<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/NCT02256423</url>
  </required_header>
  <id_info>
    <org_study_id>RD 680/25772</org_study_id>
    <nct_id>NCT02256423</nct_id>
  </id_info>
  <brief_title>A Study Comparing Three Formulations of Ibuprofen in Healthy Subjects</brief_title>
  <official_title>A Single-dose, Randomised, Crossover Study to Compare the Pharmacokinetics of Three Formulations of Ibuprofen in Healthy Fasting Male and Female Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Simbec Research</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Simbec Research</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an open-label, randomised, 3-period, 3-sequence single-dose crossover study to&#xD;
      determine the comparative pharmacokinetic profile of the Test Investigational Medicinal&#xD;
      Product (IMP) Ibuprofen 200 mg soft gel capsule (lipid formulation) with that from the&#xD;
      reference products Nurofen® 200 mg tablet and ibuprofen 200 mg soft gel capsule following&#xD;
      single dose administration in healthy male and female subjects.&#xD;
&#xD;
      The study comprises of a pre-study screen (within 14 days of the first dose), followed by 3&#xD;
      Treatment Periods (1, 2 and 3) and a post study follow up (3 - 7 days after the last dose).&#xD;
      Each Treatment Period is of 1 day in duration, from the afternoon before dosing (Day -1)&#xD;
      until 12 hours (h) post-dose (Evening of Day 1). Study drug is administered on the morning of&#xD;
      Day 1 following an overnight fast. PK samples will be collected pre-dose and up to 12 h&#xD;
      post-dose (x15 samples) for the measurement of ibuprofen. Safety is evaluated at specified&#xD;
      times throughout the study. There is at least 48 h between dose administrations.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">August 2014</completion_date>
  <primary_completion_date type="Actual">August 2014</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>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pharmacokinetics</measure>
    <time_frame>PK samples are taken up to 12 hours of each study period.</time_frame>
    <description>Maximum plasma concentration (Cmax), time to Cmax (tmax), elimination rate constant (λz), terminal half-life (t1/2), area under the concentration-time curve (AUC) from time of dosing to last measurable concentration (AUC0-t), partial area under plasma concentration time curve at the following nominal blood sampling time points 15min, 30min, 45min, 1h, 1.20h, 1.40h and 2h (AU0-n), AUC extrapolated to infinity (AUC0-∞), plasma clearance (CL/F), MRT (mean residence time) and AUC% extrapolated (residual area).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety</measure>
    <time_frame>participants will be followed for the duration of stay, an expected average of 3 weeks</time_frame>
    <description>AEs, vital signs (sitting blood pressure and pulse), ECG (heart rate, PR interval, QRS width, QT interval and QTcB interval) and laboratory (haematology, biochemistry and urinalysis) data.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Healthy Volunteer Study</condition>
  <arm_group>
    <arm_group_label>REFERENCE 1: Nurofen® 200 mg tablet</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Single group 3-way crossover study</description>
  </arm_group>
  <arm_group>
    <arm_group_label>REFERENCE 2: Ibuprofen 200 mg soft gel capsule</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Single group 3-way crossover study</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ibuprofen 200 mg soft gel capsule</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>single group, 3-way cross</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>REFERENCE 1: Nurofen® 200 mg tablet</intervention_name>
    <arm_group_label>REFERENCE 1: Nurofen® 200 mg tablet</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>REFERENCE 2: Ibuprofen 200 mg soft gel capsule</intervention_name>
    <arm_group_label>REFERENCE 2: Ibuprofen 200 mg soft gel capsule</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ibuprofen 200 mg soft gel capsule</intervention_name>
    <arm_group_label>ibuprofen 200 mg soft gel capsule</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Healthy males and females between 18 and 50 years of age.&#xD;
&#xD;
          2. Female subject of child bearing potential with a negative pregnancy test at the&#xD;
             Screening Visit and willing to use an effective method of contraception if applicable&#xD;
             (unless of non-childbearing potential or where abstaining from sexual intercourse is&#xD;
             in line with the preferred and usual lifestyle of the subject) from Day 1 until 3&#xD;
             months afterwards.&#xD;
&#xD;
