<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/NCT01713647</url>
  </required_header>
  <id_info>
    <org_study_id>AMLH423/PRO-00</org_study_id>
    <nct_id>NCT01713647</nct_id>
  </id_info>
  <brief_title>Bioequivalence Study of Amlodipine / Losartan/ Hydrochlorothiazide of PHARMALINE, Lebanon Under Fastion Conditions</brief_title>
  <official_title>Comparative, Randomized,, Single Dose, Open-label, Crossover Bioequivalence Study of LOSANET AM PLUS 10mg/100mg/12.5 mg Tablets (One Tablet) of (PHARMALINE, Lebanon) Versus NORVASC 10mg Tablets (One Tablet) of (Pfizer Canada Inc., Kirkland (Quebec)) and HYZAAR 100mg/12.5 Tablets (One Tablet) of (Merck Sharp &amp; Dohme, Quimica de Puerto Rico, Inc, Road 2 Km. 60.3, Sabana Hoyos, Arecibo, PR 00688 for Merck Sharp &amp; Dohme B.V. Haarlem, The Netherlands) in Healthy Subjects Under Fasting Conditions.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Pharmaceutical Research Unit, Jordan</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Pharmaceutical Research Unit, Jordan</source>
  <brief_summary>
    <textblock>
      To assess the bioequivalence of the investigational TEST product with the marketed REFERENCE&#xD;
      products by measurement of Plasma concentrations of Amlodipine ,Losartan, Carboxylic acid&#xD;
      losartan metabolite &amp; Hydrochlorothiazide in plasma and calculation of the bioequivalence&#xD;
      parameters from those measurements followed by ANOVA and 90% confidence interval statistical&#xD;
      evaluation.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">December 2012</completion_date>
  <primary_completion_date type="Actual">December 2012</primary_completion_date>
  <phase>Phase 1</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>To assess the bioequivalence of Test oral formulation of LOSANET AM PLUS versus References NORVASC and HYZAAR.</measure>
    <time_frame>9 weeks</time_frame>
    <description>To assess the bioequivalence of the investigational TEST product with the marketed REFERENCE products by measurement of Plasma concentrations of Amlodipine ,Losartan, Carboxylic acid losartan metabolite &amp; Hydrochlorothiazide in plasma and calculation of the bioequivalence parameters from those measurements followed by ANOVA and 90% confidence interval statistical evaluation.&#xD;
Cmax Ratio: Scaled average bioequivalence will be performed. Bioequivalence limits will be defined and widened according to the variance of σw2 within subject variability for the reference based on Amlodipine, Losartan, &amp; Hydrochlorothiazide&#xD;
AUC Ratio: The 90% confidence interval for this measure lies within an acceptance range of 80.00% - 125.00% based on Losartan, &amp; Hydrochlorothiazide&#xD;
AUC0-72 Ratio: The 90% confidence interval for this measure lies within an acceptance range of 80.00 - 125.00 % based on Amlodipine&#xD;
Carboxylic acid Losartan metabolite will be considered as supportive data</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">39</enrollment>
  <condition>Fasting</condition>
  <arm_group>
    <arm_group_label>LOSANET AM PLUS (10/100/12.5 mg) of PHARMALINE, Lebanon</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will be fasted overnight and receive one tablet by mouth in accordance with randomization table, and blood samples will be taken at specified intervals over 3 days&#xD;
intervention: Drug: LOSANET AM PLUS Amlodipine/ Losartan/Hydrochlorothiazide Other Name: NA</description>
  </arm_group>
  <arm_group>
    <arm_group_label>NORVASC &amp; HYZAAR (100/12.5 mg)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects will be fasted overnight and receive one tablet of Norvasc &amp;HYZAAR by mouth in accordance with randomization table, and blood samples will be taken over 3 days&#xD;
intervention: Drug: LOSANET AM PLUS Amlodipine/ Losartan/Hydrochlorothiazide Other Name: NA</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Amlodipin, losartan, HCTZ</intervention_name>
    <arm_group_label>LOSANET AM PLUS (10/100/12.5 mg) of PHARMALINE, Lebanon</arm_group_label>
    <arm_group_label>NORVASC &amp; HYZAAR (100/12.5 mg)</arm_group_label>
    <other_name>LOSANET AM PLUS</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Healthy subjects.&#xD;
&#xD;
          2. Ethnic Group: Arab &amp; Mediterranean&#xD;
&#xD;
          3. Race: Mixed skin (white &amp; black skin people).&#xD;
&#xD;
          4. Age 18-50 years&#xD;
&#xD;
          5. Body-mass index 18.5 to 30.0 kg/m2 inclusive (minimum of 50 kg weight).&#xD;
&#xD;
          6. Subject is available for the whole study period and gave written informed consent&#xD;
&#xD;
          7. Physical examination within normal ranges&#xD;
&#xD;
          8. All laboratory screening results within the normal range, or being assessed as&#xD;
             clinically non-significant by the attending physician&#xD;
&#xD;
          9. Vital signs within normal ranges.&#xD;
&#xD;
         10. Kidney function test, Liver function test should be within normal ranges.&#xD;
&#xD;
         11. Pre dosing blood pressure more than 110/70 mmHg.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Women of childbearing potential, pregnant and lactating women.&#xD;
&#xD;
          2. Ethnic Group (Non- Arab &amp;/ or Non- Mediterranean)&#xD;
&#xD;
          3. History of severe allergy or allergic reactions to study drug or related drugs or&#xD;
             heparin&#xD;
&#xD;
          4. Known history or presence of food allergies, or any surgical or medical condition&#xD;
             known to interfere with the absorption, distribution, metabolism or excretion of drugs&#xD;
&#xD;
          5. History of serious illness that can impact fate of drugs&#xD;
&#xD;
          6. Known history or presence of cardiac, pulmonary, gastrointestinal, endocrine,&#xD;
             musculoskeletal, neurological, hematological, liver or kidney disease, unless judged&#xD;
             not clinically significant by the Principal Investigator, or medical designate&#xD;
&#xD;
          7. Clinically significant illness 4 weeks before study Period I&#xD;
&#xD;
          8. Serious mental disease, drug, alcohol, solvents or caffeine abuse, smoking.&#xD;
&#xD;
          9. Regular use of medication&#xD;
&#xD;
         10. Having taken medication that could affect the investigated drug product: a) Regular&#xD;
             consumption of drugs during the two weeks prior to study initiation day, b)&#xD;
             consumption of enzyme stimulating or inhibiting drugs (e.g. Barbiturates,&#xD;
             Carbamazepine, Phenytoin, Amphetamine, benzodiazepine, cannabinoid, cocaine, opiates,&#xD;
             phencyclidine, and methadone) during one month before the study initiation&#xD;
&#xD;
         11. Presence of any significant physical or organ abnormality&#xD;
&#xD;
         12. Donation of 1) at least 400 ml of blood within 60 days, or 2) more than 150 ml of&#xD;
             blood within 30 days, or 3) more than 100 ml blood plasma or platelets within 14 days&#xD;
             before study Period I&#xD;
&#xD;
         13. Participation in another bioequivalence study within 80 days prior to the start of&#xD;
             this study Period I&#xD;
&#xD;
         14. Following a special diet (e.g. vegetarian) or dieting one month before the study&#xD;
             initiation.&#xD;
&#xD;
         15. Prior history of hypersensitivity to Amlodipine besylate, Losartan Potassium &amp;&#xD;
             Hydrochlorothiazide.&#xD;
&#xD;
         16. Consumption of grapefruit or grapefruit containing products within 7 days of drug&#xD;
             administration&#xD;
&#xD;
         17. Ingestion of any vitamins or herbal products within 7 days prior to the initial dose&#xD;
             of the study medication.&#xD;
&#xD;
         18. Exhausting physical exercise in the last 48 hours (e.g. weight lifting) or any recent&#xD;
             significant change in dietary or exercise habits.&#xD;
&#xD;
         19. Any significant clinical abnormality including HBsAg, HCV, and HIV&#xD;
&#xD;
         20. Abnormal vital signs.&#xD;
&#xD;
         21. Abnormal Kidney or Liver function tests.&#xD;
