<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02184364</url>
  </required_header>
  <id_info>
    <org_study_id>563.1</org_study_id>
    <nct_id>NCT02184364</nct_id>
  </id_info>
  <brief_title>Klimadynon® in Comparison to Conjugated Oestrogens in Women Suffering From Menopausal Complaints</brief_title>
  <official_title>Double-blind Dose/Response Study Comparing Klimadynon® With Conjugated Oestrogens in Women Suffering From Menopausal Complaints</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <brief_summary>
    <textblock>
      To investigate, relative to placebo and conjugated oestrogens, the efficacy, safety and&#xD;
      tolerability of a 12 weeks peroral treatment twice daily with a cimicifuga racemosa extract&#xD;
      corresponding to 20 mg, 75 mg or 150 mg plant material on menopause-related neurovegetative&#xD;
      and mental complaints&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>November 1998</start_date>
  <primary_completion_date type="Actual">September 2000</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change of score in menopause-related symptom categories of the modified menopausal rating scale (MRS)</measure>
    <time_frame>baseline, week 12</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change of score of MRS items 7-10 and items 1-10</measure>
    <time_frame>baseline, week 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of menopause index according to Kupperman</measure>
    <time_frame>Baseline up to day 98</time_frame>
    <description>a 4 point numerical scale rating of 11 weighted menopause-related symptom complexes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in daily frequency of menopausal lead symptoms</measure>
    <time_frame>Up to day 105</time_frame>
    <description>diary information</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline in serum concentration of oestradiol-17ß</measure>
    <time_frame>Up to day 98</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline in serum concentration of FSH</measure>
    <time_frame>Up to day 98</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline in serum concentration of luteinising hormone</measure>
    <time_frame>Up to day 98</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline in serum concentration of osteocalcin</measure>
    <time_frame>Up to day 98</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline in serum concentration of ß-CrossLaps</measure>
    <time_frame>Up to day 98</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline in serum concentration of bone specific alkaline phosphatase</measure>
    <time_frame>Up to day 98</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline in serum concentration of cholesterol</measure>
    <time_frame>Up to day 98</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline in serum concentration of high density lipoproteins</measure>
    <time_frame>Up to day 98</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline in serum concentration of low density lipoproteins</measure>
    <time_frame>Up to day 98</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline in serum concentration of triglycerides</measure>
    <time_frame>Up to day 98</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline in serum concentration of glucose</measure>
    <time_frame>Up to day 98</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline in maturity index of the vaginal epithelium</measure>
    <time_frame>Baseline, day 84</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of global efficacy evaluated by patient and investigator on a 4-point rating scale</measure>
    <time_frame>At day 98</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline in thickness of endometrium</measure>
    <time_frame>Baseline, day 84</time_frame>
    <description>measured in millimeters, assessed by transvaginal ultrasonography</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Diary information regarding frequency, duration and intensity of vaginal bleeding on treatment</measure>
    <time_frame>Up to day 105</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline for mammography/ ultrasonography assessment of the breasts</measure>
    <time_frame>Baseline, day 98</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline in vital signs (blood pressure, heart rate)</measure>
    <time_frame>Baseline up to day 98</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>Up to day 105</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline in clinical laboratory including coagulation parameters</measure>
    <time_frame>Baseline, day 56, day 98</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment for incidence of withdrawal bleeding upon peroral gestagen administration</measure>
    <time_frame>At day 105</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of global tolerability evaluated by patient and investigator (4-point rating scale)</measure>
    <time_frame>At day 98</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in scores of major climacteric complaints (MRS items 1, 4, 9, 10)</measure>
    <time_frame>baseline, week 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in scores of somatic complaints (MRS items 1, 2, 8, 9, 10)</measure>
    <time_frame>baseline, week 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline in body weight</measure>
    <time_frame>Baseline up to day 98</time_frame>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">161</enrollment>
  <condition>Menopause</condition>
  <arm_group>
    <arm_group_label>Low dose of Klimadynon®</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Medium dose of Klimadynon®</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>High dose of Klimadynon®</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Oestrofeminal®</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Low dose of Klimadynon®</intervention_name>
    <arm_group_label>Low dose of Klimadynon®</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Medium dose of Klimadynon®</intervention_name>
    <arm_group_label>Medium dose of Klimadynon®</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>High dose of Klimadynon®</intervention_name>
    <arm_group_label>High dose of Klimadynon®</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oestrofeminal®</intervention_name>
    <arm_group_label>Oestrofeminal®</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Only postmenopausal (amenorrhea for 6 months at least) women may be enrolled in the&#xD;
             study&#xD;
&#xD;
          -  Women after ovariectomy may also be enrolled if surgery was carried out at least 6&#xD;
             months prior to the enrollment. Only women between the age of 40 and 60 may be&#xD;
             included&#xD;
&#xD;
          -  2 weeks (control -1, week -2, day -14) before the beginning of the treatment the&#xD;
             following hormone values must have been analyzed:&#xD;
&#xD;
               -  estradiol-17ß ≤ 0.15 nmol/l corresponding to ≤ 40 pg/ml and follicle stimulating&#xD;
                  hormone (FSH) ≥ 25 milliunits per milliliter (mU/ml)&#xD;
&#xD;
               -  These hormone analyses must be carried out at the competent local laboratory&#xD;
&#xD;
          -  In addition to other menopausal complaints the women must have hot flushes / outbreaks&#xD;
             of sweating:&#xD;
&#xD;
               -  Diary: During the &quot;run-in period&quot; daily ≥ 3 hot flushes / outbreaks of sweating&#xD;
&#xD;
               -  Modified Menopause Rating Scale, 1st item twofold (week -2 and 0) ≥ 0.3&#xD;
&#xD;
          -  A sum score taken twice from the modified (only items 1 - 6) Menopause Rating Scale&#xD;
             within 2 weeks (week - 1 and 0) before the beginning of treatment must be ≥ 1.7&#xD;
&#xD;
          -  In case of a pretreatment with estrogen a wash-out phase of 6 weeks is necessary in&#xD;
             case of oral or transdermal administration. After the 4th week of wash-out the patient&#xD;
             may be included in the &quot;run-in period&quot;&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  General criteria for exclusion:&#xD;
&#xD;
               -  Non-responder (= no therapeutic success) under a pretreatment with estrogen&#xD;
&#xD;
               -  Amenorrhea for &lt; 6 months&#xD;
&#xD;
               -  In case of an estrogen pretreatment last menstruation (menopause) &gt; 3 years&#xD;
                  earlier&#xD;
&#xD;
               -  Sum score of the modified Menopause Rating Scale (items 1 - 6) during the &quot;run-in&#xD;
                  period&quot; twice (week -2 and 0) &lt; 1.7&#xD;
&#xD;
               -  No hot flushes / outbreaks of sweating (see Inclusion criteria)&#xD;
&#xD;
               -  At one of the appointments of the &quot;run-in period&quot; (week -2 and 0) more than one&#xD;
                  question of items 1 - 6 of the modified Menopause Rating Scale (MMRS) not&#xD;
                  answered&#xD;
&#xD;
               -  During the &quot;run-in period&quot; at the appointment week -2: estradiol-17ß &gt; 40 pg/ml&#xD;
                  corresponding to &gt; 0.15 nmol/l and FSH &lt; 25 mU/ml&#xD;
&#xD;
               -  Condition after hysterectomy&#xD;
&#xD;
               -  Simultaneous ingestion of estrogen-containing products in addition to the test&#xD;
                  products&#xD;
&#xD;
               -  Any addition ingestion of psychotropic drugs, antidepressants and sleeping aids&#xD;
                  (hypnotics / sedatives)&#xD;
&#xD;
               -  Treatment with another study drug in the 2 months preceding the beginning of the&#xD;
                  study&#xD;
&#xD;
               -  Considerable overweight (exceeding the target body weight [height in cm minus&#xD;
                  100] by more than 30%)&#xD;
&#xD;
               -  Poor general condition&#xD;
&#xD;
               -  Alcohol or drug abuse&#xD;
&#xD;
               -  Poor compliance&#xD;
&#xD;
          -  Exclusion criteria based on conjugated estrogens or medroxyprogesterone:&#xD;
&#xD;
               -  Any contraindication for estrogen&#xD;
&#xD;
               -  Unresolved genital bleeding&#xD;
&#xD;
               -  Suspicion / existence of estrogen-dependent mammary carcinoma (mammography and/or&#xD;
                  endometrial carcinoma)&#xD;
&#xD;
               -  Endometriosis&#xD;
&#xD;
               -  Endometrial hyperplasia (including hyperplastic polypoid endometrium, which has&#xD;
                  not yet reached the stage of a glandular cystic hyperplasia)&#xD;
&#xD;
               -  Thickness of endometrium &gt; 5 mm&#xD;
&#xD;
               -  Existing thromboembolism or thromboembolism in the past&#xD;
&#xD;
               -  Phlebitis in the past 2 years or actually existing&#xD;
&#xD;
               -  Acute or chronic hepatic lesion (aspartate transaminase and/or alanine&#xD;
                  transaminase and/or gamma glutamyl transferase twice the normal range)&#xD;
&#xD;
               -  Metabolic disorders of bile pigments (Dubin-Johnson's syndrome, Rotor syndrome,&#xD;
                  pregnancy icterus with/without pruritus in previous pregnancy)&#xD;
&#xD;
               -  Sickle cell anemia&#xD;
&#xD;
