<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/NCT01677260</url>
  </required_header>
  <id_info>
    <org_study_id>PR. 143/EQL/2009</org_study_id>
    <nct_id>NCT01677260</nct_id>
  </id_info>
  <brief_title>Bioequivalence Study of Two Formulations of 500 mg Metformin Extended Release Tablet</brief_title>
  <official_title>A Combined Single Dose Study Under Fasting Condition And Multiple Doses Study Under Normal Diabetic Meal Comparing the Bioavailability of Two Formulations of 500 mg Metformin Hydrochloride Extended Release Tablets.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dexa Medica Group</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Dexa Medica Group</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This was a single centre, single-blind, randomized, balanced, combined single dose study&#xD;
      under fasting condition and multiple doses study under fed condition with normal&#xD;
      diabetic-meal, two-period, two-sequence cross-over study to to compare the bioavailability of&#xD;
      metformin hydrochloride 500 mg extended release caplet (test drug) and metformin&#xD;
      hydrochloride 500 mg prolonged release tablet (reference formulation).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      On Day 1, to obtain pharmacokinetic profile of a single dose, the test or reference drugs&#xD;
      were given with 200 mL of water and swallowed without chewing the drug. For multiple doses&#xD;
      administration at Day 2 until Day 5, the study drugs were administered at a regimen of one&#xD;
      tablet each day, 30 minutes after breakfast. Time of drug administration was standardized for&#xD;
      all participating subjects throughout the study period.&#xD;
&#xD;
      From each subject, on Day 1 until Day 5 blood samples were drawn 5 mL before breakfast and&#xD;
      drug administration; and breakfast was provided only on Day 2 until Day 5. Only on Day 1 and&#xD;
      Day 5 after drug administration, the blood samples were drawn 5 mL each at 1, 1.5, 2, 2.5, 3,&#xD;
      3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 10, 12, 16 and 24 hours.&#xD;
&#xD;
      The blood samples drawn on Day 1 were used to show the single dose pharmacokinetic profile&#xD;
      under fasting condition; while those drawn on Day 5 were used to show the&#xD;
      multiple-dose-pharmacokinetic profile after meal intake.&#xD;
&#xD;
      One week after the first drug administration (washout period), the same procedure was&#xD;
      repeated with the alternate drug.&#xD;
&#xD;
      The plasma concentrations of metformin were determined by high performance liquid&#xD;
      chromatography with ultraviolet detection (HPLC-UV). The pharmacokinetic parameters assessed&#xD;
      in the single dose study were AUCt, AUCinf, Cmax, tmax, and t1/2. The pharmacokinetic&#xD;
      parameters assessed in multiple doses study at steady state phase were AUCtau, Cmax, Cmin,&#xD;
      and t1/2.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2009</start_date>
  <completion_date type="Actual">January 2010</completion_date>
  <primary_completion_date type="Actual">December 2009</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Bioavailability</measure>
    <time_frame>24 hours</time_frame>
    <description>Relative bioavailability (primarily measured by AUC and Cmax) between metformin hydrochloride 500 mg extended release caplet (test formulation) and metformin hydrochloride 500 mg prolonged release tablet (reference formulation) at a single dose.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Bioavailability</measure>
    <time_frame>5 days</time_frame>
    <description>Relative bioavailability (primarily measured by AUC and Cmax) between metformin hydrochloride 500 mg extended release caplet (test formulation) and metformin hydrochloride 500 mg prolonged release tablet (reference formulation)at multiple doses.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Bioavailability</measure>
    <time_frame>24 hours</time_frame>
    <description>Relative bioavailability (secondarily measured by tmax and t1/2) between metformin hydrochloride 500 mg extended release caplet (test formulation) and metformin hydrochloride 500 mg prolonged release tablet (reference formulation)at a single dose.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bioavailability</measure>
    <time_frame>5 days</time_frame>
    <description>Relative bioavailability (secondarily measured by tmax and t1/2) between metformin hydrochloride 500 mg extended release caplet (test formulation) and metformin hydrochloride 500 mg prolonged release tablet (reference formulation)at multiple doses.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>2 months</time_frame>
    <description>Adverse events occurred during the study conduct (2 months) were properly and sufficiently handled and recorded.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">38</enrollment>
  <condition>Metformin XR BE Study in Healthy Volunteers With Single and Multiple Dose</condition>
  <arm_group>
    <arm_group_label>Group I</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>500 mg metformin hydrochloride extended release caplet (PT Ferron Par Pharmaceuticals)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group II</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>500 mg metformin hydrochloride prolonged release tablet (PT Merck Pharmaceuticals)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>500 mg metformin hydrochloride extended release caplet (test drug)</intervention_name>
    <description>In each of the two study periods (separated by a washout of one week) a single and multiple dose of test or reference product was administered.</description>
    <arm_group_label>Group I</arm_group_label>
    <other_name>Glumin® XR, manufactured by PT Ferron Par Pharmaceuticals</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>500 mg metformin hydrochloride prolonged release tablet (reference drug)</intervention_name>
    <description>In each of the two study periods (separated by a washout of one week) a single and multiple dose of test or reference product was administered.</description>
    <arm_group_label>Group II</arm_group_label>
    <other_name>Glucophage® SR, manufactured by PT Merck Pharmaceuticals</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male and female subjects with absence of significant diseases or clinically&#xD;
             significant abnormal laboratory values on laboratory evaluation, medical history or&#xD;
             physical examination during screening.&#xD;
&#xD;
          -  Age of 18 - 55 years&#xD;
&#xD;
          -  Preferably non-smokers or smoke less than 10 cigarettes per day&#xD;
&#xD;
          -  Able to participate, communicate well with the investigators and willing to provide&#xD;
             written informed consent to participate in the study.&#xD;
&#xD;
          -  BMI 18 - 25 kg/m2&#xD;
&#xD;
          -  Vital signs (after 10 minutes rest) were within the following ranges:&#xD;
&#xD;
          -  SBP 100 - 120 mmHg&#xD;
&#xD;
          -  DBP 60 - 80 mmHg&#xD;
&#xD;
          -  Pulse rate 60 - 90 bpm&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Personal/family history of allergy or hypersensitivity or contraindication to&#xD;
             metformin hydrochloride or other biguanides and allied drug.&#xD;
&#xD;
          -  Pregnant or lactating women and women of childbearing potential without adequate&#xD;
             contraception&#xD;
&#xD;
          -  Any major illnesses in the past 90 days or clinically significant ongoing chronic&#xD;
             medical illnesses&#xD;
&#xD;
          -  Clinically significant illness within 4 weeks prior to the administration of study&#xD;
             medication&#xD;
&#xD;
          -  Presence of any clinically significant abnormal values during screening&#xD;
&#xD;
          -  Positive Hepatitis B surface antigen (HBsAg), anti-HCV, or anti-HIV&#xD;
&#xD;
          -  Clinically significant haematology abnormalities&#xD;
&#xD;
          -  Clinically significant electrocardiogram (ECG) abnormalities&#xD;
&#xD;
          -  Any surgical or medical condition (present or history) which might significantly alter&#xD;
             the absorption, distribution, metabolism or excretion of the study drug&#xD;
&#xD;
          -  History of drug (cocaine, amphetamines, opiates, cannabis) or alcohol abuse within 12&#xD;
             months prior to screening for this study&#xD;
&#xD;
          -  Participation in any clinical trial within the past 90 days&#xD;
&#xD;
          -  History of any bleeding or coagulative disorders&#xD;
&#xD;
          -  History or presence of asthma bronchial or related bronchospastic conditions&#xD;
&#xD;
          -  History of seizures, epilepsy or any kind of neurological disorders&#xD;
&#xD;
          -  History of difficulty with donating blood or difficulty in vein puncture of left or&#xD;
             right arm&#xD;
&#xD;
          -  A donation or loss of 500 mL (or more) of blood within 3 months before this study's&#xD;
             first dosing day&#xD;
&#xD;
          -  Intake of any prescription or non-prescription drugs, food supplements or herbal&#xD;
