syndrome, narcolepsy.
- Significant other medical illness such as acute or chronic pain, heart-, kidney-, or liver disease within the last year.
- Currently diagnosed or meet the criteria for Major Depressive Disorder (MDD) or have been treated for MDD in the last 2 years.
- Substance abuse, excessive use of alcohol (determined by the physician) or drug addiction within the last year.
Show all 9Show fewer
- Are night workers or rotating shift workers or plan to travel through more than 3 time-zones.
- Routinely nap during the day.
- Have a Body Mass Index (BMI) of 36 or more.
About this study
Official title: A 6-Month, Double-Blind, Randomized, Placebo-Controlled, Parallel Group Outpatient Trial, Investigating the Efficacy and Safety of Org 50081 in Adult Patients With Chronic Primary Insomnia
To investigate the long-term efficacy and safety of treatment with esmirtazapine (Org 50081, SCH 900265, MK-8265) compared to placebo, in participants with chronic primary insomnia. Primary efficacy variable is Total Sleep Time (TST).
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 TST (objective and subjective) and Wake Time After Sleep Onset (WASO), as compared to placebo.
The current study is designed to assess the long-term efficacy and safety of esmirtazapine in a double-blind, randomized, placebo-controlled, parallel group outpatient trial in participants suffering from chronic primary insomnia. During the 6-month treatment period, participants are randomly assigned to receive either esmirtazapine or placebo. Then, during the 7-day discontinuation period, participants who received esmirtazapine in the 6-month treatment period are randomly assigned to receive either esmirtazapine or placebo, while participants who received placebo in the 6-month treatment period continue to receive placebo.
- Conditions
- Sleep Initiation and Maintenance Disorders, Mental Disorders, Dyssomnias, Sleep Disorders, Sleep Disorder, Intrinsic
- Being tested
- Esmirtazapine, Placebo
- Keywords
- placebo controlled, randomized, double blind
- Medical subject headings
- Sleep Initiation and Maintenance Disorders, 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 esmirtazapine 4.5 mg tablet once a day
PlaceboDrug
One placebo tablet once a day
| Study group | Role | What they receive |
|---|---|---|
| Esmirtazapine 4.5 mg | Experimental | Participants receive esmirtazapine 4.5 mg tablets, administered once a day for 6 months Receives: Drug: Esmirtazapine |
| Placebo | Placebo comparator | Participants receive placebo tablets, administered once a day for 6 months Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Total Sleep Time (TST) - 6-Month Treatment Period
TST was defined as the time recorded for sleep diary question 6 "How much time did you actually spend sleeping?" as reported by participants using a LogPad (hand-held electronic data capture device). Baseline was defined as the mean TST from the Placebo Run-in Period. Change from Baseline was calculated as the mean of combined data from Weeks 14 through 26, using a last observation carried forward (LOCF) approach.
Measured: Baseline and the Mean of Weeks 14-26
Secondary outcomes (4)
Number of Participants Who Experienced Adverse Events (AEs)
An AE is defined as any unfavorable and unintended change in the structure, function or chemistry of the body whether or not considered related to study drug. The number of participants who experienced AEs is combined for the 6-Month Treatment Period and the 7-Day Discontinuation Period.
Measured: Up to 31 weeks
Number of Participants Who Discontinued Study Drug Due to an AE
An AE is defined as any unfavorable and unintended change in the structure, function or chemistry of the body whether or not considered related to study drug. The number of participants who discontinued study drug due to an AE is combined for the 6-Month Treatment Period and the 7-Day Discontinuation Period.
Measured: Up to 27 weeks
Change From Baseline in Sleep Latency (SL) - 6-Month Treatment Period
SL was defined as the time recorded for sleep diary question 3 "How long did it take you to fall asllep?", as reported by participants using a LogPad. Baseline was defined as the mean SL from the Placebo Run-in Period. Change from Baseline was calculated as the mean of combined data from Weeks 14 through 26, using an LOCF approach.
Measured: Baseline and the Mean of Weeks 14-26
Change From Baseline in Wake Time After Sleep Onset (WASO) - 6-Month Treatment Period
WASO was defined as the time recorded for sleep diary question 5 "How much time were you awake, after falling asleep initially?", as reported by participants using a LogPad. Baseline was defined as the mean WASO from the Placebo Run-in Period. Change from Baseline was calculated as the mean of combined data from Weeks 14 through 26, using an LOCF approach.
Measured: Baseline and the Mean of Weeks 14-26
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2008 (estimated)
- Study start4 Mar 2008
- Primary completion19 Nov 2009
- Study completion19 Nov 2009
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 DisordersStudies 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
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 460 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00631657
- Sponsor's protocol ID
- P05701
- Other IDs
- 21106, 2007-005236-92
- Status last verified
- Sep 2018
- First submitted
- 29 Feb 2008
- Last updated
- 2 Oct 2018
- 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, Hajak G, van Osta G, Braat S, Chang Q, Roth T. Efficacy and safety of esmirtazapine in adult outpatients with chronic primary insomnia: a randomized, double-blind placebo-controlled study and open-label extension. J Clin Sleep Med. 2020 Sep 15;16(9):1455-1467. doi: 10.5664/jcsm.8526.
