<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/NCT03803371</url>
  </required_header>
  <id_info>
    <org_study_id>B4741005</org_study_id>
    <nct_id>NCT03803371</nct_id>
  </id_info>
  <brief_title>Bioequivalence Study of Tramadol Hydrochloride /Paracetamol Tablets Versus Ultracet Tablets</brief_title>
  <official_title>A PHASE IV, OPEN LABEL, RANDOMIZED, TWO TREATMENT, TWO PERIOD, TWO SEQUENCE, CROSSOVER BIOEQUIVALENCE STUDY TO COMPARE AN ORAL FORMULATION OF TRAMADOL HYDROCHLORIDE 37.5 MG/PARACETAMOL 325 MG TABLETS (TEST PRODUCT OF PFIZER) VERSUS ULTRACET(REGISTERED) (TRAMADOL HYDROCHLORIDE/PARACETAMOL 37.5 MG/325 MG OF JANSSEN CILAG FARMACÊUTICA LTDA, REFERENCE PRODUCT OF BRAZIL) IN HEALTHY ADULT RESEARCH SUBJECTS UNDER FASTING CONDITIONS</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Pfizer</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The sponsor, Pfizer has developed a formulation of tramadol hydrochloride/ paracetamol 37.5&#xD;
      mg/ 325 mg (test drug) as a generic alternative to the reference listed product Ultracet®. In&#xD;
      order to meet the requirements for registration as a generic drug, this study is being&#xD;
      conducted to demonstrate the bioequivalence between the formulation of tramadol&#xD;
      hydrochloride/ paracetamol 37.5 mg/ 325 mg provided by Pfizer and the reference drug tramadol&#xD;
      hydrochloride/ paracetamol 37.5 mg/ 325 mg, available in the pharmaceutical market in Brazil&#xD;
      (Ultracet®, Janssen Cilag Farmacêutica Ltda).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 26, 2019</start_date>
  <completion_date type="Actual">June 28, 2019</completion_date>
  <primary_completion_date type="Actual">June 28, 2019</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>Crossover Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area under the tramadol and paracetamol plasma concentration-time curve from time zero to last time point (AUClast)</measure>
    <time_frame>Predose (0 hour), at 0.08, 0.16, 0.25, 0.33, 0.41, 0.50, 0.66, 0.83, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12, 24 and 36 hours post dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum plasma concentrations of tramadol and paracetamol (Cmax)</measure>
    <time_frame>Predose (0 hour), at 0.08, 0.16, 0.25, 0.33, 0.41, 0.50, 0.66, 0.83, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12, 24 and 36 hours post dose</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Area under the tramadol and paracetamol plasma concentration-time curve from time zero extrapolated to infinite time</measure>
    <time_frame>Predose (0 hour), at 0.08, 0.16, 0.25, 0.33, 0.41, 0.50, 0.66, 0.83, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12, 24 and 36 hours post dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to first occurrence of Cmax (Tmax) of tramadol and paracetamol</measure>
    <time_frame>Predose (0 hour), at 0.08, 0.16, 0.25, 0.33, 0.41, 0.50, 0.66, 0.83, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12, 24 and 36 hours post dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with treatment-related adverse events as assessed by CTCAE v4.0</measure>
    <time_frame>Predose (0 hour), at 0.08, 0.16, 0.25, 0.33, 0.41, 0.50, 0.66, 0.83, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12, 24 and 36 hours post dose</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Tramadol hydrochloride 37.5 mg/Paracetamol 325 mg tablets</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tramadol hydrochloride 37.5 mg/Paracetamol 325 mg tablets by mouth on Day 1 of period 1 or 2</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ultracet tablet</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Ultracet tablet (Tramadol hydrochloride 37.5 mg/Paracetamol 325 mg) by mouth on Day 1 of period 1 or 2</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ultracet Tablets</intervention_name>
    <description>Ultracet tablet (Janssen Cilag Farmacêutica Ltda) equivalent to Tramadol hydrochloride 37.5 mg/Paracetamol 325 mg</description>
    <arm_group_label>Ultracet tablet</arm_group_label>
    <other_name>Reference drug</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tramadol hydrochloride 37.5 mg/Paracetamol 325 mg tablets - tablet (Pfizer)</intervention_name>
    <description>Tramadol hydrochloride 37.5 mg/Paracetamol 325 mg tablets (Pfizer)</description>
    <arm_group_label>Tramadol hydrochloride 37.5 mg/Paracetamol 325 mg tablets</arm_group_label>
    <other_name>Test Drug</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  1. Healthy female research subjects and/or male research subjects who, at the time of&#xD;
             screening, are between the ages of 18 and 55 years, inclusive.&#xD;
&#xD;
