<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/NCT01709331</url>
  </required_header>
  <id_info>
    <org_study_id>P07937</org_study_id>
    <secondary_id>2012-001258-25</secondary_id>
    <secondary_id>MK-8962-031</secondary_id>
    <nct_id>NCT01709331</nct_id>
  </id_info>
  <brief_title>A Study of the Efficacy and Safety of Corifollitropin Alfa (MK-8962) in Combination With Human Chorionic Gonadotropin (hCG) in Adult Men With Hypogonadotropic Hypogonadism (HH) (P07937)</brief_title>
  <official_title>A Phase III, Multi-center, Open Label, Uncontrolled Trial to Investigate the Efficacy and Safety of MK-8962 (Corifollitropin Alfa) in Combination With Human Chorionic Gonadotropin (hCG) in Inducing Increased Testicular Volume and Spermatogenesis in Adult Men With Hypogonadotropic Hypogonadism Who Remain Azoospermic When Treated With hCG Alone (Phase III; Protocol No. MK-8962-031-00 [Also Known as SCH 900962, P07937])</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Organon and Co</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Organon and Co</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will assess if corifollitropin alfa (MK-8962), when administered in combination&#xD;
      with human chorionic gonadotropin (hCG), will increase testicular volume in men with HH who&#xD;
      remain azoospermic after treatment with hCG alone.&#xD;
&#xD;
      Hypothesis: The lower limit of the 95% confidence interval for the geometric mean increase in&#xD;
      testicular volume from Day 1 to Week 52 is greater than one.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 11, 2013</start_date>
  <completion_date type="Actual">April 8, 2015</completion_date>
  <primary_completion_date type="Actual">April 8, 2015</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in Log-Transformed Testicular Volume at Week 52</measure>
    <time_frame>Baseline and Week 52</time_frame>
    <description>Participants underwent testicular ultrasound in the pretreatment phase at Weeks -16, -8, -1; and during the combined treatment phase at Baseline (predose, Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52. The testicular volume was measured as the sum of volumes of left and right testes. The mean change from Day 1 in log-transformed testicular volume was analyzed using a mixed model with a fixed effect for time point and a random effect for the participant. For each time point, the mean change from Day 1 to that time point and the associated 95% confidence interval (CI) was calculated. The geometric mean fold change in testicular volume and its 95% CI was obtained by exponentiation.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Participants With Anti-Corifollitropin Alfa Antibodies</measure>
    <time_frame>Up to Week 57</time_frame>
    <description>Blood samples were collected for assessment of anti-corifollitropin alfa antibodies in the pretreatment phase at Week -16 and Week -1; during the combined treatment phase at Weeks 4, 16, 28, 50, 52; and at the post-treatment follow-up visit, which could occur from Week 53 up to Week 57.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Induced Spermatogenesis Resulting in a Sperm Count ≥1x10^6/mL at or Before Week 52</measure>
    <time_frame>Up to Week 52</time_frame>
    <description>Semen samples were produced by masturbation after at least 48 hours of sexual abstinence and collected for evaluation in the pretreatment phase at Week -1, and during the combined treatment phase at Weeks 16, 28, 40, and 52.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Hypogonadism</condition>
  <condition>Hypogonadotropic Hypogonadism</condition>
  <arm_group>
    <arm_group_label>Corifollitropin alfa 150 μg + hCG</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>During a 16-week pretreatment phase, participants will receive twice-weekly subcutaneous (SC) injections of hCG 1500 or 3000 international units (IU). Eligible participants will then be enrolled in the combined treatment phase in which they will receive a single dose of corifollitropin alfa 150 μg by SC injection once every 2 weeks for 52 weeks. In addition, eligible participants will continue to receive twice-weekly hCG injections on the same schedule as the pretreatment phase.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Corifollitropin alfa</intervention_name>
    <description>Corifollitropin alfa 150 μg by SC injection, once every 2 weeks for 52 weeks</description>
    <arm_group_label>Corifollitropin alfa 150 μg + hCG</arm_group_label>
    <other_name>MK-8962</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>hCG</intervention_name>
    <description>hCG 1500 or 3000 IU by SC injection twice a week; administered alone for 16 weeks (pre-treatment phase) and then in combination with corifollitropin alfa for 52 weeks (combined treatment phase)</description>
    <arm_group_label>Corifollitropin alfa 150 μg + hCG</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosed with hypogonadotropic hypogonadism, either congenital or acquired&#xD;
&#xD;
          -  Have low circulating levels of testosterone&#xD;
&#xD;
          -  Have low circulating levels of gonadotropins (follicle stimulating hormone [FSH];&#xD;