          3. Female subject of non-child bearing potential with negative pregnancy test at the&#xD;
             Screening Visit. For the purposes of this study, this is defined as the subject being&#xD;
             amenorrheic for at least 12 consecutive months or at least 4 months post-surgical&#xD;
             sterilisation (including bilateral fallopian tube ligation or bilateral oophorectomy&#xD;
             with or without hysterectomy). Menopausal status will be confirmed by demonstrating at&#xD;
             screening that levels of follicle stimulating hormone (FSH) fall within the respective&#xD;
             pathology reference range. In the event a subject's menopause status has been clearly&#xD;
             established (for example, the subject indicates she has been amenorrheic for 10&#xD;
             years), but FSH levels are not consistent with a post-menopausal condition,&#xD;
             determination of subject eligibility will be at the discretion of the Chief&#xD;
             Investigator following consultation with the Sponsor's Responsible Physician.&#xD;
&#xD;
          4. Subject with a Body Mass Index (BMI) of 18-30 kilogram (kg)/metre square (m2). Body&#xD;
             Mass Index = Body weight in kg / [Height in m]2.&#xD;
&#xD;
          5. Subject with no clinically significant abnormal serum biochemistry, haematology and&#xD;
             urine examination values within 14 days of the first dose.&#xD;
&#xD;
          6. Subject with a negative urinary drugs of abuse screen, determined within 14 days of&#xD;
             the first dose (a positive alcohol result may be repeated at the discretion of the&#xD;
             Investigator).&#xD;
&#xD;
          7. Subject with negative human immunodeficiency virus (HIV), hepatitis B surface antigen&#xD;
             (Hep B) and hepatitis C virus antibody (Hep C) results.&#xD;
&#xD;
          8. Subject with no clinically significant abnormalities in 12-lead ECG determined within&#xD;
             14 days of the first dose.&#xD;
&#xD;
          9. Subject must be available to complete the study (including all follow up visits) and&#xD;
             comply with study restrictions.&#xD;
&#xD;
         10. Subject must satisfy a medical examiner about their fitness to participate in the&#xD;
             study.&#xD;
&#xD;
         11. Subject must provide written informed consent to participate in the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of allergy to NSAIDs or aspirin and history of peptic ulcer or&#xD;
             gastrointestinal bleeding.&#xD;
&#xD;
          2. A clinically significant history of gastrointestinal disorder likely to influence drug&#xD;
             absorption, such as Gastroesophageal reflux disease&#xD;
&#xD;
          3. Receipt of regular medication within 14 days of the first dose that may have an impact&#xD;
             on the safety and objectives of the study (at the Investigator's discretion).&#xD;
&#xD;
          4. Evidence of renal, hepatic, central nervous system, respiratory, cardiovascular or&#xD;
             metabolic dysfunction.&#xD;
&#xD;
          5. A clinically significant history of previous allergy / sensitivity to ibuprofen.&#xD;
&#xD;
          6. A clinically significant history of drug or alcohol abuse.&#xD;
&#xD;
          7. Inability to communicate well with the Investigator (i.e., language problem, poor&#xD;
             mental development or impaired cerebral function).&#xD;
&#xD;
          8. Participation in a New Chemical Entity clinical study within the previous 4 months or&#xD;
             a marketed drug clinical study within the previous 3 months. (N.B. washout period&#xD;
             between studies is defined as the period of time elapsed between the last dose of the&#xD;
             previous study and the first dose of the next study).&#xD;
&#xD;
          9. Donation of 450 mL or more blood within the previous 3 months.&#xD;
&#xD;
         10. Subjects who are current smokers, or those who have used nicotine products within the&#xD;
             previous 3 months.&#xD;
&#xD;
         11. Subject with positive human immunodeficiency virus (HIV), hepatitis B surface antigen&#xD;
             (Hep B) and hepatitis C virus antibody (Hep C) results.&#xD;
&#xD;
         12. Any subject who, in the judgment of the Investigator, is likely to be non-compliant&#xD;
             with study procedures and/or restrictions during the study, or unable to cooperate&#xD;
             because of a language problem or poor mental development.&#xD;
&#xD;
         13. Subjects must not have taken over the counter drugs and herbal remedies and&#xD;
             supplements should not be taken from 7 days prior to the first dose and throughout the&#xD;
             duration of the study dosing periods.&#xD;
