<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/NCT03836807</url>
  </required_header>
  <id_info>
    <org_study_id>KSL0117</org_study_id>
    <nct_id>NCT03836807</nct_id>
  </id_info>
  <brief_title>A Study to Assess Efficacy and Tolerability of Ketoprofen 40 mg Granules vs Placebo</brief_title>
  <acronym>KSL0117</acronym>
  <official_title>A Multicenter, Double Blind, Randomised, Parallel Study to Assess Efficacy and Tolerability After Single Administration of Ketoprofen Lysine Salt 40 mg Granules vs Placebo in Subjects With Acute Pain Syndrome After Removal of Molar Teeth</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dompé Farmaceutici S.p.A</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Dompé Farmaceutici S.p.A</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Primary objective:&#xD;
&#xD;
      To assess the efficacy of OKITASK® 40 mg granules versus Placebo in patients with acute pain&#xD;
      syndrome after removal of one molar tooth by comparing AUC0-6h of posttreatment pain profile&#xD;
      measured by VAS.&#xD;
&#xD;
      Secondary objectives:&#xD;
&#xD;
      To assess the following efficacy and safety parameters of OKITASK® 40 mg granules versus&#xD;
      Placebo in patients with acute pain syndrome after removal of one molar tooth:&#xD;
&#xD;
        -  Time profile of pain and time profile of pain relief using VAS scales&#xD;
&#xD;
        -  Time to first perceptible pain relief (TFPR) and time to meaningful pain relief (TMPR)&#xD;
&#xD;
        -  Proportion of patients requiring rescue medication (analgesia) and time to rescue&#xD;
           analgesia&#xD;
&#xD;
        -  Patient's overall assessment&#xD;
&#xD;
        -  Rate of adverse events (AE)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a multicenter, double blind, randomised, parallel groups study to assess the efficacy&#xD;
      and tolerability after single oral administration of Ketoprofen lysine salt 40 mg granules&#xD;
      versus Placebo in male and female subjects with acute pain syndrome after removal of molar&#xD;
      teeth.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 4, 2018</start_date>
  <completion_date type="Actual">December 21, 2018</completion_date>
  <primary_completion_date type="Actual">July 24, 2018</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
    <masking_description>The double-blinding is provided by Placebo that is identical to OKITASK® 40 mg granules.&#xD;
The drug will be packaged and labeled in a manner that will exclude unblinding.IWRS will assign the study drug kit number that should be administrated by the subject.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>AUC0-6h of pain profile</measure>
    <time_frame>From time 0 (baseline value of VAS) to 6 hours post-treatment</time_frame>
    <description>Pain will be assessed by a horizontal 100 mm Visual Analogue Scale (VAS): 0 no pain - 100 worst pain imaginable at: 0' (just before taking the first medication VAS should be &gt;30 mm) and 5', 10', 15', 30', 60' (1 hour), 90' (1.5 hours), 120' (2 hours), 180' (3 hours), 240' (4 hours), 300' (5 hours), and 360' (6 hours) after the drug administration.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time profile of pain.</measure>
    <time_frame>From time 0 (baseline value of VAS) to 6 hours post-treatment at: 0', 5', 10', 15', 30', 60' (1 hour), 90' (1.5 hours), 120' (2 hours), 180' (3 hours), 240' (4 hours), 300' (5 hours), and 360' (6 hours) after the drug administration.</time_frame>
    <description>Pain will be assessed by a horizontal 100 mm Visual Analogue Scale (VAS): 0 no pain - 100 worst pain imaginable.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time profile of pain relief</measure>
    <time_frame>From time 0 (baseline value of VAS) to 6 hours post-treatment at: 5', 10', 15', 30', 60' (1 hour), 90' (1.5 hours), 120' (2 hours), 180' (3 hours), 240' (4 hours), 300' (5 hours), and 360' (6 hours) after the drug administration.</time_frame>
    <description>Pain relief will be assessed by a horizontal 100 mm VAS: 0 no relief - 100 maximum relief.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to first perceptible relief (TFPR)</measure>
    <time_frame>Day 1</time_frame>