             luteinizing hormone)&#xD;
&#xD;
          -  Presence of both scrotal testes&#xD;
&#xD;
          -  Have azoospermia (no measurable level of sperm)&#xD;
&#xD;
          -  Adequate replacement of other pituitary hormones&#xD;
&#xD;
          -  Good general physical and mental health&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Primary hypogonadism, such as Klinefelter's syndrome&#xD;
&#xD;
          -  History of unilateral or bilateral cryptorchidism (maldescended testes)&#xD;
&#xD;
          -  History or presence of testicular pathology of clinical importance (e.g.,&#xD;
             epididymitis, orchitis, testicular torsion, varicocele stage III, testicular atrophy,&#xD;
             occlusive azoospermia, etc), and/or vasectomy&#xD;
&#xD;
          -  Treated with FSH, hCG or gonadotropin-releasing hormone (GnRH) within previous 3&#xD;
             months or for more than 1 month within previous 6 months&#xD;
&#xD;
          -  Proven spermatogenesis with hCG treatment alone&#xD;
&#xD;
          -  Previous unsuccessful attempt with hCG in combination with human menopausal&#xD;
             gonadotropin (hMG)/FSH to achieve spermatogenesis&#xD;
&#xD;
          -  Required a dose of hCG of more than 6000 international units (IU) per week in a&#xD;
             previous attempt to normalize T levels&#xD;
&#xD;
          -  Untreated pituitary or hypothalamic tumor, or inadequately treated pituitary or&#xD;
             hypothalamic tumor that is likely to progress during the study&#xD;
&#xD;
          -  History or presence (known or suspected) of testicular, prostatic or breast cancer&#xD;
&#xD;
          -  Prostate pathology of clinical importance&#xD;
&#xD;
          -  Past or present oncologic treatment (chemo/radiotherapy)&#xD;
&#xD;
          -  Diabetes mellitus&#xD;
&#xD;
          -  Clinically significant, untreated hyperprolactinaemia&#xD;
&#xD;
          -  Uncontrolled non-gonadal endocrinopathies (thyroid, adrenal, pituitary disorders)&#xD;
&#xD;
          -  Tested positive for Human Immunodeficiency Virus (HIV), Hepatitis B or Hepatitis C&#xD;
&#xD;
          -  User of recreational or illicit drugs or has had a recent history (within the past&#xD;
             year) of drug abuse or dependence, or increased alcohol consumption&#xD;
&#xD;
          -  Allergy/sensitivity to gonadotropins or its/their excipients&#xD;
&#xD;
          -  Has received within previous 1 month or plans to use: Hormonal preparations other than&#xD;
             the study medication, drugs that are known to impair testicular function, agents known&#xD;
             to affect sex hormone secretion and/or drugs that are known or suspected to be&#xD;
             teratogenic&#xD;
&#xD;
          -  Used any investigational drugs within three months or actively participating in&#xD;
             another study&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Merck Sharp &amp; Dohme LLC</affiliation>
  </overall_official>
  <removed_countries>
    <country>Australia</country>
    <country>Germany</country>
    <country>Italy</country>
    <country>Poland</country>
    <country>Spain</country>
    <country>United Kingdom</country>
  </removed_countries>
  <results_reference>
    <citation>Nieschlag E, Bouloux PG, Stegmann BJ, Shankar RR, Guan Y, Tzontcheva A, McCrary Sisk C, Behre HM. An open-label clinical trial to investigate the efficacy and safety of corifollitropin alfa combined with hCG in adult men with hypogonadotropic hypogonadism. Reprod Biol Endocrinol. 2017 Mar 7;15(1):17. doi: 10.1186/s12958-017-0232-y.</citation>
    <PMID>28270212</PMID>
  </results_reference>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>October 16, 2012</study_first_submitted>
  <study_first_submitted_qc>October 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 18, 2012</study_first_posted>
  <results_first_submitted>April 4, 2016</results_first_submitted>
  <results_first_submitted_qc>April 4, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">May 9, 2016</results_first_posted>
  <last_update_submitted>February 1, 2022</last_update_submitted>
  <last_update_submitted_qc>February 1, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 3, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypogonadism</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf</ipd_description>
    <ipd_url>http://engagezone.msd.com/ds_documentation.php</ipd_url>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Twenty-three participants entered the 16-week pretreatment phase with hCG. At the end of the pretreatment phase, 18 participants were enrolled in the 52-week combined treatment phase.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Corifollitropin Alfa 150 μg + hCG</title>
          <description>During a 16-week pretreatment phase, participants received twice-weekly subcutaneous (SC) injections of human chorionic gonadotropin (hCG) 1500 or 3000 IU. Eligible participants were then enrolled in the combined treatment phase in which they received a single dose of corifollitropin alfa 150 μg by SC injection once every 2 weeks for 52 weeks. In addition, eligible participants continued to receive twice-weekly hCG injections on the same schedule begun during the pretreatment phase.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>All participants enrolled in the combined treatment phase</population>