PubMed 32351205
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A 6-Month, Double-Blind, Randomized, Placebo-Controlled, Parallel Group Outpatient Trial, Investigating the Efficacy and Safety of Org 50081 in Adult Patients With Chronic Primary Insomnia
- ClinicalTrials.gov ID
- NCT00631657
- Acronym / sponsor ID
- P05701
- Conditions
- Sleep Initiation and Maintenance Disorders, Mental Disorders, Dyssomnias, Sleep Disorders, Sleep Disorder, Intrinsic
- Keywords
- placebo controlled, randomized, double blind
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 460 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 4 Mar 2008 (actual)
- Primary completion
- 19 Nov 2009 (actual)
- Study completion
- 19 Nov 2009 (actual)
- First posted
- 10 Mar 2008 (estimated)
- Results
- Posted 1 Aug 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To investigate the long-term efficacy and safety of treatment with esmirtazapine (Org 50081, SCH 900265, MK-8265) compared to placebo, in participants with chronic primary insomnia. Primary efficacy variable is Total Sleep Time (TST).
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 TST (objective and subjective) and Wake Time After Sleep Onset (WASO), as compared to placebo.
The current study is designed to assess the long-term efficacy and safety of esmirtazapine in a double-blind, randomized, placebo-controlled, parallel group outpatient trial in participants suffering from chronic primary insomnia. During the 6-month treatment period, participants are randomly assigned to receive either esmirtazapine or placebo. Then, during the 7-day discontinuation period, participants who received esmirtazapine in the 6-month treatment period are randomly assigned to receive either esmirtazapine or placebo, while participants who received placebo in the 6-month treatment period continue to receive placebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Esmirtazapine 4.5 mg | Experimental | Drug: EsmirtazapineParticipants receive esmirtazapine 4.5 mg tablets, administered once a day for 6 months |
| Placebo | Placebo comparator | Drug: PlaceboParticipants receive placebo tablets, administered once a day for 6 months |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- are at least 18 and less than 65 years;
- sign written informed consent after the scope and nature of the investigation have been explained;
- have shown capability to complete the LogPad questionnaires;
- have difficulty falling asleep, maintaining sleep or have early morning awakening;
Key exclusion criteria (9 listed)
- Significant medical or psychiatric illness causing sleep disturbances.
- Have a history of bipolar disorder or attempted suicide or have a family (immediate family) history of suicide.
- Have a sleep disorder such as sleep-related breathing disorder, restless leg syndrome, narcolepsy.
- Significant other medical illness such as acute or chronic pain, heart-, kidney-, or liver disease within the last year.
- Currently diagnosed or meet the criteria for Major Depressive Disorder (MDD) or have been treated for MDD in the last 2 years.
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 esmirtazapine 4.5 mg tablet once a day | Drug | Esmirtazapine 4.5 mg |
| PlaceboOne placebo tablet once a day | Drug | Placebo |
Primary outcome
Change From Baseline in Total Sleep Time (TST) - 6-Month Treatment Period
Time frame: Baseline and the Mean of Weeks 14-26
TST was defined as the time recorded for sleep diary question 6 "How much time did you actually spend sleeping?" as reported by participants using a LogPad (hand-held electronic data capture device). Baseline was defined as the mean TST from the Placebo Run-in Period. Change from Baseline was calculated as the mean of combined data from Weeks 14 through 26, using a last observation carried forward (LOCF) approach.
4 secondary outcomes
Number of Participants Who Experienced Adverse Events (AEs)
Time frame: Up to 31 weeks
Number of Participants Who Discontinued Study Drug Due to an AE
Time frame: Up to 27 weeks
Change From Baseline in Sleep Latency (SL) - 6-Month Treatment Period
Time frame: Baseline and the Mean of Weeks 14-26
Change From Baseline in Wake Time After Sleep Onset (WASO) - 6-Month Treatment Period
Time frame: Baseline and the Mean of Weeks 14-26
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32351205Ivgy-May N, Hajak G, van Osta G, Braat S, Chang Q, Roth T. Efficacy and safety of esmirtazapine in adult outpatients with chronic primary insomnia: a randomized, double-blind placebo-controlled study and open-label extension. J Clin Sleep Med. 2020 Sep 15;16(9):1455-1467. doi: 10.5664/jcsm.8526.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Esmirtazapine in people with Sleep Initiation and Maintenance Disorders and Mental Disorders, 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 4 inclusion and 9 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 2 Oct 2018. 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 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 1 Aug 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?
Change From Baseline in Total Sleep Time (TST) - 6-Month Treatment Period (time frame: Baseline and the Mean of Weeks 14-26). 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 NCT00631657, 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 2 Oct 2018.