<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/NCT03018015</url>
  </required_header>
  <id_info>
    <org_study_id>1325ib16ct</org_study_id>
    <nct_id>NCT03018015</nct_id>
  </id_info>
  <brief_title>Ibuprofen Bioavailability Trial With Oral Single Dose Administration.</brief_title>
  <official_title>Characterisation of Relative Bioavailability of a Newly Developed Ibuprofen Oral Powder Formulation in Comparison With Two Marketed Reference Products in a Single Dose, 3-period-crossover Design Under Fasting Conditions; Controlled, Open-label, Randomised Study With Bioequivalence Assessment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>SocraTec R&amp;D GmbH</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>SocraMetrics GmbH</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>SocraTec R&amp;D GmbH</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The present study will be conducted in order to assess bioequivalence of the Test product&#xD;
      (Ibuprofen 400 mg oral powder) and the Reference product 1 (Brufen 400 mg film-coated&#xD;
      tablet), an approved market product in the European Union. Testing for bioequivalence will be&#xD;
      performed considering AUC0-tlast and Cmax obtained after oral single dose fasted&#xD;
      administration of ibuprofen.&#xD;
&#xD;
      In addition to the conventional immediate release tablet used as Reference 1, a soft capsule&#xD;
      formulation will be applied as Reference 2 (Spalt Forte 400 mg Weichkapseln), as an example&#xD;
      for a product with a very fast absorption rate.&#xD;
&#xD;
      All 3 immediate release preparations contain 400 mg ibuprofen.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The clinical trial will be performed in a single centre, open-label, randomised (order of&#xD;
      treatments), balanced, 3-period, 6-sequence, single dose change-over design with&#xD;
      administration under fasting conditions separated by a washout period of at least 2&#xD;
      treatment-free days.&#xD;
&#xD;
      Blood sample collection will be performed over 16 h after administration. This time is&#xD;
      considered adequate to characterise plasma concentration vs. time profiles long enough for&#xD;
      reliable estimation of the extent of absorption, i.e. the AUC derived from measurements is&#xD;
      expected to cover at least 80 % of the AUC extrapolated to infinity.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2016</start_date>
  <completion_date type="Actual">October 2016</completion_date>
  <primary_completion_date type="Actual">October 2016</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>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area under the plasma concentration versus time curve (AUC0-tlast) for ibuprofen</measure>
    <time_frame>16 hours interval</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Peak Plasma Concentration (Cmax) for ibuprofen</measure>
    <time_frame>16 hours interval</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of participants with treatment-related adverse events</measure>
    <time_frame>from first dose until discharge of the subject (approx. 2 weeks)</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Bioequivalence</condition>
  <arm_group>
    <arm_group_label>Ibuprofen 400 mg oral powder</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>oral fasted administration of 1 sachet of Ibuprofen 400 mg oral powder (Hermes Arzneimittel GmbH, Germany), containing 400 mg ibuprofen</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Brufen 400 mg film-coated tablets</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>oral fasted administration of Brufen 400 mg film-coated tablets (Abbott Scandinavia AB, Sweden), containing 400 mg ibuprofen</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Spalt forte 400 mg Weichkapseln</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>oral fasted administration of Spalt forte 400 mg Weichkapseln (Pfizer Consumer Healthcare GmbH, Germany), containing 400 mg ibuprofen</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ibuprofen 400 mg oral powder</intervention_name>
    <arm_group_label>Ibuprofen 400 mg oral powder</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ibuprofen 400 mg film-coated tablet</intervention_name>
    <arm_group_label>Brufen 400 mg film-coated tablets</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ibuprofen 400 mg soft capsule</intervention_name>
    <arm_group_label>Spalt forte 400 mg Weichkapseln</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. sex: male/female&#xD;
&#xD;
          2. ethnic origin: Caucasian&#xD;
&#xD;
          3. age: 18 years or older&#xD;
&#xD;
