<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/NCT03785756</url>
  </required_header>
  <id_info>
    <org_study_id>5003601</org_study_id>
    <nct_id>NCT03785756</nct_id>
  </id_info>
  <brief_title>Efficacy of 300mg Ibuprofen Prolonged-Release Tablets for the Treatment of Pain After Surgical Removal of Impacted Third Molars</brief_title>
  <official_title>A Randomised, Double-Blind, Double-Dummy, Parallel-Group, Multiple-Dose, Active and Placebo-Controlled Efficacy Study of Ibuprofen Prolonged-Release Tablets for the Treatment of Pain After Surgical Removal of Impacted Third Molars</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Reckitt Benckiser Healthcare (UK) Limited</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Premier Research Group plc</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Reckitt Benckiser Healthcare (UK) Limited</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a single centre, randomised, double-blind, double-dummy, parallel group,&#xD;
      multiple-dose, active and placebo-controlled efficacy study to evaluate the efficacy and&#xD;
      safety of 2×300mg ibuprofen Prolonged Release (PR) tablets in subjects with postoperative&#xD;
      dental pain.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single centre, randomised, double blind, double-dummy, parallel group ,&#xD;
      multiple-dose, active and placebo controlled efficacy study to evaluate the efficacy and&#xD;
      safety of ibuprofen 2×300 mg ibuprofen PR tablets in subjects with postoperative dental pain.&#xD;
&#xD;
      Eligible subjects will complete all screening procedures within 28 days before the surgery&#xD;
      and randomisation.&#xD;
&#xD;
      At Screening, subjects will provide written informed consent to participate in the study&#xD;
      before any protocol specified procedures or assessments are completed. On Day 1, subjects who&#xD;
      continue to be eligible for study participation after completing screening procedures and&#xD;
      assessments will undergo extraction of 2 or more third molars. At least 1 of the third molars&#xD;
      must be a fully or partially bone impacted mandibular molar. If only 2 molars are removed,&#xD;
      then they must be ipsilateral.&#xD;
&#xD;
      All subjects will receive local anaesthesia (2% lidocaine with 1:100,000 epinephrine).&#xD;
      Nitrous oxide will be allowed at the discretion of the investigator. Subjects who experience&#xD;
      moderate to severe pain intensity (a score of ≥ 5 on a numeric rating scale [NRS] from 0-10&#xD;
      where 0 = no pain, 10 = worst pain ever) within 6 hours after surgery and who continue to&#xD;
      meet all study entry criteria will be randomised in a 3:3:1 ratio to receive 2×300 mg&#xD;
      ibuprofen PR tablets every 12 hours (Q12h), 2×200 mg ibuprofen IR tablets every 8 hours&#xD;
      (Q8h), or placebo. The randomisation will be stratified by baseline pain category (moderate&#xD;
      or severe) using a categorical scale that includes the categories of none (0), mild (1-4),&#xD;
      moderate (5-7), and severe (8-10).&#xD;
&#xD;
      Subjects will re-assess their baseline pain intensity using the NRS immediately before&#xD;
      receiving study drug (pre-dose, Time 0) and their pain intensity (NRS) and pain relief (5&#xD;
      point categorical scale) at the following time points (pre-dose, if at one of the dosing&#xD;
      timepoints of 0, 8, 12 and/or 16 hours): 15, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 5, 6,&#xD;
      7, 8, 10, 12, 16, and 24 hours after Time 0; and immediately before each dose of rescue&#xD;
      medication, if any. For assessments less than 1 hour apart a window of +/-2 min is allowable&#xD;
      whilst for assessments at least 1 hour apart a +/-5 min window is allowable.&#xD;
&#xD;
      The double stopwatch method will be used to record the time to perceptible pain relief and&#xD;
      time to meaningful pain relief during the 8 hours following the first dose or until subject&#xD;
      takes rescue medication. Subjects will complete a global evaluation of study drug 24 hours&#xD;
      (+/- 5 minutes) after Time 0 or immediately before the first dose of rescue medication&#xD;
      (whichever occurs first). Vital signs will be recorded after the subject has been in a&#xD;
      sitting position for 3 minutes at the following times: before surgery, within 30 minutes&#xD;
      before Time 0, 12 and 24 hours after Time 0, and/or immediately before the first dose of&#xD;
      rescue medication. Adverse events (AEs) will be monitored and recorded from the time of&#xD;
      signing of the informed consent form (ICF) until the Follow up Visit (or Early Termination&#xD;
      Visit). During the 24 hours following Time 0, subjects will complete efficacy and safety&#xD;
      assessments. Subjects will remain at the study site overnight and will be discharged on Day&#xD;
      2.&#xD;
&#xD;
      Paracetamol / acetaminophen (1000 mg) will be permitted as the initial rescue medication.&#xD;
      Subjects will be encouraged to wait at least 60 minutes after receiving study drug before&#xD;
      taking rescue medication. If acetaminophen rescue medication is not effective in relieving&#xD;
      the subject's pain, 5 mg oxycodone rescue medication may be administered at the discretion of&#xD;
      the investigator.&#xD;
&#xD;
      Subjects are not permitted to take any concomitant medications that might confound&#xD;
      assessments of pain relief, such as psychotropic drugs, antidepressants, sedative-hypnotics&#xD;
      (other than those permitted for conscious sedation), or other analgesics taken within five&#xD;
      times of their elimination half-lives (other than those used at the surgery). Selective&#xD;
      serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors&#xD;
      (SNRIs) are permitted if the subject has been on a stable dose for at least four weeks prior&#xD;
      to Visit 1 (screening).&#xD;
&#xD;
      Other restrictions include the following: alcohol use is prohibited from 24 hours before&#xD;
      surgery until discharge on Day 2; nothing by mouth from midnight before surgery until 1 hour&#xD;
      after surgery; clear liquids only are allowed starting 1 hour after surgery until 1 hour&#xD;
      after dosing; 1 hour after dosing, the subject's diet may be advanced according to standard&#xD;
      practice.&#xD;
&#xD;
      Upon discharge from the study site, subjects may be prescribed pain medication for use at&#xD;
      home according to the standard practice of the study site. On Day 8 (± 2 days), subjects will&#xD;
      return to the study site for an abbreviated confirmatory physical assessment and AE&#xD;
      assessments.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 29, 2019</start_date>
  <completion_date type="Anticipated">December 2019</completion_date>
  <primary_completion_date type="Anticipated">December 2019</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>
    <intervention_model_description>The dental pain model used in this study is a robust and well established postsurgical pain model that produces pain that is predictable in its character, duration, and intensity. The model is widely accepted and has a proven record of assay sensitivity (i.e. separating active drugs from each other, as well as from placebo). The model is frequently used to evaluate NSAID type analgesics. Results from dental pain studies are accepted by the US Food and Drug Administration (FDA) and European authorities and have been widely extrapolated to other general pain conditions.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>This is a double-blind, double dummy study. There will be two placebo tablets designed to be comparable to each of the active products (PR and Immediate Release (IR)) in both shape, size, colour and weight. All subject packs have been designed and labelled to ensure blinding is maintained. Subjects, investigators and site staff will all be blind to the treatments.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Summed Pain Intensity Difference 0-12 hours (SPID12) vs placebo using the Numeric Rating Scale (NRS) for pain</measure>
    <time_frame>0-12 hours</time_frame>
    <description>SPID12 will be used to compare the test product (2×300 mg ibuprofen PR tablets) against the placebo product. The NRS will be used to assess the Pain Intensity, the NRS for pain is an 11-point scale (0-10) where a higher score indicates a greater amount of pain.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Summed Pain Intensity Difference 0-24 hours (SPID24) vs active comparator using the NRS for pain</measure>
    <time_frame>0-24 hours</time_frame>
    <description>SPID24 will be used to compare the test product (2×300 mg ibuprofen PR tablets twice daily (BID)) and comparator product (2×200 mg ibuprofen IR tablets three times a day (TID)). The NRS will be used to assess the Pain Intensity, the NRS for pain is an 11-point scale (0-10) where a higher score indicates a greater amount of pain.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Summed Pain Intensity Difference 0-4hours (SPID4) using NRS for pain</measure>
    <time_frame>0-4 hours</time_frame>
    <description>SPID4 after Time 0 will be assessed using the NRS to assess the Pain Intensity, the NRS for pain is an 11-point scale (0-10) where a higher score indicates a greater amount of pain.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Summed Pain Intensity Difference 0-8 hours (SPID8) using NRS for pain</measure>
    <time_frame>0-8 hours</time_frame>
    <description>SPID8 after Time 0 will be assessed using the NRS to assess the Pain Intensity, the NRS for pain is an 11-point scale (0-10) where a higher score indicates a greater amount of pain.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Summed Pain Intensity Difference 0-12 hours (SPID12) using NRS for pain</measure>
    <time_frame>0-12 hours</time_frame>
    <description>SPID12 after Time 0 will be assessed using the NRS to assess the Pain Intensity, the NRS for pain is an 11-point scale (0-10) where a higher score indicates a greater amount of pain.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sum of Total Pain Relief 0-4 hours (TOTPAR4) using Pain Relief Scale (PRS)</measure>
    <time_frame>0-4 hours</time_frame>
    <description>TOTPAR4 after Time 0 will be assessed using the PRS. PRS is used to measure pain relief and is a 5 point categorical scale, response choices of none = 0, a little = 1, some = 2, a lot = 3, and complete = 4 to be completed in response to the question &quot;How much relief have you had since your starting pain?&quot;.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sum of Total Pain Relief 0-8 hours (TOTPAR8) using PRS</measure>
    <time_frame>0-8 hours</time_frame>
    <description>TOTPAR8 after Time 0 will be assessed using the PRS. PRS is used to measure pain relief and is a 5 point categorical scale, response choices of none = 0, a little = 1, some = 2, a lot = 3, and complete = 4 to be completed in response to the question &quot;How much relief have you had since your starting pain?&quot;.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sum of Total Pain Relief 0-12 hours (TOTPAR12) using PRS</measure>
    <time_frame>0-12 hours</time_frame>
    <description>TOTPAR12 after Time 0 will be assessed using the PRS. PRS is used to measure pain relief and is a 5 point categorical scale, response choices of none = 0, a little = 1, some = 2, a lot = 3, and complete = 4 to be completed in response to the question &quot;How much relief have you had since your starting pain?&quot;.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sum of Total Pain Relief 0-24 hours (TOTPAR24) using PRS</measure>
    <time_frame>0-24 hours</time_frame>
    <description>TOTPAR24 after Time 0 will be assessed using the PRS. PRS is used to measure pain relief and is a 5 point categorical scale, response choices of none = 0, a little = 1, some = 2, a lot = 3, and complete = 4 to be completed in response to the question &quot;How much relief have you had since your starting pain?&quot;.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Summed pain relief and intensity difference (sum of TOTPAR and SPID [SPRID]) 0-4 hours (SPRID4) using PRS and NRS for pain.</measure>
    <time_frame>0-4 hours</time_frame>
    <description>SPRID4 after Time 0 will be assessed using the PRS and NRS for pain. The PRS will be used to measure pain relief and is a 5 point categorical scale, response choices of none = 0, a little = 1, some = 2, a lot = 3, and complete = 4 to be completed in response to the question &quot;How much relief have you had since your starting pain?&quot;. The NRS will be used to assess the Pain Intensity, the NRS for pain is an 11-point scale (0-10) where a higher score indicates a greater amount of pain. SPRID4 will be determined by calculating the difference in NRS for pain at the 4-hour time point and the 0-hour timepoint and adding this value to the difference in the PRS at the 4-hour time point and the 0-hour timepoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Summed pain relief and intensity difference 0-8 hours (SPRID8) using PRS and NRS for pain</measure>
    <time_frame>0-8 hours</time_frame>
