<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/NCT02252965</url>
  </required_header>
  <id_info>
    <org_study_id>200084-513</org_study_id>
    <nct_id>NCT02252965</nct_id>
  </id_info>
  <brief_title>Metformin Extended Release Versus Metformin Immediate Release in Subjects With Type 2 Diabetes</brief_title>
  <acronym>CONSENT</acronym>
  <official_title>CONSENT - Comparison of metfOrmin XR to IR as moNotherapy in the Newly diagnoSed Type 2 diabEtes Patients for the gastroiNtestinal Tolerability and Efficacy: a Randomized, Parallel Control, Open-label and Multicenter Study</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>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase 4, prospective, open label, randomized, parallel controlled multicenter trial&#xD;
      in which metformin extended release (XR) will be compared with metformin immediate release&#xD;
      (IR) for the gastrointestinal tolerability and efficacy in the newly diagnosed subjects with&#xD;
      Type 2 diabetes who have glycosylated hemoglobin (HbA1c) value between 7.0 to 10.0 percent&#xD;
      (%).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>December 2014</start_date>
  <completion_date type="Actual">April 2016</completion_date>
  <primary_completion_date type="Actual">November 2015</primary_completion_date>
  <phase>Phase 4</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>Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 16</measure>
    <time_frame>Baseline, Week 16</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Overall Gastrointestinal (GI) Tolerability Assessed as Percentage of Subjects With Gastrointestinal Adverse Events During Treatment Period</measure>
    <time_frame>Baseline up to Week 16</time_frame>
    <description>An adverse event (AE) was defined as any untoward medical occurrence in a subject which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Subjects With Pre-specified Gastrointestinal Adverse Events During Treatment Period</measure>
    <time_frame>Baseline up to Week 16</time_frame>
    <description>An adverse event (AE) was defined as any untoward medical occurrence in a subject which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. Number of subjects with pre-specified gastrointestinal adverse events (diarrhea, nausea, abdominal pain, bloating, constipation, dyspepsia and flatulence) were reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Fasting Plasma Glucose (FPG) Level at Week 1, 2, 4, 8, 12 and 16</measure>
    <time_frame>Baseline, Week 1, 2, 4, 8, 12,16</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) Level at Weeks 8 and 16</measure>
    <time_frame>Baseline, Week 8 and 16</time_frame>
    <description>The 2-hour Postprandial plasma glucose (PPG) level refers to the plasma glucose concentrations after 2 hours of eating.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Subjects With Hypoglycemia</measure>
    <time_frame>Baseline up to Week 16</time_frame>
    <description>Hypoglycemia, also called as low blood glucose or low blood sugar, is defined as the blood glucose level of less than normal (that is less than 3.9 millimole per liter [mmol/L]).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Subjects With Marked Hyperglycemia</measure>
    <time_frame>Baseline up to Week 16</time_frame>
    <description>Marked hyperglycemia was defined as the FPG level of greater than or equal to 11.1 mmol/L.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Subjects With HbA1c Less Than (&lt;) 7%</measure>
    <time_frame>Baseline up to Week 16</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Subjects Who Are Totally Intolerant to the Treatment</measure>
    <time_frame>Baseline up to Week 16</time_frame>
    <description>Subjects were considered to be totally intolerant if they experienced a Grade 3 or higher toxicity considered at least possibly related to the treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Subjects With HbA1c Less Than (&lt;) 7% and With no Severe Gastrointestinal (GI) and Other Adverse Events (AEs)</measure>
    <time_frame>Baseline up to Week 16</time_frame>
    <description>Percentage of subjects with HbA1c &lt;7% and with no severe GI and other AEs were reported. Severe adverse events were based on Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 and were defined as those events which were medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living (ADL). Self-care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Subjects Who Are Compliant to Treatment</measure>
    <time_frame>Baseline up to Week 16</time_frame>
    <description>Compliance was defined as not skipping or forgetting dosing or not delaying the dosing time. Subjects who never missed a dose of medication were considered compliant.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">532</enrollment>
  <condition>Diabetes Mellitus, Type 2</condition>
  <arm_group>
    <arm_group_label>Metformin IR</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Metformin XR</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin IR</intervention_name>
    <description>Subjects will receive Metformin Immediate Release (IR) tablets, orally once daily at a dose of 500 milligram (mg) for 1 week, and then dose will increase with increments of 500 mg every week in first 2 weeks to 1500 mg. After that dose will increase up to maximum dose of 2000 mg for the next 2 weeks and will be maintained at 2000 mg until Week 16.</description>
    <arm_group_label>Metformin IR</arm_group_label>
    <other_name>Glucophage IR</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin XR</intervention_name>
    <description>Subjects will receive Metformin Extended Release (XR) tablets, orally once daily at a dose of 500 mg for 1 week, and then dose will increase with increments of 500 mg every week in first 2 weeks to 1500 mg. After that dose will increase up to maximum dose of 2000 mg for the next 2 weeks and will be maintained at 2000 mg until Week 16.</description>
    <arm_group_label>Metformin XR</arm_group_label>
    <other_name>Glucophage XR</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Diagnosis of Type 2 diabetes mellitus before the screening visit based on the World&#xD;
             Health Organization (WHO) diagnostic and classification criteria&#xD;
&#xD;
          -  HbA1c value of 7.0-10.0%, inclusive&#xD;
&#xD;
          -  Age ranging from 18 to 79 years, inclusive&#xD;
&#xD;
          -  Treatment-naive for oral antidiabetic agents (that is, had not received antidiabetic&#xD;
             medication previously, or had received antidiabetic medication for at least 14 days&#xD;
             and not within 1 month of enrolment)&#xD;
&#xD;
          -  Male, or non-pregnant, non-breastfeeding females&#xD;
&#xD;
          -  Body mass index (BMI) greater than or equal to (&gt;=) 18.5 and less than (&lt;) 35 kilogram&#xD;
             per square meter (kg/m^2)&#xD;
&#xD;
          -  In the opinion of the investigator, subjects are well-motivated, capable and willing&#xD;
             to continue the study treatment as required during the whole study period, maintain a&#xD;
