<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/NCT01674348</url>
  </required_header>
  <id_info>
    <org_study_id>P2202/47/10</org_study_id>
    <nct_id>NCT01674348</nct_id>
  </id_info>
  <brief_title>A Clinical Trial to Study the Efficacy, Safety, Tolerability and Pharmacokinetics of P2202 in Patients of Type 2 Diabetes</brief_title>
  <official_title>A Phase II, Randomized, Double-blind, Placebo-controlled, Dose-ranging, Two-staged, Fixed Design Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of P2202 in Overweight/Obese Patients of Type 2 Diabetes Mellitus Inadequately Controlled on Metformin, Sulphonylurea, or Both.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Piramal Enterprises Limited</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Piramal Enterprises Limited</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      It is a phase II, randomized, double-blind, placebo-controlled study of P2202 in patients of&#xD;
      type 2 diabetes mellitus, inadequately controlled with a stable dose of metformin or&#xD;
      sulfonylurea or both.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      It is a phase II, prospective, randomized, double-blind, placebo-controlled, dose-ranging,&#xD;
      multi-centre, two-staged, fixed-design study of P2202 in patients of type 2 diabetes&#xD;
      mellitus, inadequately controlled with a stable dose of metformin or sulfonylurea or both.&#xD;
      This study will consist of accrual in Stage I (n=56/arm, which is 70% of the total sample&#xD;
      size required), followed by an interim analysis on completion of the treatment period, to aid&#xD;
      further decisions on accrual and dose selection in Stage II of the study, and completion of&#xD;
      Stage I.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Due to non-recruitment, the study is being halted. There are no major safety or tolerability&#xD;
    concerns in the study conducted so far.&#xD;
  </why_stopped>
  <start_date>April 2011</start_date>
  <completion_date type="Actual">July 2013</completion_date>
  <primary_completion_date type="Actual">December 2012</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in HbA1c from baseline</measure>
    <time_frame>From baseline till end of 12 weeks</time_frame>
    <description>The change in HbA1c from baseline till end of 12 weeks in patients of type 2 diabetes mellitus, in the P2202 arms as compared to placebo.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with adverse events</measure>
    <time_frame>From screening to 3 weeks (± 1 week) after the last visit at the end of Week 12 or early exit visit</time_frame>
    <description>Safety assessment will be done by eliciting information regarding AEs including evaluation of hypoglycemic events, physical examination, vital signs assessment, 12-lead ECGs, clinical laboratory tests, markers of HPA axis function, plasma ACTH and free testosterone, plasma rennin and serum aldosterone and self-monitoring of blood glucose profiles.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Pharmacokinetic profile (Cmax, Tmax and AUC)</measure>
    <time_frame>Pre dose at Day 1 Week 1 till Week 12</time_frame>
    <description>PK parameters derived will be maximum plasma concentration (Cmax), time at which Cmax is reached (Tmax), area under the plasma concentration curve calculated up to 24 hours (AUC 0-24h), area under the curve extrapolated to infinity (AUC 0-inf), elimination rate constant (Kel), volume of distribution (Vz), terminal elimination half life (t1/2) and protein binding.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">48</enrollment>
  <condition>Type 2 Diabetes Mellitus</condition>
  <arm_group>
    <arm_group_label>P2202</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Two treatment arms in Stage I- P2202 (1000 mg) and placebo&#xD;
Four treatment arms in stage II- P2202 (suggested dose levels 750 mg, 500 mg or 250 mg) or placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Two treatment arms in Stage I- P2202 (1000 mg) and placebo&#xD;
Four treatment arms in stage II- P2202 (suggested dose levels 750 mg, 500 mg or 250 mg) or placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>P2202</intervention_name>
    <description>Novel oral drug with potent and selective 11 beta-hydroxysteroid dehydrogenase type 1 (11b-HSD1) inhibitory properties, being developed for the management of type 2 diabetes mellitus</description>
    <arm_group_label>P2202</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects who understand and are willing to give informed consent to participate in the&#xD;
             trial.&#xD;
&#xD;
          -  Adult male and female subjects between 18 years to 65 years of age with a BMI ≥ 27&#xD;
             kg/m2 ≤ 40 kg/m2, inclusively.&#xD;
&#xD;
          -  Subjects with established type 2 diabetes mellitus of at least 3 months duration at&#xD;
             the time of screening.&#xD;
&#xD;
          -  Subjects with an inadequate glycemic control defined by an HbA1c level of ≥ 7.5% and&#xD;
             ≥10% at screening.&#xD;
&#xD;
          -  Subjects who are on a stable dose of:&#xD;
&#xD;
               -  Metformin (up to 2.55 gm/day or maximum tolerated dose of at least 1 gm/day)&#xD;
                  and/or&#xD;
&#xD;
               -  Sulfonylurea (glimepiride ≤ 4 mg/day, gliclazide ≤ 160 mg, glibenclamide or&#xD;
                  glyburide ≤ 10 mg and glipizide ≤ 10 mg), for ≤ 2 months prior to the screening&#xD;
                  visit.&#xD;
&#xD;
