Official Title: “A Multicenter, Randomized, Parallel-Group, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Four Different Doses of Org 50081 in the Treatment of Moderate to Severe Vasomotor Symptoms Associated With the Menopause”

The most direct treatment of a hot flush, maybe by means of5-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 Org 50081 compared to placebo was investigated in women with moderate to severe vasomotor symptoms associated with the menopause.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: January 2006

Intervention(s) in this Clinical Trial

• Drug: Org 50081
  • four different doses (2.25, 4.5, 9.0, and 18 mg) Encapsulated Org 50081 tablets in Swedish Orange hard gelatin DB-B capsules containing titanium dioxide (E171), iron oxide red (E172). Org 50081 tablets contained the following excipients: sodium starch glycolate,magnesium stearate, and lactose monohydrate. Encapsulated tablets were administered orally once daily in the evening prior to sleep for 12 weeks
• Drug: Placebo
  • Encapsulated placebo tablets in Swedish Orange hard gelatin DB-B capsules containing gelatin, titanium dioxide (E171), iron oxide red (E172). The placebo tablets contained the following excipients: maize starch, magnesium stearate, and lactose monohydrate. Batchnumbers: BX091 and CX162.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Org 50081
• Placebo Comparator: 2
  • placebo

Primary Measures

• To demonstrate superior efficacy of Org 50081 as compared to placebo on the mean change from baseline in average daily frequency and severity
  • Time Frame: At weeks 4 and 12 (Total timeframe 12 weeks)
    Safety Issue?: No

Secondary Measures

• Evaluate the effect of four different doses of Org 50081 compared to placebo on the Health Status assessment as measured by the Womens Health Questionaire
  • Time Frame: 12 weeks
    Safety Issue?: No

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 = 65 years of age;
• have a body mass index (BMI) = 18 and = 32 kg/m2;
• 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. Mammography had to have been performed within the last 9 months prior to screening, otherwise it had to be done before inclusion into the trial. For non-US sites, if local laws or guidelines did not allow or advise such frequent mammograms, the documented local laws or guidelines were to be followed;
• 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) 1and higher). A cervical smear had to have been performed within the last 9 months prior to screening, otherwise it had to be done before inclusion into the trial; hematological or biochemical values at screening outside the reference ranges considered clinically relevant in the opinion of the investigator
• high Blood Pressure (BP) (sitting systolic BP > 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: Document

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 40 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Organon

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00560833

Study ID Number: 46101

ClinicalTrials.gov Identifier: NCT00560833

Health Authority: United States: Food and Drug Administration