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Esmirtazapine

Phase 3

Insomnia | Small molecule | Psychiatry |Merck & Company, Inc.|Last Updated: Jan 27, 2021

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLED
Total Trials3
Total Enrollment1,483

FDA Designations

No designations recorded

Clinical trial landscape

Esmirtazapine · 7 trials · 11 indications

Phase 3 7
NCT00631657A 6-Month Efficacy and Safety Study of Org 50081 in Adult Patients With Chronic Primary Insomnia (21106/P05701/MK-8265-002)Sleep Initiation and Maintenance Disorders
COMPLETED460 Analytics
NCT00561574A Long-Term Safety Study of Org 50081 (Esmirtazapine) in Elderly Outpatients With Chronic Primary Insomnia (176005/P05697/MK-8265-001)Sleep Initiation and Maintenance Disorder; Elderly
COMPLETED259 Analytics
NCT00561821Efficacy and Safety Study of Org 50081 (Esmirtazapine) in Elderly Participants (P05709)Insomnia
COMPLETED538 Analytics
NCT00506389A Six Week, Double-Blind Randomized, Efficacy and Safety, Sleep Lab Trial With Esmirtazapine (Org 50081) (P05707)Insomnia
COMPLETED419 Analytics
NCT00482612Study of the Safety and Effectiveness of Esmirtazapine in Participants With Chronic Primary Insomnia (P05706)Insomnia
COMPLETED526 Analytics
NCT00560833Dose-Finding Safety and Efficacy Trial of Org50081 (Esmirtazapine) in the Treatment of Vasomotor Symptoms (46101/P06459/MK-8265-012)Menopause
COMPLETED943 Analytics
NCT00535288Dose-Finding Safety and Efficacy Trial of Org 50081 (Esmirtazapine) in the Treatment of Vasomotor Symptoms (177001/P06472/MK-8265-013)Postmenopausal Symptoms
COMPLETED946 Analytics
PHASE3COMPLETED
A 6-Month Efficacy and Safety Study of Org 50081 in Adult Patients With Chronic Primary Insomnia (21106/P05701/MK-8265-002)
Sleep Initiation and Maintenance DisordersUnlock trial analytics
PHASE3COMPLETED
A Long-Term Safety Study of Org 50081 (Esmirtazapine) in Elderly Outpatients With Chronic Primary Insomnia (176005/P05697/MK-8265-001)
Sleep Initiation and Maintenance Disorder; ElderlyUnlock trial analytics
PHASE3COMPLETED
Efficacy and Safety Study of Org 50081 (Esmirtazapine) in Elderly Participants (P05709)
InsomniaUnlock trial analytics
PHASE3COMPLETED
A Six Week, Double-Blind Randomized, Efficacy and Safety, Sleep Lab Trial With Esmirtazapine (Org 50081) (P05707)
InsomniaUnlock trial analytics
PHASE3COMPLETED
Study of the Safety and Effectiveness of Esmirtazapine in Participants With Chronic Primary Insomnia (P05706)
InsomniaUnlock trial analytics
PHASE3COMPLETED
Dose-Finding Safety and Efficacy Trial of Org50081 (Esmirtazapine) in the Treatment of Vasomotor Symptoms (46101/P06459/MK-8265-012)
MenopauseUnlock trial analytics
PHASE3COMPLETED
Dose-Finding Safety and Efficacy Trial of Org 50081 (Esmirtazapine) in the Treatment of Vasomotor Symptoms (177001/P06472/MK-8265-013)
Postmenopausal SymptomsUnlock trial analytics

Study Endpoints

Primary Endpoints

Change From Baseline in Total Sleep Time (TST) - 6-Month Treatment Period
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.

Number of Participants Who Experience at Least One Adverse Event (AE)
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
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
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
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
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
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.

Average Wake Time After Sleep Onset Measured by Polysomnography
Up to Day 16

Wake time after sleep onset (WASO) is the total time awake between sleep onset and "lights on"; i.e. from the onset of persistent sleep until the end of the 8-hour polysomnography (PSG) recording. PSG assesses the quality of sleep by monitoring brain waves, breathing, heart function, muscle activity and eye movement. PSG measurements of WASO (observed data only) taken during the 16-day double-blind treatment period, over days 1 and 2 and days 15 and 16, were averaged.

Average Wake Time After Sleep Onset (WASO) During the In-Treatment Period
From Day 1 to Day 36

WASO was defined as the total objective time awake after the onset of persistent sleep until the end of the 8-hour sleep cycle period as measured by polysomnography (PSG). WASO was calculated as the mean of Nights 1, 15, and 36.

Average Total Sleep Time (TST) as Recorded Daily in the Sleep Diary During the 14-day In-treatment Period
Day 1 to Day 15

TST was defined as the total amount of time (measured in minutes) that was actually spent sleeping the previous night as recorded daily in the participant's sleep diary. TST values over the 14-day active treatment period were averaged for each participant, and average TST was then reported by treatment arm. For participants with missing data, the average of the nights for which TST data were present was used in the analysis.

Change From Baseline in Average Daily Frequency of Vasomotor Symptoms (Frequency Score A) at Week 4
Baseline and Week 4

Participants recorded the frequency of vasomotor symptoms (hot flushes) on an electronic diary card (LogPad®) on a daily basis during screening and treatment. Frequency score A was based on the number of moderate hot flushes + the number of severe hot flushes in one day. Baseline average was derived from, at most, 7 completely observed pre-treatment days. Weekly averages during treatment were calculated if at least 4 days with non-missing data were completely observed; if less than 4 days were completely observed, the averages of the previous week were carried forward (last observation carried forward, or LOCF). If the number of days observed in Week 1 were not sufficient, baseline values were carried forward.

Change From Baseline in Average Daily Frequency of Vasomotor Symptoms (Frequency Score A) at Week 12
Baseline and Week 12

Participants recorded the frequency of vasomotor symptoms (hot flushes) on a LogPad on a daily basis during screening and treatment. Frequency score A was based on the number of moderate hot flushes + the number of severe hot flushes in one day. Baseline average was derived from, at most, 7 completely observed pre-treatment days. Weekly averages during treatment were calculated if at least 4 days with non-missing data were completely observed; if less than 4 days were completely observed, the averages of the previous week were carried forward (last observation carried forward, or LOCF). If the number of days observed in Week 1 were not sufficient, baseline values were carried forward.

Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) at Week 4
Baseline and Week 4

Participants recorded the severity of hot flushes on a LogPad on a daily basis during screening and treatment. The severity of hot flushes was defined as: mild (sensation of heat without sweating); moderate (sensation of heat with sweating, able to continue activity); and severe (sensation of heat with sweating, causing cessation of activity). Severity score A was calculated as the number of moderate hot flushes x 2 + the number of severe hot flushes x 3, divided by the total number of moderate and severe hot flushes. If no hot flushes were experienced, this was to be recorded as 'no sensation of heat'. Baseline values were based on, at most, 7 completely observed pre-treatment days. If less than 4 days were completely observed during treatment, the averages of the previous week were carried forward (last observation carried forward, or LOCF). If the number of days observed in Week 1 were not sufficient, baseline values were carried forward.

Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) at Week 12
Baseline and Week 12

Participants recorded the severity of hot flushes on a LogPad on a daily basis during screening and treatment. The severity of hot flushes was defined as: mild (sensation of heat without sweating); moderate (sensation of heat with sweating, able to continue activity); and severe (sensation of heat with sweating, causing cessation of activity). Severity score A was calculated as the number of moderate hot flushes x 2 + the number of severe hot flushes x 3, divided by the total number of moderate and severe hot flushes. If no hot flushes were experienced, this was to be recorded as 'no sensation of heat'. Baseline values were based on, at most, 7 completely observed pre-treatment days. If less than 4 days were completely observed during treatment, the averages of the previous week were carried forward (last observation carried forward, or LOCF). If the number of days observed in Week 1 were not sufficient, baseline values were carried forward.

Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) at Week 4
Baseline and Week 4

Participants recorded the frequency (number) of vasomotor symptoms (hot flushes) on an electronic diary card (LogPad®) on a daily basis during screening and treatment. Frequency Score A was based on the number of moderate hot flushes + the number of severe hot flushes in one day. Baseline average was derived from, at most, 7 completely observed pre-treatment days. Weekly averages during treatment were calculated if at least 4 days with non-missing data were completely observed; if less than 4 days were completely observed, the averages of the previous week were carried forward (last observation carried forward, or LOCF). If the number of days observed in Week 1 were not sufficient, baseline values were carried forward.

Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) at Week 12
Baseline and Week 12

Participants recorded the frequency (number) of vasomotor symptoms (hot flushes) on a LogPad on a daily basis during screening and treatment. Frequency Score A was based on the number of moderate hot flushes + the number of severe hot flushes in one day. Baseline average was derived from, at most, 7 completely observed pre-treatment days. Weekly averages during treatment were calculated if at least 4 days with non-missing data were completely observed; if less than 4 days were completely observed, the averages of the previous week were carried forward (LOCF). If the number of days observed in Week 1 were not sufficient, baseline values were carried forward.

Secondary Endpoints

Number of Participants Who Experienced Adverse Events (AEs)
Up to 31 weeks
Number of Participants Who Discontinued Study Drug Due to an AE
Up to 27 weeks
Change From Baseline in Sleep Latency (SL) - 6-Month Treatment Period
Baseline and the Mean of Weeks 14-26
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Study Design & Arms

AllocationRANDOMIZED
MaskingTRIPLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Esmirtazapine 4.5 mgEXPERIMENTALParticipants receive esmirtazapine 4.5 mg tablets, administered once a day for 6 months
PlaceboPLACEBO_COMPARATORParticipants receive placebo tablets, administered once a day for 6 months
Esmirtazapine 1.5 mgEXPERIMENTALParticipants receive esmirtazapine 1.5 mg tablets, one tablet administered orally once daily for up to 52 weeks
Esmirtazapine 3.0 mgEXPERIMENTALParticipants receive esmirtazapine 3.0 mg tablets, one tablet administered orally once daily for up to 52 weeks
Esmirtazapine 0.5 mgEXPERIMENTALone placebo tablet daily for 14 days, followed by one 0.5 mg tablet Esmirtazapine daily for 16 days, and then one placebo tablet daily for 7 days
Esmirtazapine 2.25 mgEXPERIMENTALParticipants receive esmirtazapine 2.25 mg, encapsulated tablets, PO, QD for up to 12 weeks
Esmirtazapine 9 mgEXPERIMENTALParticipants receive esmirtazapine 9 mg, encapsulated tablets, PO, QD for up to 12 weeks
Esmirtazapine 18 mgEXPERIMENTALParticipants receive esmirtazapine 18 mg, encapsulated tablets, PO, QD for up to 12 weeks

Interventions

NameTypeDescription
EsmirtazapineDRUGOne esmirtazapine 4.5 mg tablet once a day
PlaceboDRUGOne placebo tablet once a day
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Eligibility Criteria

Age Range18 Years to 65 Years
SexALL
Healthy VolunteersNo

Inclusion Criteria: * 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...

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Competitive Landscape -Insomnia and Sleep Disorders 11 trials (matched to "Insomnia")

Frequently asked questions about Esmirtazapine

What is Esmirtazapine used for?

Esmirtazapine is an investigational small molecule being studied for postmenopausal symptoms, menopause, sleep initiation and maintenance disorders, and insomnia, including insomnia in elderly patients. It is in Phase 3 clinical development and is not approved by the FDA.

Who makes Esmirtazapine?

Esmirtazapine is being developed by Merck & Company, Inc., which trades under the ticker MRK. The drug is currently in Phase 3 clinical trials for insomnia and menopause-related conditions.

What phase is Esmirtazapine in?

Esmirtazapine is in Phase 3 clinical development. It is an investigational drug and has not received FDA approval. All three of its Phase 3 trials have been completed, with a total enrollment of 1,483 participants.

What clinical trials is Esmirtazapine in?

Esmirtazapine has completed three Phase 3 trials: NCT00482612 in chronic primary insomnia, NCT00506389 in insomnia, and NCT00535288 in vasomotor symptoms of menopause. A fourth trial, NCT00561821, studied esmirtazapine in elderly participants with insomnia.

Is Esmirtazapine the same as Org 50081?

Yes, Esmirtazapine is also known as Org 50081. Clinical trials reference this alternative name, including NCT00506389 and NCT00535288, which study the drug under the Org 50081 designation.