Dose-Finding Safety and Efficacy Trial in the Treatment of Vasomotor Symptoms (P06472)(COMPLETED)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00535288
First received: September 24, 2007
Last updated: September 30, 2013
Last verified: September 2013
  Purpose

To investigate efficacy and safety of 4 doses of Org 50081, compared to placebo, in the treatment of moderate to severe hot flushes 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.


Condition Intervention Phase
Postmenopausal Symptoms
Menopause
Vasomotor Symptoms
Drug: Org 50081
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • To demonstrate superior efficacy of Org 50081 as compared to placebo on the mean change from baseline in average daily frequency and severity after 4 and 12 weeks of treatment. [ Time Frame: At weeks 4 and 12 (Total timeframe 12 weeks) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Evaluate the effect of four different doses of Org 50081 compared to placebo on the Health Status assessment as measured by the Women's Health Questionnaire. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Enrollment: 946
Study Start Date: September 2004
Study Completion Date: January 2006
Primary Completion Date: January 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
ORG 50081
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 for blinding purposes. Encapsulated tablets were administered orally once daily in the evening prior to sleep for 12 weeks.

Other Names:
  • Esmirtazapine maleate
  • SCH 900265
  • Org 50081
Placebo Comparator: 2
Placebo
Drug: Placebo
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.

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 Org 50081 compared to placebo was 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 Org 50081 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.

  Eligibility

Ages Eligible for Study:   40 Years to 65 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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) 1and 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.
  Contacts and Locations
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  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00535288     History of Changes
Other Study ID Numbers: P06472, White Moonstone, 177001
Study First Received: September 24, 2007
Last Updated: September 30, 2013
Health Authority: United States: Food and Drug Administration
Belgium: Federal Agency for Medicinal Products and Health Products
Brazil: Ministry of Health
Canada: Health Canada
Czech Republic: State Institute for Drug Control
Denmark: Danish Medicines Agency
Hungary: National Institute of Pharmacy
Netherlands: Medicines Evaluation Board (MEB)
Norway: Norwegian Medicines Agency
Slovakia: State Institute for Drug Control
Spain: Spanish Agency of Medicines
Switzerland: Swissmedic
United Kingdom: Medicines and Healthcare Products Regulatory Agency

ClinicalTrials.gov processed this record on July 22, 2014