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NCT00535288

Dose-Finding Safety and Efficacy Trial of Org 50081 (Esmirtazapine) in the Treatment of Vasomotor Symptoms (177001/P06472/MK-8265-013)

Completed Phase 3 Results posted Last updated 2 April 2019
What this trial tests

Phase 3 trial testing Esmirtazapine in Postmenopausal Symptoms in 946 participants. Completed in 15 January 2006.

Timeline
15 September 2004
Primary endpoint
15 January 2006
15 January 2006

Quick facts

Lead sponsorMerck Sharp & Dohme LLC
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment946
Start date15 September 2004
Primary completion15 January 2006
Estimated completion15 January 2006

Drugs / interventions tested

Conditions studied

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

Adults 40 to 65, female only, with Postmenopausal Symptoms or Menopause. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

Baseline
GroupValue95% CI
Placebo12.1± 5.1
Esmirtazapine 2.25 mg12.2± 5.1
Esmirtazapine 4.5 mg12.6± 4.7
Esmirtazapine 9 mg12.3± 4.4
Esmirtazapine 18 mg11.5± 4.7
Week 4
GroupValue95% CI
Placebo-3.8± 4.5
Esmirtazapine 2.25 mg-5.1± 4.1
Esmirtazapine 4.5 mg-5.7± 4.8
Esmirtazapine 9 mg-5.3± 3.8
Esmirtazapine 18 mg-5.6± 4.4
Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) at Week 4 Primary · 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

Baseline
GroupValue95% CI
Placebo2.45± 0.30
Esmirtazapine 2.25 mg2.45± 0.30
Esmirtazapine 4.5 mg2.45± 0.32
Esmirtazapine 9 mg2.46± 0.30
Esmirtazapine 18 mg2.40± 0.27
Week 4
GroupValue95% CI
Placebo-0.07± 0.20
Esmirtazapine 2.25 mg-0.14± 0.23
Esmirtazapine 4.5 mg-0.13± 0.23
Esmirtazapine 9 mg-0.15± 0.24
Esmirtazapine 18 mg-0.15± 0.23
Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) at Week 12 Primary · 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

Baseline
GroupValue95% CI
Placebo12.1± 5.1
Esmirtazapine 2.25 mg12.2± 5.1
Esmirtazapine 4.5 mg12.6± 4.7
Esmirtazapine 9 mg12.3± 4.4
Esmirtazapine 18 mg11.5± 4.7
Week 12
GroupValue95% CI
Placebo-4.2± 5.3
Esmirtazapine 2.25 mg-5.2± 4.6
Esmirtazapine 4.5 mg-6.0± 4.9
Esmirtazapine 9 mg-5.8± 4.3
Esmirtazapine 18 mg-6.0± 4.6
Change From Baseline in Average Daily Frequency of Moderate/Severe Vasomotor Symptoms (Frequency Score A) by Week Excluding Weeks 4 and 12 Secondary · 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

Baseline
GroupValue95% CI
Placebo12.10± 5.10
Esmirtazapine 2.25 mg12.19± 5.07
Esmirtazapine 4.5 mg12.56± 4.66
Esmirtazapine 9 mg12.30± 4.39
Esmirtazapine 18 mg11.52± 4.67
Week 1
GroupValue95% CI
Placebo-2.21± 3.37
Esmirtazapine 2.25 mg-3.20± 3.35
Esmirtazapine 4.5 mg-4.08± 3.79
Esmirtazapine 9 mg-3.63± 2.89
Esmirtazapine 18 mg-4.18± 3.83
Week 2
GroupValue95% CI
Placebo-3.25± 4.08
Esmirtazapine 2.25 mg-4.72± 3.85
Esmirtazapine 4.5 mg-5.19± 4.59
Esmirtazapine 9 mg-4.88± 3.24
Esmirtazapine 18 mg-5.39± 3.96
Week 3
GroupValue95% CI
Placebo-3.71± 4.39
Esmirtazapine 2.25 mg-4.82± 4.08
Esmirtazapine 4.5 mg-5.68± 4.74
Esmirtazapine 9 mg-5.13± 3.68
Esmirtazapine 18 mg-5.59± 4.05
Week 5
GroupValue95% CI
Placebo-3.90± 4.82
Esmirtazapine 2.25 mg-5.29± 4.28
Esmirtazapine 4.5 mg-5.83± 4.72
Esmirtazapine 9 mg-5.50± 3.79
Esmirtazapine 18 mg-5.54± 4.48
Week 6
GroupValue95% CI
Placebo-4.02± 4.90
Esmirtazapine 2.25 mg-5.41± 4.43
Esmirtazapine 4.5 mg-5.96± 4.79
Esmirtazapine 9 mg-5.58± 3.89
Esmirtazapine 18 mg-5.62± 4.71
Week 7
GroupValue95% CI
Placebo-4.11± 4.96
Esmirtazapine 2.25 mg-5.33± 4.30
Esmirtazapine 4.5 mg-6.10± 4.87
Esmirtazapine 9 mg-5.69± 4.28
Esmirtazapine 18 mg-5.93± 4.63
Week 8
GroupValue95% CI
Placebo-4.04± 5.05
Esmirtazapine 2.25 mg-5.19± 4.49
Esmirtazapine 4.5 mg-6.14± 4.72
Esmirtazapine 9 mg-5.86± 4.52
Esmirtazapine 18 mg-5.72± 4.36
Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) by Week Excluding Weeks 4 and 12 Secondary · 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

