<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/NCT01735422</url>
  </required_header>
  <id_info>
    <org_study_id>21321</org_study_id>
    <nct_id>NCT01735422</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate Safety and Efficacy of Recombinant Human Luteinizing Hormone (r-hLH) Compared With Urinary Human Chorionic Gonadotrophin (u-hCG) to Trigger Ovulation in Infertile Women</brief_title>
  <official_title>A Phase II, Single Center, Open, Randomized, Parallel Group, Dose Finding Study to Assess the Safety and Efficacy of Recombinant Human Luteinizing Hormone (r-hLH), Compared With Urinary Human Chorionic Gonadotrophin (u-hCG), in Inducing Ovulation in Infertile Women Undergoing Stimulation of Follicular Development With Recombinant Human Follicle Stimulating Hormone (Gonal F®).</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Merck KGaA, Darmstadt, Germany</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Merck KGaA, Darmstadt, Germany</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a single center, open-label, randomized, parallel group, dose finding study to&#xD;
      evaluate safety and efficacy of recombinant human luteinizing hormone (r-hLH, LHadi®),&#xD;
      compared with urinary human chorionic gonadotrophin (u-hCG, Profasi®), both given&#xD;
      subcutaneously, in inducing ovulation in infertile women undergoing stimulation of follicular&#xD;
      growth with recombinant human follicle stimulating hormone (r-hFSH, Gonal-F®).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>December 1999</start_date>
  <completion_date type="Actual">July 2001</completion_date>
  <primary_completion_date type="Actual">July 2001</primary_completion_date>
  <phase>Phase 2</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Ovulation rate</measure>
    <time_frame>Day 4 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Ratio of ruptured follicles per follicle with diameter greater than or equal to (&gt;=) 15 millimeter (mm)</measure>
    <time_frame>Day 4 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of follicles with diameter greater than or equal to (&gt;=) 11 millimeter (mm)</measure>
    <time_frame>Day 4 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Ratio of ruptured follicles per follicle with diameter greater than or equal to (&gt;=) 11 millimeter (mm)</measure>
    <time_frame>Day 4 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of participants with mono-follicular ovulation</measure>
    <time_frame>Day 4 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with biochemical pregnancy</measure>
    <time_frame>Day 25-30 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum estradiol (E2) levels</measure>
    <time_frame>Day 1, 2 and 6-9 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum androstenedione levels</measure>
    <time_frame>Day 1, 2 and 6-9 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum total renin levels</measure>
    <time_frame>Day 1, 2 and 6-9 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum vascular endothelial growth factor (VEGF) levels</measure>
    <time_frame>Day 1, 2 and 6-9 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Endometrial thickness</measure>
    <time_frame>Day 0, 1, 2, 3, 4 and 6-9 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with clinical pregnancy</measure>
    <time_frame>Day 25-30 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum progesterone (P4) levels</measure>
    <time_frame>Day 1, 2 and 6-9 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])</time_frame>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">67</enrollment>
  <condition>Infertility</condition>
  <arm_group>
    <arm_group_label>r-hLH (825 International Units [IU])</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>r-hLH (2750 IU)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>r-hLH (5500 IU)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>r-hLH (11000 IU)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>r-hLH (22000 IU)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>u-hCG (5000 IU)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>r-hFSH</intervention_name>
    <description>Daily r-hFSH treatment will be administered subcutaneously at a starting dose according to the site's standard practice from Day 3-5 of menstrual cycle up to follicular development or 28 days. Dose can be altered according to ovarian response (reduced to 75 IU/day; increased to 225 IU/day).</description>
    <arm_group_label>r-hLH (11000 IU)</arm_group_label>
    <arm_group_label>r-hLH (22000 IU)</arm_group_label>
    <arm_group_label>r-hLH (2750 IU)</arm_group_label>
    <arm_group_label>r-hLH (5500 IU)</arm_group_label>
    <arm_group_label>r-hLH (825 International Units [IU])</arm_group_label>
    <arm_group_label>u-hCG (5000 IU)</arm_group_label>
    <other_name>Gonal-f®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>r-hLH</intervention_name>
    <description>Ovulation triggering will be performed using a single injection of r-hLH injection subcutaneously at a dose of 825 or 2750 or 5500 or 11,000 or 22,000 IU as soon as follicles satisfy the criteria for follicular development, that is at least 1 follicle with diameter &gt;= 18 mm, not more than 5 follicles with diameter &gt;= 15 mm and with E2 levels less than 9000 picomoles per liter (pmol/L).</description>
    <arm_group_label>r-hLH (11000 IU)</arm_group_label>
    <arm_group_label>r-hLH (22000 IU)</arm_group_label>
    <arm_group_label>r-hLH (2750 IU)</arm_group_label>
    <arm_group_label>r-hLH (5500 IU)</arm_group_label>
    <arm_group_label>r-hLH (825 International Units [IU])</arm_group_label>
    <other_name>LHadi®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>u-hCG</intervention_name>
    <description>Ovulation triggering will be performed using a single injection of 5000 IU of u-hCG as soon as follicles satisfy the criteria for follicular development, that is at least 1 follicle with diameter &gt;= 18 mm, not more than 5 follicles with diameter &gt;= 15 mm and with E2 levels less than 9000 picomoles per liter (pmol/L).</description>
    <arm_group_label>u-hCG (5000 IU)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Infertile woman wishing to conceive and justifying ovarian stimulation treatment with&#xD;
             gonadotrophins for in vivo conception&#xD;
&#xD;
          -  Aged 20-40 years (inclusive)&#xD;
&#xD;
          -  Male partner with acceptable semen analysis for intra-uterine insemination, according&#xD;
             to center's standard practice&#xD;
&#xD;
          -  Have the following hormone serum levels measured locally during early (Day 2-4)&#xD;
             follicular phase (if menstruating) or at anytime (if not menstruating):&#xD;
&#xD;
               -  Follicle stimulating hormone (FSH) less than 12 international unit per liter&#xD;
                  (IU/L)&#xD;
&#xD;
               -  Prolactin (PRL) less than 800 milli international unit per liter (mIU/l)&#xD;
&#xD;
               -  Lutenizing hormone (LH), P4, Testosterone (T) and Dehydroepiandrosterone sulphate&#xD;
                  (DHEA-S) for documentation purposes&#xD;
&#xD;
          -  At least one patent tube, as assessed with hysterosalpingography (HSG), ultrasound&#xD;
             (U/S) or laparoscopy performed within 3 years prior to beginning r-hFSH treatment&#xD;
&#xD;
          -  Uterine cavity without abnormalities which, in the Investigator's opinion, could&#xD;
             impair embryo implantation or pregnancy evolution as assessed with HSG, hysteroscopy&#xD;
             (HSC) or U/S performed within 3 years prior to beginning r-hFSH treatment&#xD;
&#xD;
          -  Body mass index (BMI) greater than or equal to 18 and less than or equal to 35&#xD;
             kilogram per square meter (kg/m^2)&#xD;
&#xD;
          -  Negative serum or urinary pregnancy test prior to beginning r-hFSH treatment&#xD;
&#xD;
          -  Be willing and able to comply with the protocol for the duration of the study&#xD;
&#xD;
          -  Have given written informed consent, prior to any study-related procedure not part of&#xD;
             normal medical care, with the understanding that consent may be withdrawn by the&#xD;
             patient at any time without prejudice to their future medical care&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any contraindication to being pregnant and/or carrying a pregnancy to term&#xD;
&#xD;
          -  Clinically significant systemic disease (screening for Human Immunodeficiency Virus&#xD;
             (HIV) and Hepatitis B and C surface antigens had to be performed to confirm&#xD;
             eligibility, unless data obtained within one year prior to beginning r-hFSH treatment&#xD;
             was available)&#xD;
&#xD;
          -  Any medical condition which in the judgment of the Investigator's and sponsor may have&#xD;
             interfered with the absorption, distribution, metabolism or excretion of the study&#xD;
             drug&#xD;
&#xD;
          -  Persistent ovarian cyst with a mean diameter larger than 20 mm or ovarian&#xD;
             endometrioma, as assessed with U/S performed prior to beginning r-hFSH treatment&#xD;
&#xD;
          -  Severe endometriosis (American Fertility Society Classification Stage III or IV)&#xD;
&#xD;
          -  World health organization (WHO) Group I anovulation&#xD;
&#xD;
          -  Pelvic inflammatory disease within 1 year prior to beginning r-hFSH treatment&#xD;
&#xD;
          -  Treatment with clomiphene citrate or gonadotrophins within 1 month prior to beginning&#xD;
             r-hFSH treatment&#xD;
&#xD;
          -  Abnormal undiagnosed gynecological bleeding&#xD;
&#xD;
          -  Known allergy or hypersensitivity to human gonadotrophins preparations&#xD;
&#xD;
          -  Known or current substance abuse&#xD;
&#xD;
          -  Previous participation in this study or simultaneous participation in another clinical&#xD;
             trial&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Responsible</last_name>
    <role>Study Director</role>
    <affiliation>Merck Serono International SA</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Royal University Hospital</name>
      <address>
        <city>Saskatoon</city>
        <state>Saskatchewan</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>February 2014</verification_date>
  <study_first_submitted>November 23, 2012</study_first_submitted>
  <study_first_submitted_qc>November 27, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 28, 2012</study_first_posted>
  <last_update_submitted>February 3, 2014</last_update_submitted>
  <last_update_submitted_qc>February 3, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 4, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Infertility</keyword>
  <keyword>Ovulation induction</keyword>
  <keyword>Recombinant human Luteinizing Hormone (r-hLH)</keyword>
  <keyword>Urinary human Chorionic Gonadotrophin (u-hCG)</keyword>
  <keyword>Recombinant human Follicle Stimulating Hormone (Gonal-f®)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infertility</mesh_term>
  </condition_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/NCT01735422
org study id: 21321
nct id: NCT01735422
lead sponsor: 
has dmc: No
This is a single center, open-label, randomized, parallel group, dose finding study to
      evaluate safety and efficacy of recombinant human luteinizing hormone (r-hLH, LHadi®),
      compared with urinary human chorionic gonadotrophin (u-hCG, Profasi®), both given
      subcutaneously, in inducing ovulation in infertile women undergoing stimulation of follicular
      growth with recombinant human follicle stimulating hormone (r-hFSH, Gonal-F®).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Ovulation rate
time frame: Day 4 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
measure: Ratio of ruptured follicles per follicle with diameter greater than or equal to (>=) 15 millimeter (mm)
time frame: Day 4 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
measure: Number of follicles with diameter greater than or equal to (>=) 11 millimeter (mm)
time frame: Day 4 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
measure: Ratio of ruptured follicles per follicle with diameter greater than or equal to (>=) 11 millimeter (mm)
time frame: Day 4 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
measure: Percentage of participants with mono-follicular ovulation
time frame: Day 4 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
measure: Number of participants with biochemical pregnancy
time frame: Day 25-30 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
measure: Serum estradiol (E2) levels
time frame: Day 1, 2 and 6-9 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
measure: Serum androstenedione levels
time frame: Day 1, 2 and 6-9 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
measure: Serum total renin levels
time frame: Day 1, 2 and 6-9 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
measure: Serum vascular endothelial growth factor (VEGF) levels
time frame: Day 1, 2 and 6-9 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
measure: Endometrial thickness
time frame: Day 0, 1, 2, 3, 4 and 6-9 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
measure: Number of participants with clinical pregnancy
time frame: Day 25-30 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
measure: Serum progesterone (P4) levels
time frame: Day 1, 2 and 6-9 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
arm group label: r-hLH (825 International Units [IU])
arm group type: Experimental
arm group label: r-hLH (2750 IU)
arm group type: Experimental
arm group label: r-hLH (5500 IU)
arm group type: Experimental
arm group label: r-hLH (11000 IU)
arm group type: Experimental
arm group label: r-hLH (22000 IU)
arm group type: Experimental
arm group label: u-hCG (5000 IU)
arm group type: Active Comparator
intervention type: Drug
intervention name: r-hFSH
description: Daily r-hFSH treatment will be administered subcutaneously at a starting dose according to the site's standard practice from Day 3-5 of menstrual cycle up to follicular development or 28 days. Dose can be altered according to ovarian response (reduced to 75 IU/day; increased to 225 IU/day).
arm group label: r-hLH (11000 IU)
arm group label: r-hLH (22000 IU)
arm group label: r-hLH (2750 IU)
arm group label: r-hLH (5500 IU)
arm group label: r-hLH (825 International Units [IU])
arm group label: u-hCG (5000 IU)
other name: Gonal-f®
intervention type: Drug
intervention name: r-hLH
description: Ovulation triggering will be performed using a single injection of r-hLH injection subcutaneously at a dose of 825 or 2750 or 5500 or 11,000 or 22,000 IU as soon as follicles satisfy the criteria for follicular development, that is at least 1 follicle with diameter >= 18 mm, not more than 5 follicles with diameter >= 15 mm and with E2 levels less than 9000 picomoles per liter (pmol/L).
arm group label: r-hLH (11000 IU)
arm group label: r-hLH (22000 IU)
arm group label: r-hLH (2750 IU)
arm group label: r-hLH (5500 IU)
arm group label: r-hLH (825 International Units [IU])
other name: LHadi®
intervention type: Drug
intervention name: u-hCG
description: Ovulation triggering will be performed using a single injection of 5000 IU of u-hCG as soon as follicles satisfy the criteria for follicular development, that is at least 1 follicle with diameter >= 18 mm, not more than 5 follicles with diameter >= 15 mm and with E2 levels less than 9000 picomoles per liter (pmol/L).
arm group label: u-hCG (5000 IU)
criteria: 
gender: Female
minimum age: 20 Years
maximum age: 40 Years
healthy volunteers: No
last name: Medical Responsible
role: Study Director
affiliation: Merck Serono International SA
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Infertility