               -  Clinically relevant hypertriglyceridemia or hypercholesterolemia&#xD;
&#xD;
               -  Heart attack in the past&#xD;
&#xD;
               -  Severe varicosis&#xD;
&#xD;
               -  Known sensitivity to medroxyprogesterone&#xD;
&#xD;
               -  Case history of anaphylactic reaction&#xD;
&#xD;
               -  Any neoplasm at the genitals&#xD;
&#xD;
               -  Case history of antidepressant treatment&#xD;
&#xD;
               -  Diabetes mellitus with or without treatment&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <link>
    <url>http://trials.boehringer-ingelheim.com/content/dam/internet/opu/clinicaltrial/com_EN/results/563/563.1_U02-0003.pdf</url>
    <description>Related Info</description>
  </link>
  <verification_date>July 2014</verification_date>
  <study_first_submitted>July 8, 2014</study_first_submitted>
  <study_first_submitted_qc>July 8, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 9, 2014</study_first_posted>
  <last_update_submitted>July 11, 2014</last_update_submitted>
  <last_update_submitted_qc>July 11, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 14, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Estrogens, Conjugated (USP)</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02184364
org study id: 563.1
nct id: NCT02184364
lead sponsor: 
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
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double
measure: Change of score in menopause-related symptom categories of the modified menopausal rating scale (MRS)
time frame: baseline, week 12
measure: Change of score of MRS items 7-10 and items 1-10
time frame: baseline, week 12
measure: Change of menopause index according to Kupperman
time frame: Baseline up to day 98
description: a 4 point numerical scale rating of 11 weighted menopause-related symptom complexes
measure: Changes in daily frequency of menopausal lead symptoms
time frame: Up to day 105
description: diary information
measure: Changes from baseline in serum concentration of oestradiol-17ß
time frame: Up to day 98
measure: Changes from baseline in serum concentration of FSH
time frame: Up to day 98
measure: Changes from baseline in serum concentration of luteinising hormone
time frame: Up to day 98
measure: Changes from baseline in serum concentration of osteocalcin
time frame: Up to day 98
measure: Changes from baseline in serum concentration of ß-CrossLaps
time frame: Up to day 98
measure: Changes from baseline in serum concentration of bone specific alkaline phosphatase
time frame: Up to day 98
measure: Changes from baseline in serum concentration of cholesterol
time frame: Up to day 98
measure: Changes from baseline in serum concentration of high density lipoproteins
time frame: Up to day 98
measure: Changes from baseline in serum concentration of low density lipoproteins
time frame: Up to day 98
measure: Changes from baseline in serum concentration of triglycerides
time frame: Up to day 98
measure: Changes from baseline in serum concentration of glucose
time frame: Up to day 98
measure: Changes from baseline in maturity index of the vaginal epithelium
time frame: Baseline, day 84
measure: Assessment of global efficacy evaluated by patient and investigator on a 4-point rating scale
time frame: At day 98
measure: Changes from baseline in thickness of endometrium
time frame: Baseline, day 84
description: measured in millimeters, assessed by transvaginal ultrasonography
measure: Diary information regarding frequency, duration and intensity of vaginal bleeding on treatment
time frame: Up to day 105
measure: Changes from baseline for mammography/ ultrasonography assessment of the breasts
time frame: Baseline, day 98
measure: Changes from baseline in vital signs (blood pressure, heart rate)
time frame: Baseline up to day 98
measure: Number of patients with adverse events
time frame: Up to day 105
measure: Changes from baseline in clinical laboratory including coagulation parameters
time frame: Baseline, day 56, day 98
measure: Assessment for incidence of withdrawal bleeding upon peroral gestagen administration
time frame: At day 105
measure: Assessment of global tolerability evaluated by patient and investigator (4-point rating scale)
time frame: At day 98
measure: Change in scores of major climacteric complaints (MRS items 1, 4, 9, 10)
time frame: baseline, week 12
measure: Change in scores of somatic complaints (MRS items 1, 2, 8, 9, 10)
time frame: baseline, week 12
measure: Changes from baseline in body weight
time frame: Baseline up to day 98
arm group label: Low dose of Klimadynon®
arm group type: Experimental
arm group label: Medium dose of Klimadynon®
arm group type: Experimental
arm group label: High dose of Klimadynon®
arm group type: Experimental
arm group label: Oestrofeminal®
arm group type: Active Comparator
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Low dose of Klimadynon®
arm group label: Low dose of Klimadynon®
intervention type: Drug
intervention name: Medium dose of Klimadynon®
arm group label: Medium dose of Klimadynon®
intervention type: Drug
intervention name: High dose of Klimadynon®
arm group label: High dose of Klimadynon®
intervention type: Drug
intervention name: Oestrofeminal®
arm group label: Oestrofeminal®
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: Female
minimum age: 40 Years
maximum age: 60 Years
healthy volunteers: No
url: http://trials.boehringer-ingelheim.com/content/dam/internet/opu/clinicaltrial/com_EN/results/563/563.1_U02-0003.pdf
description: Related Info
responsible party type: Sponsor
mesh term: Estrogens, Conjugated (USP)