Klimadynon® in Comparison to Conjugated Oestrogens in Women Suffering From Menopausal Complaints

Boehringer Ingelheim

Status and phase: Completed; Phase 3

Conditions: Menopause

Treatments: Drug: Low dose of Klimadynon®; Drug: Medium dose of Klimadynon®; Drug: Oestrofeminal®; Drug: High dose of Klimadynon®; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02184364

563.1

Details and patient eligibility

About

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

Enrollment: 161 patients

Sex: Female

Ages: 40 to 60 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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"

Exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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161 participants in 5 patient groups, including a placebo group

Low dose of Klimadynon®

Experimental group

Treatment:

Drug: Low dose of Klimadynon®

Medium dose of Klimadynon®

Experimental group

Treatment:

Drug: Medium dose of Klimadynon®

High dose of Klimadynon®

Experimental group

Treatment:

Drug: High dose of Klimadynon®

Oestrofeminal®

Active Comparator group

Treatment:

Drug: Oestrofeminal®

Placebo

Placebo Comparator group

Treatment:

Drug: Placebo