    <description>TFPR will be measured by stopwatches. Upon study drug administration the patients will immediately start a stopwatch, once the patient feels first perceptible pain relief.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to meaningful pain relief (TMPR)</measure>
    <time_frame>Day 1</time_frame>
    <description>TFPR will be measured by stopwatches. Upon study drug administration the patients will immediately start a stopwatch, once the patient feels first perceptible pain relief.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients requiring rescue medication (analgesia)</measure>
    <time_frame>Day 1</time_frame>
    <description>Should the patient require rescue medication at any time during 6 hours post-dose, the last VAS measurement and patient's overall assessment will be performed before the rescue medication dosing. Subjects will be encouraged to postpone the rescue medication until after 1 hour post-dose.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to rescue analgesia</measure>
    <time_frame>Day 1</time_frame>
    <description>In the event of poor pain control, subjects will be allowed access to rescue medication for analgesia (Paracetamol 500-1000 mg). Time to REMD (rescue) with an alternative analgesic, if it occurred, will be recorded. Subject will be encouraged to postpone the rescue medication until after 1 h post dose. If Paracetamol 500-1000 mg is not effective, the patient will be allowed to take another dose of Paracetamol 500-1000 mg every 6-8 hours; maximum daily dose is 4000 mg.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient's overall assessment</measure>
    <time_frame>Day 1 at 360' or &gt; 60' in case of early discontinuation.</time_frame>
    <description>Patient's overall assessment (5-point scale): 1 = very good, 2 = good, 3= satisfactory, 4 = poor, 5 = very poor.&#xD;
If a patient takes rescue medication, the Patient's overall assessment will be performed after the last VAS assessment.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">70</enrollment>
  <condition>Acute Pain</condition>
  <arm_group>
    <arm_group_label>Ketoprofen</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single oral administration of Ketoprofen lysine salt 40 mg granules</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Single oral administration of placebo granules</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ketoprofen</intervention_name>
    <description>40 mg KLS granules (corresponding to 25 mg ketoprofen)</description>
    <arm_group_label>Ketoprofen</arm_group_label>
    <other_name>Okitask, ketoprofen lysine salt (KLS)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>0 mg KLS granules</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Control</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Signed Informed Consent Form;&#xD;
&#xD;
          2. Male and female, from 18 years to 65 years (inclusively);&#xD;
&#xD;
          3. Subjects who undergo removal of a non-impacted molar tooth within 3 hours before&#xD;
             randomization in the study;&#xD;
&#xD;
          4. Subjects in generally good health (based upon criteria for safe administration of&#xD;
             outpatient conscious sedation);&#xD;
&#xD;
          5. Subjects requesting relief for postoperative pain within 3 h after the tooth&#xD;
             extraction (VAS ≥30 mm);&#xD;
&#xD;
          6. Subjects willing to undergo observation period for up to 9 hours after the tooth&#xD;
             extraction;&#xD;
&#xD;
          7. Ability to complete a 100 mm VAS and a category scale during the observation period&#xD;
             (about 9 hours);&#xD;
&#xD;
          8. Full comprehension: ability to comprehend the full nature and purpose of the study,&#xD;
             including possible risks and side effects; ability to co-operate with the Investigator&#xD;
             and to comply with the requirements of the entire study;&#xD;
&#xD;
          9. Contraception (for females): females of child-bearing potential must be using at least&#xD;
             one reliable method of contraception, as follows:&#xD;
&#xD;
               1. hormonal oral, implantable, transdermal, or injectable contraceptives;&#xD;
&#xD;
               2. a non-hormonal intrauterine device [IUD] or female condom with spermicide or&#xD;
                  contraceptive sponge with spermicide or diaphragm with spermicide or cervical cap&#xD;
                  with spermicide; or should have:&#xD;
&#xD;
               3. a male sexual partner who agrees to use a male condom with spermicide;&#xD;
&#xD;
               4. a sterile sexual partner.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subjects undergoing extraction of impacted and dystopic teeth, tooth preserving&#xD;
             operations, apically positioning flap/vestibuloplasty with free gingival graft from&#xD;
             the palate;&#xD;
&#xD;
          2. Subjects undergoing more than one tooth extraction in the same extraction procedure;&#xD;
&#xD;
          3. Subjects undergoing dental implantation simultaneously with tooth extraction;&#xD;
&#xD;
          4. Allergy: ascertained or presumptive hypersensitivity to the active substances&#xD;
             (ketoprofen and paracetamol as rescue medication) and/or formulations' ingredients;&#xD;
             history of hypersensitivity to drugs (in particular to NSAIDs) or allergic reactions&#xD;
             in general, which the Investigator considers may affect the outcome of the study;&#xD;
&#xD;
          5. Diseases: relevant history of renal, hepatic, cardiovascular, respiratory (including&#xD;
             asthma), skin, haematological, endocrine, gastro-enteric and genitourinary tract or&#xD;
             neurological and autoimmune diseases, that may interfere with the aim of the study;&#xD;
&#xD;
          6. Medications: non-steroidal anti-inflammatory drugs (NSAIDS) and other analgesics [in&#xD;
             particular ketoprofen, paracetamol and acetylsalicylic acid (ASA)], antihistamines,&#xD;
             sedating medications, including herbal and BASs, taken 48 h beforesurgery;&#xD;
&#xD;
          7. Investigational drug trials: participation in the evaluation of any drug within 3&#xD;
             months before screening (including the last study procedure);&#xD;
&#xD;
          8. Relevant history of drug and alcohol abuse.&#xD;
&#xD;
          9. Positive Pregnancy test in female patients of childbearing potential (including&#xD;
             patients in post-menopausal status for less than 2 years).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mauro P. Ferrari, Pharm D</last_name>
    <role>Study Director</role>
    <affiliation>Dompé SpA Milan</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>LLC &quot;Centre for Interdisciplinary Dentistry and Neurology&quot;</name>
      <address>
        <city>Moscow</city>
        <zip>119146</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Federal State Educational Institution &quot;Moscow State Medical Dental University named after Yevdokimov &quot;of the Russian Federation Ministry of Health</name>
      <address>
        <city>Moscow</city>
        <zip>127473</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State Autonomous Healthcare Institution of Yaroslavl Region &quot;Clinical Hospital of Emergency care n.a. N.V. Solovyev&quot;</name>
      <address>
        <city>Yaroslavl</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Russian Federation</country>
  </location_countries>
  <verification_date>May 2018</verification_date>
  <study_first_submitted>January 28, 2019</study_first_submitted>
  <study_first_submitted_qc>February 8, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 11, 2019</study_first_posted>
  <last_update_submitted>February 8, 2019</last_update_submitted>
  <last_update_submitted_qc>February 8, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 11, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acute Pain</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ketoprofen</mesh_term>
    <mesh_term>Ketoprofen lysine</mesh_term>
  </intervention_browse>
  <pending_results>
    <submitted>September 20, 2022</submitted>
    <returned>August 4, 2023</returned>
  </pending_results>
  <!-- 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/NCT03836807
org study id: KSL0117
nct id: NCT03836807
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Primary objective:

      To assess the efficacy of OKITASK® 40 mg granules versus Placebo in patients with acute pain
      syndrome after removal of one molar tooth by comparing AUC0-6h of posttreatment pain profile
      measured by VAS.

      Secondary objectives:

      To assess the following efficacy and safety parameters of OKITASK® 40 mg granules versus
      Placebo in patients with acute pain syndrome after removal of one molar tooth:

        -  Time profile of pain and time profile of pain relief using VAS scales

        -  Time to first perceptible pain relief (TFPR) and time to meaningful pain relief (TMPR)

        -  Proportion of patients requiring rescue medication (analgesia) and time to rescue
           analgesia

        -  Patient's overall assessment

        -  Rate of adverse events (AE)
This is a multicenter, double blind, randomised, parallel groups study to assess the efficacy
      and tolerability after single oral administration of Ketoprofen lysine salt 40 mg granules
      versus Placebo in male and female subjects with acute pain syndrome after removal of molar
      teeth.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
masking description: The double-blinding is provided by Placebo that is identical to OKITASK® 40 mg granules.
The drug will be packaged and labeled in a manner that will exclude unblinding.IWRS will assign the study drug kit number that should be administrated by the subject.
measure: AUC0-6h of pain profile
time frame: From time 0 (baseline value of VAS) to 6 hours post-treatment
description: Pain will be assessed by a horizontal 100 mm Visual Analogue Scale (VAS): 0 no pain - 100 worst pain imaginable at: 0' (just before taking the first medication VAS should be >30 mm) and 5', 10', 15', 30', 60' (1 hour), 90' (1.5 hours), 120' (2 hours), 180' (3 hours), 240' (4 hours), 300' (5 hours), and 360' (6 hours) after the drug administration.
measure: Time profile of pain.
time frame: From time 0 (baseline value of VAS) to 6 hours post-treatment at: 0', 5', 10', 15', 30', 60' (1 hour), 90' (1.5 hours), 120' (2 hours), 180' (3 hours), 240' (4 hours), 300' (5 hours), and 360' (6 hours) after the drug administration.
description: Pain will be assessed by a horizontal 100 mm Visual Analogue Scale (VAS): 0 no pain - 100 worst pain imaginable.
measure: Time profile of pain relief
time frame: From time 0 (baseline value of VAS) to 6 hours post-treatment at: 5', 10', 15', 30', 60' (1 hour), 90' (1.5 hours), 120' (2 hours), 180' (3 hours), 240' (4 hours), 300' (5 hours), and 360' (6 hours) after the drug administration.
description: Pain relief will be assessed by a horizontal 100 mm VAS: 0 no relief - 100 maximum relief.
measure: Time to first perceptible relief (TFPR)
time frame: Day 1
description: TFPR will be measured by stopwatches. Upon study drug administration the patients will immediately start a stopwatch, once the patient feels first perceptible pain relief.
measure: Time to meaningful pain relief (TMPR)
time frame: Day 1
description: TFPR will be measured by stopwatches. Upon study drug administration the patients will immediately start a stopwatch, once the patient feels first perceptible pain relief.
measure: Proportion of patients requiring rescue medication (analgesia)
time frame: Day 1
description: Should the patient require rescue medication at any time during 6 hours post-dose, the last VAS measurement and patient's overall assessment will be performed before the rescue medication dosing. Subjects will be encouraged to postpone the rescue medication until after 1 hour post-dose.
measure: Time to rescue analgesia
time frame: Day 1
description: In the event of poor pain control, subjects will be allowed access to rescue medication for analgesia (Paracetamol 500-1000 mg). Time to REMD (rescue) with an alternative analgesic, if it occurred, will be recorded. Subject will be encouraged to postpone the rescue medication until after 1 h post dose. If Paracetamol 500-1000 mg is not effective, the patient will be allowed to take another dose of Paracetamol 500-1000 mg every 6-8 hours; maximum daily dose is 4000 mg.
measure: Patient's overall assessment
time frame: Day 1 at 360' or > 60' in case of early discontinuation.
description: Patient's overall assessment (5-point scale): 1 = very good, 2 = good, 3= satisfactory, 4 = poor, 5 = very poor.
If a patient takes rescue medication, the Patient's overall assessment will be performed after the last VAS assessment.
arm group label: Ketoprofen
arm group type: Experimental
description: Single oral administration of Ketoprofen lysine salt 40 mg granules
arm group label: Placebo
arm group type: Placebo Comparator
description: Single oral administration of placebo granules
intervention type: Drug
intervention name: Ketoprofen
description: 40 mg KLS granules (corresponding to 25 mg ketoprofen)
arm group label: Ketoprofen
other name: Okitask, ketoprofen lysine salt (KLS)
intervention type: Other
intervention name: Placebo
description: 0 mg KLS granules
arm group label: Placebo
other name: Control
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Mauro P. Ferrari, Pharm D
role: Study Director
affiliation: Dompé SpA Milan
facility: 
facility: 
facility: 
country: Russian Federation
responsible party type: Sponsor
mesh term: Acute Pain
mesh term: Ketoprofen
mesh term: Ketoprofen lysine
submitted: September 20, 2022
returned: August 4, 2023