             study dietary, as required for this protocol, attend scheduled visits and be willing&#xD;
             to receive phone calls between visits, avoid pregnancy by using an adequate method of&#xD;
             contraception throughout the duration of the study for the female subjects of child&#xD;
             bearing potential (and if appropriate male subjects with female partners of&#xD;
             childbearing potential)&#xD;
&#xD;
          -  Written informed consent given before any trial-related activities are carried out&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Type 1 diabetes&#xD;
&#xD;
          -  Previous treatment with insulin or other antidiabetics (including Chinese traditional&#xD;
             medicine) for more than 14 days continuously or within 1 month of enrolment&#xD;
&#xD;
          -  Any of the protocol-specified cardiovascular conditions within 3 months prior to the&#xD;
             screening visit&#xD;
&#xD;
          -  Impaired liver function as defined in the protocol&#xD;
&#xD;
          -  Serum creatinine values as specified in the protocol&#xD;
&#xD;
          -  Known proliferative retinopathy or maculopathy requiring acute treatment, or recurrent&#xD;
             major hypoglycemia or hypoglycemic unawareness as judged by the investigator&#xD;
&#xD;
          -  Persistent uncontrolled hypertension&#xD;
&#xD;
          -  Severe chronic gastrointestinal disease&#xD;
&#xD;
          -  Previous history of 1 or more episodes of ketoacidosis or hyperosmolar state/coma&#xD;
&#xD;
          -  Currently receiving chronic (&gt;14 days) systemic glucocorticoid therapy (excluding&#xD;
             topical, intraocular, inhaled or intranasal preparations) or have received such&#xD;
             therapy within 4 weeks of the screening visit&#xD;
&#xD;
          -  Current use of beta-blockers, thiazide diuretic, thyroid products, estrogens, oral&#xD;
             contraceptives, phenytoin, nicotinic acid, sympathomimetics, nifedipine and isoniazid&#xD;
             and cannot be replaced by any other treatment&#xD;
&#xD;
          -  Have any hematologic condition that may interfere with HbA1c measurement (for example,&#xD;
             hemolytic anemia, sickle-cell disease)&#xD;
&#xD;
          -  Have any other condition (such as, known drug or alcohol abuse or a psychiatric&#xD;
             disorder) that may prevent the subject from following and completing the protocol&#xD;
&#xD;
          -  Known hypersensitivity to Metformin Hydrochloride&#xD;
&#xD;
          -  Currently enrolled in, or discontinued within the last 30 days from, a clinical trial&#xD;
             involving an investigational product or non-approved use of a drug or device, or&#xD;
             concurrently enrolled in any other type of medical research judged not to be&#xD;
             scientifically or medically compatible with this study&#xD;
&#xD;
          -  Any contraindications to Metformin according to local package insert&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>79 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Responsible</last_name>
    <role>Study Director</role>
    <affiliation>Merck Serono Co., Ltd., Beijing, China</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Please contact the Merck KGaA Communication Center</name>
      <address>
        <city>Darmstadt</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>November 2016</verification_date>
  <study_first_submitted>September 26, 2014</study_first_submitted>
  <study_first_submitted_qc>September 26, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 30, 2014</study_first_posted>
  <results_first_submitted>November 28, 2016</results_first_submitted>
  <results_first_submitted_qc>November 28, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">January 24, 2017</results_first_posted>
  <last_update_submitted>November 28, 2016</last_update_submitted>
  <last_update_submitted_qc>November 28, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 24, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Diabetes Mellitus, Type 2</keyword>
  <keyword>Metformin XR</keyword>
  <keyword>Metformin IR</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metformin</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Metformin IR</title>
          <description>Subjects received Metformin Immediate Release (IR) tablets, orally once daily (QD) at a dose of 500 milligram (mg) for 1 week, and then the dose was increased with increments of 500 mg every week in the first 2 weeks to 1500 mg. After that, the dose was increased up to a maximum dose of 2000 mg for the next two weeks and maintained at 2000 mg until Week 16.</description>
        </group>
        <group group_id="P2">
          <title>Metformin XR</title>
          <description>Subjects received Metformin Extended Release (XR) tablets, orally QD at a dose of 500 mg for 1 week, and then the dose was increased with increments of 500 mg every week in the first 2 weeks to 1500 mg. After that, the dose was increased up to a maximum dose of 2000 mg for next 2 weeks and maintained at 2000 mg until Week 16.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="267"/>
                <participants group_id="P2" count="265"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Safety Population</title>
              <participants_list>
                <participants group_id="P1" count="261">Out of 261, 12 subjects intolerant to the Metformin IR switched to Metformin XR group.</participants>
                <participants group_id="P2" count="264"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="227"/>
                <participants group_id="P2" count="222"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="40"/>
                <participants group_id="P2" count="43"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="14"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="8"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Intent to Treat (ITT) population included all subjects who were randomly allocated to a treatment based on the intention to treat</population>
      <group_list>
        <group group_id="B1">
          <title>Metformin IR</title>
          <description>Subjects received Metformin IR tablets, orally QD at a dose of 500 milligram (mg) for 1 week, and then the dose was increased with increments of 500 mg every week in the first 2 weeks to 1500 mg. After that, the dose was increased up to a maximum dose of 2000 mg for the next two weeks and maintained at 2000 mg until Week 16.</description>
        </group>
        <group group_id="B2">
          <title>Metformin XR</title>
          <description>Subjects received Metformin XR tablets, orally QD at a dose of 500 mg for 1 week, and then the dose was increased with increments of 500 mg every week in the first 2 weeks to 1500 mg. After that, the dose was increased up to a maximum dose of 2000 mg for next 2 weeks and maintained at 2000 mg until Week 16.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="267"/>
            <count group_id="B2" value="265"/>
            <count group_id="B3" value="532"/>
          </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="54.4" spread="10.21"/>
