Intervention: Mirtazapine
Trial phase: Phase 3
ATC code: N06AX11
SMILES: CN1CCN2c3ncccc3Cc3ccccc3C2C1
Sex: Female
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 151
Group description: Participants receive esmirtazapine, 9 mg, encapsulated tablets, orally QD for up to 12 weeks.
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.
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.