    <description>SPRID8 after Time 0 will be assessed using the PRS and NRS for pain. The PRS will be used to measure pain relief and is a 5 point categorical scale, response choices of none = 0, a little = 1, some = 2, a lot = 3, and complete = 4 to be completed in response to the question &quot;How much relief have you had since your starting pain?&quot;. The NRS will be used to assess the Pain Intensity, the NRS for pain is an 11-point scale (0-10) where a higher score indicates a greater amount of pain. SPRID8 will be determined by calculating the difference in NRS for pain at the 8-hour time point and the 0-hour timepoint and adding this value to the difference in the PRS at the 8-hour time point and the 0-hour timepoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Summed pain relief and intensity difference 0-12 hours (SPRID12) using PRS and NRS for pain</measure>
    <time_frame>0-12 hours</time_frame>
    <description>SPRID12 after Time 0 will be assessed using the PRS and NRS for pain. The PRS will be used to measure pain relief and is a 5 point categorical scale, response choices of none = 0, a little = 1, some = 2, a lot = 3, and complete = 4 to be completed in response to the question &quot;How much relief have you had since your starting pain?&quot;. The NRS will be used to assess the Pain Intensity, the NRS for pain is an 11-point scale (0-10) where a higher score indicates a greater amount of pain. SPRID12 will be determined by calculating the difference in NRS for pain at the 12-hour time point and the 0-hour timepoint and adding this value to the difference in the PRS at the 12-hour time point and the 0-hour timepoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Summed pain relief and intensity difference 0-24 hours (SPRID24) using PRS and NRS for pain</measure>
    <time_frame>0-24 hours</time_frame>
    <description>SPRID24 after Time 0 will be assessed using the PRS and NRS for pain. The PRS will be used to measure pain relief and is a 5 point categorical scale, response choices of none = 0, a little = 1, some = 2, a lot = 3, and complete = 4 to be completed in response to the question &quot;How much relief have you had since your starting pain?&quot;. The NRS will be used to assess the Pain Intensity, the NRS for pain is an 11-point scale (0-10) where a higher score indicates a greater amount of pain.SPRID24 will be determined by calculating the difference in NRS for pain at the 24-hour time point and the 0-hour timepoint and adding this value to the difference in the PRS at the 24-hour time point and the 0-hour timepoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of participants who show response to study drug using NRS for pain</measure>
    <time_frame>0-8 hours</time_frame>
    <description>A responder will be defined as a subject with ≥30% improvement in pain intensity without rescue medication during the first 8 hours. The NRS will be used to assess the Pain Intensity, the NRS for pain is an 11-point scale (0-10) where a higher score indicates a greater amount of pain.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NRS (for pain) Pain Intensity Difference at each timepoint</measure>
    <time_frame>0-24 hours</time_frame>
    <description>NRS pain intensity difference (PID) at each scheduled time point after Time 0. The NRS will be used to assess the Pain Intensity, the NRS for pain is an 11-point scale (0-10) where a higher score indicates a greater amount of pain.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak Pain intensity score using NRS for pain</measure>
    <time_frame>0-24 hours</time_frame>
    <description>Pain intensity score at each scheduled time point will be assessed using the NRS for pain. The NRS for pain is an 11-point scale (0-10) where a higher score indicates a greater amount of pain.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain relief score using Pain Relief Scale</measure>
    <time_frame>0-24hours</time_frame>
    <description>Pain relief score at each scheduled time point after Time 0 will be measured using the PRS. The PRS will be used to measure pain relief and is a 5 point categorical scale, response choices of none = 0, a little = 1, some = 2, a lot = 3, and complete = 4 to be completed in response to the question &quot;How much relief have you had since your starting pain?&quot;.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak Pain Relief at all timepoints using PRS</measure>
    <time_frame>0-24hours</time_frame>
    <description>Peak Pain relief at each time point will be measured using PRS. The PRS will be used to measure pain relief and is a 5 point categorical scale, response choices of none = 0, a little = 1, some = 2, a lot = 3, and complete = 4 to be completed in response to the question &quot;How much relief have you had since your starting pain?&quot;.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to onset of analgesia using double stopwatch assessment</measure>
    <time_frame>0-24 hours</time_frame>
    <description>Time to onset of analgesia (measured as time to perceptible pain relief confirmed by time to meaningful pain relief) using double stopwatch. Two stopwatches will be started immediately after the subject has swallowed the study drug with 8 ounces of water. Each subject will be instructed, &quot;Stop the first stopwatch when you first feel any pain relief whatsoever. This does not mean you feel completely better, although you might, but when you first feel any relief in the pain you have now&quot; (perceptible pain relief). The subject will also be instructed, &quot;Stop the second stopwatch when you feel the pain relief is meaningful to you&quot; (meaningful pain relief). If the subject does not press the stopwatches within 8 hours after Time 0 the subject will discontinue use of the stopwatches.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to first perceptible pain relief using double stopwatch assessment</measure>
    <time_frame>0-8 hours</time_frame>
    <description>Time to first perceptible pain relief using stopwatch assessment. Two stopwatches will be started immediately after the subject has swallowed the study drug with 8 ounces of water. Each subject will be instructed, &quot;Stop the first stopwatch when you first feel any pain relief whatsoever. This does not mean you feel completely better, although you might, but when you first feel any relief in the pain you have now&quot; (perceptible pain relief). If the subject does not press the stopwatches within 8 hours after Time 0 the subject will discontinue use of the stopwatches.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to meaningful pain relief using double stopwatch assessment</measure>
    <time_frame>0-8 hours</time_frame>
    <description>Time to meaningful pain relief. Two stopwatches will be started immediately after the subject has swallowed the study drug with 8 ounces of water. The subject will be instructed, &quot;Stop the second stopwatch when you feel the pain relief is meaningful to you&quot; (meaningful pain relief). If the subject does not press the stopwatches within 8 hours after Time 0 the subject will discontinue use of the stopwatches.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to peak pain relief using PRS</measure>
    <time_frame>0-24 hours</time_frame>
    <description>Time to peak pain relief. The PRS will be used to measure pain relief and is a 5 point categorical scale, response choices of none = 0, a little = 1, some = 2, a lot = 3, and complete = 4 to be completed in response to the question &quot;How much relief have you had since your starting pain?&quot;.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of subjects using rescue medication</measure>
    <time_frame>0-24 hours</time_frame>
    <description>Proportion of subjects using rescue medication.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to first use of rescue medication</measure>
    <time_frame>0-24 hours</time_frame>
    <description>Time to first use of rescue medication.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Incidence of Treatment Emergent Adverse Events as assessed by patient response to questions and spontaneous reporting of TEAEs</measure>
    <time_frame>0-10 days</time_frame>
    <description>Incidence of treatment emergent adverse events (TEAEs). Data listings will be provided for protocol specified safety data.</description>
  </other_outcome>
  <other_outcome>
    <measure>Vital signs measurements - Blood pressure in mm/Hg</measure>
    <time_frame>0-10 days</time_frame>
    <description>Incidence of changes in vital sign measurements. Descriptive statistics will be provided at each scheduled time point for each treatment group. Changes from Baseline for vital signs will be calculated for each subject.</description>
  </other_outcome>
  <other_outcome>
    <measure>Vital signs measurements - Heart rate in beats per minute</measure>
    <time_frame>0-10 days</time_frame>
    <description>Incidence of changes in vital sign measurements. Descriptive statistics will be provided at each scheduled time point for each treatment group. Changes from Baseline for vital signs will be calculated for each subject.</description>
  </other_outcome>
  <other_outcome>
    <measure>Vital signs measurements - Respiratory rate in breaths per minute</measure>
    <time_frame>0-10 days</time_frame>
    <description>Incidence of changes in vital sign measurements. Descriptive statistics will be provided at each scheduled time point for each treatment group. Changes from Baseline for vital signs will be calculated for each subject.</description>
  </other_outcome>
  <other_outcome>
    <measure>Vital signs measurements - Body Temperature in ºC</measure>
    <time_frame>0-10 days</time_frame>
    <description>Incidence of changes in vital sign measurements. Descriptive statistics will be provided at each scheduled time point for each treatment group. Changes from Baseline for vital signs will be calculated for each subject.</description>
  </other_outcome>
  <other_outcome>
    <measure>Global Evaluation of efficacy using 5 point categorical scale</measure>
    <time_frame>0-24 hours</time_frame>
    <description>Patient's global evaluation of study drug using 5 point categorical scale, response choices of 0 = poor, 1 = fair, 2 = good, 3 = very good, or 4 = excellent to be completed by the patient in response to the question &quot;How effective do you think the study drug is as a treatment for pain?&quot;. Subjects will complete the global evaluation of study drug 24 hours after Time 0 or immediately before the first dose of rescue medication (whichever occurs first).</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">280</enrollment>
  <condition>Pain</condition>
  <arm_group>
    <arm_group_label>Prolonged Release Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ibuprofen 300 mg Oral Tablet Placebo of IR tablet Placebo of PR tablet</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Immediate Release Group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Ibuprofen 200 mg Oral Tablet Placebo of IR tablet Placebo of PR tablet</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo of IR tablet Placebo of PR tablet</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ibuprofen 300 mg Oral Tablet</intervention_name>
    <description>2 x 300 mg tablets twice in 24 hours</description>
    <arm_group_label>Prolonged Release Group</arm_group_label>
    <other_name>Prolonged Release Tablet</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ibuprofen 200 mg Oral Tablet</intervention_name>
    <description>2 x 200 mg tablets three times in 24 hours</description>
    <arm_group_label>Immediate Release Group</arm_group_label>
    <other_name>Nurofen, Immediate Release Tablet</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo of PR tablet</intervention_name>
    <description>Up to 2 tablets four times in 24 hours</description>
    <arm_group_label>Immediate Release Group</arm_group_label>
    <arm_group_label>Placebo Group</arm_group_label>
    <arm_group_label>Prolonged Release Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo of IR tablet</intervention_name>
    <description>Up to 2 tablets four times in 24 hours</description>
    <arm_group_label>Immediate Release Group</arm_group_label>
    <arm_group_label>Placebo Group</arm_group_label>
    <arm_group_label>Prolonged Release Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Is male or female ≥ 18 and ≤ 50 years of age.&#xD;
&#xD;
          -  Requires extraction of 2 or more third molars. At least 1 of the third molars must be&#xD;
             a fully or partially bone impacted mandibular molar. If only 2 molars are removed,&#xD;
             then they must be ipsilateral.&#xD;
&#xD;
          -  Experiences moderate to severe pain intensity within 6 hours after surgery, as&#xD;
             measured by a numeric rating scale (NRS) score of ≥ 5 on a 0-10 scale.&#xD;
&#xD;
          -  Has a body weight ≥ 45 kg and a body mass index (BMI) ≤ 35 kg/m2.&#xD;
&#xD;
          -  Female subjects of child-bearing potential must be willing to use a highly effective&#xD;
             method of contraception throughout the study. A highly effective method of birth&#xD;
             control is defined as one which results in a low failure rate (i.e. less than 1% per&#xD;
             year) when used consistently and correctly, such as the following:&#xD;
&#xD;
               1. surgical sterilisation&#xD;
&#xD;
               2. contraceptive implants or injectables&#xD;
&#xD;
               3. combined oral contraceptives&#xD;
&#xD;
               4. some intrauterine devices (IUDs)&#xD;
&#xD;
               5. true sexual abstinence, when this is in line with the preferred and usual&#xD;
                  lifestyle of the subject (periodic abstinence such as calendar, ovulation,&#xD;
                  symptothermal, or post-ovulation methods; declaration of abstinence for the&#xD;
                  duration of the trial; or withdrawal are not acceptable methods of&#xD;