&#xD;
         14. Prescribed drugs should not be taken for 7 days before the first dose and throughout&#xD;
             the duration of the study dosing periods. This does not include the oral contraceptive&#xD;
             pill.&#xD;
      </textblock>
    </criteria>
    <gender>All</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>Girish Sharma, MBBS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Simbec Research</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Simbec Research Limited</name>
      <address>
        <city>Merthyr Tydfil</city>
        <zip>CF48 4DR</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>September 2014</verification_date>
  <study_first_submitted>September 16, 2014</study_first_submitted>
  <study_first_submitted_qc>September 30, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 3, 2014</study_first_posted>
  <last_update_submitted>September 30, 2014</last_update_submitted>
  <last_update_submitted_qc>September 30, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 3, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Simbec Research</investigator_affiliation>
    <investigator_full_name>Girish Sharma</investigator_full_name>
    <investigator_title>Associate Medical Director</investigator_title>
  </responsible_party>
  <keyword>Ibuprofen</keyword>
  <keyword>healthy volunteer study</keyword>
  <keyword>pharmacokinetics</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/NCT02256423
org study id: RD 680/25772
nct id: NCT02256423
lead sponsor: 
has dmc: No
This is an open-label, randomised, 3-period, 3-sequence single-dose crossover study to
      determine the comparative pharmacokinetic profile of the Test Investigational Medicinal
      Product (IMP) Ibuprofen 200 mg soft gel capsule (lipid formulation) with that from the
      reference products Nurofen® 200 mg tablet and ibuprofen 200 mg soft gel capsule following
      single dose administration in healthy male and female subjects.

      The study comprises of a pre-study screen (within 14 days of the first dose), followed by 3
      Treatment Periods (1, 2 and 3) and a post study follow up (3 - 7 days after the last dose).
      Each Treatment Period is of 1 day in duration, from the afternoon before dosing (Day -1)
      until 12 hours (h) post-dose (Evening of Day 1). Study drug is administered on the morning of
      Day 1 following an overnight fast. PK samples will be collected pre-dose and up to 12 h
      post-dose (x15 samples) for the measurement of ibuprofen. Safety is evaluated at specified
      times throughout the study. There is at least 48 h between dose administrations.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Pharmacokinetics
time frame: PK samples are taken up to 12 hours of each study period.
description: Maximum plasma concentration (Cmax), time to Cmax (tmax), elimination rate constant (λz), terminal half-life (t1/2), area under the concentration-time curve (AUC) from time of dosing to last measurable concentration (AUC0-t), partial area under plasma concentration time curve at the following nominal blood sampling time points 15min, 30min, 45min, 1h, 1.20h, 1.40h and 2h (AU0-n), AUC extrapolated to infinity (AUC0-∞), plasma clearance (CL/F), MRT (mean residence time) and AUC% extrapolated (residual area).
measure: Safety
time frame: participants will be followed for the duration of stay, an expected average of 3 weeks
description: AEs, vital signs (sitting blood pressure and pulse), ECG (heart rate, PR interval, QRS width, QT interval and QTcB interval) and laboratory (haematology, biochemistry and urinalysis) data.
arm group label: REFERENCE 1: Nurofen® 200 mg tablet
arm group type: Active Comparator
description: Single group 3-way crossover study
arm group label: REFERENCE 2: Ibuprofen 200 mg soft gel capsule
arm group type: Active Comparator
description: Single group 3-way crossover study
arm group label: ibuprofen 200 mg soft gel capsule
arm group type: Experimental
description: single group, 3-way cross
intervention type: Drug
intervention name: REFERENCE 1: Nurofen® 200 mg tablet
arm group label: REFERENCE 1: Nurofen® 200 mg tablet
intervention type: Drug
intervention name: REFERENCE 2: Ibuprofen 200 mg soft gel capsule
arm group label: REFERENCE 2: Ibuprofen 200 mg soft gel capsule
intervention type: Drug
intervention name: ibuprofen 200 mg soft gel capsule
arm group label: ibuprofen 200 mg soft gel capsule
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Girish Sharma, MBBS
role: Principal Investigator
affiliation: Simbec Research
facility: 
country: United Kingdom
responsible party type: Principal Investigator
investigator affiliation: Simbec Research
investigator full name: Girish Sharma
investigator title: Associate Medical Director
mesh term: Ibuprofen