<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/NCT01733459</url>
  </required_header>
  <id_info>
    <org_study_id>DLBS3233-0811</org_study_id>
    <nct_id>NCT01733459</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of DLBS3233 in Subjects With Polycystic Ovary Syndrome (PCOS)</brief_title>
  <official_title>The Role of DLBS3233 in the Management of Polycystic Ovary Syndrome (PCOS)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dexa Medica Group</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Dexa Medica Group</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a 2-arm, randomized, double-blind, double-dummy, and controlled clinical study, with&#xD;
      6 months of treatment to evaluate the clinical and metabolic efficacy of DLBS3233 in&#xD;
      improving reproductive parameters and to evaluate the safety of DLBS3233 in women with&#xD;
      polycystic ovary syndrome compared with metformin, as an active control.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      There will be 2 groups of treatment; each group will consist of 62 subjects with the&#xD;
      treatment regimens :&#xD;
&#xD;
        -  Treatment I : 1 capsule of DLBS3233 100 mg (once daily) and 1 placebo caplet of&#xD;
           Metformin XR (twice daily)&#xD;
&#xD;
        -  Treatment II : 1 caplet of Metformin XR 750 mg (twice daily) and 1 placebo capsule of&#xD;
           DLBS3233 (once daily) for 6 months of treatment.&#xD;
&#xD;
      Clinical examination to evaluate the efficacy of the investigational drug will be performed&#xD;
      at baseline and every interval of 1 month.&#xD;
&#xD;
      Laboratory examinations to evaluate the metabolic efficacy parameters and ultrasonography&#xD;
      (USG) examination will be performed at baseline, Month 3rd, and end of study (Month 6th). In&#xD;
      addition to that, USG will also be performed about 2 weeks after Month 3rd (Month 3.5th) and&#xD;
      after Month 5th (Month 5.5th).&#xD;
&#xD;
      Laboratory examinations to evaluate the reproductive efficacy parameters (reproductive&#xD;
      hormone levels) and safety, at baseline and Month 6th (end of study).&#xD;
&#xD;
      General counseling on lifestyle modification will be provided to the subjects by the assigned&#xD;
      Nutritionist. All study subjects should follow a lifestyle modification. Evaluation on&#xD;
      subjects' performance on lifestyle modification will be conducted every follow-up visit by&#xD;
      Investigator, but particularly at baseline, Month 3rd, and end of study (Month 6th) by the&#xD;
      Nutritionist.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>March 2013</start_date>
  <completion_date type="Actual">June 2018</completion_date>
  <primary_completion_date type="Actual">April 2018</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>HOMA-IR reduction</measure>
    <time_frame>6 months</time_frame>
    <description>HOMA-IR reduction from baseline to Month 6th (end of study)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Reduction of S/A ratio</measure>
    <time_frame>3 and 6 months</time_frame>
    <description>Reduction (indicating improvement) of S/A ratio (i.e. ratio of mean stromal echogenicity to mean echogenicity of entire ovary) from baseline to Month 3rd and Month 6th (end of study)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reduction of free testosterone level (calculated)</measure>
    <time_frame>6 months</time_frame>
    <description>Reduction of free testosterone level (calculated) from baseline to Month 6th (end of study)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of luteinizing hormone (LH) level</measure>
    <time_frame>6 months</time_frame>
    <description>Change of luteinizing hormone (LH) level from baseline to Month 6th (end of study)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of luteinizing hormone (LH) / follicle stimulating hormone (FSH) ratio</measure>
    <time_frame>6 months</time_frame>
    <description>Change of luteinizing hormone (LH) / follicle stimulating hormone (FSH) ratio from baseline to Month 6th (end of study)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of Ferriman-Gallwey Score</measure>
    <time_frame>3 and 6 months</time_frame>
    <description>Change of Ferriman-Gallwey Score from baseline to Month 3rd and Month 6th (end of study)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvement of glucose tolerance</measure>
    <time_frame>3 and 6 months</time_frame>
    <description>Improvement of glucose tolerance (reduction of FPG and 2-hour PPPG) from baseline to Month 3rd and Month 6th (end of study)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fasting insulin level reduction</measure>
    <time_frame>3 and 6 months</time_frame>
    <description>Fasting insulin level reduction from baseline to Month 3rd and Month 6th (end of study)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HOMA-IR reduction</measure>
    <time_frame>3 months</time_frame>
    <description>HOMA-IR reduction from baseline to Month 3rd</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lipid profile improvement</measure>
    <time_frame>3 and 6 months</time_frame>
    <description>Lipid profile improvement (total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides level) from baseline to Month 3rd and Month 6th (end of study)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Liver function</measure>
    <time_frame>6 months</time_frame>
    <description>Liver function (serum AST, ALT, alkaline phosphatase, γ-glutamyl transferase) from baseline to Month 6th (end of study)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Renal function</measure>
    <time_frame>6 months</time_frame>
    <description>Renal function (serum creatinine, BUN) from baseline to Month 6th (end of study)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of adverse events and subjects with events</measure>
    <time_frame>During 6 months</time_frame>
    <description>Adverse events as well as number of events and subjects experiencing the events will be observed and evaluated throughout study period (6 months) and until all adverse events have been recovered or stabilized</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">124</enrollment>
  <condition>Polycystic Ovary Syndrome (PCOS)</condition>
  <arm_group>
    <arm_group_label>Treatment I</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1 DLBS3233 capsule 100 mg (once daily) and 1 placebo caplet of Metformin XR (twice daily)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment II</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>1 Metformin XR caplet 750 mg (twice daily) and 1 placebo capsule of DLBS3233 (once daily)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>DLBS3233</intervention_name>
    <description>1 DLBS3233 capsule 100 mg once daily for 6 months</description>
    <arm_group_label>Treatment I</arm_group_label>
    <other_name>Inlacin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin XR</intervention_name>
    <description>1 Metformin XR caplet 750 mg twice daily for 6 months</description>
    <arm_group_label>Treatment II</arm_group_label>
    <other_name>Glumin XR</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo caplet of Metformin XR</intervention_name>
    <description>1 placebo caplet of Metformin XR twice daily for 6 months</description>
    <arm_group_label>Treatment I</arm_group_label>
    <other_name>Placebo caplet of Glumin XR</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo capsule of DLBS3233</intervention_name>
    <description>1 placebo capsule of DLBS3233 once daily for 6 months</description>
    <arm_group_label>Treatment II</arm_group_label>
    <other_name>Placebo capsule of Inlacin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Female subjects in reproductive age (i.e. 18-40 years)&#xD;
&#xD;
          -  Subject with a diagnosis of polycystic ovary syndrome confirmed by two of the&#xD;
             Rotterdam Criteria&#xD;
&#xD;
          -  Subject with insulin resistance defined by: HOMA-IR of &gt; 2.00&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant and lactating women&#xD;
&#xD;
          -  Subjects known to have Cushing's syndrome, late onset of congenital adrenal&#xD;
             hyperplasia, androgen-secreting tumors, uncontrolled thyroid disease,&#xD;
             hyperprolactinemia&#xD;
&#xD;
          -  Known to have current medical condition, which, is judged by the Investigator could&#xD;
             jeopardize subject's health or interfere with the study evaluation, such as diabetes&#xD;
             mellitus, uncontrolled hypertension, other cardiovascular diseases, acute or chronic&#xD;
             infections, and any known malignancies&#xD;
&#xD;
          -  Impaired renal function (serum creatinine level &gt; 1.5 ULN)&#xD;
&#xD;
          -  Impaired liver function (serum ALT level ≥ 2.5 ULN)&#xD;
&#xD;
          -  Medically-assisted weight loss with medications or surgical procedures&#xD;
&#xD;
          -  Currently having laparoscopic ovarian diathermy (LOD)&#xD;
&#xD;
          -  Currently under treatment with in vitro fertilization (IVF) techniques&#xD;
&#xD;
          -  Have been regularly taking any medications which affect insulin sensitivity as well as&#xD;
             reproductive function (i.e. ovulation, menstrual cycle), within ≤ 3 months prior to&#xD;
             screening&#xD;
&#xD;
          -  Participating in other clinical trial within 30 days prior to screening&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Andon Hestiantoro, dr., SpOG(K)</last_name>
    <role>Principal Investigator</role>
    <affiliation>Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Indonesia, dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Wiryawan Permadi, Dr., dr., SpOG(K)</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Obstetrics and Gynecology, Faculty of Medicine, University of Padjadjaran, Hasan Sadikin Hospital, Bandung, Indonesia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Obstetrics and Gynecology, Faculty of Medicine, University of Padjadjaran, Hasan Sadikin Hospital</name>
      <address>
        <city>Bandung</city>
        <state>West Java</state>
        <zip>40161</zip>
        <country>Indonesia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Indonesia, dr. Cipto Mangunkusumo Hospital</name>
      <address>
        <city>Jakarta</city>
        <zip>10430</zip>
        <country>Indonesia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Indonesia</country>
  </location_countries>
  <verification_date>July 2018</verification_date>
  <study_first_submitted>November 21, 2012</study_first_submitted>
  <study_first_submitted_qc>November 21, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 27, 2012</study_first_posted>
  <last_update_submitted>July 24, 2018</last_update_submitted>
  <last_update_submitted_qc>July 24, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">July 26, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>PCOS, DLBS3233, metformin,oral anti-hyperglycemic agent</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Polycystic Ovary Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metformin</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/NCT01733459
org study id: DLBS3233-0811
nct id: NCT01733459
lead sponsor: 
has dmc: No
This is a 2-arm, randomized, double-blind, double-dummy, and controlled clinical study, with
      6 months of treatment to evaluate the clinical and metabolic efficacy of DLBS3233 in
      improving reproductive parameters and to evaluate the safety of DLBS3233 in women with
      polycystic ovary syndrome compared with metformin, as an active control.
There will be 2 groups of treatment; each group will consist of 62 subjects with the
      treatment regimens :

        -  Treatment I : 1 capsule of DLBS3233 100 mg (once daily) and 1 placebo caplet of
           Metformin XR (twice daily)

        -  Treatment II : 1 caplet of Metformin XR 750 mg (twice daily) and 1 placebo capsule of
           DLBS3233 (once daily) for 6 months of treatment.

      Clinical examination to evaluate the efficacy of the investigational drug will be performed
      at baseline and every interval of 1 month.

      Laboratory examinations to evaluate the metabolic efficacy parameters and ultrasonography
      (USG) examination will be performed at baseline, Month 3rd, and end of study (Month 6th). In
      addition to that, USG will also be performed about 2 weeks after Month 3rd (Month 3.5th) and
      after Month 5th (Month 5.5th).

      Laboratory examinations to evaluate the reproductive efficacy parameters (reproductive
      hormone levels) and safety, at baseline and Month 6th (end of study).

      General counseling on lifestyle modification will be provided to the subjects by the assigned
      Nutritionist. All study subjects should follow a lifestyle modification. Evaluation on
      subjects' performance on lifestyle modification will be conducted every follow-up visit by
      Investigator, but particularly at baseline, Month 3rd, and end of study (Month 6th) by the
      Nutritionist.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: HOMA-IR reduction
time frame: 6 months
description: HOMA-IR reduction from baseline to Month 6th (end of study)
measure: Reduction of S/A ratio
time frame: 3 and 6 months
description: Reduction (indicating improvement) of S/A ratio (i.e. ratio of mean stromal echogenicity to mean echogenicity of entire ovary) from baseline to Month 3rd and Month 6th (end of study)
measure: Reduction of free testosterone level (calculated)
time frame: 6 months
description: Reduction of free testosterone level (calculated) from baseline to Month 6th (end of study)
measure: Change of luteinizing hormone (LH) level
time frame: 6 months
description: Change of luteinizing hormone (LH) level from baseline to Month 6th (end of study)
measure: Change of luteinizing hormone (LH) / follicle stimulating hormone (FSH) ratio
time frame: 6 months
description: Change of luteinizing hormone (LH) / follicle stimulating hormone (FSH) ratio from baseline to Month 6th (end of study)
measure: Change of Ferriman-Gallwey Score
time frame: 3 and 6 months
description: Change of Ferriman-Gallwey Score from baseline to Month 3rd and Month 6th (end of study)
measure: Improvement of glucose tolerance
time frame: 3 and 6 months
description: Improvement of glucose tolerance (reduction of FPG and 2-hour PPPG) from baseline to Month 3rd and Month 6th (end of study)
measure: Fasting insulin level reduction
time frame: 3 and 6 months
description: Fasting insulin level reduction from baseline to Month 3rd and Month 6th (end of study)
measure: HOMA-IR reduction
time frame: 3 months
description: HOMA-IR reduction from baseline to Month 3rd
measure: Lipid profile improvement
time frame: 3 and 6 months
description: Lipid profile improvement (total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides level) from baseline to Month 3rd and Month 6th (end of study)
measure: Liver function
time frame: 6 months
description: Liver function (serum AST, ALT, alkaline phosphatase, γ-glutamyl transferase) from baseline to Month 6th (end of study)
measure: Renal function
time frame: 6 months
description: Renal function (serum creatinine, BUN) from baseline to Month 6th (end of study)
measure: Number of adverse events and subjects with events
time frame: During 6 months
description: Adverse events as well as number of events and subjects experiencing the events will be observed and evaluated throughout study period (6 months) and until all adverse events have been recovered or stabilized
arm group label: Treatment I
arm group type: Experimental
description: 1 DLBS3233 capsule 100 mg (once daily) and 1 placebo caplet of Metformin XR (twice daily)
arm group label: Treatment II
arm group type: Active Comparator
description: 1 Metformin XR caplet 750 mg (twice daily) and 1 placebo capsule of DLBS3233 (once daily)
intervention type: Drug
intervention name: DLBS3233
description: 1 DLBS3233 capsule 100 mg once daily for 6 months
arm group label: Treatment I
other name: Inlacin
intervention type: Drug
intervention name: Metformin XR
description: 1 Metformin XR caplet 750 mg twice daily for 6 months
arm group label: Treatment II
other name: Glumin XR
intervention type: Drug
intervention name: Placebo caplet of Metformin XR
description: 1 placebo caplet of Metformin XR twice daily for 6 months
arm group label: Treatment I
other name: Placebo caplet of Glumin XR
intervention type: Drug
intervention name: Placebo capsule of DLBS3233
description: 1 placebo capsule of DLBS3233 once daily for 6 months
arm group label: Treatment II
other name: Placebo capsule of Inlacin
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: No
last name: Andon Hestiantoro, dr., SpOG(K)
role: Principal Investigator
affiliation: Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Indonesia, dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia
last name: Wiryawan Permadi, Dr., dr., SpOG(K)
role: Principal Investigator
affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, University of Padjadjaran, Hasan Sadikin Hospital, Bandung, Indonesia
facility: 
facility: 
country: Indonesia
responsible party type: Sponsor
mesh term: Polycystic Ovary Syndrome
mesh term: Syndrome
mesh term: Metformin