          -  Subjects with fasting plasma glucose of ≤14.4 mmol/L (260 mg/dL) and at least 5.5&#xD;
             mmol/L or 100 mg/dL.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects who have type 1 diabetes mellitus, maturity-onset diabetes of the young or&#xD;
             any rare form of diabetes. Subjects with hyperglycemia due to secondary causes.&#xD;
&#xD;
          -  Subjects who have had more than 4 episodes of severe hypoglycemia in the 6 months&#xD;
             prior to screening.&#xD;
&#xD;
          -  Subjects with a history of acute diabetic complications&#xD;
&#xD;
          -  Subjects who have been treated with insulin (except for use of insulin for short term&#xD;
             management of acute conditions), thiazolidinediones, dual proliferator activated&#xD;
             receptors agonists, glucagon-like peptide analogues, dipeptidyl peptidase inhibitors&#xD;
             or 11bHSD-1 inhibitors in any form, in the 3 months prior to screening.&#xD;
&#xD;
          -  Subjects who are receiving systemic glucocorticoids (≥14 days)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dr. Ronnie Aronson, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Health Canada</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Dr. Robert Petrella, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Health Canada</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Dr. Naresh Aggarwal, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Health Canada</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>LMC Endocrinolgy Centres Ltd</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M4G 3E8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>August 2013</verification_date>
  <study_first_submitted>August 21, 2012</study_first_submitted>
  <study_first_submitted_qc>August 27, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 28, 2012</study_first_posted>
  <last_update_submitted>August 2, 2013</last_update_submitted>
  <last_update_submitted_qc>August 2, 2013</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 5, 2013</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Diabetes Mellitus</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>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01674348
org study id: P2202/47/10
nct id: NCT01674348
lead sponsor: 
has dmc: Yes
It is a phase II, randomized, double-blind, placebo-controlled study of P2202 in patients of
      type 2 diabetes mellitus, inadequately controlled with a stable dose of metformin or
      sulfonylurea or both.
It is a phase II, prospective, randomized, double-blind, placebo-controlled, dose-ranging,
      multi-centre, two-staged, fixed-design study of P2202 in patients of type 2 diabetes
      mellitus, inadequately controlled with a stable dose of metformin or sulfonylurea or both.
      This study will consist of accrual in Stage I (n=56/arm, which is 70% of the total sample
      size required), followed by an interim analysis on completion of the treatment period, to aid
      further decisions on accrual and dose selection in Stage II of the study, and completion of
      Stage I.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change in HbA1c from baseline
time frame: From baseline till end of 12 weeks
description: The change in HbA1c from baseline till end of 12 weeks in patients of type 2 diabetes mellitus, in the P2202 arms as compared to placebo.
measure: Number of subjects with adverse events
time frame: From screening to 3 weeks (± 1 week) after the last visit at the end of Week 12 or early exit visit
description: Safety assessment will be done by eliciting information regarding AEs including evaluation of hypoglycemic events, physical examination, vital signs assessment, 12-lead ECGs, clinical laboratory tests, markers of HPA axis function, plasma ACTH and free testosterone, plasma rennin and serum aldosterone and self-monitoring of blood glucose profiles.
measure: Pharmacokinetic profile (Cmax, Tmax and AUC)
time frame: Pre dose at Day 1 Week 1 till Week 12
description: PK parameters derived will be maximum plasma concentration (Cmax), time at which Cmax is reached (Tmax), area under the plasma concentration curve calculated up to 24 hours (AUC 0-24h), area under the curve extrapolated to infinity (AUC 0-inf), elimination rate constant (Kel), volume of distribution (Vz), terminal elimination half life (t1/2) and protein binding.
arm group label: P2202
arm group type: Active Comparator
description: Two treatment arms in Stage I- P2202 (1000 mg) and placebo
Four treatment arms in stage II- P2202 (suggested dose levels 750 mg, 500 mg or 250 mg) or placebo
arm group label: Placebo
arm group type: Placebo Comparator
description: Two treatment arms in Stage I- P2202 (1000 mg) and placebo
Four treatment arms in stage II- P2202 (suggested dose levels 750 mg, 500 mg or 250 mg) or placebo
intervention type: Drug
intervention name: P2202
description: Novel oral drug with potent and selective 11 beta-hydroxysteroid dehydrogenase type 1 (11b-HSD1) inhibitory properties, being developed for the management of type 2 diabetes mellitus
arm group label: P2202
intervention type: Drug
intervention name: Placebo
description: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Dr. Ronnie Aronson, M.D.
role: Principal Investigator
affiliation: Health Canada
last name: Dr. Robert Petrella, M.D.
role: Principal Investigator
affiliation: Health Canada
last name: Dr. Naresh Aggarwal, M.D.
role: Principal Investigator
affiliation: Health Canada
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2