        Female subjects of nonchildbearing potential must meet at least 1 of the following&#xD;
        criteria:&#xD;
&#xD;
          1. Achieved postmenopausal status, defined as follows: cessation of regular menses for at&#xD;
             least 12 consecutive months with no alternative pathological or physiological cause,&#xD;
             and have a serum follicle stimulating hormone (FSH) level confirming the&#xD;
             postmenopausal state;&#xD;
&#xD;
          2. Have undergone a documented hysterectomy and/or bilateral oophorectomy;&#xD;
&#xD;
          3. Have medically confirmed ovarian failure. All other female subjects (including female&#xD;
             subjects with tubal ligations) are considered to be of childbearing potential.&#xD;
&#xD;
             2. Body mass index (BMI) of 18.5 kg/m2 to 24.9 kg/m2 (the upper limit may vary up to&#xD;
             15% to allow subjects with a BMI from 18.5 kg/m2 to 28.6 kg/m2 to participate), and a&#xD;
             total body weight &gt;50 kg (&gt;110 lbs).&#xD;
&#xD;
             3. Evidence of a personally signed and dated informed consent document indicating that&#xD;
             the research subject has been informed of all pertinent aspects of the study.&#xD;
&#xD;
             4. Research subjects who are willing and able to comply with all scheduled visits,&#xD;
             treatment plan, laboratory tests, and other study procedures&#xD;
&#xD;
             Exclusion Criteria:&#xD;
&#xD;
               1. Evidence or history of clinically significant hematological, renal, endocrine,&#xD;
                  pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological,&#xD;
                  or allergic disease (including drug allergies, but excluding untreated,&#xD;
                  asymptomatic, seasonal allergies at the time of dosing).&#xD;
&#xD;
               2. Clinically significant infections within the past 3 months (eg, those requiring&#xD;
                  hospitalization or parenteral antibiotics, or as judged by the Investigator),&#xD;
                  evidence of any infection within the past 7 days, history of disseminated herpes&#xD;
                  simplex infection or recurrent or disseminated herpes zoster.&#xD;
&#xD;
               3. Any condition possibly affecting drug absorption (eg, gastrectomy, colon&#xD;
                  resection, etc.).&#xD;
&#xD;
               4. Research subjects with a history of, or current evidence for, severe&#xD;
                  gastrointestinal narrowing (pathologic or iatrogenic).&#xD;
&#xD;
               5. History of or current positive results for any of the following serological&#xD;
                  tests: hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb),&#xD;
                  anti hepatitis C core antibody (HCV Ab), or human immunodeficiency virus (HIV) 1&#xD;
                  and 2.&#xD;
&#xD;
               6. Malignancy or a history of malignancy&#xD;
&#xD;
               7. A positive urine drug test.&#xD;
&#xD;
               8. A positive alcohol screen.&#xD;
&#xD;
               9. History of regular alcohol consumption exceeding 14 drinks/week for female&#xD;
                  subjects or 21 drinks/week for male subjects [1 drink = 5 ounces (150 mL) of wine&#xD;
                  or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor] within 6&#xD;
                  months before screening.&#xD;
&#xD;
              10. Use of tobacco or nicotine containing products in excess of the equivalent of 5&#xD;
                  cigarettes per day.&#xD;
&#xD;
              11. Treatment with an investigational drug within 6 months or 4 or 5 half lives&#xD;
                  preceding the first dose of investigational product (whichever is longer).&#xD;
&#xD;
              12. Pregnant female subjects, breastfeeding female subjects, fertile male subjects&#xD;
                  and female subjects of childbearing potential who are unwilling or unable to use&#xD;
                  a highly effective method of contraception as outlined in this protocol from at&#xD;
                  least 14 days prior to the first dose of investigational product until at least&#xD;
                  28 days after the last dose of investigational product.&#xD;
&#xD;
              13. Use of prescription or nonprescription drugs and dietary supplements within 14&#xD;
                  days or 5 half lives (whichever is longer) prior to the first dose of&#xD;
                  investigational product. Limited use of non prescription medications that are not&#xD;
                  believed to affect research subject safety or the overall results of the study&#xD;
                  may be permitted on a case by case basis following approval by the sponsor.&#xD;
&#xD;
                  • Herbal supplements, hormonal methods of contraception (including oral and&#xD;