Baseline
GroupValue95% CI
Placebo2.447± 0.301
Esmirtazapine 2.25 mg2.451± 0.297
Esmirtazapine 4.5 mg2.449± 0.315
Esmirtazapine 9 mg2.460± 0.296
Esmirtazapine 18 mg2.400± 0.274
Week 1
GroupValue95% CI
Placebo-0.045± 0.124
Esmirtazapine 2.25 mg-0.081± 0.153
Esmirtazapine 4.5 mg-0.085± 0.151
Esmirtazapine 9 mg-0.085± 0.159
Esmirtazapine 18 mg-0.108± 0.150
Week 2
GroupValue95% CI
Placebo-0.063± 0.172
Esmirtazapine 2.25 mg-0.117± 0.199
Esmirtazapine 4.5 mg-0.111± 0.212
Esmirtazapine 9 mg-0.140± 0.200
Esmirtazapine 18 mg-0.136± 0.178
Week 3
GroupValue95% CI
Placebo-0.071± 0.195
Esmirtazapine 2.25 mg-0.133± 0.214
Esmirtazapine 4.5 mg-0.119± 0.214
Esmirtazapine 9 mg-0.150± 0.200
Esmirtazapine 18 mg-0.137± 0.240
Week 5
GroupValue95% CI
Placebo-0.080± 0.215
Esmirtazapine 2.25 mg-0.141± 0.233
Esmirtazapine 4.5 mg-0.123± 0.227
Esmirtazapine 9 mg-0.154± 0.225
Esmirtazapine 18 mg-0.151± 0.232
Week 6
GroupValue95% CI
Placebo-0.075± 0.215
Esmirtazapine 2.25 mg-0.136± 0.246
Esmirtazapine 4.5 mg-0.127± 0.234
Esmirtazapine 9 mg-0.140± 0.236
Esmirtazapine 18 mg-0.152± 0.245
Week 7
GroupValue95% CI
Placebo-0.088± 0.233
Esmirtazapine 2.25 mg-0.144± 0.236
Esmirtazapine 4.5 mg-0.131± 0.260
Esmirtazapine 9 mg-0.140± 0.253
Esmirtazapine 18 mg-0.144± 0.257
Week 8
GroupValue95% CI
Placebo-0.082± 0.239
Esmirtazapine 2.25 mg-0.142± 0.242
Esmirtazapine 4.5 mg-0.124± 0.270
Esmirtazapine 9 mg-0.139± 0.254
Esmirtazapine 18 mg-0.133± 0.247
Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) at Week 12 Primary · 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

Baseline
GroupValue95% CI
Placebo2.45± 0.30
Esmirtazapine 2.25 mg2.45± 0.30
Esmirtazapine 4.5 mg2.45± 0.32
Esmirtazapine 9 mg2.46± 0.30
Esmirtazapine 18 mg2.40± 0.27
Week 12
GroupValue95% CI
Placebo-0.08± 0.26
Esmirtazapine 2.25 mg-0.15± 0.27
Esmirtazapine 4.5 mg-0.13± 0.27
Esmirtazapine 9 mg-0.13± 0.26
Esmirtazapine 18 mg-0.15± .026
Change From Baseline in Average Daily Moderate/Severe Composite Score (Composite Score A) by Week Secondary · Baseline and up to Week 12

Composite Score A was calculated as Severity Score A x Frequency Score A.

