Conditions: Postmenopausal Symptoms Menopause Vasomotor Symptoms
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 946
Healthy volunteers: no

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.

Arms:
arm 1: Participants receive encapsulated tablets, orally, once daily (QD) for up to 12 weeks. arm 2: Participants receive esmirtazapine, 2.25 mg, encapsulated tablets, orally QD for up to 12 weeks. arm 3: Participants receive esmirtazapine, 4.5 mg, encapsulated tablets, orally QD for up to 12 weeks. arm 4: Participants receive esmirtazapine, 9 mg, encapsulated tablets, orally QD for up to 12 weeks. arm 5: Participants receive esmirtazapine, 18 mg, encapsulated tablets, orally QD for up to 12 weeks.

Interventions: intervention 1: Esmirtazapine intervention 2: Placebo
Intervention descriptions: intervention 1: 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. intervention 2: 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.

Protocol document: