Menopause, Postmenopausal Symptoms, Vasomotor Symptoms
Conditions
Brief summary
To investigate efficacy and safety of 4 doses of esmirtazapine, compared to placebo, in the treatment of moderate to severe hot flushes (vasomotor symptoms) associated with the menopause. Co-primary efficacy endpoints are the frequency and severity of hot flushes after 4 and 12 weeks as compared to Baseline.
Detailed description
The most direct treatment of hot flushes may be by means of 5-HT2A receptor antagonist. Mirtazapine is a potent blocker of 5-HT2A receptors and was found to be effective in reducing the number and intensity of hot flushes in preliminary trials. Also several Selective Serotonin Reuptake Inhibitors (SSRIs) and other similar compounds have been investigated to manage hot flushes, confirming the role of the serotonergic system. In the present trial, the efficacy and safety of four different doses of esmirtazapine compared to placebo were investigated in women with moderate to severe vasomotor symptoms associated with the menopause. The primary objective of this trial was to demonstrate superior efficacy in at least one of the four doses of esmirtazapine as compared to placebo on the four following co-primary endpoints: 1) the mean change from baseline in average daily frequency of moderate and severe vasomotor symptoms at Week 4; 2) the mean change from baseline in average daily frequency of moderate and severe vasomotor symptoms at Week 12; 3) the mean change from baseline in average daily severity of moderate and severe vasomotor symptoms at Week 4; 4) the mean change from baseline in average daily severity of moderate and severe vasomotor symptoms at Week 12. The number and severity of hot flushes was recorded by means of electronic diary by the subjects.
Interventions
DRUGEsmirtazapine
Four different doses (2.25, 4.5, 9.0, and 18 mg) encapsulated esmirtazapine tablets in Swedish Orange hard gelatin DB-B capsules for blinding purposes. Encapsulated tablets were administered orally once daily in the evening prior to sleep for 12 weeks.
DRUGPlacebo
Encapsulated placebo tablets in Swedish Orange hard gelatin DB-B capsules for blinding purposes. Encapsulated tablets were administered orally once daily in the evening prior to sleep for 12 weeks.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
40 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Postmenopausal women, defined as: * 12 months of spontaneous amenorrhea; * OR 6 months of spontaneous amenorrhea with serum Follicle Stimulating Hormone (FSH) levels \>40 mIU/mL; * OR 6 weeks post surgical bilateral oophorectomy with or without hysterectomy. * Be ≥ 40 and ≤ 65 years of age; * Have a body mass index (BMI) ≥ 18 and ≤ 32 kg/m\^2; * Minimum of 7 moderate to severe hot flushes per day or 50 per week, as quantified from daily diary recordings during at least 7 days preceding randomization to trial medication; * Able to handle the electronic diary device after training and having at least 80% compliance on complete daily diary entries during the period prior to randomization; * Give voluntary written Informed Consent (IC) after the scope and nature of the investigation had been explained, before screening evaluations.
Exclusion criteria
* History or presence of any malignancy, except non-melanoma skin cancers; * Any clinically unstable or uncontrolled renal, hepatic, endocrine, respiratory, hematological, neurological, cardiovascular or cerebrovascular disease that would put the subject at safety risk or mask measure of efficacy; * History of seizures or epilepsy; * History or presence of clinically significant depression or other psychiatric disorder which, in the opinion of the investigator, might compromise or confound the subject's participation in the trial; * Abnormal clinically relevant vaginal bleeding; * Any clinically relevant (opinion of investigator) abnormal finding during physical, gynecological and breast examination at screening; * Abnormal, clinically significant results of mammography; * Abnormal cervical smear test results (corresponding to Pap III and higher, including Low-Grade Squamous Intraepithelial Lesion (LSIL), High-Grade Squamous Intraepithelial Lesion (HSIL), Cervical Intraepithelial Neoplasia (CIN) 1 and higher); * Hematological or biochemical values at screening outside the reference ranges considered clinically relevant in the opinion of the investigator; * High Blood Pressure (BP); * Use of any drug product containing estrogens, progestins, androgens or tibolone prior to screening (and up to and including randomization) within a pre-specified period; * Any of the following treatments within the last 4 weeks prior to screening (and up to and including randomization): * tricyclic antidepressants, Serotonin Noradrenergic Reuptake Inhibitors (SNRIs), SSRIs, Monoamine Oxidase (MAO)-inhibitors, mirtazapine * antianxiety drugs, antipsychotics * coumarin-derivatives * α-adrenergic agents * β-blockers * dopamine agonists/antagonists * opiates, barbiturates * raloxifene * homeopathic menopausal preparations or other preparations intended to treat climacteric or Central Nervous System (CNS) symptoms * hepatic microsomal enzyme-inducing drugs or drugs known to affect or interfere with the pharmacokinetics of mirtazapine; * Any condition or disease that could affect or interfere with the pharmacokinetics of mirtazapine; * Subjects sensitive to trial medication or its components; * Use of any investigational drug and/or participation in another clinical trial within the last eight weeks prior to screening; * History of alcohol and/or drug abuse within the last two years prior to screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 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 per week. 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 (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. |
| 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 per week. 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 (LOCF). If the number of days observed in Week 1 were not sufficient, baseline values were carried forward. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Baseline and Up to 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. |
| Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Baseline and up to 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 per week. 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 (LOCF). If the number of days observed in Week 1 were not sufficient, baseline values were carried forward. |
| Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Baseline and up to Week 12 | Composite Score A was calculated as Severity Score A x Frequency Score A. |
| Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Baseline and up to 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 B was based on the number of mild hot flushes + 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. |
| Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Baseline and up to 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 B was calculated as the number of mild hot flushes + the number of moderate hot flushes x 2 + the number of severe hot flushes x 3, divided by the total number of all hot flushes per week. 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 (LOCF). If the number of days observed in Week 1 were not sufficient, baseline values were carried forward. |
| Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Baseline and up to Week 12 | Composite Score B was calculated as Severity Score B x Frequency Score B. |
| Total Number of Responders by Week | Up to 12 weeks | A participant was defined as a (hot flush) responder for a study week if a reduction of at least 50% for average daily frequency of moderate/severe vasomotor symptoms (hot flushes) (Frequency Score A) compared to Baseline was recorded. A study week was taken into account if at least 4 days were completely observed. The last observation was carried forward if there were less than 4 complete days observed. In cases where Week 1 did not have 4 days that were completely observed, the participant was considered a non-responder. An LOCF approach was used. |
| Total Number of Remitters by Week | Up to 12 weeks | A participant was defined as a (hot flush) remitter for a study week if at most one moderate/severe vasomotor symptom per day on average was recorded. A study week was taken into account if at least 4 days were completely observed. The last observation was carried forward if there were less than 4 complete days observed. In cases where Week 1 did not have 4 days that were completely observed, the participant was considered a non-remitter. |
| Change From Baseline in Women's Health Questionnaire (WHQ) Sleep Problems Symptoms Domain Score at Week 12 | Baseline and Week 12 | The WHQ is a 36-item, user-friendly, and rapid way of assessing nine domains of physical and emotional health for mid-aged women. Participants self-administered the WHQ questionnaire; scoring is based on a 4-point scale as follows: 'Yes definitely=1', 'Yes sometimes=2', 'No not much=3' and 'No not at all=4'. Each score is transformed to a value '1' for scores '1' and '2' and to a value '0' for scores '3' and '4'. Sleep problems encompass Items 1, 11, and 29 of the 36 total items. The transformed sums of items 1, 11, and 29 were divided by 3 to get the score; therefore, the domain ranges from 0 to 1, where lower values are better. |
| Change From Baseline in WHQ Vasomotor Symptoms Domain Score at Week 12 | Baseline and Week 12 | The WHQ is a 36-item, user-friendly, and rapid way of assessing nine domains of physical and emotional health for mid-aged women. Participants self-administered the WHQ questionnaire; scoring is based on a 4-point scale as follows: 'Yes definitely=1', 'Yes sometimes=2', 'No not much=3' and 'No not at all=4'. Each score is transformed to a value '1' for scores '1' and '2' and to a value '0' for scores '3' and '4'. Vasomotor symptoms encompass Items 19 and 27 of the 36 total items. The transformed sums of items 19+27 are divided by 2 to get the score; therefore, the domain ranges from 0 to 1, where lower values are better. |
