<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/NCT04417972</url>
  </required_header>
  <id_info>
    <org_study_id>SHR7280-102</org_study_id>
    <nct_id>NCT04417972</nct_id>
  </id_info>
  <brief_title>The Pharmacokinetic(PK)/Pharmacodynamics(PD) Study of SHR7280 Tablets in Premenopausal Subjects With Endometriosis.</brief_title>
  <official_title>A Phase I/II, Randomized, Double-Blind, Placebo-Controlled, Multiple-Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics ,Pharmacodynamics and Efficacy of SHR7280 Tablets in Premenopausal Subjects With Endometriosis.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jiangsu HengRui Medicine Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Jiangsu HengRui Medicine Co., Ltd.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this study is to assess the safety, tolerability, pharmacokinetics&#xD;
      and pharmacodynamics of SHR7280 tablets in premenopausal subjects with endometriosis. In&#xD;
      addition, this study will provide information on efficacy of SHR7280 tablets in premenopausal&#xD;
      subjects with endometriosis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Endometriosis is a common disease, aﬀecting 5-10% of women of reproductive age . It is an&#xD;
      estrogen-dependent and estrogen-driven disease and so hormonal manipulation and suppression&#xD;
      of estrogen production form the basis of the majority of medical treatment. The primary&#xD;
      objective of this study is to assess the safety, tolerability, pharmacokinetics and&#xD;
      pharmacodynamics of SHR7280 tablets in premenopausal subjects with endometriosis. In&#xD;
      addition, this study will provide information on efficacy of SHR7280 tablets in premenopausal&#xD;
      subjects with endometriosis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 30, 2020</start_date>
  <completion_date type="Anticipated">January 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">January 30, 2024</primary_completion_date>
  <phase>Phase 1/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>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants with Adverse events</measure>
    <time_frame>Pre-dose to 28±2 days after dose administration</time_frame>
    <description>Phase I</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in the 7-day mean score for pelvic pain as measured by VAS at weeks 12</measure>
    <time_frame>Baseline and weeks 12</time_frame>
    <description>Phase II daily assessment of dysmenorrhea score on a 4-point scale (0 = none, 1 = mild, 2 = moderate, 3 = severe) using an e-Diary.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>PK markers of SHR7280: area under the plasma concentration versus time curve (AUC)</measure>
    <time_frame>At pre-defined intervals from initial dose through final study visit</time_frame>
    <description>Phase I &amp; II</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK markers of SHR7280: time to maximum plasma concentration(Tmax)</measure>
    <time_frame>At pre-defined intervals from initial dose through final study visit</time_frame>
    <description>Phase I &amp; II</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK markers of SHR7280: maximum plasma concentration(Cmax)</measure>
    <time_frame>At pre-defined intervals from initial dose through final study visit</time_frame>
    <description>Phase I &amp; II</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK markers of SHR7280: half-time(t1/2)</measure>
    <time_frame>At pre-defined intervals from initial dose through final study visit</time_frame>
    <description>Phase I &amp; II</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK markers of SHR7280: apparent clearance(CL/F)</measure>
    <time_frame>At pre-defined intervals from initial dose through final study visit</time_frame>
    <description>Phase I &amp; II</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK markers of SHR7280: apparent volume of distribution(Vz/F)</measure>
    <time_frame>At pre-defined intervals from initial dose through final study visit</time_frame>
    <description>Phase I &amp; II</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PD markers of SHR7280: Concentration of Estradiol(E2)</measure>
    <time_frame>At pre-defined intervals from initial dose through final study visit</time_frame>
    <description>Phase I &amp; II</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PD markers of SHR7280: Concentration of Progesterone(P)</measure>
    <time_frame>At pre-defined intervals from initial dose through final study visit</time_frame>
    <description>Phase I &amp; II</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PD markers of SHR7280: Concentration of Follicle stimulating hormone(FSH)</measure>
    <time_frame>At pre-defined intervals from initial dose through final study visit</time_frame>
    <description>Phase I &amp; II</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PD markers of SHR7280: Concentration of Luteinizing hormone(LH)</measure>
    <time_frame>At pre-defined intervals from initial dose through final study visit</time_frame>
    <description>Phase I &amp; II</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the 7-day mean score for pelvic pain as measured by VAS</measure>
    <time_frame>Baseline and weeks 4、8</time_frame>
    <description>Phase II</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the Monthly Mean score for pelvic pain as measured by VAS</measure>
    <time_frame>Baseline and weeks 4、8、12</time_frame>
    <description>Phase II</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the Monthly Mean Dysmenorrhea Score</measure>
    <time_frame>Baseline and weeks 8、12</time_frame>
    <description>Phase II</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the Monthly Mean Non-menstrual Pelvic Pain Score and Dyspareunia Score</measure>
    <time_frame>Baseline and weeks 4、8、12</time_frame>
    <description>Phase II</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline to monthly analgesic use to treat endometriosis-associated pain</measure>
    <time_frame>Baseline and weeks 4、8、12</time_frame>
    <description>Phase II</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient Global Impression of Change (PGIC) score at week 12</measure>
    <time_frame>Week 12</time_frame>
    <description>Phase II</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>during Pre and 28±3 days after dose administration</time_frame>
  </secondary_outcome>
  <number_of_arms>7</number_of_arms>
  <enrollment type="Anticipated">207</enrollment>
  <condition>Endometriosis</condition>
  <arm_group>
    <arm_group_label>SHR7280 dose 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>oral administration for 21days,Phase I</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SHR7280 dose 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>oral administration for 21days,Phase I</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SHR7280 dose 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>oral administration for 21days,Phase I</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SHR7280 dose 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>oral administration for 21days,Phase I</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SHR7280 low dose</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>oral administration for 84days,Phase II</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SHR7280 high dose</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>oral administration for 84days, Phase II</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>oral administration for 84days, Phase II</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SHR7280</intervention_name>
    <description>treatment</description>
    <arm_group_label>SHR7280 dose 1</arm_group_label>
    <arm_group_label>SHR7280 dose 2</arm_group_label>
    <arm_group_label>SHR7280 dose 3</arm_group_label>
    <arm_group_label>SHR7280 dose 4</arm_group_label>
    <arm_group_label>SHR7280 high dose</arm_group_label>
    <arm_group_label>SHR7280 low dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo oral tablet</intervention_name>
    <description>blank control</description>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>SHR7280 dose 1</arm_group_label>
    <arm_group_label>SHR7280 dose 2</arm_group_label>
    <arm_group_label>SHR7280 dose 3</arm_group_label>
    <arm_group_label>SHR7280 dose 4</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Phase I/II&#xD;
&#xD;
          1. premenopausal females, aged 18-45&#xD;
&#xD;
          2. History of regular menstrual cycles&#xD;
&#xD;
          3. Endometriosis participant diagnosed by surgical (e.g., laparoscopy or laparotomy) or&#xD;
             by magnetic resonance imaging or ultrasonography.&#xD;
&#xD;
          4. Participant must agree to use only protocol specified rescue analgesics during the&#xD;
             Screening and Treatment Periods for endometriosis-associated pain.&#xD;
&#xD;
          5. Participant in general good health. No clinically significant findings in laboratory&#xD;
             parameters or clinically significant abnormality on X-ray Phase I (only) Participant&#xD;
             has mild or moderate pelvic pain associated with endometriosis at Screening.&#xD;
&#xD;
        Phase II(only) Participant has moderate or severe pelvic pain associated with endometriosis&#xD;
        at Screening.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Phase I/II&#xD;
&#xD;
          1. Subjects with severe trauma or surgery within 6 months prior to the screening；&#xD;
&#xD;
          2. Known blood donation within 30 days pre-dose; donating≥200 ml of blood 2 months&#xD;
             pre-dose;&#xD;
&#xD;
          3. Pregnant or Serum β-human chorionic gonadotropin (hCG)&gt; 5 Million International&#xD;
             Units(mIU)/mL at screening or baseline&#xD;
&#xD;
          4. Pregnant or breast feeding ;&#xD;
&#xD;
          5. Have pelvic pain that is not caused by endometriosis&#xD;
&#xD;
          6. Abnormal uterine bleeding&#xD;
&#xD;
          7. Are currently receiving gonadotropin-releasing hormone (GnRH) agonist, a GnRH&#xD;
             antagonist or danazol or have received any of these agents within 6 months of the&#xD;
             start of screening.&#xD;
&#xD;
          8. Are currently receiving subcutaneous medroxyprogesterone acetate (DMPA-SC) or&#xD;
             intramuscular medroxyprogesterone acetate (DMPA-IM) or have received any of these&#xD;
             agents within 3 months of the start of screening.&#xD;
&#xD;
          9. Are currently using hormonal contraception or other forms of hormonal therapy or&#xD;
             received such treatment within 2 months of the start of screening.&#xD;
&#xD;
        Phase I (only) one month prior to screening involved in any drug or medical device clinical&#xD;
        subjects, or within 5 half-life of drugs before screening; Phase II (only) Screening&#xD;
        dual-energy x-ray absorptiometry (DXA) scan results of the lumbar spine, femoral neck, or&#xD;
        total hip bone mineral density corresponding to 1.5 or more standard deviations below&#xD;
        normal (T-score at or below -1.5)&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hongyan Guo, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Peking University Third Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Zhenyi Zhu, M.D</last_name>
    <phone>+86 0518-82342973</phone>
    <email>zhenyi.zhu@hengrui.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Peking University Third Hospital</name>
      <address>
        <city>Peking</city>
        <state>Beijing</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hongyan Guo, PhD</last_name>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>May 21, 2020</study_first_submitted>
  <study_first_submitted_qc>June 2, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 5, 2020</study_first_posted>
  <last_update_submitted>December 19, 2022</last_update_submitted>
  <last_update_submitted_qc>December 19, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 22, 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>Endometriosis</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/NCT04417972
org study id: SHR7280-102
nct id: NCT04417972
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The primary objective of this study is to assess the safety, tolerability, pharmacokinetics
      and pharmacodynamics of SHR7280 tablets in premenopausal subjects with endometriosis. In
      addition, this study will provide information on efficacy of SHR7280 tablets in premenopausal
      subjects with endometriosis.
Endometriosis is a common disease, aﬀecting 5-10% of women of reproductive age . It is an
      estrogen-dependent and estrogen-driven disease and so hormonal manipulation and suppression
      of estrogen production form the basis of the majority of medical treatment. The primary
      objective of this study is to assess the safety, tolerability, pharmacokinetics and
      pharmacodynamics of SHR7280 tablets in premenopausal subjects with endometriosis. In
      addition, this study will provide information on efficacy of SHR7280 tablets in premenopausal
      subjects with endometriosis.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Number of Participants with Adverse events
time frame: Pre-dose to 28±2 days after dose administration
description: Phase I
measure: Change From Baseline in the 7-day mean score for pelvic pain as measured by VAS at weeks 12
time frame: Baseline and weeks 12
description: Phase II daily assessment of dysmenorrhea score on a 4-point scale (0 = none, 1 = mild, 2 = moderate, 3 = severe) using an e-Diary.
measure: PK markers of SHR7280: area under the plasma concentration versus time curve (AUC)
time frame: At pre-defined intervals from initial dose through final study visit
description: Phase I & II
measure: PK markers of SHR7280: time to maximum plasma concentration(Tmax)
time frame: At pre-defined intervals from initial dose through final study visit
description: Phase I & II
measure: PK markers of SHR7280: maximum plasma concentration(Cmax)
time frame: At pre-defined intervals from initial dose through final study visit
description: Phase I & II
measure: PK markers of SHR7280: half-time(t1/2)
time frame: At pre-defined intervals from initial dose through final study visit
description: Phase I & II
measure: PK markers of SHR7280: apparent clearance(CL/F)
time frame: At pre-defined intervals from initial dose through final study visit
description: Phase I & II
measure: PK markers of SHR7280: apparent volume of distribution(Vz/F)
time frame: At pre-defined intervals from initial dose through final study visit
description: Phase I & II
measure: PD markers of SHR7280: Concentration of Estradiol(E2)
time frame: At pre-defined intervals from initial dose through final study visit
description: Phase I & II
measure: PD markers of SHR7280: Concentration of Progesterone(P)
time frame: At pre-defined intervals from initial dose through final study visit
description: Phase I & II
measure: PD markers of SHR7280: Concentration of Follicle stimulating hormone(FSH)
time frame: At pre-defined intervals from initial dose through final study visit
description: Phase I & II
measure: PD markers of SHR7280: Concentration of Luteinizing hormone(LH)
time frame: At pre-defined intervals from initial dose through final study visit
description: Phase I & II
measure: Change From Baseline in the 7-day mean score for pelvic pain as measured by VAS
time frame: Baseline and weeks 4、8
description: Phase II
measure: Change From Baseline in the Monthly Mean score for pelvic pain as measured by VAS
time frame: Baseline and weeks 4、8、12
description: Phase II
measure: Change From Baseline in the Monthly Mean Dysmenorrhea Score
time frame: Baseline and weeks 8、12
description: Phase II
measure: Change From Baseline in the Monthly Mean Non-menstrual Pelvic Pain Score and Dyspareunia Score
time frame: Baseline and weeks 4、8、12
description: Phase II
measure: Change from baseline to monthly analgesic use to treat endometriosis-associated pain
time frame: Baseline and weeks 4、8、12
description: Phase II
measure: Patient Global Impression of Change (PGIC) score at week 12
time frame: Week 12
description: Phase II
measure: Adverse events
time frame: during Pre and 28±3 days after dose administration
arm group label: SHR7280 dose 1
arm group type: Experimental
description: oral administration for 21days,Phase I
arm group label: SHR7280 dose 2
arm group type: Experimental
description: oral administration for 21days,Phase I
arm group label: SHR7280 dose 3
arm group type: Experimental
description: oral administration for 21days,Phase I
arm group label: SHR7280 dose 4
arm group type: Experimental
description: oral administration for 21days,Phase I
arm group label: SHR7280 low dose
arm group type: Active Comparator
description: oral administration for 84days,Phase II
arm group label: SHR7280 high dose
arm group type: Active Comparator
description: oral administration for 84days, Phase II
arm group label: Placebo
arm group type: Placebo Comparator
description: oral administration for 84days, Phase II
intervention type: Drug
intervention name: SHR7280
description: treatment
arm group label: SHR7280 dose 1
arm group label: SHR7280 dose 2
arm group label: SHR7280 dose 3
arm group label: SHR7280 dose 4
arm group label: SHR7280 high dose
arm group label: SHR7280 low dose
intervention type: Drug
intervention name: Placebo oral tablet
description: blank control
arm group label: Placebo
arm group label: SHR7280 dose 1
arm group label: SHR7280 dose 2
arm group label: SHR7280 dose 3
arm group label: SHR7280 dose 4
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: No
last name: Hongyan Guo, PhD
role: Principal Investigator
affiliation: Peking University Third Hospital
last name: Zhenyi Zhu, M.D
phone: +86 0518-82342973
email: zhenyi.zhu@hengrui.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Endometriosis