                  transdermal contraceptives, injectable progesterone, progestin subdermal&#xD;
                  implants, progesterone releasing intrauterine devices [IUDs], vaginal ring, and&#xD;
                  postcoital contraceptive methods), and hormone replacement therapy must have been&#xD;
                  discontinued at least 28 days prior to the first dose of investigational product.&#xD;
&#xD;
              14. Consumption of grapefruit or grapefruit related citrus fruits (eg, Seville&#xD;
                  oranges, pomelos) or juices within 7 days prior to dosing.&#xD;
&#xD;
              15. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or&#xD;
                  more within 3 months prior to screening.&#xD;
&#xD;
              16. History of sensitivity to heparin or heparin induced thrombocytopenia.&#xD;
&#xD;
              17. History of hypersensitivity to tramadol or paracetamol or any of the components&#xD;
                  in the formulation of the study products.&#xD;
&#xD;
              18. Unwilling or unable to comply with the criteria in the Lifestyle Requirements&#xD;
                  section of this protocol.&#xD;
&#xD;
              19. Other acute or chronic medical or psychiatric condition including recent (within&#xD;
                  the past year) or active suicidal ideation or behavior or laboratory abnormality&#xD;
                  that may increase the risk associated with study participation or investigational&#xD;
                  product administration or may interfere with the interpretation of study results&#xD;
                  and, in the judgment of the investigator, would make the research subject&#xD;
                  inappropriate for entry into this study.&#xD;
&#xD;
              20. Research subjects who are investigator site staff members directly involved in&#xD;
                  the conduct of the study and their family members, site staff members otherwise&#xD;
                  supervised by the Investigator, or research subjects who are the sponsor's&#xD;
                  employees, including their family members, directly involved in the conduct of&#xD;
                  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>Pfizer CT.gov Call Center</last_name>
    <role>Study Director</role>
    <affiliation>Pfizer</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>ICF - Instituto de Ciencias Farmaceuticas de Estudos e Pesquisas Ltda</name>
      <address>
        <city>Aparecida de Goiania</city>
        <state>GO</state>
        <zip>74935-530</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <link>
    <url>https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B4741005&amp;StudyName=A+PHASE+IV%2C+OPEN+LABEL%2C+RANDOMIZED%2C+TWO+TREATMENT%2C+TWO+PERIOD%2C+TWO+SEQUENCE%2C+CROSSOVER+BIOEQUIVALENCE+STUDY+TO+COMPARE+AN+ORAL+FORMULATION+OF+TRAMADOL+HYDROCHLORIDE+37.5+MG%2FPARACETAMOL+325+MG+TABLETS+%28TEST+PRODUCT+OF+PFIZER%29+VERSUS+ULTRACET%28REGISTERED%29+%28TRAMADOL+HYDROCHLORIDE%2FPARACETAMOL+37.5+MG%2F325+MG+OF+JANSSEN+CILAG+FARMAC%C3%8AUTICA+LTDA%2C+REFERENCE+PRODUCT+OF+BRAZIL%29+IN+HEALTHY+ADULT+RESEARCH+SUBJECTS+UNDER+FASTING+CONDITIONS</url>
    <description>To obtain contact information for a study center near you, click here.</description>
  </link>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>January 2, 2019</study_first_submitted>
  <study_first_submitted_qc>January 10, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 14, 2019</study_first_posted>
  <last_update_submitted>July 16, 2019</last_update_submitted>
  <last_update_submitted_qc>July 16, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">July 17, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acetaminophen</mesh_term>
    <mesh_term>Tramadol</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.</ipd_description>
    <ipd_url>https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests</ipd_url>
  </patient_data>
  <!-- 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/NCT03803371
org study id: B4741005
nct id: NCT03803371
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
The sponsor, Pfizer has developed a formulation of tramadol hydrochloride/ paracetamol 37.5
      mg/ 325 mg (test drug) as a generic alternative to the reference listed product Ultracet®. In
      order to meet the requirements for registration as a generic drug, this study is being
      conducted to demonstrate the bioequivalence between the formulation of tramadol
      hydrochloride/ paracetamol 37.5 mg/ 325 mg provided by Pfizer and the reference drug tramadol
      hydrochloride/ paracetamol 37.5 mg/ 325 mg, available in the pharmaceutical market in Brazil
      (Ultracet®, Janssen Cilag Farmacêutica Ltda).