Baseline
GroupValue95% CI
Placebo30.19± 15.42
Esmirtazapine 2.25 mg30.41± 14.56
Esmirtazapine 4.5 mg31.03± 12.98
Esmirtazapine 9 mg30.40± 11.81
Esmirtazapine 18 mg27.87± 12.56
Week 1
GroupValue95% CI
Placebo-5.65± 8.99
Esmirtazapine 2.25 mg-8.48± 9.10
Esmirtazapine 4.5 mg-10.28± 9.19
Esmirtazapine 9 mg-9.43± 7.84
Esmirtazapine 18 mg-10.63± 9.63
Week 2
GroupValue95% CI
Placebo-8.28± 10.93
Esmirtazapine 2.25 mg-12.32± 10.18
Esmirtazapine 4.5 mg-12.98± 11.36
Esmirtazapine 9 mg-12.70± 8.75
Esmirtazapine 18 mg-13.54± 9.89
Week 3
GroupValue95% CI
Placebo-9.46± 11.92
Esmirtazapine 2.25 mg-12.63± 11.09
Esmirtazapine 4.5 mg-14.22± 11.88
Esmirtazapine 9 mg-13.39± 9.82
Esmirtazapine 18 mg-13.89± 10.28
Week 4
GroupValue95% CI
Placebo-9.79± 12.39
Esmirtazapine 2.25 mg-13.18± 11.29
Esmirtazapine 4.5 mg-14.42± 11.88
Esmirtazapine 9 mg-13.70± 10.28
Esmirtazapine 18 mg-13.72± 11.38
Week 5
GroupValue95% CI
Placebo-9.96± 13.19
Esmirtazapine 2.25 mg-13.65± 11.77
Esmirtazapine 4.5 mg-14.47± 11.65
Esmirtazapine 9 mg-14.16± 10.09
Esmirtazapine 18 mg-13.72± 11.33
Week 6
GroupValue95% CI
Placebo-10.22± 13.40
Esmirtazapine 2.25 mg-13.89± 11.88
Esmirtazapine 4.5 mg-14.84± 11.92
Esmirtazapine 9 mg-14.24± 10.26
Esmirtazapine 18 mg-13.95± 12.05
Week 7
GroupValue95% CI
Placebo-10.42± 13.49
Esmirtazapine 2.25 mg-13.73± 11.66
Esmirtazapine 4.5 mg-15.11± 12.32
Esmirtazapine 9 mg-14.42± 11.23
Esmirtazapine 18 mg-14.72± 11.87
Change From Baseline in Average Daily Frequency of Mild to Severe Vasomotor Symptoms (Frequency Score B) by Week Secondary · 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). I

Baseline
GroupValue95% CI
Placebo13.29± 5.35
Esmirtazapine 2.25 mg13.48± 5.35
Esmirtazapine 4.5 mg13.66± 4.96
Esmirtazapine 9 mg13.41± 4.61
Esmirtazapine 18 mg13.00± 6.09
Week 1
GroupValue95% CI
Placebo-2.22± 3.41
Esmirtazapine 2.25 mg-3.24± 3.23
Esmirtazapine 4.5 mg-3.81± 3.33
Esmirtazapine 9 mg-3.57± 2.96
Esmirtazapine 18 mg-4.16± 4.69
Week 2
GroupValue95% CI
Placebo-3.35± 4.17
Esmirtazapine 2.25 mg-4.81± 4.03
Esmirtazapine 4.5 mg-5.19± 4.46
Esmirtazapine 9 mg-4.79± 3.28
Esmirtazapine 18 mg-5.50± 4.75
Week 3
GroupValue95% CI
Placebo-3.83± 4.46
Esmirtazapine 2.25 mg-5.05± 4.15
Esmirtazapine 4.5 mg-5.66± 4.74
Esmirtazapine 9 mg-5.08± 3.72
Esmirtazapine 18 mg-5.79± 4.88
Week 4
GroupValue95% CI
Placebo-3.97± 4.63
Esmirtazapine 2.25 mg-5.37± 4.14
Esmirtazapine 4.5 mg-6.01± 4.80
Esmirtazapine 9 mg-5.38± 3.98
Esmirtazapine 18 mg-5.85± 5.30
Week 5
GroupValue95% CI
Placebo-4.06± 4.91
Esmirtazapine 2.25 mg-5.61± 4.46
Esmirtazapine 4.5 mg-6.13± 4.81
Esmirtazapine 9 mg-5.57± 4.03
Esmirtazapine 18 mg-5.90± 5.31
Week 6
GroupValue95% CI
Placebo-4.25± 4.86
Esmirtazapine 2.25 mg-5.82± 4.51
Esmirtazapine 4.5 mg-6.32± 4.89
Esmirtazapine 9 mg-5.75± 4.11
Esmirtazapine 18 mg-5.89± 5.24
Week 7
GroupValue95% CI
Placebo-4.27± 4.85
Esmirtazapine 2.25 mg-5.69± 4.36
Esmirtazapine 4.5 mg-6.47± 4.89
Esmirtazapine 9 mg-5.90± 4.45
Esmirtazapine 18 mg-6.15± 5.18
Change From Baseline in Average Daily Severity of Mild to Severe Vasomotor Symptoms (Severity Score B) by Week Secondary · 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

