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

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.