      <group_list>
        <group group_id="B1">
          <title>Corifollitropin Alfa 150 μg + hCG</title>
          <description>During a 16-week pretreatment phase, participants received twice-weekly SC injections of hCG 1500 or 3000 IU. Eligible participants were then enrolled in the combined treatment phase in which they received a single dose of corifollitropin alfa 150 μg by SC injection once every 2 weeks for 52 weeks. In addition, eligible participants continued to receive twice-weekly hCG injections on the same schedule begun during the pretreatment phase.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="18"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="31.5" spread="8.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Log-Transformed Testicular Volume at Week 52</title>
        <description>Participants underwent testicular ultrasound in the pretreatment phase at Weeks -16, -8, -1; and during the combined treatment phase at Baseline (predose, Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52. The testicular volume was measured as the sum of volumes of left and right testes. The mean change from Day 1 in log-transformed testicular volume was analyzed using a mixed model with a fixed effect for time point and a random effect for the participant. For each time point, the mean change from Day 1 to that time point and the associated 95% confidence interval (CI) was calculated. The geometric mean fold change in testicular volume and its 95% CI was obtained by exponentiation.</description>
        <time_frame>Baseline and Week 52</time_frame>
        <population>Full Analysis Set (FAS) population, which consisted of all participants who received any dose of corifollitropin alfa and who had a baseline and at least one post-baseline measurement of testicular volume.</population>
        <group_list>
          <group group_id="O1">
            <title>Corifollitropin Alfa 150 μg + hCG</title>
            <description>During a 16-week pretreatment phase, participants received twice-weekly SC injections of hCG 1500 or 3000 IU. Eligible participants were then enrolled in the combined treatment phase in which they received a single dose of corifollitropin alfa 150 μg by SC injection once every 2 weeks for 52 weeks. In addition, eligible participants continued to receive twice-weekly hCG injections on the same schedule begun during the pretreatment phase.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Log-Transformed Testicular Volume at Week 52</title>
          <description>Participants underwent testicular ultrasound in the pretreatment phase at Weeks -16, -8, -1; and during the combined treatment phase at Baseline (predose, Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52. The testicular volume was measured as the sum of volumes of left and right testes. The mean change from Day 1 in log-transformed testicular volume was analyzed using a mixed model with a fixed effect for time point and a random effect for the participant. For each time point, the mean change from Day 1 to that time point and the associated 95% confidence interval (CI) was calculated. The geometric mean fold change in testicular volume and its 95% CI was obtained by exponentiation.</description>
          <population>Full Analysis Set (FAS) population, which consisted of all participants who received any dose of corifollitropin alfa and who had a baseline and at least one post-baseline measurement of testicular volume.</population>
          <units>Fold change</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.3" lower_limit="2.03" upper_limit="2.62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants With Anti-Corifollitropin Alfa Antibodies</title>
        <description>Blood samples were collected for assessment of anti-corifollitropin alfa antibodies in the pretreatment phase at Week -16 and Week -1; during the combined treatment phase at Weeks 4, 16, 28, 50, 52; and at the post-treatment follow-up visit, which could occur from Week 53 up to Week 57.</description>
        <time_frame>Up to Week 57</time_frame>
        <population>All-Subjects-as-Treated (ASaT) population, which consisted of all participants who received any dose of corifollitropin alfa.</population>
        <group_list>
          <group group_id="O1">
            <title>Corifollitropin Alfa 150 μg + hCG</title>
            <description>During a 16-week pretreatment phase, participants received twice-weekly SC injections of hCG 1500 or 3000 IU. Eligible participants were then enrolled in the combined treatment phase in which they received a single dose of corifollitropin alfa 150 μg by SC injection once every 2 weeks for 52 weeks. In addition, eligible participants continued to receive twice-weekly hCG injections on the same schedule begun during the pretreatment phase.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Anti-Corifollitropin Alfa Antibodies</title>
          <description>Blood samples were collected for assessment of anti-corifollitropin alfa antibodies in the pretreatment phase at Week -16 and Week -1; during the combined treatment phase at Weeks 4, 16, 28, 50, 52; and at the post-treatment follow-up visit, which could occur from Week 53 up to Week 57.</description>
          <population>All-Subjects-as-Treated (ASaT) population, which consisted of all participants who received any dose of corifollitropin alfa.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="52.4" upper_limit="93.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Induced Spermatogenesis Resulting in a Sperm Count ≥1x10^6/mL at or Before Week 52</title>
        <description>Semen samples were produced by masturbation after at least 48 hours of sexual abstinence and collected for evaluation in the pretreatment phase at Week -1, and during the combined treatment phase at Weeks 16, 28, 40, and 52.</description>
        <time_frame>Up to Week 52</time_frame>
        <population>FAS population, which consisted of all participants who received any dose of corifollitropin alfa and who had a baseline and at least one post-baseline measurement of testicular volume.</population>
        <group_list>
          <group group_id="O1">
            <title>Corifollitropin Alfa 150 μg + hCG</title>
            <description>During a 16-week pretreatment phase, participants received twice-weekly SC injections of hCG 1500 or 3000 IU. Eligible participants were then enrolled in the combined treatment phase in which they received a single dose of corifollitropin alfa 150 μg by SC injection once every 2 weeks for 52 weeks. In addition, eligible participants continued to receive twice-weekly hCG injections on the same schedule begun during the pretreatment phase.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Induced Spermatogenesis Resulting in a Sperm Count ≥1x10^6/mL at or Before Week 52</title>
          <description>Semen samples were produced by masturbation after at least 48 hours of sexual abstinence and collected for evaluation in the pretreatment phase at Week -1, and during the combined treatment phase at Weeks 16, 28, 40, and 52.</description>
          <population>FAS population, which consisted of all participants who received any dose of corifollitropin alfa and who had a baseline and at least one post-baseline measurement of testicular volume.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="77.8" lower_limit="52.4" upper_limit="93.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to Week 57</time_frame>
      <desc>The Safety Analysis was based on the ASaT population, which consisted of all participants who received any dose of corifollitropin alfa.</desc>
      <group_list>
        <group group_id="E1">
          <title>Corifollitropin Alfa 150 μg + hCG</title>
          <description>During a 16-week pretreatment phase, participants received twice-weekly SC injections of hCG 1500 or 3000 IU. Eligible participants were then enrolled in the combined treatment phase in which they received a single dose of corifollitropin alfa 150 μg by SC injection once every 2 weeks for 52 weeks. In addition, eligible participants continued to receive twice-weekly hCG injections on the same schedule begun during the pretreatment phase.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 18.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Haemorrhoids</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Seasonal allergy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood pressure increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Blood testosterone increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Oestradiol increased</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Testicular scan abnormal</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Blood testosterone decreased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Breast tenderness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Acne</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Flushing</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The investigator further agrees to provide to the sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication (including, without limitation, slides and texts of oral or other public presentations and texts of any transmission through any electronic media, e.g., any computer access system such as the Internet, World Wide Web, etc) that report any results of the trial.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Senior Vice President, Global Clinical Development</name_or_title>
      <organization>Merck Sharp &amp; Dohme Corp.</organization>
      <phone>1-800-672-6372</phone>
      <email>ClinicalTrialsDisclosure@merck.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01709331
org study id: P07937
secondary id: 2012-001258-25
secondary id: MK-8962-031
nct id: NCT01709331
lead sponsor: 
has dmc: No
This study will assess if corifollitropin alfa (MK-8962), when administered in combination
      with human chorionic gonadotropin (hCG), will increase testicular volume in men with HH who
      remain azoospermic after treatment with hCG alone.

      Hypothesis: The lower limit of the 95% confidence interval for the geometric mean increase in
      testicular volume from Day 1 to Week 52 is greater than one.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change From Baseline in Log-Transformed Testicular Volume at Week 52
time frame: Baseline and Week 52
description: Participants underwent testicular ultrasound in the pretreatment phase at Weeks -16, -8, -1; and during the combined treatment phase at Baseline (predose, Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52. The testicular volume was measured as the sum of volumes of left and right testes. The mean change from Day 1 in log-transformed testicular volume was analyzed using a mixed model with a fixed effect for time point and a random effect for the participant. For each time point, the mean change from Day 1 to that time point and the associated 95% confidence interval (CI) was calculated. The geometric mean fold change in testicular volume and its 95% CI was obtained by exponentiation.
measure: Percentage of Participants With Anti-Corifollitropin Alfa Antibodies
time frame: Up to Week 57
description: Blood samples were collected for assessment of anti-corifollitropin alfa antibodies in the pretreatment phase at Week -16 and Week -1; during the combined treatment phase at Weeks 4, 16, 28, 50, 52; and at the post-treatment follow-up visit, which could occur from Week 53 up to Week 57.
measure: Percentage of Participants With Induced Spermatogenesis Resulting in a Sperm Count ≥1x10^6/mL at or Before Week 52
time frame: Up to Week 52
description: Semen samples were produced by masturbation after at least 48 hours of sexual abstinence and collected for evaluation in the pretreatment phase at Week -1, and during the combined treatment phase at Weeks 16, 28, 40, and 52.
arm group label: Corifollitropin alfa 150 μg + hCG
arm group type: Experimental
description: During a 16-week pretreatment phase, participants will receive twice-weekly subcutaneous (SC) injections of hCG 1500 or 3000 international units (IU). Eligible participants will then be enrolled in the combined treatment phase in which they will receive a single dose of corifollitropin alfa 150 μg by SC injection once every 2 weeks for 52 weeks. In addition, eligible participants will continue to receive twice-weekly hCG injections on the same schedule as the pretreatment phase.
intervention type: Drug
intervention name: Corifollitropin alfa
description: Corifollitropin alfa 150 μg by SC injection, once every 2 weeks for 52 weeks
arm group label: Corifollitropin alfa 150 μg + hCG
other name: MK-8962
intervention type: Drug
intervention name: hCG
description: hCG 1500 or 3000 IU by SC injection twice a week; administered alone for 16 weeks (pre-treatment phase) and then in combination with corifollitropin alfa for 52 weeks (combined treatment phase)
arm group label: Corifollitropin alfa 150 μg + hCG
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: No
last name: Medical Director
role: Study Director
affiliation: Merck Sharp & Dohme LLC
country: Australia
country: Germany
country: Italy
country: Poland
country: Spain
country: United Kingdom
citation: Nieschlag E, Bouloux PG, Stegmann BJ, Shankar RR, Guan Y, Tzontcheva A, McCrary Sisk C, Behre HM. An open-label clinical trial to investigate the efficacy and safety of corifollitropin alfa combined with hCG in adult men with hypogonadotropic hypogonadism. Reprod Biol Endocrinol. 2017 Mar 7;15(1):17. doi: 10.1186/s12958-017-0232-y.
PMID: 28270212
responsible party type: Sponsor
mesh term: Hypogonadism
sharing ipd: Yes
ipd description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
ipd url: http://engagezone.msd.com/ds_documentation.php
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 