&#xD;
         22. Vomiting, Diarrhea.&#xD;
&#xD;
         23. Pre dosing blood pressure less than 110/70 mmHg&#xD;
&#xD;
         24. Positive test for elicit drugs and alcohol prior to dosing in each period.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Rana .T Bustami, Phd.pharmacy</last_name>
    <role>Principal Investigator</role>
    <affiliation>PRU</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Pharmaceutical research unit</name>
      <address>
        <city>Amman</city>
        <zip>1084</zip>
        <country>Jordan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Jordan</country>
  </location_countries>
  <verification_date>October 2012</verification_date>
  <study_first_submitted>October 16, 2012</study_first_submitted>
  <study_first_submitted_qc>October 23, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 25, 2012</study_first_posted>
  <last_update_submitted>July 24, 2013</last_update_submitted>
  <last_update_submitted_qc>July 24, 2013</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 25, 2013</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Bio-equivalence, crossover</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Losartan</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/NCT01713647
org study id: AMLH423/PRO-00
nct id: NCT01713647
lead sponsor: 
To assess the bioequivalence of the investigational TEST product with the marketed REFERENCE
      products by measurement of Plasma concentrations of Amlodipine ,Losartan, Carboxylic acid
      losartan metabolite & Hydrochlorothiazide in plasma and calculation of the bioequivalence
      parameters from those measurements followed by ANOVA and 90% confidence interval statistical
      evaluation.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: To assess the bioequivalence of Test oral formulation of LOSANET AM PLUS versus References NORVASC and HYZAAR.
time frame: 9 weeks
description: To assess the bioequivalence of the investigational TEST product with the marketed REFERENCE products by measurement of Plasma concentrations of Amlodipine ,Losartan, Carboxylic acid losartan metabolite & Hydrochlorothiazide in plasma and calculation of the bioequivalence parameters from those measurements followed by ANOVA and 90% confidence interval statistical evaluation.
Cmax Ratio: Scaled average bioequivalence will be performed. Bioequivalence limits will be defined and widened according to the variance of σw2 within subject variability for the reference based on Amlodipine, Losartan, & Hydrochlorothiazide
AUC Ratio: The 90% confidence interval for this measure lies within an acceptance range of 80.00% - 125.00% based on Losartan, & Hydrochlorothiazide
AUC0-72 Ratio: The 90% confidence interval for this measure lies within an acceptance range of 80.00 - 125.00 % based on Amlodipine
Carboxylic acid Losartan metabolite will be considered as supportive data
arm group label: LOSANET AM PLUS (10/100/12.5 mg) of PHARMALINE, Lebanon
arm group type: Experimental
description: Subjects will be fasted overnight and receive one tablet by mouth in accordance with randomization table, and blood samples will be taken at specified intervals over 3 days
intervention: Drug: LOSANET AM PLUS Amlodipine/ Losartan/Hydrochlorothiazide Other Name: NA
arm group label: NORVASC & HYZAAR (100/12.5 mg)
arm group type: Active Comparator
description: Subjects will be fasted overnight and receive one tablet of Norvasc &HYZAAR by mouth in accordance with randomization table, and blood samples will be taken over 3 days
intervention: Drug: LOSANET AM PLUS Amlodipine/ Losartan/Hydrochlorothiazide Other Name: NA
intervention type: Drug
intervention name: Amlodipin, losartan, HCTZ
arm group label: LOSANET AM PLUS (10/100/12.5 mg) of PHARMALINE, Lebanon
arm group label: NORVASC & HYZAAR (100/12.5 mg)
other name: LOSANET AM PLUS
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Rana .T Bustami, Phd.pharmacy
role: Principal Investigator
affiliation: PRU
facility: 
country: Jordan
responsible party type: Sponsor
mesh term: Losartan