                    <measurement group_id="B2" value="53.1" spread="9.72"/>
                    <measurement group_id="B3" value="53.8" spread="9.98"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Gender</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="112"/>
                    <measurement group_id="B2" value="108"/>
                    <measurement group_id="B3" value="220"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="155"/>
                    <measurement group_id="B2" value="157"/>
                    <measurement group_id="B3" value="312"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 16</title>
        <time_frame>Baseline, Week 16</time_frame>
        <population>Per-protocol (PP) population included all subjects who were randomly allocated to a treatment based on intent to treat and were compliant with protocol (absence of any major protocol violations). Here &quot;Number of Participants Analyzed&quot; signifies those subjects who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Metformin IR</title>
            <description>Subjects received Metformin IR tablets, orally QD at a dose of 500 mg for 1 week, and then the dose was increased with increments of 500 mg every week in the first 2 weeks to 1500 mg. After that, the dose was increased up to a maximum dose of 2000 mg for the next two weeks and maintained at 2000 mg until Week 16.</description>
          </group>
          <group group_id="O2">
            <title>Metformin XR</title>
            <description>Subjects received Metformin XR tablets, orally QD at a dose of 500 mg for 1 week, and then the dose was increased with increments of 500 mg every week in the first 2 weeks to 1500 mg. After that, the dose was increased up to a maximum dose of 2000 mg for next 2 weeks and maintained at 2000 mg until Week 16.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 16</title>
          <population>Per-protocol (PP) population included all subjects who were randomly allocated to a treatment based on intent to treat and were compliant with protocol (absence of any major protocol violations). Here &quot;Number of Participants Analyzed&quot; signifies those subjects who were evaluable for this outcome measure.</population>
          <units>Percentage of HbA1c</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="208"/>
                <count group_id="O2" value="204"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.61" spread="0.05"/>
                    <measurement group_id="O2" value="-1.58" spread="0.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Non-Inferiority or Equivalence</non_inferiority_type>
            <non_inferiority_desc>The non-inferiority margin of this efficacy outcome measure is -0.4%.</non_inferiority_desc>
            <param_type>Least Squares (LS) Mean Difference</param_type>
            <param_value>0.03</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.10</ci_lower_limit>
            <ci_upper_limit>0.17</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Overall Gastrointestinal (GI) Tolerability Assessed as Percentage of Subjects With Gastrointestinal Adverse Events During Treatment Period</title>
        <description>An adverse event (AE) was defined as any untoward medical occurrence in a subject which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product.</description>
        <time_frame>Baseline up to Week 16</time_frame>
        <population>The safety population included all subjects who received at least 1 dose of trial treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Metformin IR</title>
            <description>Subjects received Metformin IR tablets, orally QD at a dose of 500 mg for 1 week, and then the dose was increased with increments of 500 mg every week in the first 2 weeks to 1500 mg. After that, the dose was increased up to a maximum dose of 2000 mg for the next two weeks and maintained at 2000 mg until Week 16.</description>
          </group>
          <group group_id="O2">
            <title>Metformin XR</title>
            <description>Subjects received Metformin XR tablets, orally QD at a dose of 500 mg for 1 week, and then the dose was increased with increments of 500 mg every week in the first 2 weeks to 1500 mg. After that, the dose was increased up to a maximum dose of 2000 mg for next 2 weeks and maintained at 2000 mg until Week 16.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Gastrointestinal (GI) Tolerability Assessed as Percentage of Subjects With Gastrointestinal Adverse Events During Treatment Period</title>
          <description>An adverse event (AE) was defined as any untoward medical occurrence in a subject which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product.</description>
          <population>The safety population included all subjects who received at least 1 dose of trial treatment.</population>
          <units>percentage of subjects</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="261"/>
                <count group_id="O2" value="264"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.8" lower_limit="18.72" upper_limit="29.39"/>
                    <measurement group_id="O2" value="22.3" lower_limit="17.47" upper_limit="27.86"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.674</p_value>
            <method>Mantel Haenszel</method>
            <param_type>Percentage difference</param_type>
            <param_value>-1.52</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-8.60</ci_lower_limit>
            <ci_upper_limit>5.56</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Subjects With Pre-specified Gastrointestinal Adverse Events During Treatment Period</title>
        <description>An adverse event (AE) was defined as any untoward medical occurrence in a subject which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. Number of subjects with pre-specified gastrointestinal adverse events (diarrhea, nausea, abdominal pain, bloating, constipation, dyspepsia and flatulence) were reported.</description>
        <time_frame>Baseline up to Week 16</time_frame>
        <population>The safety population included all subjects who received at least 1 dose of trial treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Metformin IR</title>
            <description>Subjects received Metformin IR tablets, orally QD at a dose of 500 mg for 1 week, and then the dose was increased with increments of 500 mg every week in the first 2 weeks to 1500 mg. After that, the dose was increased up to a maximum dose of 2000 mg for the next two weeks and maintained at 2000 mg until Week 16.</description>
          </group>
          <group group_id="O2">
            <title>Metformin XR</title>
            <description>Subjects received Metformin XR tablets, orally QD at a dose of 500 mg for 1 week, and then the dose was increased with increments of 500 mg every week in the first 2 weeks to 1500 mg. After that, the dose was increased up to a maximum dose of 2000 mg for next 2 weeks and maintained at 2000 mg until Week 16</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Subjects With Pre-specified Gastrointestinal Adverse Events During Treatment Period</title>