Participant flow
Pre-assignment details
946 participants were randomly assigned in this study, however, one participant assigned to placebo never received treatment and one participant assigned to placebo actually received esmirtazapine 18 mg and is included in that group for all study analyses.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants receive encapsulated tablets, orally, QD for up to 12 weeks. | 314 |
| Esmirtazapine 2.25 mg Participants receive esmirtazapine, 2.25 mg, encapsulated tablets, orally QD for up to 12 weeks. | 162 |
| Esmirtazapine 4.5 mg Participants receive esmirtazapine, 4.5 mg, encapsulated tablets, orally QD for up to 12 weeks. | 160 |
| Esmirtazapine 9 mg Participants receive esmirtazapine, 9 mg, encapsulated tablets, orally QD for up to 12 weeks. | 151 |
| Esmirtazapine 18 mg Participants receive esmirtazapine, 18 mg, encapsulated tablets, orally QD for up to 12 weeks. | 158 |
| Total | 945 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 20 | 19 | 25 | 20 | 30 |
| Overall Study | Lack of Efficacy | 26 | 3 | 4 | 4 | 7 |
| Overall Study | Lost to Follow-up | 0 | 3 | 0 | 0 | 0 |
| Overall Study | Other | 2 | 1 | 1 | 2 | 1 |
| Overall Study | Unwilling to cooperate | 6 | 6 | 3 | 3 | 4 |
Baseline characteristics
| Characteristic | Placebo | Esmirtazapine 2.25 mg | Esmirtazapine 4.5 mg | Esmirtazapine 9 mg | Esmirtazapine 18 mg | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 53.5 Years STANDARD_DEVIATION 4.9 | 53.8 Years STANDARD_DEVIATION 5 | 53.7 Years STANDARD_DEVIATION 4.8 | 54.7 Years STANDARD_DEVIATION 4.6 | 53.5 Years STANDARD_DEVIATION 4.7 | 53.8 Years STANDARD_DEVIATION 4.8 |
| Sex: Female, Male Female | 314 Participants | 162 Participants | 160 Participants | 151 Participants | 158 Participants | 945 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 91 / 314 | 71 / 162 | 70 / 160 | 58 / 151 | 80 / 158 |
| serious Total, serious adverse events | 2 / 314 | 1 / 162 | 1 / 160 | 3 / 151 | 1 / 158 |
Outcome results
Primary
Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) at 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.
Time frame: Baseline and Week 12
Population: The ITT population, defined as all randomized participants who had at least one pre-baseline and at least one post-baseline average of the number of hot flushes in a week.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) at Week 12 | Baseline | 12.1 Events per day | Standard Deviation 5.1 |
| Placebo | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) at Week 12 | Week 12 | -4.2 Events per day | Standard Deviation 5.3 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) at Week 12 | Baseline | 12.2 Events per day | Standard Deviation 5.1 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) at Week 12 | Week 12 | -5.2 Events per day | Standard Deviation 4.6 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) at Week 12 | Baseline | 12.6 Events per day | Standard Deviation 4.7 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) at Week 12 | Week 12 | -6.0 Events per day | Standard Deviation 4.9 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) at Week 12 | Week 12 | -5.8 Events per day | Standard Deviation 4.3 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) at Week 12 | Baseline | 12.3 Events per day | Standard Deviation 4.4 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) at Week 12 | Baseline | 11.5 Events per day | Standard Deviation 4.7 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) at Week 12 | Week 12 | -6.0 Events per day | Standard Deviation 4.6 |
p-value: 0.0895% CI: [-2.1, 0.1]ANCOVA
p-value: <0.0195% CI: [-2.7, -0.5]ANCOVA
p-value: <0.0195% CI: [-2.7, -0.4]ANCOVA
p-value: <0.0195% CI: [-3.1, -0.9]ANCOVA
Primary
Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) at 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.
Time frame: Baseline and Week 4
Population: The Intent-to-Treat (ITT) population, defined as all randomized participants who had at least one pre-baseline and at least one post-baseline average of the number of hot flushes in a week.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) at Week 4 | Baseline | 12.1 Events per day | Standard Deviation 5.1 |
| Placebo | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) at Week 4 | Week 4 | -3.8 Events per day | Standard Deviation 4.5 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) at Week 4 | Baseline | 12.2 Events per day | Standard Deviation 5.1 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) at Week 4 | Week 4 | -5.1 Events per day | Standard Deviation 4.1 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) at Week 4 | Baseline | 12.6 Events per day | Standard Deviation 4.7 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) at Week 4 | Week 4 | -5.7 Events per day | Standard Deviation 4.8 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) at Week 4 | Week 4 | -5.3 Events per day | Standard Deviation 3.8 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) at Week 4 | Baseline | 12.3 Events per day | Standard Deviation 4.4 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) at Week 4 | Baseline | 11.5 Events per day | Standard Deviation 4.7 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) at Week 4 | Week 4 | -5.6 Events per day | Standard Deviation 4.4 |
p-value: <0.0195% CI: [-2.2, -0.2]ANCOVA
p-value: <0.0195% CI: [-2.7, -0.7]ANCOVA
p-value: <0.0195% CI: [-2.4, -0.4]ANCOVA
p-value: <0.0195% CI: [-2.9, -0.9]ANCOVA
Primary
Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) at 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 per week. 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 (LOCF). If the number of days observed in Week 1 were not sufficient, baseline values were carried forward.
Time frame: Baseline and Week 12
Population: The ITT population, defined as all randomized participants who had at least one pre-baseline and at least one post-baseline average of the number of hot flushes in a week.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) at Week 12 | Baseline | 2.45 Severity score | Standard Deviation 0.3 |
| Placebo | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) at Week 12 | Week 12 | -0.08 Severity score | Standard Deviation 0.26 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) at Week 12 | Baseline | 2.45 Severity score | Standard Deviation 0.3 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) at Week 12 | Week 12 | -0.15 Severity score | Standard Deviation 0.27 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) at Week 12 | Baseline | 2.45 Severity score | Standard Deviation 0.32 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) at Week 12 | Week 12 | -0.13 Severity score | Standard Deviation 0.27 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) at Week 12 | Week 12 | -0.13 Severity score | Standard Deviation 0.26 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) at Week 12 | Baseline | 2.46 Severity score | Standard Deviation 0.3 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) at Week 12 | Baseline | 2.40 Severity score | Standard Deviation 0.27 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) at Week 12 | Week 12 | -0.15 Severity score | Standard Deviation 0.026 |
p-value: 0.0795% CI: [-0.12, 0]ANCOVA
p-value: 0.2495% CI: [-0.11, 0.02]ANCOVA
p-value: 0.2995% CI: [-0.11, 0.02]ANCOVA
p-value: 0.0295% CI: [-0.14, -0.01]ANCOVA
Primary
Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) at 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 per week. 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 (LOCF). If the number of days observed in Week 1 were not sufficient, baseline values were carried forward.
Time frame: Baseline and Week 4
Population: The ITT population, defined as all randomized participants who had at least one pre-baseline and at least one post-baseline average of the number of hot flushes in a week.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) at Week 4 | Baseline | 2.45 Severity score | Standard Deviation 0.3 |
| Placebo | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) at Week 4 | Week 4 | -0.07 Severity score | Standard Deviation 0.2 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) at Week 4 | Baseline | 2.45 Severity score | Standard Deviation 0.3 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) at Week 4 | Week 4 | -0.14 Severity score | Standard Deviation 0.23 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) at Week 4 | Baseline | 2.45 Severity score | Standard Deviation 0.32 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) at Week 4 | Week 4 | -0.13 Severity score | Standard Deviation 0.23 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) at Week 4 | Week 4 | -0.15 Severity score | Standard Deviation 0.24 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) at Week 4 | Baseline | 2.46 Severity score | Standard Deviation 0.3 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) at Week 4 | Baseline | 2.40 Severity score | Standard Deviation 0.27 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) at Week 4 | Week 4 | -0.15 Severity score | Standard Deviation 0.23 |
p-value: <0.0195% CI: [-0.12, -0.01]ANCOVA
p-value: 0.0295% CI: [-0.11, -0.01]ANCOVA
p-value: <0.0195% CI: [-0.13, -0.02]ANCOVA
p-value: <0.0195% CI: [-0.14, -0.03]ANCOVA
Secondary
Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week
Participants recorded the frequency (number) of vasomotor symptoms (hot flushes) on a LogPad on a daily basis during screening and treatment. Frequency Score B was based on the number of mild hot flushes + 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.