             medicines within 14 days of this study's first dosing day&#xD;
&#xD;
          -  Any food allergy, intolerance, restriction or special diet that in the opinion of the&#xD;
             Research Physician, could contraindicate the subject's participation in this study&#xD;
&#xD;
          -  Any reason in the opinion of the Research Physician, would prevent the subject from&#xD;
             participating in the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Danang A. Yunaidi, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>PT Equilab International</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>PT Equilab International</name>
      <address>
        <city>Jakarta</city>
        <zip>12430</zip>
        <country>Indonesia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Indonesia</country>
  </location_countries>
  <reference>
    <citation>Caille G, Lacasse Y, Raymond M, Landriault H, Perrotta M, Picirilli G, Thiffault J, Spenard J. Bioavailability of metformin in tablet form using a new high pressure liquid chromatography assay method. Biopharm Drug Dispos. 1993 Apr;14(3):257-63. doi: 10.1002/bdd.2510140308.</citation>
    <PMID>8490112</PMID>
  </reference>
  <reference>
    <citation>Cheng CL, Chou CH. Determination of metformin in human plasma by high-performance liquid chromatography with spectrophotometric detection. J Chromatogr B Biomed Sci Appl. 2001 Oct 5;762(1):51-8. doi: 10.1016/s0378-4347(01)00342-5.</citation>
    <PMID>11589458</PMID>
  </reference>
  <reference>
    <citation>Najib N, Idkaidek N, Beshtawi M, Bader M, Admour I, Alam SM, Zaman Q, Dham R. Bioequivalence evaluation of two brands of metformin 500 mg tablets (Dialon &amp; Glucophage)--in healthy human volunteers. Biopharm Drug Dispos. 2002 Oct;23(7):301-6. doi: 10.1002/bdd.326.</citation>
    <PMID>12355581</PMID>
  </reference>
  <reference>
    <citation>Scheen AJ. Clinical pharmacokinetics of metformin. Clin Pharmacokinet. 1996 May;30(5):359-71. doi: 10.2165/00003088-199630050-00003.</citation>
    <PMID>8743335</PMID>
  </reference>
  <verification_date>August 2012</verification_date>
  <study_first_submitted>August 29, 2012</study_first_submitted>
  <study_first_submitted_qc>August 30, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 31, 2012</study_first_posted>
  <last_update_submitted>August 30, 2012</last_update_submitted>
  <last_update_submitted_qc>August 30, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 31, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Biguanide</keyword>
  <keyword>anti-hyperglycaemic</keyword>
  <keyword>bioavailability</keyword>
  <keyword>bioequivalence</keyword>
  <keyword>metformin</keyword>
  <keyword>pharmacokinetics</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metformin</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01677260
org study id: PR. 143/EQL/2009
nct id: NCT01677260
lead sponsor: 
has dmc: No
This was a single centre, single-blind, randomized, balanced, combined single dose study
      under fasting condition and multiple doses study under fed condition with normal
      diabetic-meal, two-period, two-sequence cross-over study to to compare the bioavailability of
      metformin hydrochloride 500 mg extended release caplet (test drug) and metformin
      hydrochloride 500 mg prolonged release tablet (reference formulation).
On Day 1, to obtain pharmacokinetic profile of a single dose, the test or reference drugs
      were given with 200 mL of water and swallowed without chewing the drug. For multiple doses
      administration at Day 2 until Day 5, the study drugs were administered at a regimen of one
      tablet each day, 30 minutes after breakfast. Time of drug administration was standardized for
      all participating subjects throughout the study period.

      From each subject, on Day 1 until Day 5 blood samples were drawn 5 mL before breakfast and
      drug administration; and breakfast was provided only on Day 2 until Day 5. Only on Day 1 and
      Day 5 after drug administration, the blood samples were drawn 5 mL each at 1, 1.5, 2, 2.5, 3,
      3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 10, 12, 16 and 24 hours.

      The blood samples drawn on Day 1 were used to show the single dose pharmacokinetic profile
      under fasting condition; while those drawn on Day 5 were used to show the
      multiple-dose-pharmacokinetic profile after meal intake.

      One week after the first drug administration (washout period), the same procedure was
      repeated with the alternate drug.