Baseline
GroupValue95% CI
Placebo2.332± 0.369
Esmirtazapine 2.25 mg2.331± 0.375
Esmirtazapine 4.5 mg2.349± 0.373
Esmirtazapine 9 mg2.350± 0.347
Esmirtazapine 18 mg2.270± 0.332
Week 1
GroupValue95% CI
Placebo-0.080± 0.220
Esmirtazapine 2.25 mg-0.132± 0.246
Esmirtazapine 4.5 mg-0.167± 0.245
Esmirtazapine 9 mg-0.140± 0.245
Esmirtazapine 18 mg-0.192± 0.273
Week 2
GroupValue95% CI
Placebo-0.111± 0.291
Esmirtazapine 2.25 mg-0.210± 0.342
Esmirtazapine 4.5 mg-0.223± 0.341
Esmirtazapine 9 mg-0.225± 0.341
Esmirtazapine 18 mg-0.250± 0.312
Week 3
GroupValue95% CI
Placebo-0.121± 0.307
Esmirtazapine 2.25 mg-0.217± 0.373
Esmirtazapine 4.5 mg-0.246± 0.400
Esmirtazapine 9 mg-0.240± 0.337
Esmirtazapine 18 mg-0.272± 0.389
Week 4
GroupValue95% CI
Placebo-0.113± 0.312
Esmirtazapine 2.25 mg-0.224± 0.409
Esmirtazapine 4.5 mg-0.240± 0.388
Esmirtazapine 9 mg-0.249± 0.387
Esmirtazapine 18 mg-0.273± 0.411
Week 5
GroupValue95% CI
Placebo-0.124± 0.354
Esmirtazapine 2.25 mg-0.234± 0.411
Esmirtazapine 4.5 mg-0.228± 0.403
Esmirtazapine 9 mg-0.254± 0.368
Esmirtazapine 18 mg-0.266± 0.409
Week 6
GroupValue95% CI
Placebo-0.121± 0.360
Esmirtazapine 2.25 mg-0.222± 0.429
Esmirtazapine 4.5 mg-0.214± 0.386
Esmirtazapine 9 mg-0.245± 0.396
Esmirtazapine 18 mg-0.275± 0.436
Week 7
GroupValue95% CI
Placebo-0.142± 0.389
Esmirtazapine 2.25 mg-0.234± 0.433
Esmirtazapine 4.5 mg-0.232± 0.444
Esmirtazapine 9 mg-0.242± 0.424
Esmirtazapine 18 mg-0.287± 0.460
Change From Baseline in Average Daily Mild to Severe Composite Symptoms Score (Composite Score B) by Week Secondary · Baseline and up to Week 12

Composite Score B was calculated as Severity Score B x Frequency Score B.

Baseline
GroupValue95% CI
Placebo31.39± 15.37
Esmirtazapine 2.25 mg31.70± 14.47
Esmirtazapine 4.5 mg32.13± 12.91
Esmirtazapine 9 mg31.51± 11.80
Esmirtazapine 18 mg29.35± 13.55
Week 1
GroupValue95% CI
Placebo-5.66± 8.94
Esmirtazapine 2.25 mg-8.53± 8.85
Esmirtazapine 4.5 mg-10.01± 8.60
Esmirtazapine 9 mg-9.37± 7.74
Esmirtazapine 18 mg-10.61± 10.31
Week 2
GroupValue95% CI
Placebo-8.38± 10.91
Esmirtazapine 2.25 mg-12.40± 10.12
Esmirtazapine 4.5 mg-12.98± 11.05
Esmirtazapine 9 mg-12.60± 8.58
Esmirtazapine 18 mg-13.64± 10.46
Week 3
GroupValue95% CI
Placebo-9.57± 11.88
Esmirtazapine 2.25 mg-12.86± 10.89
Esmirtazapine 4.5 mg-14.40± 11.69
Esmirtazapine 9 mg-13.34± 9.69
Esmirtazapine 18 mg-14.09± 10.80
Week 4
GroupValue95% CI
Placebo-9.93± 12.36
Esmirtazapine 2.25 mg-13.48± 11.06
Esmirtazapine 4.5 mg-14.69± 11.89
Esmirtazapine 9 mg-13.75± 10.24
Esmirtazapine 18 mg-14.01± 11.91
Week 5
GroupValue95% CI
Placebo-10.12± 13.13
Esmirtazapine 2.25 mg-13.96± 11.65
Esmirtazapine 4.5 mg014.78± 11.54
Esmirtazapine 9 mg-14.22± 10.12
Esmirtazapine 18 mg-14.08± 11.82
Week 6
GroupValue95% CI
Placebo-10.45± 13.24
Esmirtazapine 2.25 mg-14.29± 11.65
Esmirtazapine 4.5 mg-15.19± 11.83
Esmirtazapine 9 mg-14.40± 10.30
Esmirtazapine 18 mg-14.21± 12.22
Week 7
GroupValue95% CI
Placebo-10.58± 13.23
Esmirtazapine 2.25 mg-14.09± 11.45
Esmirtazapine 4.5 mg-15.48± 12.16
Esmirtazapine 9 mg-14.63± 11.18
Esmirtazapine 18 mg-14.93± 12.04
Total Number of Responders by Week Secondary · 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.

Week 1
GroupValue95% CI
Placebo37
Esmirtazapine 2.25 mg29
Esmirtazapine 4.5 mg35
Esmirtazapine 9 mg32
Esmirtazapine 18 mg42
Week 2
GroupValue95% CI
Placebo56
Esmirtazapine 2.25 mg49
Esmirtazapine 4.5 mg60
Esmirtazapine 9 mg48
Esmirtazapine 18 mg65
Week 3
GroupValue95% CI
Placebo85
Esmirtazapine 2.25 mg53
Esmirtazapine 4.5 mg63
Esmirtazapine 9 mg47
Esmirtazapine 18 mg72
Week 4
GroupValue95% CI
Placebo76
Esmirtazapine 2.25 mg58
Esmirtazapine 4.5 mg70
Esmirtazapine 9 mg52
Esmirtazapine 18 mg71
Week 5
GroupValue95% CI
Placebo76
Esmirtazapine 2.25 mg63
Esmirtazapine 4.5 mg65
Esmirtazapine 9 mg56
Esmirtazapine 18 mg71
Week 6
GroupValue95% CI
Placebo84
Esmirtazapine 2.25 mg67
Esmirtazapine 4.5 mg70
Esmirtazapine 9 mg55
Esmirtazapine 18 mg69
Week 7
GroupValue95% CI
Placebo89
Esmirtazapine 2.25 mg59
Esmirtazapine 4.5 mg72
Esmirtazapine 9 mg60
Esmirtazapine 18 mg75
Week 8
GroupValue95% CI
Placebo93
Esmirtazapine 2.25 mg65
Esmirtazapine 4.5 mg73
Esmirtazapine 9 mg66
Esmirtazapine 18 mg72
Total Number of Remitters by Week Secondary · 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.

