A double-blind, randomized, placebo and active controlled, multicenter study to investigate efficacy and safety after oral administration of 2 and 3 mg ZK 283197, 1 mg 17ß-estradiol and placebo once daily for 8 weeks in postmenopausal women with hot flushes

Recruitment & Eligibility

Status: ot Recruiting

Sex: Female

Target Recruitment: 0

Inclusion Criteria

•Women with at least 35 moderate to severe hot flushes in seven consecutive days during the 2-week run-in phase •Age: 45 – 65 years (inclusive) •Body mass index (BMI) : 20 - 30 kg/m² (inclusive) •Signed informed consent prior to study participation •Postmenopausal status, revealed by last spontaneous bleeding at least 12 months prior to enrollment or 6 months spontaneous amenorrhea with serum FSH levels ? 40 mIU/ml or bilateral oophorectomy (without hysterectomy) at least six weeks prior to enrollment
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Medical and surgical history •Incompletely cured pre-existing diseases for which it can be assumed that the absorption, distribution, metabolism, excretion and effect of the study drugs will not be normal •Previous diagnosis of cancer of any type as well as benign tumors of the liver and pituitary, including after treatment or suspicion thereof •Known or suspected liver disorders •History of thrombophlebitis, venous / arterial thromboembolic diseases (particularly deep vein thrombosis, pulmonary embolism, stroke, myocardial infarction, cerebrovascular accident, ischemic heart disease) •Other conditions that increase susceptibility to thromboembolic diseases (e.g. known disturbance of the coagulation system, thromboembolic diseases in close relatives at young age) •Migraine accompanied by disturbances in sensory perception and / or locomotion (migraine accompagnée) •Diabetes mellitus with vascular involvement •Severe hypertriglyceridemia •Known sensitivity to the study drugs or components of the preparations •Abnormal, clinically significant findings which, according to the assessment of the investigator, may worsen under hormonal treatment Medication and drug use •Hormonal therapy (estrogen mono-therapy or combined hormone therapy, i.e. including progestin, oral, transdermal) or intrauterine hormone releasing device within 4 weeks prior to study entry or any long-acting injectable or implant up to 6 months before study entry, or any other therapy of menopausal symptoms, e.g. plant-based products within 4 weeks prior to study entry •Intake of an investigational compound within 8 weeks before study screening •Concomitant repeated medication with drugs which could affect the study aim under consideration of their elimination and/or the duration of their influencing effects on the study drug: Drugs which might affect absorption (e.g. laxatives, loperamide, metoclopramide, antacids, H2-receptor antagonists) Anticoagulants (e.g. heparin, coumarin) Antiepileptics (hydantoin derivates e.g. phenytoin, or carboxamid derivates e.g. carbamazepin, oxcarbamazepin, other antiepileptics e.g. Felbamat, Topiramate) Hypnotica and sedativa (barbiturate derivates e.g. phenobarbital, primidone) Tuberculostatics (e.g. rifampicin) Oral antimycotics (e.g. griseofulvin, ketoconazol, itraconazol, fluoconazol) Virostatic agents (systemic, e.g. oral, or genital administration, e.g. ritonavir) Selective estrogen receptor modulators (e.g. raloxifene, tamoxifen) Products containing St. John’s wort, grapefruit juice Continuous systemic use of antibiotics for >14 days Corticosteroids (systemic, e.g. oral, or genital administration) •Suspicion of drug or alcohol abuse (within the last 2 years) Special behavioral patterns •Smoking (former smokers who have stopped smoking at least 3 months before study drug administration may be included) Electrocardiogram (ECG), blood pressure, heart rate •Clinically relevant ECG findings •Systolic blood pressure > 160 mmHg (after at least 3 min in supine position) •Diastolic blood pressure > 95 mmHg (after at least 3 min in supine position) •Heart rate < 45 or > 100 beats/min (after at least 3 min in supine position) Physical examination •Clinically relevant findings in the physical examination (e.g. pronounced varicosis, thrombophlebitis, evidence of peripheral circulatory disturbances) Mammography •Suspicious structures in mammography (to be performed within the last 9 months before screening) that may indicate a malignant t

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To investigate the influence of a 8-weeks multiple dose treatment with two oral doses of ZK 283197 in comparison to E2 and placebo on the reduction of moderate to severe hot flushes;Secondary Objective: Safety and tolerability, Pharmacodynamics incl. vaginal cytology, endometrial thickness, endometrial histology and exploratory mRNA expression profiling of endometrial biopsies and blood cells, Pharmacokinetics, Exposure - response relationship;Primary end point(s): Change in frequency of moderate to severe hot flushes per week between baseline (at least 2 week run-in phase) and week 8 of the treatment phase Standard safety laboratory parameters in blood/urine, vital signs (blood pressure/heart rate), electrocardiogram (ECG), adverse events, body weight, endometrial thickness, endometrial histology, vaginal cytology, bone resorption markers in blood, marker of hepatic estrogenicity in blood, bleeding pattern

Secondary Outcome Measures

Name	Time	Method

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