                  contraception), or&#xD;
&#xD;
               6. vasectomised partner. To be considered not of child-bearing potential, females&#xD;
                  must be surgically sterile (defined as bilateral tubal ligation, bilateral&#xD;
                  oophorectomy, or hysterectomy) or post-menopausal (defined as no menses for 12&#xD;
                  months in women not using hormonal contraception or hormone replacement therapy,&#xD;
                  confirmed by a follicle stimulating hormone (FSH) level in the postmenopausal&#xD;
                  range at Screening).&#xD;
&#xD;
          -  Free of clinically significant abnormal findings as determined by medical history,&#xD;
             physical examination, vital signs, laboratory tests and ECG.&#xD;
&#xD;
          -  Is able to provide written informed consent.&#xD;
&#xD;
          -  Is willing and able to comply with study requirements (including diet and smoking&#xD;
             restrictions), complete the pain evaluations, remain at the study site overnight, and&#xD;
             return for followup 7 (± 2) days after surgery.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known hypersensitivity reactions or allergy (e.g., asthma, rhinitis, angioedema or&#xD;
             urticaria) in response to nonsteroidal anti-inflammatory drugs (NSAIDs, including&#xD;
             ibuprofen), acetylsalicylic acid (aspirin), ingredients of the study drug, or any&#xD;
             other drugs used in the study, including anaesthetics and antibiotics that may be&#xD;
             required on the day of surgery.&#xD;
&#xD;
          -  A history of active or previous peptic ulceration/ haemorrhage, gastrointestinal&#xD;
             bleeding or perforation, heart failure, renal or hepatic failure, uncontrolled&#xD;
             hypertension, asthma, nasal polyps, or chronic rhinitis.&#xD;
&#xD;
          -  Has complications from the tooth extraction or any other clinically significant&#xD;
             medical history that, in the opinion of the investigator, would affect the subject's&#xD;
             ability to comply or otherwise contraindicate study participation, including but not&#xD;
             limited to the following: cardiac, respiratory, gastroenterological, neurological,&#xD;
             psychological, immunological, haematological, oncological, or renal disease.&#xD;
&#xD;
          -  Has undergone another dental surgery within 60 days prior to the day of surgery.&#xD;
&#xD;
          -  A positive urine drugs of abuse screen or alcohol breathalyser test at screening and&#xD;
             during the study (with the exception of a positive drugs of abuse screen that is a&#xD;
             consequence of permitted prescription medicines).&#xD;
&#xD;
          -  If female, has a positive pregnancy test at screening (serum) or on the day of surgery&#xD;
             prior to surgery (urine), or is lactating.&#xD;
&#xD;
          -  Has known or suspected, (in the opinion of the investigator), history of alcoholism or&#xD;
             drug abuse within 2 years of screening or evidence of tolerance or physical dependence&#xD;
             before dosing with study drug.&#xD;
&#xD;
          -  Taking any concomitant medications that might confound assessments of pain relief,&#xD;
             such as psychotropic drugs, antidepressants, sedative-hypnotics (other than those&#xD;
             permitted for conscious sedation), or other analgesics taken within five times of&#xD;
             their elimination half-lives. Selective serotonin reuptake inhibitors (SSRIs) and&#xD;
             serotonin and noradrenaline reuptake inhibitors (SNRIs) are permitted if the subject&#xD;
             has been on a stable dose for at least four weeks prior to Visit 1 (screening).&#xD;
&#xD;
          -  Is considered by the investigator, for any reason (including, but not limited to the&#xD;
             risks described as precautions, warnings and contraindications in the current version&#xD;
             of the investigator's brochure (IB) for 300 mg ibuprofen PR tablets), to be an&#xD;
             unsuitable candidate to receive the study drug.&#xD;
&#xD;
          -  Has a history of chronic use (defined as daily use for &gt; 2 weeks) of nonsteroidal&#xD;
             anti-inflammatory (NSAIDs), opiates, or glucocorticoids (except inhaled nasal steroids&#xD;
             and topical corticosteroids), for any condition within 6 months before dosing with&#xD;
             study drug.&#xD;
&#xD;
          -  Has significant difficulties swallowing capsules or tablets or is unable to tolerate&#xD;
             oral medication.&#xD;
&#xD;
          -  Previously participated in another clinical study of 300 mg ibuprofen PR tablets, or&#xD;
             received any investigational drug, device, or therapy within 90 days before screening.&#xD;
&#xD;
          -  Enrolment of the Investigator, his / her family members, employees and other dependent&#xD;
             persons.&#xD;
&#xD;
          -  Failure to satisfy the investigator of fitness to participate for any other reason.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Todd Bertoch, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>JBR Clinical Research</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Paul Brittain, M.P.H</last_name>
    <phone>+15128526917</phone>
    <email>paul.brittain@premier-research.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>JBR Clinical Research</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84107</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Todd M Bertoch, MD</last_name>
      <phone>928-830-7354</phone>
      <email>tbertoch@jbrutah.com</email>
    </contact>
    <investigator>
      <last_name>Todd M Bertoch, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://wayback.archive-it.org/7993/20170405155045/https://www.fda.gov/ohrms/dockets/ac/02/briefing/3882B2_04_Wyeth-Ibuprophen.pdf</url>
    <description>Wyeth Consumer Healthcare. (2002). Nonprescription Drug Advisory Committee (NDAC) Meeting on Risks of NSAIDs</description>
  </link>
  <reference>
    <citation>Farrar JT, Young JP Jr, LaMoreaux L, Werth JL, Poole MR. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain. 2001 Nov;94(2):149-158. doi: 10.1016/S0304-3959(01)00349-9.</citation>
    <PMID>11690728</PMID>
  </reference>
  <reference>
    <citation>Davies NM. Clinical pharmacokinetics of ibuprofen. The first 30 years. Clin Pharmacokinet. 1998 Feb;34(2):101-54. doi: 10.2165/00003088-199834020-00002.</citation>
    <PMID>9515184</PMID>
  </reference>
  <reference>
    <citation>Miles L, Hall J, Jenner B, Addis R, Hutchings S. Predicting rapid analgesic onset of ibuprofen salts compared with ibuprofen acid: Tlag, Tlow, Tmed, and a novel parameter, TCmaxRef. Curr Med Res Opin. 2018 Aug;34(8):1483-1490. doi: 10.1080/03007995.2018.1466697. Epub 2018 Apr 27.</citation>