      The plasma concentrations of metformin were determined by high performance liquid
      chromatography with ultraviolet detection (HPLC-UV). The pharmacokinetic parameters assessed
      in the single dose study were AUCt, AUCinf, Cmax, tmax, and t1/2. The pharmacokinetic
      parameters assessed in multiple doses study at steady state phase were AUCtau, Cmax, Cmin,
      and t1/2.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Single (Investigator)
measure: Bioavailability
time frame: 24 hours
description: Relative bioavailability (primarily measured by AUC and Cmax) between metformin hydrochloride 500 mg extended release caplet (test formulation) and metformin hydrochloride 500 mg prolonged release tablet (reference formulation) at a single dose.
measure: Bioavailability
time frame: 5 days
description: Relative bioavailability (primarily measured by AUC and Cmax) between metformin hydrochloride 500 mg extended release caplet (test formulation) and metformin hydrochloride 500 mg prolonged release tablet (reference formulation)at multiple doses.
measure: Bioavailability
time frame: 24 hours
description: Relative bioavailability (secondarily measured by tmax and t1/2) between metformin hydrochloride 500 mg extended release caplet (test formulation) and metformin hydrochloride 500 mg prolonged release tablet (reference formulation)at a single dose.
measure: Bioavailability
time frame: 5 days
description: Relative bioavailability (secondarily measured by tmax and t1/2) between metformin hydrochloride 500 mg extended release caplet (test formulation) and metformin hydrochloride 500 mg prolonged release tablet (reference formulation)at multiple doses.
measure: Adverse events
time frame: 2 months
description: Adverse events occurred during the study conduct (2 months) were properly and sufficiently handled and recorded.
arm group label: Group I
arm group type: Experimental
description: 500 mg metformin hydrochloride extended release caplet (PT Ferron Par Pharmaceuticals)
arm group label: Group II
arm group type: Active Comparator
description: 500 mg metformin hydrochloride prolonged release tablet (PT Merck Pharmaceuticals)
intervention type: Drug
intervention name: 500 mg metformin hydrochloride extended release caplet (test drug)
description: In each of the two study periods (separated by a washout of one week) a single and multiple dose of test or reference product was administered.
arm group label: Group I
other name: Glumin® XR, manufactured by PT Ferron Par Pharmaceuticals
intervention type: Drug
intervention name: 500 mg metformin hydrochloride prolonged release tablet (reference drug)
description: In each of the two study periods (separated by a washout of one week) a single and multiple dose of test or reference product was administered.
arm group label: Group II
other name: Glucophage® SR, manufactured by PT Merck Pharmaceuticals
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Danang A. Yunaidi, MD
role: Principal Investigator
affiliation: PT Equilab International
facility: 
country: Indonesia
citation: Caille G, Lacasse Y, Raymond M, Landriault H, Perrotta M, Picirilli G, Thiffault J, Spenard J. Bioavailability of metformin in tablet form using a new high pressure liquid chromatography assay method. Biopharm Drug Dispos. 1993 Apr;14(3):257-63. doi: 10.1002/bdd.2510140308.
PMID: 8490112
citation: Cheng CL, Chou CH. Determination of metformin in human plasma by high-performance liquid chromatography with spectrophotometric detection. J Chromatogr B Biomed Sci Appl. 2001 Oct 5;762(1):51-8. doi: 10.1016/s0378-4347(01)00342-5.
PMID: 11589458
citation: Najib N, Idkaidek N, Beshtawi M, Bader M, Admour I, Alam SM, Zaman Q, Dham R. Bioequivalence evaluation of two brands of metformin 500 mg tablets (Dialon & Glucophage)--in healthy human volunteers. Biopharm Drug Dispos. 2002 Oct;23(7):301-6. doi: 10.1002/bdd.326.
PMID: 12355581
citation: Scheen AJ. Clinical pharmacokinetics of metformin. Clin Pharmacokinet. 1996 May;30(5):359-71. doi: 10.2165/00003088-199630050-00003.
PMID: 8743335
responsible party type: Sponsor
mesh term: Metformin