          <description>An adverse event (AE) was defined as any untoward medical occurrence in a subject which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. Number of subjects with pre-specified gastrointestinal adverse events (diarrhea, nausea, abdominal pain, bloating, constipation, dyspepsia and flatulence) were reported.</description>
          <population>The safety population included all subjects who received at least 1 dose of trial treatment.</population>
          <units>percentage of subjects</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="261"/>
                <count group_id="O2" value="264"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Diarrhoea</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.5" lower_limit="12.19" upper_limit="21.54"/>
                    <measurement group_id="O2" value="12.5" lower_limit="8.76" upper_limit="17.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Abdominal Distension</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.1" lower_limit="3.54" upper_limit="9.76"/>
                    <measurement group_id="O2" value="6.4" lower_limit="3.80" upper_limit="10.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nausea</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.1" lower_limit="3.54" upper_limit="9.76"/>
                    <measurement group_id="O2" value="4.5" lower_limit="2.37" upper_limit="7.81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Abdominal Pain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.3" lower_limit="0.85" upper_limit="4.94"/>
                    <measurement group_id="O2" value="1.9" lower_limit="0.62" upper_limit="4.36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Constipation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.9" lower_limit="0.62" upper_limit="4.41"/>
                    <measurement group_id="O2" value="1.9" lower_limit="0.62" upper_limit="4.36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dyspepsia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.1" lower_limit="0.24" upper_limit="3.32"/>
                    <measurement group_id="O2" value="0.8" lower_limit="0.09" upper_limit="2.71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Flatulence</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.4" lower_limit="0.01" upper_limit="2.12"/>
                    <measurement group_id="O2" value="0" lower_limit="0.00" upper_limit="1.39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Fasting Plasma Glucose (FPG) Level at Week 1, 2, 4, 8, 12 and 16</title>
        <time_frame>Baseline, Week 1, 2, 4, 8, 12,16</time_frame>
        <population>ITT population included all subjects who were randomly allocated to a treatment based on the intention to treat. Here &quot;Number of Participants Analyzed&quot; signifies those subjects who were evaluable for this outcome measure. Here &quot;n&quot; signifies those subjects who were evaluable for the specified time points for each arm, respectively.</population>
        <group_list>
          <group group_id="O1">
            <title>Metformin IR</title>
            <description>Subjects received Metformin IR tablets, orally QD at a dose of 500 mg for 1 week, and then the dose was increased with increments of 500 mg every week in the first 2 weeks to 1500 mg. After that, the dose was increased up to a maximum dose of 2000 mg for the next two weeks and maintained at 2000 mg until Week 16.</description>
          </group>
          <group group_id="O2">
            <title>Metformin XR</title>
            <description>Subjects received Metformin XR tablets, orally QD at a dose of 500 mg for 1 week, and then the dose was increased with increments of 500 mg every week in the first 2 weeks to 1500 mg. After that, the dose was increased up to a maximum dose of 2000 mg for next 2 weeks and maintained at 2000 mg until Week 16.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Fasting Plasma Glucose (FPG) Level at Week 1, 2, 4, 8, 12 and 16</title>
          <population>ITT population included all subjects who were randomly allocated to a treatment based on the intention to treat. Here &quot;Number of Participants Analyzed&quot; signifies those subjects who were evaluable for this outcome measure. Here &quot;n&quot; signifies those subjects who were evaluable for the specified time points for each arm, respectively.</population>
          <units>Millimole Per Liter (mmol/L)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="251"/>
                <count group_id="O2" value="254"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline (n=251, 254)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.464" spread="1.7470"/>
                    <measurement group_id="O2" value="8.690" spread="2.0977"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 1 (n= 249, 248)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.647" spread="1.5615"/>
                    <measurement group_id="O2" value="-0.736" spread="1.4305"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 2 (n= 243, 244)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.324" spread="1.4426"/>
                    <measurement group_id="O2" value="-1.267" spread="1.9346"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 4 (n= 240, 239)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.558" spread="1.6245"/>
                    <measurement group_id="O2" value="-1.604" spread="1.7971"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 8 (n= 219, 230)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.075" spread="1.7359"/>
                    <measurement group_id="O2" value="-1.999" spread="2.0192"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 12 (n= 216, 221)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.053" spread="1.7599"/>
                    <measurement group_id="O2" value="-2.048" spread="1.8532"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 16 (n= 214, 218)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.976" spread="1.7529"/>
                    <measurement group_id="O2" value="-2.183" spread="1.8481"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) Level at Weeks 8 and 16</title>
        <description>The 2-hour Postprandial plasma glucose (PPG) level refers to the plasma glucose concentrations after 2 hours of eating.</description>
        <time_frame>Baseline, Week 8 and 16</time_frame>
        <population>ITT population included all subjects who were randomly allocated to a treatment based on the intention to treat. Here &quot;Number of Participants Analyzed&quot; signifies those subjects who were evaluable for this outcome measure. Here &quot;n&quot; signifies those subjects who were evaluable for the specified time points for each arm, respectively.</population>
        <group_list>
          <group group_id="O1">
            <title>Metformin IR</title>
            <description>Subjects received Metformin IR tablets, orally QD at a dose of 500 mg for 1 week, and then the dose was increased with increments of 500 mg every week in the first 2 weeks to 1500 mg. After that, the dose was increased up to a maximum dose of 2000 mg for the next two weeks and maintained at 2000 mg until Week 16.</description>
          </group>
          <group group_id="O2">
            <title>Metformin XR</title>
            <description>Subjects received Metformin XR tablets, orally QD at a dose of 500 mg for 1 week, and then the dose was increased with increments of 500 mg every week in the first 2 weeks to 1500 mg. After that, the dose was increased up to a maximum dose of 2000 mg for next 2 weeks and maintained at 2000 mg until Week 16</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) Level at Weeks 8 and 16</title>
          <description>The 2-hour Postprandial plasma glucose (PPG) level refers to the plasma glucose concentrations after 2 hours of eating.</description>
          <population>ITT population included all subjects who were randomly allocated to a treatment based on the intention to treat. Here &quot;Number of Participants Analyzed&quot; signifies those subjects who were evaluable for this outcome measure. Here &quot;n&quot; signifies those subjects who were evaluable for the specified time points for each arm, respectively.</population>
          <units>mmol/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="223"/>
                <count group_id="O2" value="231"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline (n= 223, 231)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.604" spread="3.4334"/>
                    <measurement group_id="O2" value="14.764" spread="3.7705"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 8 (n= 215, 229)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.608" spread="3.6964"/>
                    <measurement group_id="O2" value="-3.264" spread="5.9134"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 16 (n= 213, 215)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.642" spread="3.7261"/>
                    <measurement group_id="O2" value="-3.693" spread="3.5414"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Subjects With Hypoglycemia</title>
        <description>Hypoglycemia, also called as low blood glucose or low blood sugar, is defined as the blood glucose level of less than normal (that is less than 3.9 millimole per liter [mmol/L]).</description>
        <time_frame>Baseline up to Week 16</time_frame>
        <population>The safety population included all subjects who received at least 1 dose of trial treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Metformin IR</title>
            <description>Subjects received Metformin IR tablets, orally QD at a dose of 500 mg for 1 week, and then the dose was increased with increments of 500 mg every week in the first 2 weeks to 1500 mg. After that, the dose was increased up to a maximum dose of 2000 mg for the next two weeks and maintained at 2000 mg until Week 16.</description>
          </group>
          <group group_id="O2">
            <title>Metformin XR</title>
            <description>Subjects received Metformin XR tablets, orally QD at a dose of 500 mg for 1 week, and then the dose was increased with increments of 500 mg every week in the first 2 weeks to 1500 mg. After that, the dose was increased up to a maximum dose of 2000 mg for next 2 weeks and maintained at 2000 mg until Week 16.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Subjects With Hypoglycemia</title>
          <description>Hypoglycemia, also called as low blood glucose or low blood sugar, is defined as the blood glucose level of less than normal (that is less than 3.9 millimole per liter [mmol/L]).</description>
          <population>The safety population included all subjects who received at least 1 dose of trial treatment.</population>
          <units>percentage of subjects</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="261"/>
                <count group_id="O2" value="264"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.1" lower_limit="0.24" upper_limit="3.32"/>
                    <measurement group_id="O2" value="3.0" lower_limit="1.32" upper_limit="5.88"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Subjects With Marked Hyperglycemia</title>
        <description>Marked hyperglycemia was defined as the FPG level of greater than or equal to 11.1 mmol/L.</description>
        <time_frame>Baseline up to Week 16</time_frame>
        <population>ITT population included all subjects who were randomly allocated to a treatment based on the intention to treat.</population>
        <group_list>
          <group group_id="O1">
            <title>Metformin IR</title>
            <description>Subjects received Metformin IR tablets, orally QD at a dose of 500 mg for 1 week, and then the dose was increased with increments of 500 mg every week in the first 2 weeks to 1500 mg. After that, the dose was increased up to a maximum dose of 2000 mg for the next two weeks and maintained at 2000 mg until Week 16.</description>
          </group>
          <group group_id="O2">
            <title>Metformin XR</title>
            <description>Subjects received Metformin XR tablets, orally QD at a dose of 500 mg for 1 week, and then the dose was increased with increments of 500 mg every week in the first 2 weeks to 1500 mg. After that, the dose was increased up to a maximum dose of 2000 mg for next 2 weeks and maintained at 2000 mg until Week 16.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Subjects With Marked Hyperglycemia</title>
          <description>Marked hyperglycemia was defined as the FPG level of greater than or equal to 11.1 mmol/L.</description>
          <population>ITT population included all subjects who were randomly allocated to a treatment based on the intention to treat.</population>
          <units>percentage of subjects</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="267"/>
                <count group_id="O2" value="265"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.7" lower_limit="0.09" upper_limit="2.68"/>
                    <measurement group_id="O2" value="2.3" lower_limit="0.84" upper_limit="4.86"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Subjects With HbA1c Less Than (&lt;) 7%</title>
        <time_frame>Baseline up to Week 16</time_frame>
        <population>ITT population included all subjects who were randomly allocated to a treatment based on the intention to treat.</population>
        <group_list>
          <group group_id="O1">
            <title>Metformin IR</title>
            <description>Subjects received Metformin IR tablets, orally QD at a dose of 500 mg for 1 week, and then the dose was increased with increments of 500 mg every week in the first 2 weeks to 1500 mg. After that, the dose was increased up to a maximum dose of 2000 mg for the next two weeks and maintained at 2000 mg until Week 16.</description>
          </group>
          <group group_id="O2">
            <title>Metformin XR</title>
            <description>Subjects received Metformin XR tablets, orally QD at a dose of 500 mg for 1 week, and then the dose was increased with increments of 500 mg every week in the first 2 weeks to 1500 mg. After that, the dose was increased up to a maximum dose of 2000 mg for next 2 weeks and maintained at 2000 mg until Week 16.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Subjects With HbA1c Less Than (&lt;) 7%</title>
          <population>ITT population included all subjects who were randomly allocated to a treatment based on the intention to treat.</population>
          <units>percentage of subjects</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="267"/>
                <count group_id="O2" value="265"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="68.5" lower_limit="62.60" upper_limit="74.06"/>
                    <measurement group_id="O2" value="69.8" lower_limit="63.90" upper_limit="75.28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Subjects Who Are Totally Intolerant to the Treatment</title>
        <description>Subjects were considered to be totally intolerant if they experienced a Grade 3 or higher toxicity considered at least possibly related to the treatment.</description>
        <time_frame>Baseline up to Week 16</time_frame>
        <population>The safety population included all subjects who received at least 1 dose of trial treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Metformin IR</title>
            <description>Subjects received Metformin IR tablets, orally QD at a dose of 500 mg for 1 week, and then the dose was increased with increments of 500 mg every week in the first 2 weeks to 1500 mg. After that, the dose was increased up to a maximum dose of 2000 mg for the next two weeks and maintained at 2000 mg until Week 16.</description>
          </group>
          <group group_id="O2">
            <title>Metformin XR</title>
            <description>Subjects received Metformin XR tablets, orally QD at a dose of 500 mg for 1 week, and then the dose was increased with increments of 500 mg every week in the first 2 weeks to 1500 mg. After that, the dose was increased up to a maximum dose of 2000 mg for next 2 weeks and maintained at 2000 mg until Week 16.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Subjects Who Are Totally Intolerant to the Treatment</title>
          <description>Subjects were considered to be totally intolerant if they experienced a Grade 3 or higher toxicity considered at least possibly related to the treatment.</description>
          <population>The safety population included all subjects who received at least 1 dose of trial treatment.</population>
          <units>percentage of subjects</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="261"/>
                <count group_id="O2" value="264"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.3" lower_limit="4.44" upper_limit="11.13"/>
                    <measurement group_id="O2" value="5.7" lower_limit="3.21" upper_limit="9.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Subjects With HbA1c Less Than (&lt;) 7% and With no Severe Gastrointestinal (GI) and Other Adverse Events (AEs)</title>
        <description>Percentage of subjects with HbA1c &lt;7% and with no severe GI and other AEs were reported. Severe adverse events were based on Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 and were defined as those events which were medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living (ADL). Self-care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden.</description>
        <time_frame>Baseline up to Week 16</time_frame>
        <population>ITT population included all subjects who were randomly allocated to a treatment based on the intention to treat.</population>
        <group_list>
          <group group_id="O1">
            <title>Metformin IR</title>
            <description>Subjects received Metformin IR tablets, orally QD at a dose of 500 mg for 1 week, and then the dose was increased with increments of 500 mg every week in the first 2 weeks to 1500 mg. After that, the dose was increased up to a maximum dose of 2000 mg for the next two weeks and maintained at 2000 mg until Week 16.</description>
          </group>
          <group group_id="O2">
            <title>Metformin XR</title>
            <description>Subjects received Metformin XR tablets, orally QD at a dose of 500 mg for 1 week, and then the dose was increased with increments of 500 mg every week in the first 2 weeks to 1500 mg. After that, the dose was increased up to a maximum dose of 2000 mg for next 2 weeks and maintained at 2000 mg until Week 16.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Subjects With HbA1c Less Than (&lt;) 7% and With no Severe Gastrointestinal (GI) and Other Adverse Events (AEs)</title>
          <description>Percentage of subjects with HbA1c &lt;7% and with no severe GI and other AEs were reported. Severe adverse events were based on Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 and were defined as those events which were medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living (ADL). Self-care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden.</description>
          <population>ITT population included all subjects who were randomly allocated to a treatment based on the intention to treat.</population>
          <units>percentage of subjects</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="267"/>
                <count group_id="O2" value="265"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="68.2" lower_limit="62.21" upper_limit="73.71"/>
                    <measurement group_id="O2" value="69.8" lower_limit="63.90" upper_limit="75.28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Subjects Who Are Compliant to Treatment</title>
        <description>Compliance was defined as not skipping or forgetting dosing or not delaying the dosing time. Subjects who never missed a dose of medication were considered compliant.</description>
        <time_frame>Baseline up to Week 16</time_frame>
        <population>The safety population included all subjects who received at least 1 dose of trial treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Metformin IR</title>
            <description>Subjects received Metformin IR tablets, orally QD at a dose of 500 mg for 1 week, and then the dose was increased with increments of 500 mg every week in the first 2 weeks to 1500 mg. After that, the dose was increased up to a maximum dose of 2000 mg for the next two weeks and maintained at 2000 mg until Week 16.</description>
          </group>
          <group group_id="O2">
            <title>Metformin XR</title>
            <description>Subjects received Metformin XR tablets, orally QD at a dose of 500 mg for 1 week, and then the dose was increased with increments of 500 mg every week in the first 2 weeks to 1500 mg. After that, the dose was increased up to a maximum dose of 2000 mg for next 2 weeks and maintained at 2000 mg until Week 16.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Subjects Who Are Compliant to Treatment</title>
          <description>Compliance was defined as not skipping or forgetting dosing or not delaying the dosing time. Subjects who never missed a dose of medication were considered compliant.</description>
          <population>The safety population included all subjects who received at least 1 dose of trial treatment.</population>
          <units>percentage of subjects</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="261"/>
                <count group_id="O2" value="264"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="99.2"/>
                    <measurement group_id="O2" value="99.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Baseline up to Week 18</time_frame>
      <desc>Serious adverse events (SAEs) and Non-SAEs were presented separately for subjects who switched from Metformin IR to Metformin XR group due to intolerance to Metformin IR treatment.</desc>
      <group_list>
        <group group_id="E1">
          <title>Metformin IR</title>
          <description>Subjects received Metformin IR tablets, orally QD at a dose of 500 mg for 1 week, and then the dose was increased with increments of 500 mg every week in the first 2 weeks to 1500 mg. After that, the dose was increased up to a maximum dose of 2000 mg for the next two weeks and maintained at 2000 mg until Week 16.</description>
        </group>
        <group group_id="E2">
          <title>Metformin XR</title>
          <description>Subjects received Metformin XR tablets, orally QD at a dose of 500 mg for 1 week, and then the dose was increased with increments of 500 mg every week in the first 2 weeks to 1500 mg. After that, the dose was increased up to a maximum dose of 2000 mg for next 2 weeks and maintained at 2000 mg until Week 16.</description>
        </group>
        <group group_id="E3">
          <title>Metformin IR to XR</title>
          <description>Subjects who received Metformin IR tablets initially, but were shifted to Metformin XR group due to intolerance to Metformin IR.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (18.1)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac failure chronic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Retinal detachment</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Liver injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Foot fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood glucose increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Blood ketone body increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Adrenal adenoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Brain neoplasm</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Haemangioma of liver</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA (18.1)</default_vocab>
        <default_assessment>Non-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="96" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="136" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="12" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Thrombocytosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Angina pectoris</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Cardiac Discomfort</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Right Ventricular Hypertrophy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Sinus bradycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Inner Ear Disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Thyroiditis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Cataract</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Eye Ulcer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Visual Acuity Reduced</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal Discomfort</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Abdominal Distension</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="17" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Abdominal Pain Upper</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Abnormal Faeces</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Bowel Movement Irregularity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Defaecation urgency</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="34" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="33" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Eructation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Faeces Discoloured</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Faeces Hard</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Food Poisoning</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Frequent Bowel Movements</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal Reflux Disease</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Haemorrhoids</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Chest Disconfort</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hangover</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Non-Cardiac Chest Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Oedema Peripheral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholecystitis Chronic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Cholelithiasis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hepatic Function Abnormal</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hepatic Steatosis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Periphatic Discomfort</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Drug Hypersensitivity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hypersensitivity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Chronic Hepatitis B</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Herpes Zoster</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Upper Respiratory Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Urinary tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Muscle Injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Muscle Strain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine Aminotransferase Increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Aspartate Aminotransferase Increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Blood Bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Blood Glucose Decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Blood Potassium Decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Blood Potassium Increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Blood pressure Decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Blood Sodium Increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Blood Triglycerides Increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Blood uric Acid Increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Electrocardiogram Abnormal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Electrocardiogram ST Segment Depression</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Electrocardiogram ST Segment Elevation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Electrocardiogram T Wave Abnormal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Electrocardiogram T Wave Amplitude Decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Gastric PH Decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Liver Function Test Abnormal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Low Density Lipoprotein Increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Platelet Count Decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Protein Urine Present</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Urine Ketone Body Present</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Weight Decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>White Blood Cell Count Decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>White Blood Cell Count Increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased Appetite</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Dyslipidaemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Electrolyte Imbalance</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hyperlipidaemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hyperuricaemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hypoglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Muscular Weakness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Musculoskeletal Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Pain in Extremity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Periarthritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Spinal Osteoarthritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cerebral Ischaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Head Discomfort</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Initial Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Libido Decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Listless</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Nephrolithiasis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Renal Cyst</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Renal Impairment</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Benign Prostatic Hyperplasia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Prostatic Calcification</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hiccups</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Generalized Erythema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Pigmentation Disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="249"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="264"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </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>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Merck KGaA Communication Center</name_or_title>
      <organization>Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany</organization>
      <phone>+49-6151-72-5200</phone>
      <email>service@merckgroup.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/NCT02252965
org study id: 200084-513
nct id: NCT02252965
lead sponsor: 
has dmc: Yes
This is a Phase 4, prospective, open label, randomized, parallel controlled multicenter trial
      in which metformin extended release (XR) will be compared with metformin immediate release
      (IR) for the gastrointestinal tolerability and efficacy in the newly diagnosed subjects with
      Type 2 diabetes who have glycosylated hemoglobin (HbA1c) value between 7.0 to 10.0 percent
      (%).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 16
time frame: Baseline, Week 16
measure: Overall Gastrointestinal (GI) Tolerability Assessed as Percentage of Subjects With Gastrointestinal Adverse Events During Treatment Period
time frame: Baseline up to Week 16
description: An adverse event (AE) was defined as any untoward medical occurrence in a subject which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product.
measure: Percentage of Subjects With Pre-specified Gastrointestinal Adverse Events During Treatment Period
time frame: Baseline up to Week 16
description: An adverse event (AE) was defined as any untoward medical occurrence in a subject which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. Number of subjects with pre-specified gastrointestinal adverse events (diarrhea, nausea, abdominal pain, bloating, constipation, dyspepsia and flatulence) were reported.
measure: Change From Baseline in Fasting Plasma Glucose (FPG) Level at Week 1, 2, 4, 8, 12 and 16
time frame: Baseline, Week 1, 2, 4, 8, 12,16
measure: Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) Level at Weeks 8 and 16
time frame: Baseline, Week 8 and 16
description: The 2-hour Postprandial plasma glucose (PPG) level refers to the plasma glucose concentrations after 2 hours of eating.
measure: Percentage of Subjects With Hypoglycemia
time frame: Baseline up to Week 16
description: Hypoglycemia, also called as low blood glucose or low blood sugar, is defined as the blood glucose level of less than normal (that is less than 3.9 millimole per liter [mmol/L]).
measure: Percentage of Subjects With Marked Hyperglycemia
time frame: Baseline up to Week 16
description: Marked hyperglycemia was defined as the FPG level of greater than or equal to 11.1 mmol/L.
measure: Percentage of Subjects With HbA1c Less Than (<) 7%
time frame: Baseline up to Week 16
measure: Percentage of Subjects Who Are Totally Intolerant to the Treatment
time frame: Baseline up to Week 16
description: Subjects were considered to be totally intolerant if they experienced a Grade 3 or higher toxicity considered at least possibly related to the treatment.
measure: Percentage of Subjects With HbA1c Less Than (<) 7% and With no Severe Gastrointestinal (GI) and Other Adverse Events (AEs)
time frame: Baseline up to Week 16
description: Percentage of subjects with HbA1c <7% and with no severe GI and other AEs were reported. Severe adverse events were based on Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 and were defined as those events which were medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living (ADL). Self-care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden.
measure: Percentage of Subjects Who Are Compliant to Treatment
time frame: Baseline up to Week 16
description: Compliance was defined as not skipping or forgetting dosing or not delaying the dosing time. Subjects who never missed a dose of medication were considered compliant.
arm group label: Metformin IR
arm group type: Active Comparator
arm group label: Metformin XR
arm group type: Experimental
intervention type: Drug
intervention name: Metformin IR
description: Subjects will receive Metformin Immediate Release (IR) tablets, orally once daily at a dose of 500 milligram (mg) for 1 week, and then dose will increase with increments of 500 mg every week in first 2 weeks to 1500 mg. After that dose will increase up to maximum dose of 2000 mg for the next 2 weeks and will be maintained at 2000 mg until Week 16.
arm group label: Metformin IR
other name: Glucophage IR
intervention type: Drug
intervention name: Metformin XR
description: Subjects will receive Metformin Extended Release (XR) tablets, orally once daily at a dose of 500 mg for 1 week, and then dose will increase with increments of 500 mg every week in first 2 weeks to 1500 mg. After that dose will increase up to maximum dose of 2000 mg for the next 2 weeks and will be maintained at 2000 mg until Week 16.
arm group label: Metformin XR
other name: Glucophage XR
criteria: 
gender: All
minimum age: 18 Years
maximum age: 79 Years
healthy volunteers: No
last name: Medical Responsible
role: Study Director
affiliation: Merck Serono Co., Ltd., Beijing, China
facility: 
country: Germany
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
mesh term: Metformin
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 