    <PMID>29667449</PMID>
  </reference>
  <reference>
    <citation>Cooper SA, Desjardins PJ, Turk DC, Dworkin RH, Katz NP, Kehlet H, Ballantyne JC, Burke LB, Carragee E, Cowan P, Croll S, Dionne RA, Farrar JT, Gilron I, Gordon DB, Iyengar S, Jay GW, Kalso EA, Kerns RD, McDermott MP, Raja SN, Rappaport BA, Rauschkolb C, Royal MA, Segerdahl M, Stauffer JW, Todd KH, Vanhove GF, Wallace MS, West C, White RE, Wu C. Research design considerations for single-dose analgesic clinical trials in acute pain: IMMPACT recommendations. Pain. 2016 Feb;157(2):288-301. doi: 10.1097/j.pain.0000000000000375.</citation>
    <PMID>26683233</PMID>
  </reference>
  <reference>
    <citation>Singla NK, Desjardins PJ, Chang PD. A comparison of the clinical and experimental characteristics of four acute surgical pain models: dental extraction, bunionectomy, joint replacement, and soft tissue surgery. Pain. 2014 Mar;155(3):441-456. doi: 10.1016/j.pain.2013.09.002. Epub 2013 Sep 6.</citation>
    <PMID>24012952</PMID>
  </reference>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>December 17, 2018</study_first_submitted>
  <study_first_submitted_qc>December 20, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 24, 2018</study_first_posted>
  <last_update_submitted>August 28, 2019</last_update_submitted>
  <last_update_submitted_qc>August 28, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 29, 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>Tooth, Impacted</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ibuprofen</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>May 12, 2022</submitted>
    <returned>June 9, 2022</returned>
    <submitted>July 25, 2022</submitted>
    <returned>August 18, 2022</returned>
    <submitted>November 16, 2022</submitted>
    <returned>December 13, 2022</returned>
    <submitted>March 10, 2023</submitted>
    <returned>April 3, 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/NCT03785756
org study id: 5003601
nct id: NCT03785756
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a single centre, randomised, double-blind, double-dummy, parallel group,
      multiple-dose, active and placebo-controlled efficacy study to evaluate the efficacy and
      safety of 2×300mg ibuprofen Prolonged Release (PR) tablets in subjects with postoperative
      dental pain.
This is a single centre, randomised, double blind, double-dummy, parallel group ,
      multiple-dose, active and placebo controlled efficacy study to evaluate the efficacy and
      safety of ibuprofen 2×300 mg ibuprofen PR tablets in subjects with postoperative dental pain.

      Eligible subjects will complete all screening procedures within 28 days before the surgery
      and randomisation.

      At Screening, subjects will provide written informed consent to participate in the study
      before any protocol specified procedures or assessments are completed. On Day 1, subjects who
      continue to be eligible for study participation after completing screening procedures and
      assessments will undergo extraction of 2 or more third molars. At least 1 of the third molars
      must be a fully or partially bone impacted mandibular molar. If only 2 molars are removed,
      then they must be ipsilateral.

      All subjects will receive local anaesthesia (2% lidocaine with 1:100,000 epinephrine).
      Nitrous oxide will be allowed at the discretion of the investigator. Subjects who experience
      moderate to severe pain intensity (a score of ≥ 5 on a numeric rating scale [NRS] from 0-10
      where 0 = no pain, 10 = worst pain ever) within 6 hours after surgery and who continue to
      meet all study entry criteria will be randomised in a 3:3:1 ratio to receive 2×300 mg
      ibuprofen PR tablets every 12 hours (Q12h), 2×200 mg ibuprofen IR tablets every 8 hours
      (Q8h), or placebo. The randomisation will be stratified by baseline pain category (moderate
      or severe) using a categorical scale that includes the categories of none (0), mild (1-4),
      moderate (5-7), and severe (8-10).

      Subjects will re-assess their baseline pain intensity using the NRS immediately before
      receiving study drug (pre-dose, Time 0) and their pain intensity (NRS) and pain relief (5
      point categorical scale) at the following time points (pre-dose, if at one of the dosing
      timepoints of 0, 8, 12 and/or 16 hours): 15, 30, and 45 minutes, and 1, 1.5, 2, 3, 4, 5, 6,
      7, 8, 10, 12, 16, and 24 hours after Time 0; and immediately before each dose of rescue
      medication, if any. For assessments less than 1 hour apart a window of +/-2 min is allowable
      whilst for assessments at least 1 hour apart a +/-5 min window is allowable.

      The double stopwatch method will be used to record the time to perceptible pain relief and
      time to meaningful pain relief during the 8 hours following the first dose or until subject
      takes rescue medication. Subjects will complete a global evaluation of study drug 24 hours
      (+/- 5 minutes) after Time 0 or immediately before the first dose of rescue medication
      (whichever occurs first). Vital signs will be recorded after the subject has been in a
      sitting position for 3 minutes at the following times: before surgery, within 30 minutes
      before Time 0, 12 and 24 hours after Time 0, and/or immediately before the first dose of
      rescue medication. Adverse events (AEs) will be monitored and recorded from the time of
      signing of the informed consent form (ICF) until the Follow up Visit (or Early Termination
      Visit). During the 24 hours following Time 0, subjects will complete efficacy and safety
      assessments. Subjects will remain at the study site overnight and will be discharged on Day
      2.

      Paracetamol / acetaminophen (1000 mg) will be permitted as the initial rescue medication.
      Subjects will be encouraged to wait at least 60 minutes after receiving study drug before
      taking rescue medication. If acetaminophen rescue medication is not effective in relieving
      the subject's pain, 5 mg oxycodone rescue medication may be administered at the discretion of
      the investigator.

      Subjects are not permitted to take any concomitant medications that might confound
      assessments of pain relief, such as psychotropic drugs, antidepressants, sedative-hypnotics
      (other than those permitted for conscious sedation), or other analgesics taken within five
      times of their elimination half-lives (other than those used at the surgery). Selective
      serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors
      (SNRIs) are permitted if the subject has been on a stable dose for at least four weeks prior
      to Visit 1 (screening).