          4. body-mass index (BMI): ≥ 18.5 kg/m² and ≤ 30.0 kg/m², body weight &gt; 40 kg&#xD;
&#xD;
          5. good state of health&#xD;
&#xD;
          6. non-smoker or ex-smoker for at least 3 months&#xD;
&#xD;
          7. written informed consent, after having been informed about benefits and potential&#xD;
             risks of the clinical trial, as well as details of the insurance taken out to cover&#xD;
             the subjects participating in the clinical trial&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. existing cardiac and/or haematological diseases or pathological findings, which might&#xD;
             interfere with the safety or tolerability of the active ingredient&#xD;
&#xD;
          2. existing hepatic and/or renal diseases or pathological findings, which might interfere&#xD;
             with the safety or tolerability, and/or pharmacokinetics of the active ingredient&#xD;
&#xD;
          3. existing gastrointestinal diseases or pathological findings, which might interfere&#xD;
             with the safety, tolerability, absorption and/or pharmacokinetics of the active&#xD;
             ingredient&#xD;
&#xD;
          4. history of gastrointestinal bleeding or perforation, related to previous NSAID therapy&#xD;
&#xD;
          5. existing, or history of, recurrent gastrointestinal ulcer/ bleeding&#xD;
&#xD;
          6. conditions involving an increased tendency to bleeding&#xD;
&#xD;
          7. active or known inflammatory bowel diseases (e.g. colitis ulcerosa, Crohn´s disease)&#xD;
&#xD;
          8. history of relevant CNS and/or psychiatric disorders and/or currently treated CNS&#xD;
             and/or psychiatric disorders&#xD;
&#xD;
          9. known allergic reactions to the active ingredients used or to constituents of the&#xD;
             pharmaceutical preparations&#xD;
&#xD;
         10. history of hypersensitivity reactions (e.g. bronchial spasm, asthma, rhinitis,&#xD;
             urticaria, or angioedema) after intake of acetylsalicylic acid or other NSAIDs&#xD;
&#xD;
         11. subjects with severe allergies or multiple drug allergies unless it is judged as not&#xD;
             relevant for the clinical trial by the investigator&#xD;
&#xD;
         12. existing, or history of, bronchial asthma, chronic rhinitis or allergic diseases&#xD;
             unless it is judged as not relevant for the clinical trial by the investigator&#xD;
&#xD;
         13. subjects with hereditary problems of galactose intolerance, lactase deficiency or&#xD;
             glucose-galactose malabsorption&#xD;
&#xD;
         14. systolic blood pressure &lt; 90 or &gt; 145 mmHg&#xD;
&#xD;
         15. diastolic blood pressure &lt; 60 or &gt;90 mmHg&#xD;
&#xD;
         16. heart rate &lt; 50 bpm or &gt; 90 bpm&#xD;
&#xD;
         17. laboratory values out of normal range unless the deviation from normal is judged as&#xD;
             not relevant for the clinical trial by the investigator except parameters ASAT, ALAT,&#xD;
             bilirubin and creatinine (see exclusion criterion No. 18)&#xD;
&#xD;
         18. laboratory values: ASAT &gt; 20 % ULN, ALAT &gt; 10 % ULN, bilirubin &gt; 20 % ULN and&#xD;
             creatinine &gt; 9 μmol/l ULN&#xD;
&#xD;
         19. positive anti-HIV-test (if positive to be verified by western blot), HBs-AG-test (if&#xD;
             positive to be verified by test for HBc-IgM) or anti-HCVtest&#xD;
&#xD;
         20. acute or chronic diseases which may interfere with the pharmacokinetics of the IMP&#xD;
&#xD;
         21. history of or current drug or alcohol dependence&#xD;
&#xD;
         22. positive alcohol or drug test at screening examination&#xD;
&#xD;
         23. regular intake of alcoholic food or beverages of ≥ 40 g pure ethanol for male or ≥ 20&#xD;
             g pure ethanol for female per day&#xD;
&#xD;
         24. subjects who are on a diet which could affect the pharmacokinetics of the active&#xD;
             ingredient&#xD;
&#xD;
         25. regular intake of caffeine containing food or beverages of ≥ 500 mg caffeine per day&#xD;
&#xD;
         26. blood donation or other blood loss of more than 400 ml within the last 2 months prior&#xD;
             to individual enrolment of the subject&#xD;
&#xD;
         27. administration of any investigational medicinal product during the last 2 months prior&#xD;
             to individual enrolment of the subject&#xD;
&#xD;
         28. regular treatment with any systemically available medication (except hormonal&#xD;
             contraceptives)&#xD;
&#xD;
         29. subjects, who report a frequent occurrence of migraine attacks&#xD;
&#xD;
         30. positive pregnancy test at screening examination&#xD;
&#xD;