Time frame: Baseline and up to Week 12
Population: The ITT population, defined as all randomized participants who had at least one pre-baseline and at least one post-baseline average of the number of hot flushes in a week.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 9 | -4.30 Events per day | Standard Deviation 5.06 |
| Placebo | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 7 | -4.27 Events per day | Standard Deviation 4.85 |
| Placebo | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 8 | -4.19 Events per day | Standard Deviation 4.94 |
| Placebo | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Baseline | 13.29 Events per day | Standard Deviation 5.35 |
| Placebo | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 2 | -3.35 Events per day | Standard Deviation 4.17 |
| Placebo | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 12 | -4.40 Events per day | Standard Deviation 5.44 |
| Placebo | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 3 | -3.83 Events per day | Standard Deviation 4.46 |
| Placebo | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 4 | -3.97 Events per day | Standard Deviation 4.63 |
| Placebo | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 1 | -2.22 Events per day | Standard Deviation 3.41 |
| Placebo | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 11 | -4.43 Events per day | Standard Deviation 5.42 |
| Placebo | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 5 | -4.06 Events per day | Standard Deviation 4.91 |
| Placebo | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 10 | -4.29 Events per day | Standard Deviation 5.39 |
| Placebo | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 6 | -4.25 Events per day | Standard Deviation 4.86 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 6 | -5.82 Events per day | Standard Deviation 4.51 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 11 | -5.68 Events per day | Standard Deviation 4.83 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 7 | -5.69 Events per day | Standard Deviation 4.36 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 3 | -5.05 Events per day | Standard Deviation 4.15 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 8 | -5.54 Events per day | Standard Deviation 4.5 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 10 | -5.59 Events per day | Standard Deviation 4.73 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Baseline | 13.48 Events per day | Standard Deviation 5.35 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 4 | -5.37 Events per day | Standard Deviation 4.14 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 1 | -3.24 Events per day | Standard Deviation 3.23 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 2 | -4.81 Events per day | Standard Deviation 4.03 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 5 | -5.61 Events per day | Standard Deviation 4.46 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 12 | -5.63 Events per day | Standard Deviation 4.71 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 9 | -5.47 Events per day | Standard Deviation 4.71 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 6 | -6.32 Events per day | Standard Deviation 4.89 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 1 | -3.81 Events per day | Standard Deviation 3.33 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 2 | -5.19 Events per day | Standard Deviation 4.46 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 4 | -6.01 Events per day | Standard Deviation 4.8 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Baseline | 13.66 Events per day | Standard Deviation 4.96 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 7 | -6.47 Events per day | Standard Deviation 4.89 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 8 | -6.51 Events per day | Standard Deviation 4.72 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 9 | -6.59 Events per day | Standard Deviation 4.79 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 10 | -6.36 Events per day | Standard Deviation 4.81 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 11 | -6.45 Events per day | Standard Deviation 4.91 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 12 | -6.45 Events per day | Standard Deviation 4.96 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 5 | -6.13 Events per day | Standard Deviation 4.81 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 3 | -5.66 Events per day | Standard Deviation 4.74 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 5 | -5.57 Events per day | Standard Deviation 4.03 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 2 | -4.79 Events per day | Standard Deviation 3.28 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Baseline | 13.41 Events per day | Standard Deviation 4.61 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 12 | -6.10 Events per day | Standard Deviation 4.48 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 4 | -5.38 Events per day | Standard Deviation 3.98 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 9 | -6.08 Events per day | Standard Deviation 4.51 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 3 | -5.08 Events per day | Standard Deviation 3.72 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 7 | -5.90 Events per day | Standard Deviation 4.45 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 1 | -3.57 Events per day | Standard Deviation 2.96 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 8 | -6.06 Events per day | Standard Deviation 4.55 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 11 | -6.08 Events per day | Standard Deviation 4.48 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 10 | -6.18 Events per day | Standard Deviation 4.46 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 6 | -5.75 Events per day | Standard Deviation 4.11 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 2 | -5.50 Events per day | Standard Deviation 4.75 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 9 | -6.26 Events per day | Standard Deviation 5.26 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 5 | -5.90 Events per day | Standard Deviation 5.31 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Baseline | 13.00 Events per day | Standard Deviation 6.09 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 10 | -6.35 Events per day | Standard Deviation 5.05 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 3 | -5.79 Events per day | Standard Deviation 4.88 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 11 | -6.28 Events per day | Standard Deviation 4.98 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 4 | -5.85 Events per day | Standard Deviation 5.3 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 12 | -6.32 Events per day | Standard Deviation 4.99 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 1 | -4.16 Events per day | Standard Deviation 4.69 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 7 | -6.15 Events per day | Standard Deviation 5.18 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 8 | -6.03 Events per day | Standard Deviation 4.73 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week | Week 6 | -5.89 Events per day | Standard Deviation 5.24 |
Secondary
Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 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.
Time frame: Baseline and Up to Week 12
Population: The ITT population, defined as all randomized participants who had at least one pre-baseline and at least one post-baseline average of the number of hot flushes in a week.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 6 | -4.02 Events per day | Standard Deviation 4.9 |
| Placebo | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 7 | -4.11 Events per day | Standard Deviation 4.96 |
| Placebo | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Baseline | 12.10 Events per day | Standard Deviation 5.1 |
| Placebo | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 9 | -4.11 Events per day | Standard Deviation 5.18 |
| Placebo | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 3 | -3.71 Events per day | Standard Deviation 4.39 |
| Placebo | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 10 | -4.11 Events per day | Standard Deviation 5.42 |
| Placebo | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 11 | -4.20 Events per day | Standard Deviation 5.38 |
| Placebo | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 2 | -3.25 Events per day | Standard Deviation 4.08 |
| Placebo | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 8 | -4.04 Events per day | Standard Deviation 5.05 |
| Placebo | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 5 | -3.90 Events per day | Standard Deviation 4.82 |
| Placebo | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 1 | -2.21 Events per day | Standard Deviation 3.37 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 5 | -5.29 Events per day | Standard Deviation 4.28 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 7 | -5.33 Events per day | Standard Deviation 4.3 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 6 | -5.41 Events per day | Standard Deviation 4.43 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 1 | -3.20 Events per day | Standard Deviation 3.35 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Baseline | 12.19 Events per day | Standard Deviation 5.07 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 10 | -5.18 Events per day | Standard Deviation 4.54 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 2 | -4.72 Events per day | Standard Deviation 3.85 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 11 | -5.30 Events per day | Standard Deviation 4.65 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 9 | -5.15 Events per day | Standard Deviation 4.65 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 3 | -4.82 Events per day | Standard Deviation 4.08 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 8 | -5.19 Events per day | Standard Deviation 4.49 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 6 | -5.96 Events per day | Standard Deviation 4.79 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Baseline | 12.56 Events per day | Standard Deviation 4.66 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 1 | -4.08 Events per day | Standard Deviation 3.79 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 2 | -5.19 Events per day | Standard Deviation 4.59 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 3 | -5.68 Events per day | Standard Deviation 4.74 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 5 | -5.83 Events per day | Standard Deviation 4.72 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 7 | -6.10 Events per day | Standard Deviation 4.87 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 8 | -6.14 Events per day | Standard Deviation 4.72 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 9 | -6.23 Events per day | Standard Deviation 4.9 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 10 | -5.97 Events per day | Standard Deviation 4.79 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 11 | -6.03 Events per day | Standard Deviation 4.86 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 3 | -5.13 Events per day | Standard Deviation 3.68 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Baseline | 12.30 Events per day | Standard Deviation 4.39 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 1 | -3.63 Events per day | Standard Deviation 2.89 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 11 | -5.86 Events per day | Standard Deviation 4.34 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 10 | -6.00 Events per day | Standard Deviation 4.36 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 2 | -4.88 Events per day | Standard Deviation 3.24 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 6 | -5.58 Events per day | Standard Deviation 3.89 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 8 | -5.86 Events per day | Standard Deviation 4.52 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 9 | -5.96 Events per day | Standard Deviation 4.39 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 5 | -5.50 Events per day | Standard Deviation 3.79 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 7 | -5.69 Events per day | Standard Deviation 4.28 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Baseline | 11.52 Events per day | Standard Deviation 4.67 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 7 | -5.93 Events per day | Standard Deviation 4.63 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 3 | -5.59 Events per day | Standard Deviation 4.05 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 8 | -5.72 Events per day | Standard Deviation 4.36 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 2 | -5.39 Events per day | Standard Deviation 3.96 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 11 | -5.91 Events per day | Standard Deviation 4.57 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 9 | -5.95 Events per day | Standard Deviation 4.77 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 1 | -4.18 Events per day | Standard Deviation 3.83 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 10 | -6.11 Events per day | Standard Deviation 4.66 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 6 | -5.62 Events per day | Standard Deviation 4.71 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 | Week 5 | -5.54 Events per day | Standard Deviation 4.48 |
Secondary
Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week
Composite Score B was calculated as Severity Score B x Frequency Score B.
Time frame: Baseline and up to Week 12
Population: The ITT population, defined as all randomized participants who had at least one pre-baseline and at least one post-baseline average of the number of hot flushes in a week.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 5 | -10.12 Composite score | Standard Deviation 13.13 |
| Placebo | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 8 | -10.34 Composite score | Standard Deviation 13.43 |
| Placebo | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 6 | -10.45 Composite score | Standard Deviation 13.24 |
| Placebo | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 7 | -10.58 Composite score | Standard Deviation 13.23 |
| Placebo | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 12 | -10.66 Composite score | Standard Deviation 14.44 |
| Placebo | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 2 | -8.38 Composite score | Standard Deviation 10.91 |
| Placebo | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Baseline | 31.39 Composite score | Standard Deviation 15.37 |
| Placebo | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 11 | -10.76 Composite score | Standard Deviation 14.57 |
| Placebo | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 3 | -9.57 Composite score | Standard Deviation 11.88 |
| Placebo | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 10 | -10.44 Composite score | Standard Deviation 14.56 |
| Placebo | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 4 | -9.93 Composite score | Standard Deviation 12.36 |
| Placebo | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 1 | -5.66 Composite score | Standard Deviation 8.94 |
| Placebo | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 9 | -10.49 Composite score | Standard Deviation 13.78 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 5 | -13.96 Composite score | Standard Deviation 11.65 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 1 | -8.53 Composite score | Standard Deviation 8.85 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 10 | -13.71 Composite score | Standard Deviation 12.27 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 7 | -14.09 Composite score | Standard Deviation 11.45 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 4 | -13.48 Composite score | Standard Deviation 11.06 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 6 | -14.29 Composite score | Standard Deviation 11.65 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Baseline | 31.70 Composite score | Standard Deviation 14.47 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 3 | -12.86 Composite score | Standard Deviation 10.89 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 12 | -13.66 Composite score | Standard Deviation 12.32 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 11 | -13.96 Composite score | Standard Deviation 12.53 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 8 | -13.66 Composite score | Standard Deviation 11.73 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 2 | -12.40 Composite score | Standard Deviation 10.12 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 9 | -13.53 Composite score | Standard Deviation 12.33 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 12 | -15.32 Composite score | Standard Deviation 12.38 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Baseline | 32.13 Composite score | Standard Deviation 12.91 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 1 | -10.01 Composite score | Standard Deviation 8.6 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 2 | -12.98 Composite score | Standard Deviation 11.05 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 3 | -14.40 Composite score | Standard Deviation 11.69 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 4 | -14.69 Composite score | Standard Deviation 11.89 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 5 | 014.78 Composite score | Standard Deviation 11.54 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 6 | -15.19 Composite score | Standard Deviation 11.83 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 7 | -15.48 Composite score | Standard Deviation 12.16 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 8 | -15.56 Composite score | Standard Deviation 11.76 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 9 | -15.77 Composite score | Standard Deviation 11.91 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 10 | -15.15 Composite score | Standard Deviation 11.92 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 11 | -15.34 Composite score | Standard Deviation 12.27 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 11 | -14.79 Composite score | Standard Deviation 11.16 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 7 | -14.63 Composite score | Standard Deviation 11.18 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 5 | -14.22 Composite score | Standard Deviation 10.12 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 8 | -14.92 Composite score | Standard Deviation 11.38 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 4 | -13.75 Composite score | Standard Deviation 10.24 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 1 | -9.37 Composite score | Standard Deviation 7.74 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 9 | -15.05 Composite score | Standard Deviation 11.09 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 3 | -13.34 Composite score | Standard Deviation 9.69 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 10 | -15.21 Composite score | Standard Deviation 11.11 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 2 | -12.60 Composite score | Standard Deviation 8.58 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Baseline | 31.51 Composite score | Standard Deviation 11.8 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 6 | -14.40 Composite score | Standard Deviation 10.3 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 12 | -14.71 Composite score | Standard Deviation 11.11 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 5 | -14.08 Composite score | Standard Deviation 11.82 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 2 | -13.64 Composite score | Standard Deviation 10.46 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 7 | -14.93 Composite score | Standard Deviation 12.04 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Baseline | 29.35 Composite score | Standard Deviation 13.55 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 4 | -14.01 Composite score | Standard Deviation 11.91 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 11 | -14.95 Composite score | Standard Deviation 11.95 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 6 | -14.21 Composite score | Standard Deviation 12.22 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 8 | -14.40 Composite score | Standard Deviation 11.18 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 10 | -15.32 Composite score | Standard Deviation 12.09 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 3 | -14.09 Composite score | Standard Deviation 10.8 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 12 | -15.04 Composite score | Standard Deviation 12.17 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 1 | -10.61 Composite score | Standard Deviation 10.31 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week | Week 9 | -14.98 Composite score | Standard Deviation 12.44 |
Secondary
Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week
Composite Score A was calculated as Severity Score A x Frequency Score A.
Time frame: Baseline and up to Week 12
Population: The ITT population, defined as all randomized participants who had at least one pre-baseline and at least one post-baseline average of the number of hot flushes in a week.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 12 | -10.42 Composite score | Standard Deviation 14.56 |
| Placebo | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 5 | -9.96 Composite score | Standard Deviation 13.19 |
| Placebo | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 4 | -9.79 Composite score | Standard Deviation 12.39 |
| Placebo | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 3 | -9.46 Composite score | Standard Deviation 11.92 |
| Placebo | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 2 | -8.28 Composite score | Standard Deviation 10.93 |
| Placebo | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 10 | -10.26 Composite score | Standard Deviation 14.77 |
| Placebo | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 9 | -10.30 Composite score | Standard Deviation 14.06 |
| Placebo | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Baseline | 30.19 Composite score | Standard Deviation 15.42 |
| Placebo | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 11 | -10.53 Composite score | Standard Deviation 14.73 |
| Placebo | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 8 | -10.20 Composite score | Standard Deviation 13.71 |
| Placebo | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 7 | -10.42 Composite score | Standard Deviation 13.49 |
| Placebo | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 6 | -10.22 Composite score | Standard Deviation 13.4 |
| Placebo | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 1 | -5.65 Composite score | Standard Deviation 8.99 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 7 | -13.73 Composite score | Standard Deviation 11.66 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 8 | -13.31 Composite score | Standard Deviation 11.98 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 9 | -13.20 Composite score | Standard Deviation 12.54 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Baseline | 30.41 Composite score | Standard Deviation 14.56 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 1 | -8.48 Composite score | Standard Deviation 9.1 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 2 | -12.32 Composite score | Standard Deviation 10.18 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 3 | -12.63 Composite score | Standard Deviation 11.09 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 4 | -13.18 Composite score | Standard Deviation 11.29 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 5 | -13.65 Composite score | Standard Deviation 11.77 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 6 | -13.89 Composite score | Standard Deviation 11.88 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 10 | -13.30 Composite score | Standard Deviation 12.34 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 11 | -13.58 Composite score | Standard Deviation 12.61 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 12 | -13.25 Composite score | Standard Deviation 12.52 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 6 | -14.84 Composite score | Standard Deviation 11.92 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 3 | -14.22 Composite score | Standard Deviation 11.88 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 10 | -14.76 Composite score | Standard Deviation 12.07 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 1 | -10.28 Composite score | Standard Deviation 9.19 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 11 | -14.92 Composite score | Standard Deviation 12.41 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 9 | -15.40 Composite score | Standard Deviation 12.18 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Baseline | 31.03 Composite score | Standard Deviation 12.98 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 5 | -14.47 Composite score | Standard Deviation 11.65 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 12 | -14.88 Composite score | Standard Deviation 12.49 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 4 | -14.42 Composite score | Standard Deviation 11.88 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 2 | -12.98 Composite score | Standard Deviation 11.36 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 8 | -15.19 Composite score | Standard Deviation 11.93 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 7 | -15.11 Composite score | Standard Deviation 12.32 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 3 | -13.39 Composite score | Standard Deviation 9.82 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 1 | -9.43 Composite score | Standard Deviation 7.84 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 11 | -14.58 Composite score | Standard Deviation 11.28 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 4 | -13.70 Composite score | Standard Deviation 10.28 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 5 | -14.16 Composite score | Standard Deviation 10.09 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 6 | -14.24 Composite score | Standard Deviation 10.26 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Baseline | 30.40 Composite score | Standard Deviation 11.81 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 7 | -14.42 Composite score | Standard Deviation 11.23 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 8 | -14.73 Composite score | Standard Deviation 11.56 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 9 | -14.93 Composite score | Standard Deviation 11.2 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 10 | -15.03 Composite score | Standard Deviation 11.24 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 12 | -14.36 Composite score | Standard Deviation 11.17 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 2 | -12.70 Composite score | Standard Deviation 8.75 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 12 | -14.71 Composite score | Standard Deviation 12.17 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 6 | -13.95 Composite score | Standard Deviation 12.05 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 11 | 14.57 Composite score | Standard Deviation 11.85 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 10 | -15.08 Composite score | Standard Deviation 12.09 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Baseline | 27.87 Composite score | Standard Deviation 12.56 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 4 | -13.72 Composite score | Standard Deviation 11.38 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 5 | -13.72 Composite score | Standard Deviation 11.33 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 3 | -13.89 Composite score | Standard Deviation 10.28 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 2 | -13.54 Composite score | Standard Deviation 9.89 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 8 | -14.08 Composite score | Standard Deviation 11.21 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 1 | -10.63 Composite score | Standard Deviation 9.63 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 9 | -14.67 Composite score | Standard Deviation 12.3 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week | Week 7 | -14.72 Composite score | Standard Deviation 11.87 |
Secondary
Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week
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 B was calculated as the number of mild hot flushes + the number of moderate hot flushes x 2 + the number of severe hot flushes x 3, divided by the total number of all hot flushes per week. 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 (LOCF). If the number of days observed in Week 1 were not sufficient, baseline values were carried forward.
Time frame: Baseline and up to Week 12
Population: The ITT population, defined as all randomized participants who had at least one pre-baseline and at least one post-baseline average of the number of hot flushes in a week.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 11 | -0.149 Severity score | Standard Deviation 0.439 |
| Placebo | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 6 | -0.121 Severity score | Standard Deviation 0.36 |
| Placebo | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 10 | -0.143 Severity score | Standard Deviation 0.431 |
| Placebo | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 7 | -0.142 Severity score | Standard Deviation 0.389 |
| Placebo | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 8 | -0.139 Severity score | Standard Deviation 0.408 |
| Placebo | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 9 | -0.136 Severity score | Standard Deviation 0.408 |
| Placebo | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 2 | -0.111 Severity score | Standard Deviation 0.291 |
| Placebo | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 12 | -0.152 Severity score | Standard Deviation 0.457 |
| Placebo | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 3 | -0.121 Severity score | Standard Deviation 0.307 |
| Placebo | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 4 | -0.113 Severity score | Standard Deviation 0.312 |
| Placebo | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 1 | -0.080 Severity score | Standard Deviation 0.22 |
| Placebo | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Baseline | 2.332 Severity score | Standard Deviation 0.369 |
| Placebo | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 5 | -0.124 Severity score | Standard Deviation 0.354 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 1 | -0.132 Severity score | Standard Deviation 0.246 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 3 | -0.217 Severity score | Standard Deviation 0.373 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Baseline | 2.331 Severity score | Standard Deviation 0.375 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 10 | -0.244 Severity score | Standard Deviation 0.452 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 9 | -0.245 Severity score | Standard Deviation 0.438 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 6 | -0.222 Severity score | Standard Deviation 0.429 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 11 | -0.260 Severity score | Standard Deviation 0.467 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 4 | -0.224 Severity score | Standard Deviation 0.409 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 8 | -0.251 Severity score | Standard Deviation 0.44 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 7 | -0.234 Severity score | Standard Deviation 0.433 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 5 | -0.234 Severity score | Standard Deviation 0.411 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 2 | -0.210 Severity score | Standard Deviation 0.342 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 12 | -0.255 Severity score | Standard Deviation 0.471 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 11 | -0.245 Severity score | Standard Deviation 0.463 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Baseline | 2.349 Severity score | Standard Deviation 0.373 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 1 | -0.167 Severity score | Standard Deviation 0.245 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 2 | -0.223 Severity score | Standard Deviation 0.341 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 3 | -0.246 Severity score | Standard Deviation 0.4 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 4 | -0.240 Severity score | Standard Deviation 0.388 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 5 | -0.228 Severity score | Standard Deviation 0.403 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 6 | -0.214 Severity score | Standard Deviation 0.386 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 7 | -0.232 Severity score | Standard Deviation 0.444 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 8 | -0.234 Severity score | Standard Deviation 0.467 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 10 | -0.257 Severity score | Standard Deviation 0.465 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 9 | -0.256 Severity score | Standard Deviation 0.454 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 12 | -0.240 Severity score | Standard Deviation 0.465 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 7 | -0.242 Severity score | Standard Deviation 0.424 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 9 | -0.256 Severity score | Standard Deviation 0.462 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 6 | -0.245 Severity score | Standard Deviation 0.396 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 10 | -0.257 Severity score | Standard Deviation 0.467 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 5 | -0.254 Severity score | Standard Deviation 0.368 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 11 | -0.224 Severity score | Standard Deviation 0.459 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 4 | -0.249 Severity score | Standard Deviation 0.387 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 12 | -0.210 Severity score | Standard Deviation 0.45 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 2 | -0.225 Severity score | Standard Deviation 0.341 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 3 | -0.240 Severity score | Standard Deviation 0.337 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 1 | -0.140 Severity score | Standard Deviation 0.245 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Baseline | 2.350 Severity score | Standard Deviation 0.347 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 8 | -0.251 Severity score | Standard Deviation 0.447 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 8 | -0.273 Severity score | Standard Deviation 0.463 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 12 | -0.280 Severity score | Standard Deviation 0.472 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 9 | -0.292 Severity score | Standard Deviation 0.474 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 6 | -0.275 Severity score | Standard Deviation 0.436 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Baseline | 2.270 Severity score | Standard Deviation 0.332 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 2 | -0.250 Severity score | Standard Deviation 0.312 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 10 | -0.307 Severity score | Standard Deviation 0.46 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 5 | -0.266 Severity score | Standard Deviation 0.409 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 3 | -0.272 Severity score | Standard Deviation 0.389 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 4 | -0.273 Severity score | Standard Deviation 0.411 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 7 | -0.287 Severity score | Standard Deviation 0.46 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 11 | -0.308 Severity score | Standard Deviation 0.477 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week | Week 1 | -0.192 Severity score | Standard Deviation 0.273 |
Secondary
Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 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 per week. 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 (LOCF). If the number of days observed in Week 1 were not sufficient, baseline values were carried forward.
Time frame: Baseline and up to Week 12
Population: The ITT population, defined as all randomized participants who had at least one pre-baseline and at least one post-baseline average of the number of hot flushes in a week.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 1 | -0.045 Severity score | Standard Deviation 0.124 |
| Placebo | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 6 | -0.075 Severity score | Standard Deviation 0.215 |
| Placebo | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Baseline | 2.447 Severity score | Standard Deviation 0.301 |
| Placebo | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 9 | -0.083 Severity score | Standard Deviation 0.242 |
| Placebo | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 3 | -0.071 Severity score | Standard Deviation 0.195 |
| Placebo | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 7 | -0.088 Severity score | Standard Deviation 0.233 |
| Placebo | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 10 | -0.084 Severity score | Standard Deviation 0.255 |
| Placebo | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 2 | -0.063 Severity score | Standard Deviation 0.172 |
| Placebo | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 8 | -0.082 Severity score | Standard Deviation 0.239 |
| Placebo | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 5 | -0.080 Severity score | Standard Deviation 0.215 |
| Placebo | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 11 | -0.078 Severity score | Standard Deviation 0.261 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 5 | -0.141 Severity score | Standard Deviation 0.233 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 7 | -0.144 Severity score | Standard Deviation 0.236 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 6 | -0.136 Severity score | Standard Deviation 0.246 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 1 | -0.081 Severity score | Standard Deviation 0.153 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 10 | -0.147 Severity score | Standard Deviation 0.261 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 2 | -0.117 Severity score | Standard Deviation 0.199 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Baseline | 2.451 Severity score | Standard Deviation 0.297 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 9 | -0.142 Severity score | Standard Deviation 0.257 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 3 | -0.133 Severity score | Standard Deviation 0.214 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 11 | -0.159 Severity score | Standard Deviation 0.273 |
| Esmirtazapine 2.25 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 8 | -0.142 Severity score | Standard Deviation 0.242 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 2 | -0.111 Severity score | Standard Deviation 0.212 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 1 | -0.085 Severity score | Standard Deviation 0.151 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Baseline | 2.449 Severity score | Standard Deviation 0.315 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 3 | -0.119 Severity score | Standard Deviation 0.214 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 5 | -0.123 Severity score | Standard Deviation 0.227 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 6 | -0.127 Severity score | Standard Deviation 0.234 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 7 | -0.131 Severity score | Standard Deviation 0.26 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 8 | -0.124 Severity score | Standard Deviation 0.27 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 9 | -0.137 Severity score | Standard Deviation 0.26 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 10 | -0.125 Severity score | Standard Deviation 0.263 |
| Esmirtazapine 4.5 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 11 | -0.130 Severity score | Standard Deviation 0.273 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 3 | -0.150 Severity score | Standard Deviation 0.2 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Baseline | 2.460 Severity score | Standard Deviation 0.296 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 1 | -0.085 Severity score | Standard Deviation 0.159 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 11 | -0.124 Severity score | Standard Deviation 0.257 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 10 | -0.141 Severity score | Standard Deviation 0.258 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 2 | -0.140 Severity score | Standard Deviation 0.2 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 6 | -0.140 Severity score | Standard Deviation 0.236 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 8 | -0.139 Severity score | Standard Deviation 0.254 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 9 | -0.130 Severity score | Standard Deviation 0.265 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 5 | -0.154 Severity score | Standard Deviation 0.225 |
| Esmirtazapine 9 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 7 | -0.140 Severity score | Standard Deviation 0.253 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Baseline | 2.400 Severity score | Standard Deviation 0.274 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 7 | -0.144 Severity score | Standard Deviation 0.257 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 3 | -0.137 Severity score | Standard Deviation 0.24 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 8 | -0.133 Severity score | Standard Deviation 0.247 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 2 | -0.136 Severity score | Standard Deviation 0.178 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 11 | -0.156 Severity score | Standard Deviation 0.257 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 9 | -0.144 Severity score | Standard Deviation 0.246 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 1 | -0.108 Severity score | Standard Deviation 0.15 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 10 | -0.162 Severity score | Standard Deviation 0.252 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 6 | -0.152 Severity score | Standard Deviation 0.245 |
| Esmirtazapine 18 mg | Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 | Week 5 | -0.151 Severity score | Standard Deviation 0.232 |
Secondary
Change From Baseline in WHQ Vasomotor Symptoms Domain Score at Week 12
The WHQ is a 36-item, user-friendly, and rapid way of assessing nine domains of physical and emotional health for mid-aged women. Participants self-administered the WHQ questionnaire; scoring is based on a 4-point scale as follows: 'Yes definitely=1', 'Yes sometimes=2', 'No not much=3' and 'No not at all=4'. Each score is transformed to a value '1' for scores '1' and '2' and to a value '0' for scores '3' and '4'. Vasomotor symptoms encompass Items 19 and 27 of the 36 total items. The transformed sums of items 19+27 are divided by 2 to get the score; therefore, the domain ranges from 0 to 1, where lower values are better.
Time frame: Baseline and Week 12
Population: All participants who received study drug and had valid answers recorded for the WHQ domain for vasomotor symptoms.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in WHQ Vasomotor Symptoms Domain Score at Week 12 | Baseline | 0.983 Score on a scale | Standard Deviation 0.091 |
| Placebo | Change From Baseline in WHQ Vasomotor Symptoms Domain Score at Week 12 | Week 12 | -0.085 Score on a scale | Standard Deviation 0.26 |
| Esmirtazapine 2.25 mg | Change From Baseline in WHQ Vasomotor Symptoms Domain Score at Week 12 | Baseline | 0.989 Score on a scale | Standard Deviation 0.0873 |
| Esmirtazapine 2.25 mg | Change From Baseline in WHQ Vasomotor Symptoms Domain Score at Week 12 | Week 12 | -0.196 Score on a scale | Standard Deviation 0.349 |
| Esmirtazapine 4.5 mg | Change From Baseline in WHQ Vasomotor Symptoms Domain Score at Week 12 | Baseline | 0.993 Score on a scale | Standard Deviation 0.061 |
| Esmirtazapine 4.5 mg | Change From Baseline in WHQ Vasomotor Symptoms Domain Score at Week 12 | Week 12 | -0.224 Score on a scale | Standard Deviation 0.381 |
| Esmirtazapine 9 mg | Change From Baseline in WHQ Vasomotor Symptoms Domain Score at Week 12 | Week 12 | -0.117 Score on a scale | Standard Deviation 0.277 |
| Esmirtazapine 9 mg | Change From Baseline in WHQ Vasomotor Symptoms Domain Score at Week 12 | Baseline | 0.984 Score on a scale | Standard Deviation 0.087 |
| Esmirtazapine 18 mg | Change From Baseline in WHQ Vasomotor Symptoms Domain Score at Week 12 | Baseline | 0.984 Score on a scale | Standard Deviation 0.087 |
| Esmirtazapine 18 mg | Change From Baseline in WHQ Vasomotor Symptoms Domain Score at Week 12 | Week 12 | -0.164 Score on a scale | Standard Deviation 0.314 |
Secondary
Change From Baseline in Women's Health Questionnaire (WHQ) Sleep Problems Symptoms Domain Score at Week 12
The WHQ is a 36-item, user-friendly, and rapid way of assessing nine domains of physical and emotional health for mid-aged women. Participants self-administered the WHQ questionnaire; scoring is based on a 4-point scale as follows: 'Yes definitely=1', 'Yes sometimes=2', 'No not much=3' and 'No not at all=4'. Each score is transformed to a value '1' for scores '1' and '2' and to a value '0' for scores '3' and '4'. Sleep problems encompass Items 1, 11, and 29 of the 36 total items. The transformed sums of items 1, 11, and 29 were divided by 3 to get the score; therefore, the domain ranges from 0 to 1, where lower values are better.
Time frame: Baseline and Week 12
Population: All participants who received study drug and had valid answers recorded for the WHQ domain for sleep problems.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Women's Health Questionnaire (WHQ) Sleep Problems Symptoms Domain Score at Week 12 | Baseline | 0.714 Score on a scale | Standard Deviation 0.291 |
| Placebo | Change From Baseline in Women's Health Questionnaire (WHQ) Sleep Problems Symptoms Domain Score at Week 12 | Week 12 | -0.140 Score on a scale | Standard Deviation 0.325 |
| Esmirtazapine 2.25 mg | Change From Baseline in Women's Health Questionnaire (WHQ) Sleep Problems Symptoms Domain Score at Week 12 | Baseline | 0.659 Score on a scale | Standard Deviation 0.321 |
| Esmirtazapine 2.25 mg | Change From Baseline in Women's Health Questionnaire (WHQ) Sleep Problems Symptoms Domain Score at Week 12 | Week 12 | -0.232 Score on a scale | Standard Deviation 0.338 |
| Esmirtazapine 4.5 mg | Change From Baseline in Women's Health Questionnaire (WHQ) Sleep Problems Symptoms Domain Score at Week 12 | Baseline | 0.684 Score on a scale | Standard Deviation 0.298 |
| Esmirtazapine 4.5 mg | Change From Baseline in Women's Health Questionnaire (WHQ) Sleep Problems Symptoms Domain Score at Week 12 | Week 12 | -0.251 Score on a scale | Standard Deviation 0.336 |
| Esmirtazapine 9 mg | Change From Baseline in Women's Health Questionnaire (WHQ) Sleep Problems Symptoms Domain Score at Week 12 | Week 12 | -0.224 Score on a scale | Standard Deviation 0.381 |
| Esmirtazapine 9 mg | Change From Baseline in Women's Health Questionnaire (WHQ) Sleep Problems Symptoms Domain Score at Week 12 | Baseline | 0.688 Score on a scale | Standard Deviation 0.27 |
| Esmirtazapine 18 mg | Change From Baseline in Women's Health Questionnaire (WHQ) Sleep Problems Symptoms Domain Score at Week 12 | Baseline | 0.693 Score on a scale | Standard Deviation 0.26 |
| Esmirtazapine 18 mg | Change From Baseline in Women's Health Questionnaire (WHQ) Sleep Problems Symptoms Domain Score at Week 12 | Week 12 | -0.195 Score on a scale | Standard Deviation 0.328 |
Secondary
Total Number of Remitters by Week
A participant was defined as a (hot flush) remitter for a study week if at most one moderate/severe vasomotor symptom per day on average was recorded. A study week was taken into account if at least 4 days were completely observed. The last observation was carried forward if there were less than 4 complete days observed. In cases where Week 1 did not have 4 days that were completely observed, the participant was considered a non-remitter.
Time frame: Up to 12 weeks
Population: The ITT population, defined as all randomized participants who had at least one pre-baseline and at least one post-baseline average of the number of hot flushes in a week. An LOCF approach was used.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Total Number of Remitters by Week | Week 9 | 24 Participants |
| Placebo | Total Number of Remitters by Week | Week 12 | 27 Participants |
| Placebo | Total Number of Remitters by Week | Week 2 | 6 Participants |
| Placebo | Total Number of Remitters by Week | Week 10 | 25 Participants |
| Placebo | Total Number of Remitters by Week | Week 11 | 25 Participants |
| Placebo | Total Number of Remitters by Week | Week 1 | 3 Participants |
| Placebo | Total Number of Remitters by Week | Week 6 | 15 Participants |
| Placebo | Total Number of Remitters by Week | Week 3 | 8 Participants |
| Placebo | Total Number of Remitters by Week | Week 8 | 23 Participants |
| Placebo | Total Number of Remitters by Week | Week 7 | 19 Participants |
| Placebo | Total Number of Remitters by Week | Week 5 | 13 Participants |
| Placebo | Total Number of Remitters by Week | Week 4 | 10 Participants |
| Esmirtazapine 2.25 mg | Total Number of Remitters by Week | Week 12 | 23 Participants |
| Esmirtazapine 2.25 mg | Total Number of Remitters by Week | Week 9 | 19 Participants |
| Esmirtazapine 2.25 mg | Total Number of Remitters by Week | Week 8 | 19 Participants |
| Esmirtazapine 2.25 mg | Total Number of Remitters by Week | Week 2 | 11 Participants |
| Esmirtazapine 2.25 mg | Total Number of Remitters by Week | Week 7 | 19 Participants |
| Esmirtazapine 2.25 mg | Total Number of Remitters by Week | Week 6 | 15 Participants |
| Esmirtazapine 2.25 mg | Total Number of Remitters by Week | Week 10 | 19 Participants |
| Esmirtazapine 2.25 mg | Total Number of Remitters by Week | Week 4 | 15 Participants |
| Esmirtazapine 2.25 mg | Total Number of Remitters by Week | Week 1 | 2 Participants |
| Esmirtazapine 2.25 mg | Total Number of Remitters by Week | Week 11 | 22 Participants |
| Esmirtazapine 2.25 mg | Total Number of Remitters by Week | Week 3 | 15 Participants |
| Esmirtazapine 2.25 mg | Total Number of Remitters by Week | Week 5 | 18 Participants |
| Esmirtazapine 4.5 mg | Total Number of Remitters by Week | Week 8 | 25 Participants |
| Esmirtazapine 4.5 mg | Total Number of Remitters by Week | Week 1 | 7 Participants |
| Esmirtazapine 4.5 mg | Total Number of Remitters by Week | Week 4 | 18 Participants |
| Esmirtazapine 4.5 mg | Total Number of Remitters by Week | Week 5 | 16 Participants |
| Esmirtazapine 4.5 mg | Total Number of Remitters by Week | Week 6 | 21 Participants |
| Esmirtazapine 4.5 mg | Total Number of Remitters by Week | Week 7 | 22 Participants |
| Esmirtazapine 4.5 mg | Total Number of Remitters by Week | Week 9 | 25 Participants |
| Esmirtazapine 4.5 mg | Total Number of Remitters by Week | Week 2 | 13 Participants |
| Esmirtazapine 4.5 mg | Total Number of Remitters by Week | Week 3 | 16 Participants |
| Esmirtazapine 4.5 mg | Total Number of Remitters by Week | Week 10 | 25 Participants |
| Esmirtazapine 4.5 mg | Total Number of Remitters by Week | Week 11 | 23 Participants |
| Esmirtazapine 4.5 mg | Total Number of Remitters by Week | Week 12 | 24 Participants |
| Esmirtazapine 9 mg | Total Number of Remitters by Week | Week 7 | 16 Participants |
| Esmirtazapine 9 mg | Total Number of Remitters by Week | Week 10 | 23 Participants |
| Esmirtazapine 9 mg | Total Number of Remitters by Week | Week 3 | 7 Participants |
| Esmirtazapine 9 mg | Total Number of Remitters by Week | Week 6 | 13 Participants |
| Esmirtazapine 9 mg | Total Number of Remitters by Week | Week 4 | 15 Participants |
| Esmirtazapine 9 mg | Total Number of Remitters by Week | Week 12 | 20 Participants |
| Esmirtazapine 9 mg | Total Number of Remitters by Week | Week 11 | 21 Participants |
| Esmirtazapine 9 mg | Total Number of Remitters by Week | Week 5 | 12 Participants |
| Esmirtazapine 9 mg | Total Number of Remitters by Week | Week 1 | 2 Participants |
| Esmirtazapine 9 mg | Total Number of Remitters by Week | Week 8 | 18 Participants |
| Esmirtazapine 9 mg | Total Number of Remitters by Week | Week 2 | 8 Participants |
| Esmirtazapine 9 mg | Total Number of Remitters by Week | Week 9 | 19 Participants |
| Esmirtazapine 18 mg | Total Number of Remitters by Week | Week 5 | 17 Participants |
| Esmirtazapine 18 mg | Total Number of Remitters by Week | Week 2 | 13 Participants |
| Esmirtazapine 18 mg | Total Number of Remitters by Week | Week 3 | 17 Participants |
| Esmirtazapine 18 mg | Total Number of Remitters by Week | Week 7 | 21 Participants |
| Esmirtazapine 18 mg | Total Number of Remitters by Week | Week 6 | 18 Participants |
| Esmirtazapine 18 mg | Total Number of Remitters by Week | Week 8 | 21 Participants |
| Esmirtazapine 18 mg | Total Number of Remitters by Week | Week 11 | 28 Participants |
| Esmirtazapine 18 mg | Total Number of Remitters by Week | Week 10 | 25 Participants |
| Esmirtazapine 18 mg | Total Number of Remitters by Week | Week 4 | 17 Participants |
| Esmirtazapine 18 mg | Total Number of Remitters by Week | Week 12 | 26 Participants |
| Esmirtazapine 18 mg | Total Number of Remitters by Week | Week 1 | 2 Participants |
| Esmirtazapine 18 mg | Total Number of Remitters by Week | Week 9 | 26 Participants |
Secondary
Total Number of Responders by Week
A participant was defined as a (hot flush) responder for a study week if a reduction of at least 50% for average daily frequency of moderate/severe vasomotor symptoms (hot flushes) (Frequency Score A) compared to Baseline was recorded. A study week was taken into account if at least 4 days were completely observed. The last observation was carried forward if there were less than 4 complete days observed. In cases where Week 1 did not have 4 days that were completely observed, the participant was considered a non-responder. An LOCF approach was used.
Time frame: Up to 12 weeks
Population: The ITT population, defined as all randomized participants who had at least one pre-baseline and at least one post-baseline average of the number of hot flushes in a week.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Total Number of Responders by Week | Week 12 | 99 Participants |
| Placebo | Total Number of Responders by Week | Week 3 | 85 Participants |
| Placebo | Total Number of Responders by Week | Week 7 | 89 Participants |
| Placebo | Total Number of Responders by Week | Week 8 | 93 Participants |
| Placebo | Total Number of Responders by Week | Week 2 | 56 Participants |
| Placebo | Total Number of Responders by Week | Week 9 | 96 Participants |
| Placebo | Total Number of Responders by Week | Week 1 | 37 Participants |
| Placebo | Total Number of Responders by Week | Week 4 | 76 Participants |
| Placebo | Total Number of Responders by Week | Week 11 | 95 Participants |
| Placebo | Total Number of Responders by Week | Week 5 | 76 Participants |
| Placebo | Total Number of Responders by Week | Week 10 | 97 Participants |
| Placebo | Total Number of Responders by Week | Week 6 | 84 Participants |
| Esmirtazapine 2.25 mg | Total Number of Responders by Week | Week 5 | 63 Participants |
| Esmirtazapine 2.25 mg | Total Number of Responders by Week | Week 6 | 67 Participants |
| Esmirtazapine 2.25 mg | Total Number of Responders by Week | Week 10 | 65 Participants |
| Esmirtazapine 2.25 mg | Total Number of Responders by Week | Week 1 | 29 Participants |
| Esmirtazapine 2.25 mg | Total Number of Responders by Week | Week 2 | 49 Participants |
| Esmirtazapine 2.25 mg | Total Number of Responders by Week | Week 9 | 67 Participants |
| Esmirtazapine 2.25 mg | Total Number of Responders by Week | Week 7 | 59 Participants |
| Esmirtazapine 2.25 mg | Total Number of Responders by Week | Week 3 | 53 Participants |
| Esmirtazapine 2.25 mg | Total Number of Responders by Week | Week 12 | 70 Participants |
| Esmirtazapine 2.25 mg | Total Number of Responders by Week | Week 11 | 70 Participants |
| Esmirtazapine 2.25 mg | Total Number of Responders by Week | Week 8 | 65 Participants |
| Esmirtazapine 2.25 mg | Total Number of Responders by Week | Week 4 | 58 Participants |
| Esmirtazapine 4.5 mg | Total Number of Responders by Week | Week 8 | 73 Participants |
| Esmirtazapine 4.5 mg | Total Number of Responders by Week | Week 9 | 74 Participants |
| Esmirtazapine 4.5 mg | Total Number of Responders by Week | Week 10 | 73 Participants |
| Esmirtazapine 4.5 mg | Total Number of Responders by Week | Week 3 | 63 Participants |
| Esmirtazapine 4.5 mg | Total Number of Responders by Week | Week 12 | 75 Participants |
| Esmirtazapine 4.5 mg | Total Number of Responders by Week | Week 4 | 70 Participants |
| Esmirtazapine 4.5 mg | Total Number of Responders by Week | Week 1 | 35 Participants |
| Esmirtazapine 4.5 mg | Total Number of Responders by Week | Week 5 | 65 Participants |
| Esmirtazapine 4.5 mg | Total Number of Responders by Week | Week 6 | 70 Participants |
| Esmirtazapine 4.5 mg | Total Number of Responders by Week | Week 2 | 60 Participants |
| Esmirtazapine 4.5 mg | Total Number of Responders by Week | Week 11 | 78 Participants |
| Esmirtazapine 4.5 mg | Total Number of Responders by Week | Week 7 | 72 Participants |
| Esmirtazapine 9 mg | Total Number of Responders by Week | Week 2 | 48 Participants |
| Esmirtazapine 9 mg | Total Number of Responders by Week | Week 5 | 56 Participants |
| Esmirtazapine 9 mg | Total Number of Responders by Week | Week 1 | 32 Participants |
| Esmirtazapine 9 mg | Total Number of Responders by Week | Week 3 | 47 Participants |
| Esmirtazapine 9 mg | Total Number of Responders by Week | Week 4 | 52 Participants |
| Esmirtazapine 9 mg | Total Number of Responders by Week | Week 6 | 55 Participants |
| Esmirtazapine 9 mg | Total Number of Responders by Week | Week 7 | 60 Participants |
| Esmirtazapine 9 mg | Total Number of Responders by Week | Week 8 | 66 Participants |
| Esmirtazapine 9 mg | Total Number of Responders by Week | Week 9 | 68 Participants |
| Esmirtazapine 9 mg | Total Number of Responders by Week | Week 10 | 67 Participants |
| Esmirtazapine 9 mg | Total Number of Responders by Week | Week 11 | 65 Participants |
| Esmirtazapine 9 mg | Total Number of Responders by Week | Week 12 | 65 Participants |
| Esmirtazapine 18 mg | Total Number of Responders by Week | Week 8 | 72 Participants |
| Esmirtazapine 18 mg | Total Number of Responders by Week | Week 7 | 75 Participants |
| Esmirtazapine 18 mg | Total Number of Responders by Week | Week 6 | 69 Participants |
| Esmirtazapine 18 mg | Total Number of Responders by Week | Week 2 | 65 Participants |
| Esmirtazapine 18 mg | Total Number of Responders by Week | Week 11 | 72 Participants |
| Esmirtazapine 18 mg | Total Number of Responders by Week | Week 5 | 71 Participants |
| Esmirtazapine 18 mg | Total Number of Responders by Week | Week 4 | 71 Participants |
| Esmirtazapine 18 mg | Total Number of Responders by Week | Week 3 | 72 Participants |
| Esmirtazapine 18 mg | Total Number of Responders by Week | Week 1 | 42 Participants |
| Esmirtazapine 18 mg | Total Number of Responders by Week | Week 9 | 75 Participants |
| Esmirtazapine 18 mg | Total Number of Responders by Week | Week 12 | 77 Participants |
| Esmirtazapine 18 mg | Total Number of Responders by Week | Week 10 | 77 Participants |