Week 1
GroupValue95% CI
Placebo3
Esmirtazapine 2.25 mg2
Esmirtazapine 4.5 mg7
Esmirtazapine 9 mg2
Esmirtazapine 18 mg2
Week 2
GroupValue95% CI
Placebo6
Esmirtazapine 2.25 mg11
Esmirtazapine 4.5 mg13
Esmirtazapine 9 mg8
Esmirtazapine 18 mg13
Week 3
GroupValue95% CI
Placebo8
Esmirtazapine 2.25 mg15
Esmirtazapine 4.5 mg16
Esmirtazapine 9 mg7
Esmirtazapine 18 mg17
Week 4
GroupValue95% CI
Placebo10
Esmirtazapine 2.25 mg15
Esmirtazapine 4.5 mg18
Esmirtazapine 9 mg15
Esmirtazapine 18 mg17
Week 5
GroupValue95% CI
Placebo13
Esmirtazapine 2.25 mg18
Esmirtazapine 4.5 mg16
Esmirtazapine 9 mg12
Esmirtazapine 18 mg17
Week 6
GroupValue95% CI
Placebo15
Esmirtazapine 2.25 mg15
Esmirtazapine 4.5 mg21
Esmirtazapine 9 mg13
Esmirtazapine 18 mg18
Week 7
GroupValue95% CI
Placebo19
Esmirtazapine 2.25 mg19
Esmirtazapine 4.5 mg22
Esmirtazapine 9 mg16
Esmirtazapine 18 mg21
Week 8
GroupValue95% CI
Placebo23
Esmirtazapine 2.25 mg19
Esmirtazapine 4.5 mg25
Esmirtazapine 9 mg18
Esmirtazapine 18 mg21

Adverse events — posted to ClinicalTrials.gov

Time frame: Non-serious adverse events were collected up to 7 days after the last dose of study drug; serious adverse events were collected for up to 30 days after the last dose of study drug.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo
Serious: 2/314 (1%)
Deaths: —
Esmirtazapine 2.25 mg
Serious: 1/162 (1%)
Deaths: —
Esmertazapine 4.5 mg
Serious: 1/160 (1%)
Deaths: —
Esmirtazapine 9 mg
Serious: 3/151 (2%)
Deaths: —
Esmirtazapine 18 mg
Serious: 1/158 (1%)
Deaths: —

Serious adverse events (9 terms)

ReactionSystemPlaceboEsmirtazapine 2.25 mgEsmertazapine 4.5 mgEsmirtazapine 9 mgEsmirtazapine 18 mg
Wolff-Parkinson-White SyndromeCardiac disorders—————
Diverticular perforationGastrointestinal disorders—————
AstheniaGeneral disorders—————
Non-cardiac chest painGeneral disorders—————
DiverticulitisInfections and infestations—————
Ovarian fibromaNeoplasms benign, malignant and unspecified (incl cysts and polyps)—————
Syncope vasovagalNervous system disorders—————
NightmarePsychiatric disorders—————
Suicidal ideationPsychiatric disorders—————
Other adverse events (12 terms — click to expand)

ReactionSystemPlaceboEsmirtazapine 2.25 mgEsmertazapine 4.5 mgEsmirtazapine 9 mgEsmirtazapine 18 mg
HeadacheNervous system disorders—————
SomnolenceNervous system disorders—————
FatigueGeneral disorders—————
Weight increasedInvestigations—————
ArthralgiaMusculoskeletal and connective tissue disorders—————
InfluenzaInfections and infestations—————
Increased appetiteMetabolism and nutrition disorders—————
DizzinessNervous system disorders—————
Dry mouthGastrointestinal disorders—————
Abdominal distensionGastrointestinal disorders—————
Menopausal symptomsReproductive system and breast disorders—————
Oedema peripheralGeneral disorders—————

Most-reported serious reactions: Wolff-Parkinson-White Syndrome, Diverticular perforation, Asthenia, Non-cardiac chest pain, Diverticulitis, Ovarian fibroma, Syncope vasovagal, Nightmare.

Data from ClinicalTrials.gov NCT00535288 adverse events section.

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

  1. Esmirtazapine treatment of postmenopausal vasomotor symptoms: two randomized controlled trials.
    Birkhaeuser M, Bitzer J, Braat S, Ramos Y. · · 2019 · cited 5× · PMID 30712391 · DOI 10.1080/13697137.2018.1561664

Verify or expand the search:

Other trials of Esmirtazapine

Trials testing the same drug.

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Currently open trials in the same condition.

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Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT00535288.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing