Klimadynon® in Comparison to Conjugated Oestrogens in Women Suffering From Menopausal Complaints
- Conditions
- Menopause
- Interventions
- Drug: Oestrofeminal®Drug: High dose of Klimadynon®Drug: PlaceboDrug: Medium dose of Klimadynon®Drug: Low dose of Klimadynon®
- Registration Number
- NCT02184364
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
To investigate, relative to placebo and conjugated oestrogens, the efficacy, safety and tolerability of a 12 weeks peroral treatment twice daily with a cimicifuga racemosa extract corresponding to 20 mg, 75 mg or 150 mg plant material on menopause-related neurovegetative and mental complaints
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 161
-
Only postmenopausal (amenorrhea for 6 months at least) women may be enrolled in the study
-
Women after ovariectomy may also be enrolled if surgery was carried out at least 6 months prior to the enrollment. Only women between the age of 40 and 60 may be included
-
2 weeks (control -1, week -2, day -14) before the beginning of the treatment the following hormone values must have been analyzed:
- estradiol-17ß ≤ 0.15 nmol/l corresponding to ≤ 40 pg/ml and follicle stimulating hormone (FSH) ≥ 25 milliunits per milliliter (mU/ml)
- These hormone analyses must be carried out at the competent local laboratory
-
In addition to other menopausal complaints the women must have hot flushes / outbreaks of sweating:
- Diary: During the "run-in period" daily ≥ 3 hot flushes / outbreaks of sweating
- Modified Menopause Rating Scale, 1st item twofold (week -2 and 0) ≥ 0.3
-
A sum score taken twice from the modified (only items 1 - 6) Menopause Rating Scale within 2 weeks (week - 1 and 0) before the beginning of treatment must be ≥ 1.7
-
In case of a pretreatment with estrogen a wash-out phase of 6 weeks is necessary in case of oral or transdermal administration. After the 4th week of wash-out the patient may be included in the "run-in period"
-
General criteria for exclusion:
- Non-responder (= no therapeutic success) under a pretreatment with estrogen
- Amenorrhea for < 6 months
- In case of an estrogen pretreatment last menstruation (menopause) > 3 years earlier
- Sum score of the modified Menopause Rating Scale (items 1 - 6) during the "run-in period" twice (week -2 and 0) < 1.7
- No hot flushes / outbreaks of sweating (see Inclusion criteria)
- At one of the appointments of the "run-in period" (week -2 and 0) more than one question of items 1 - 6 of the modified Menopause Rating Scale (MMRS) not answered
- During the "run-in period" at the appointment week -2: estradiol-17ß > 40 pg/ml corresponding to > 0.15 nmol/l and FSH < 25 mU/ml
- Condition after hysterectomy
- Simultaneous ingestion of estrogen-containing products in addition to the test products
- Any addition ingestion of psychotropic drugs, antidepressants and sleeping aids (hypnotics / sedatives)
- Treatment with another study drug in the 2 months preceding the beginning of the study
- Considerable overweight (exceeding the target body weight [height in cm minus 100] by more than 30%)
- Poor general condition
- Alcohol or drug abuse
- Poor compliance
-
Exclusion criteria based on conjugated estrogens or medroxyprogesterone:
- Any contraindication for estrogen
- Unresolved genital bleeding
- Suspicion / existence of estrogen-dependent mammary carcinoma (mammography and/or endometrial carcinoma)
- Endometriosis
- Endometrial hyperplasia (including hyperplastic polypoid endometrium, which has not yet reached the stage of a glandular cystic hyperplasia)
- Thickness of endometrium > 5 mm
- Existing thromboembolism or thromboembolism in the past
- Phlebitis in the past 2 years or actually existing
- Acute or chronic hepatic lesion (aspartate transaminase and/or alanine transaminase and/or gamma glutamyl transferase twice the normal range)
- Metabolic disorders of bile pigments (Dubin-Johnson's syndrome, Rotor syndrome, pregnancy icterus with/without pruritus in previous pregnancy)
- Sickle cell anemia
- Clinically relevant hypertriglyceridemia or hypercholesterolemia
- Heart attack in the past
- Severe varicosis
- Known sensitivity to medroxyprogesterone
- Case history of anaphylactic reaction
- Any neoplasm at the genitals
- Case history of antidepressant treatment
- Diabetes mellitus with or without treatment
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Oestrofeminal® Oestrofeminal® - High dose of Klimadynon® High dose of Klimadynon® - Placebo Placebo - Medium dose of Klimadynon® Medium dose of Klimadynon® - Low dose of Klimadynon® Low dose of Klimadynon® -
- Primary Outcome Measures
Name Time Method Change of score in menopause-related symptom categories of the modified menopausal rating scale (MRS) baseline, week 12
- Secondary Outcome Measures
Name Time Method Changes in daily frequency of menopausal lead symptoms Up to day 105 diary information
Changes from baseline in serum concentration of FSH Up to day 98 Changes from baseline in serum concentration of oestradiol-17ß Up to day 98 Changes from baseline in serum concentration of luteinising hormone Up to day 98 Changes from baseline in serum concentration of high density lipoproteins Up to day 98 Changes from baseline in serum concentration of glucose Up to day 98 Changes from baseline in maturity index of the vaginal epithelium Baseline, day 84 Changes from baseline in clinical laboratory including coagulation parameters Baseline, day 56, day 98 Change in scores of somatic complaints (MRS items 1, 2, 8, 9, 10) baseline, week 12 Changes from baseline in serum concentration of ß-CrossLaps Up to day 98 Changes from baseline in serum concentration of bone specific alkaline phosphatase Up to day 98 Assessment of global efficacy evaluated by patient and investigator on a 4-point rating scale At day 98 Changes from baseline in vital signs (blood pressure, heart rate) Baseline up to day 98 Number of patients with adverse events Up to day 105 Assessment for incidence of withdrawal bleeding upon peroral gestagen administration At day 105 Change in scores of major climacteric complaints (MRS items 1, 4, 9, 10) baseline, week 12 Changes from baseline in serum concentration of low density lipoproteins Up to day 98 Changes from baseline for mammography/ ultrasonography assessment of the breasts Baseline, day 98 Assessment of global tolerability evaluated by patient and investigator (4-point rating scale) At day 98 Change of score of MRS items 7-10 and items 1-10 baseline, week 12 Change of menopause index according to Kupperman Baseline up to day 98 a 4 point numerical scale rating of 11 weighted menopause-related symptom complexes
Changes from baseline in serum concentration of osteocalcin Up to day 98 Changes from baseline in serum concentration of cholesterol Up to day 98 Changes from baseline in thickness of endometrium Baseline, day 84 measured in millimeters, assessed by transvaginal ultrasonography
Diary information regarding frequency, duration and intensity of vaginal bleeding on treatment Up to day 105 Changes from baseline in serum concentration of triglycerides Up to day 98 Changes from baseline in body weight Baseline up to day 98