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Other
masking: None (Open Label)
measure: Area under the tramadol and paracetamol plasma concentration-time curve from time zero to last time point (AUClast)
time frame: Predose (0 hour), at 0.08, 0.16, 0.25, 0.33, 0.41, 0.50, 0.66, 0.83, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12, 24 and 36 hours post dose
measure: Maximum plasma concentrations of tramadol and paracetamol (Cmax)
time frame: Predose (0 hour), at 0.08, 0.16, 0.25, 0.33, 0.41, 0.50, 0.66, 0.83, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12, 24 and 36 hours post dose
measure: Area under the tramadol and paracetamol plasma concentration-time curve from time zero extrapolated to infinite time
time frame: Predose (0 hour), at 0.08, 0.16, 0.25, 0.33, 0.41, 0.50, 0.66, 0.83, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12, 24 and 36 hours post dose
measure: Time to first occurrence of Cmax (Tmax) of tramadol and paracetamol
time frame: Predose (0 hour), at 0.08, 0.16, 0.25, 0.33, 0.41, 0.50, 0.66, 0.83, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12, 24 and 36 hours post dose
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
time frame: Predose (0 hour), at 0.08, 0.16, 0.25, 0.33, 0.41, 0.50, 0.66, 0.83, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12, 24 and 36 hours post dose
arm group label: Tramadol hydrochloride 37.5 mg/Paracetamol 325 mg tablets
arm group type: Experimental
description: Tramadol hydrochloride 37.5 mg/Paracetamol 325 mg tablets by mouth on Day 1 of period 1 or 2
arm group label: Ultracet tablet
arm group type: Active Comparator
description: Ultracet tablet (Tramadol hydrochloride 37.5 mg/Paracetamol 325 mg) by mouth on Day 1 of period 1 or 2
intervention type: Drug
intervention name: Ultracet Tablets
description: Ultracet tablet (Janssen Cilag Farmacêutica Ltda) equivalent to Tramadol hydrochloride 37.5 mg/Paracetamol 325 mg
arm group label: Ultracet tablet
other name: Reference drug
intervention type: Drug
intervention name: Tramadol hydrochloride 37.5 mg/Paracetamol 325 mg tablets - tablet (Pfizer)
description: Tramadol hydrochloride 37.5 mg/Paracetamol 325 mg tablets (Pfizer)
arm group label: Tramadol hydrochloride 37.5 mg/Paracetamol 325 mg tablets
other name: Test Drug
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Pfizer CT.gov Call Center
role: Study Director
affiliation: Pfizer
facility: 
country: Brazil
url: https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B4741005&StudyName=A+PHASE+IV%2C+OPEN+LABEL%2C+RANDOMIZED%2C+TWO+TREATMENT%2C+TWO+PERIOD%2C+TWO+SEQUENCE%2C+CROSSOVER+BIOEQUIVALENCE+STUDY+TO+COMPARE+AN+ORAL+FORMULATION+OF+TRAMADOL+HYDROCHLORIDE+37.5+MG%2FPARACETAMOL+325+MG+TABLETS+%28TEST+PRODUCT+OF+PFIZER%29+VERSUS+ULTRACET%28REGISTERED%29+%28TRAMADOL+HYDROCHLORIDE%2FPARACETAMOL+37.5+MG%2F325+MG+OF+JANSSEN+CILAG+FARMAC%C3%8AUTICA+LTDA%2C+REFERENCE+PRODUCT+OF+BRAZIL%29+IN+HEALTHY+ADULT+RESEARCH+SUBJECTS+UNDER+FASTING+CONDITIONS
description: To obtain contact information for a study center near you, click here.
responsible party type: Sponsor
mesh term: Acetaminophen
mesh term: Tramadol
sharing ipd: Yes
ipd description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
ipd url: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests