Phase 3
N=943
Dose-Finding Safety and Efficacy Trial of Org50081 (Esmirtazapine) in the Treatment of Vasomotor Symptoms (46101/P06459/MK-8265-012)
Menopause · Vasomotor Symptoms
Bottom Line
View on ClinicalTrials.gov: NCT00560833 ↗Enrolled (actual)
943
Serious AEs
0.9%
Results posted
Jun 2014
Primary outcome: Primary: Change From Baseline in Average Daily Frequency of Vasomotor Symptoms (Frequency Score A) at Week 4 — -3.9; -5.6; -6.0; -6.0 Number of events — p=<0.01
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- esmirtazapine (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 40+ yrs
- Sex
- Female
- Sponsor
- Merck Sharp & Dohme LLC
- Primary completion
- Jan 2006
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in Average Daily Frequency of Vasomotor Symptoms (Frequency Score A) at Week 4 |
-3.9; -5.6; -6.0; -6.0; -6.0 | <0.01 sig |
| PRIMARY Change From Baseline in Average Daily Frequency of Vasomotor Symptoms (Frequency Score A) at Week 12 |
-4.9; -6.2; -6.7; -6.9; -6.5 | 0.06 |
| PRIMARY Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) at Week 4 |
-0.09; -0.11; -0.15; -0.16; -0.15 | 0.62 |
| PRIMARY Change From Baseline in Average Daily Severity of Moderate/Severe Vasomotor Symptoms (Severity Score A) at Week 12 |
-0.12; -0.10; -0.15; -0.18; -0.17 | 1.0 |
| SECONDARY Change From Baseline in Vasomotor Symptoms Score Per Women's Health Questionnaire (WHQ) at Week 12 |
0.984; 0.993; 0.985; 0.981; 0.985; -0.151 | — |
Summary
The most direct treatment of vasomotor symptions (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 was investigated in women with moderate to severe vasomotor symptoms associated with the menopause. The primary study hypothesis was that esmirtazapine would show superior efficacy to placebo.
Eligibility Criteria
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.
- In case the menopausal status of a subject was unclear because of a hysterectomy, the serum FSH level had to be >40 mIU/mL. If the date of the last menstruation was not clear because of perimenopausal hormone use, then the subject had to have a serum FSH level >40 mIU/mL after completion of a washout period (see exclusion criteria below); be >= 40 and = 18 and 170 mmHg and/or diastolic BP >100 mmHg)
- use of any drug product containing estrogens, progestins, androgens, or tibolone prior to screening (and up to and including randomization) within specified time frames
Data sourced from ClinicalTrials.gov (NCT00560833). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.