Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as ORG 50081, MK-8265, SCH 900265
Esmirtazapine · 9 trials · 11 indications
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
An Adverse Event (AE) is any untoward occurrence in a participant who is administered any pharmaceutical product, and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding) symptom, or disease temporarily associated with the use of an investigational medicinal product (IMP), whether or not it is related to the IMP.
An Adverse Event (AE) is any untoward occurrence in a participant who is administered any pharmaceutical product, and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding) symptom, or disease temporarily associated with the use of an IMP, whether or not it is related to the IMP.
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.
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.
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.
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.
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.
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.
| Arm | Type | Description |
|---|---|---|
| Esmirtazapine 4.5 mg | EXPERIMENTAL | Participants receive esmirtazapine 4.5 mg tablets, administered once a day for 6 months |
| Placebo | PLACEBO_COMPARATOR | Participants receive placebo tablets, administered once a day for 6 months |
| Esmirtazapine 1.5 mg | EXPERIMENTAL | Participants receive esmirtazapine 1.5 mg tablets, one tablet administered orally once daily for up to 52 weeks |
| Esmirtazapine 3.0 mg | EXPERIMENTAL | Participants receive esmirtazapine 3.0 mg tablets, one tablet administered orally once daily for up to 52 weeks |
| Esmirtazapine 0.5 mg | EXPERIMENTAL | one 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 | EXPERIMENTAL | One tablet of Esmirtazapine, 4.5 mg orally, daily for up to 52 weeks |
| Esmirtazapine 2.25 mg | EXPERIMENTAL | Participants receive esmirtazapine 2.25 mg, encapsulated tablets, PO, QD for up to 12 weeks |
| Esmirtazapine 9 mg | EXPERIMENTAL | Participants receive esmirtazapine 9 mg, encapsulated tablets, PO, QD for up to 12 weeks |
| Esmirtazapine 18 mg | EXPERIMENTAL | Participants receive esmirtazapine 18 mg, encapsulated tablets, PO, QD for up to 12 weeks |
| Treatment 1 | EXPERIMENTAL | - |
| Treatment 2 | EXPERIMENTAL | - |
| Treatment 3 | PLACEBO_COMPARATOR | - |
| Treatment 4 | ACTIVE_COMPARATOR | - |
| Name | Type | Description |
|---|---|---|
| Esmirtazapine | DRUG | One esmirtazapine 4.5 mg tablet once a day |
| Placebo | DRUG | One placebo tablet once a day |
| Org 50081 | DRUG | One tablet daily |
| zopiclone | DRUG | Single dose of 7.5 mg |
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...
Top 2 of 6 competitors
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Merck & Co., Inc. | MRK | 1 | PHASE3 | Suvorexant |
| Vanda Pharmaceuticals Inc. | VNDA | 2 | PHASE3 | tasimelteon |
Esmirtazapine is an investigational small molecule developed by Merck & Company, Inc. (MRK) for sleep and menopause-related conditions. It has been studied in Phase 3 trials for chronic primary insomnia in adults and elderly patients, and for vasomotor symptoms associated with menopause. It is not described as approved.
Esmirtazapine has been studied for insomnia, including sleep initiation and maintenance disorders in adults and in elderly patients, and for vasomotor symptoms in menopausal and postmenopausal women. All of its recorded trials are completed Phase 3 studies, and the drug remains investigational rather than an approved treatment.
Esmirtazapine acts as an antagonist at the HTR2A, HTR2C, ADRA2A, ADRA2C, ADRA2B and HRH1 receptors. Its target class is antagonist. These receptor activities were the basis for its clinical development in sleep disorders and in menopausal vasomotor symptoms.
Esmirtazapine is developed by Merck & Company, Inc., which trades under the ticker MRK. The compound was studied under the development codes Org 50081 and MK-8265 in Merck-sponsored Phase 3 programs covering insomnia and vasomotor symptoms.
Esmirtazapine is in Phase 3 development. Three completed Phase 3 trials are recorded, with no active trials listed, and total enrollment across the program is 1,483 participants. The studies were randomized, double-blind and placebo-controlled.
Completed Phase 3 trials of esmirtazapine include NCT00631657, a 6-month efficacy and safety study in adults with chronic primary insomnia; NCT00561821, an efficacy and safety study in elderly participants; NCT00561574, a long-term safety study in elderly outpatients with chronic primary insomnia; and NCT00560833, a dose-finding trial in vasomotor symptoms.