         31. pregnant or lactating women&#xD;
&#xD;
         32. female subjects who do not agree to apply highly effective contraceptive methods&#xD;
&#xD;
         33. subjects suspected or known not to follow instructions&#xD;
&#xD;
         34. subjects who are unable to understand the written and verbal instructions, in&#xD;
             particular regarding the risks and inconveniences they will be exposed to during their&#xD;
             participation in the clinical trial.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Cornelius Koch, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>SocraTec R&amp;D GmbH, Clinical Pharmacology Unit</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>SocraTec R&amp;D GmbH Clinical Pharmacology Unit</name>
      <address>
        <city>Erfurt</city>
        <state>Thüringen</state>
        <zip>99084</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>January 10, 2017</study_first_submitted>
  <study_first_submitted_qc>January 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 11, 2017</study_first_posted>
  <last_update_submitted>January 10, 2017</last_update_submitted>
  <last_update_submitted_qc>January 10, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 11, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Bioequivalence</keyword>
  <keyword>Healthy</keyword>
  <keyword>Bioavailability</keyword>
  <keyword>Ibuprofen</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ibuprofen</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/NCT03018015
org study id: 1325ib16ct
nct id: NCT03018015
lead sponsor: 
collaborator: 
has dmc: No
The present study will be conducted in order to assess bioequivalence of the Test product
      (Ibuprofen 400 mg oral powder) and the Reference product 1 (Brufen 400 mg film-coated
      tablet), an approved market product in the European Union. Testing for bioequivalence will be
      performed considering AUC0-tlast and Cmax obtained after oral single dose fasted
      administration of ibuprofen.

      In addition to the conventional immediate release tablet used as Reference 1, a soft capsule
      formulation will be applied as Reference 2 (Spalt Forte 400 mg Weichkapseln), as an example
      for a product with a very fast absorption rate.

      All 3 immediate release preparations contain 400 mg ibuprofen.
The clinical trial will be performed in a single centre, open-label, randomised (order of
      treatments), balanced, 3-period, 6-sequence, single dose change-over design with
      administration under fasting conditions separated by a washout period of at least 2
      treatment-free days.

      Blood sample collection will be performed over 16 h after administration. This time is
      considered adequate to characterise plasma concentration vs. time profiles long enough for
      reliable estimation of the extent of absorption, i.e. the AUC derived from measurements is
      expected to cover at least 80 % of the AUC extrapolated to infinity.
allocation: Randomized
intervention model: Crossover Assignment
masking: None (Open Label)
measure: Area under the plasma concentration versus time curve (AUC0-tlast) for ibuprofen
time frame: 16 hours interval
measure: Peak Plasma Concentration (Cmax) for ibuprofen
time frame: 16 hours interval
measure: Number of participants with treatment-related adverse events
time frame: from first dose until discharge of the subject (approx. 2 weeks)
arm group label: Ibuprofen 400 mg oral powder
arm group type: Experimental
description: oral fasted administration of 1 sachet of Ibuprofen 400 mg oral powder (Hermes Arzneimittel GmbH, Germany), containing 400 mg ibuprofen
arm group label: Brufen 400 mg film-coated tablets
arm group type: Active Comparator
description: oral fasted administration of Brufen 400 mg film-coated tablets (Abbott Scandinavia AB, Sweden), containing 400 mg ibuprofen
arm group label: Spalt forte 400 mg Weichkapseln
arm group type: Active Comparator
description: oral fasted administration of Spalt forte 400 mg Weichkapseln (Pfizer Consumer Healthcare GmbH, Germany), containing 400 mg ibuprofen
intervention type: Drug
intervention name: Ibuprofen 400 mg oral powder
arm group label: Ibuprofen 400 mg oral powder
intervention type: Drug
intervention name: Ibuprofen 400 mg film-coated tablet
arm group label: Brufen 400 mg film-coated tablets
intervention type: Drug
intervention name: Ibuprofen 400 mg soft capsule
arm group label: Spalt forte 400 mg Weichkapseln
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Cornelius Koch, MD
role: Principal Investigator
affiliation: SocraTec R&D GmbH, Clinical Pharmacology Unit
facility: 
country: Germany
responsible party type: Sponsor
mesh term: Ibuprofen