      Other restrictions include the following: alcohol use is prohibited from 24 hours before
      surgery until discharge on Day 2; nothing by mouth from midnight before surgery until 1 hour
      after surgery; clear liquids only are allowed starting 1 hour after surgery until 1 hour
      after dosing; 1 hour after dosing, the subject's diet may be advanced according to standard
      practice.

      Upon discharge from the study site, subjects may be prescribed pain medication for use at
      home according to the standard practice of the study site. On Day 8 (± 2 days), subjects will
      return to the study site for an abbreviated confirmatory physical assessment and AE
      assessments.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: The dental pain model used in this study is a robust and well established postsurgical pain model that produces pain that is predictable in its character, duration, and intensity. The model is widely accepted and has a proven record of assay sensitivity (i.e. separating active drugs from each other, as well as from placebo). The model is frequently used to evaluate NSAID type analgesics. Results from dental pain studies are accepted by the US Food and Drug Administration (FDA) and European authorities and have been widely extrapolated to other general pain conditions.
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: This is a double-blind, double dummy study. There will be two placebo tablets designed to be comparable to each of the active products (PR and Immediate Release (IR)) in both shape, size, colour and weight. All subject packs have been designed and labelled to ensure blinding is maintained. Subjects, investigators and site staff will all be blind to the treatments.
measure: Summed Pain Intensity Difference 0-12 hours (SPID12) vs placebo using the Numeric Rating Scale (NRS) for pain
time frame: 0-12 hours
description: SPID12 will be used to compare the test product (2×300 mg ibuprofen PR tablets) against the placebo product. The NRS will be used to assess the Pain Intensity, the NRS for pain is an 11-point scale (0-10) where a higher score indicates a greater amount of pain.
measure: Summed Pain Intensity Difference 0-24 hours (SPID24) vs active comparator using the NRS for pain
time frame: 0-24 hours
description: SPID24 will be used to compare the test product (2×300 mg ibuprofen PR tablets twice daily (BID)) and comparator product (2×200 mg ibuprofen IR tablets three times a day (TID)). The NRS will be used to assess the Pain Intensity, the NRS for pain is an 11-point scale (0-10) where a higher score indicates a greater amount of pain.
measure: Summed Pain Intensity Difference 0-4hours (SPID4) using NRS for pain
time frame: 0-4 hours
description: SPID4 after Time 0 will be assessed using the NRS to assess the Pain Intensity, the NRS for pain is an 11-point scale (0-10) where a higher score indicates a greater amount of pain.
measure: Summed Pain Intensity Difference 0-8 hours (SPID8) using NRS for pain
time frame: 0-8 hours
description: SPID8 after Time 0 will be assessed using the NRS to assess the Pain Intensity, the NRS for pain is an 11-point scale (0-10) where a higher score indicates a greater amount of pain.
measure: Summed Pain Intensity Difference 0-12 hours (SPID12) using NRS for pain
time frame: 0-12 hours
description: SPID12 after Time 0 will be assessed using the NRS to assess the Pain Intensity, the NRS for pain is an 11-point scale (0-10) where a higher score indicates a greater amount of pain.
measure: Sum of Total Pain Relief 0-4 hours (TOTPAR4) using Pain Relief Scale (PRS)
time frame: 0-4 hours
description: TOTPAR4 after Time 0 will be assessed using the PRS. PRS is used to measure pain relief and is a 5 point categorical scale, response choices of none = 0, a little = 1, some = 2, a lot = 3, and complete = 4 to be completed in response to the question "How much relief have you had since your starting pain?".
measure: Sum of Total Pain Relief 0-8 hours (TOTPAR8) using PRS
time frame: 0-8 hours
description: TOTPAR8 after Time 0 will be assessed using the PRS. PRS is used to measure pain relief and is a 5 point categorical scale, response choices of none = 0, a little = 1, some = 2, a lot = 3, and complete = 4 to be completed in response to the question "How much relief have you had since your starting pain?".
measure: Sum of Total Pain Relief 0-12 hours (TOTPAR12) using PRS
time frame: 0-12 hours
description: TOTPAR12 after Time 0 will be assessed using the PRS. PRS is used to measure pain relief and is a 5 point categorical scale, response choices of none = 0, a little = 1, some = 2, a lot = 3, and complete = 4 to be completed in response to the question "How much relief have you had since your starting pain?".
measure: Sum of Total Pain Relief 0-24 hours (TOTPAR24) using PRS
time frame: 0-24 hours
description: TOTPAR24 after Time 0 will be assessed using the PRS. PRS is used to measure pain relief and is a 5 point categorical scale, response choices of none = 0, a little = 1, some = 2, a lot = 3, and complete = 4 to be completed in response to the question "How much relief have you had since your starting pain?".
measure: Summed pain relief and intensity difference (sum of TOTPAR and SPID [SPRID]) 0-4 hours (SPRID4) using PRS and NRS for pain.
time frame: 0-4 hours
description: SPRID4 after Time 0 will be assessed using the PRS and NRS for pain. The PRS will be used to measure pain relief and is a 5 point categorical scale, response choices of none = 0, a little = 1, some = 2, a lot = 3, and complete = 4 to be completed in response to the question "How much relief have you had since your starting pain?". The NRS will be used to assess the Pain Intensity, the NRS for pain is an 11-point scale (0-10) where a higher score indicates a greater amount of pain. SPRID4 will be determined by calculating the difference in NRS for pain at the 4-hour time point and the 0-hour timepoint and adding this value to the difference in the PRS at the 4-hour time point and the 0-hour timepoint.
measure: Summed pain relief and intensity difference 0-8 hours (SPRID8) using PRS and NRS for pain
time frame: 0-8 hours
description: SPRID8 after Time 0 will be assessed using the PRS and NRS for pain. The PRS will be used to measure pain relief and is a 5 point categorical scale, response choices of none = 0, a little = 1, some = 2, a lot = 3, and complete = 4 to be completed in response to the question "How much relief have you had since your starting pain?". The NRS will be used to assess the Pain Intensity, the NRS for pain is an 11-point scale (0-10) where a higher score indicates a greater amount of pain. SPRID8 will be determined by calculating the difference in NRS for pain at the 8-hour time point and the 0-hour timepoint and adding this value to the difference in the PRS at the 8-hour time point and the 0-hour timepoint.
measure: Summed pain relief and intensity difference 0-12 hours (SPRID12) using PRS and NRS for pain
time frame: 0-12 hours
description: SPRID12 after Time 0 will be assessed using the PRS and NRS for pain. The PRS will be used to measure pain relief and is a 5 point categorical scale, response choices of none = 0, a little = 1, some = 2, a lot = 3, and complete = 4 to be completed in response to the question "How much relief have you had since your starting pain?". The NRS will be used to assess the Pain Intensity, the NRS for pain is an 11-point scale (0-10) where a higher score indicates a greater amount of pain. SPRID12 will be determined by calculating the difference in NRS for pain at the 12-hour time point and the 0-hour timepoint and adding this value to the difference in the PRS at the 12-hour time point and the 0-hour timepoint.
measure: Summed pain relief and intensity difference 0-24 hours (SPRID24) using PRS and NRS for pain
time frame: 0-24 hours
description: SPRID24 after Time 0 will be assessed using the PRS and NRS for pain. The PRS will be used to measure pain relief and is a 5 point categorical scale, response choices of none = 0, a little = 1, some = 2, a lot = 3, and complete = 4 to be completed in response to the question "How much relief have you had since your starting pain?". The NRS will be used to assess the Pain Intensity, the NRS for pain is an 11-point scale (0-10) where a higher score indicates a greater amount of pain.SPRID24 will be determined by calculating the difference in NRS for pain at the 24-hour time point and the 0-hour timepoint and adding this value to the difference in the PRS at the 24-hour time point and the 0-hour timepoint.
measure: Proportion of participants who show response to study drug using NRS for pain
time frame: 0-8 hours
description: A responder will be defined as a subject with ≥30% improvement in pain intensity without rescue medication during the first 8 hours. The NRS will be used to assess the Pain Intensity, the NRS for pain is an 11-point scale (0-10) where a higher score indicates a greater amount of pain.
measure: NRS (for pain) Pain Intensity Difference at each timepoint
time frame: 0-24 hours
description: NRS pain intensity difference (PID) at each scheduled time point after Time 0. The NRS will be used to assess the Pain Intensity, the NRS for pain is an 11-point scale (0-10) where a higher score indicates a greater amount of pain.
measure: Peak Pain intensity score using NRS for pain
time frame: 0-24 hours
description: Pain intensity score at each scheduled time point will be assessed using the NRS for pain. The NRS for pain is an 11-point scale (0-10) where a higher score indicates a greater amount of pain.
measure: Pain relief score using Pain Relief Scale
time frame: 0-24hours
description: Pain relief score at each scheduled time point after Time 0 will be measured using the PRS. The PRS will be used to measure pain relief and is a 5 point categorical scale, response choices of none = 0, a little = 1, some = 2, a lot = 3, and complete = 4 to be completed in response to the question "How much relief have you had since your starting pain?".
measure: Peak Pain Relief at all timepoints using PRS
time frame: 0-24hours
description: Peak Pain relief at each time point will be measured using PRS. The PRS will be used to measure pain relief and is a 5 point categorical scale, response choices of none = 0, a little = 1, some = 2, a lot = 3, and complete = 4 to be completed in response to the question "How much relief have you had since your starting pain?".
measure: Time to onset of analgesia using double stopwatch assessment
time frame: 0-24 hours
description: Time to onset of analgesia (measured as time to perceptible pain relief confirmed by time to meaningful pain relief) using double stopwatch. Two stopwatches will be started immediately after the subject has swallowed the study drug with 8 ounces of water. Each subject will be instructed, "Stop the first stopwatch when you first feel any pain relief whatsoever. This does not mean you feel completely better, although you might, but when you first feel any relief in the pain you have now" (perceptible pain relief). The subject will also be instructed, "Stop the second stopwatch when you feel the pain relief is meaningful to you" (meaningful pain relief). If the subject does not press the stopwatches within 8 hours after Time 0 the subject will discontinue use of the stopwatches.
measure: Time to first perceptible pain relief using double stopwatch assessment
time frame: 0-8 hours
description: Time to first perceptible pain relief using stopwatch assessment. Two stopwatches will be started immediately after the subject has swallowed the study drug with 8 ounces of water. Each subject will be instructed, "Stop the first stopwatch when you first feel any pain relief whatsoever. This does not mean you feel completely better, although you might, but when you first feel any relief in the pain you have now" (perceptible pain relief). If the subject does not press the stopwatches within 8 hours after Time 0 the subject will discontinue use of the stopwatches.
measure: Time to meaningful pain relief using double stopwatch assessment
time frame: 0-8 hours
description: Time to meaningful pain relief. Two stopwatches will be started immediately after the subject has swallowed the study drug with 8 ounces of water. The subject will be instructed, "Stop the second stopwatch when you feel the pain relief is meaningful to you" (meaningful pain relief). If the subject does not press the stopwatches within 8 hours after Time 0 the subject will discontinue use of the stopwatches.
measure: Time to peak pain relief using PRS
time frame: 0-24 hours
description: Time to peak pain relief. The PRS will be used to measure pain relief and is a 5 point categorical scale, response choices of none = 0, a little = 1, some = 2, a lot = 3, and complete = 4 to be completed in response to the question "How much relief have you had since your starting pain?".
measure: Proportion of subjects using rescue medication
time frame: 0-24 hours
description: Proportion of subjects using rescue medication.
measure: Time to first use of rescue medication
time frame: 0-24 hours
description: Time to first use of rescue medication.
measure: Incidence of Treatment Emergent Adverse Events as assessed by patient response to questions and spontaneous reporting of TEAEs
time frame: 0-10 days
description: Incidence of treatment emergent adverse events (TEAEs). Data listings will be provided for protocol specified safety data.
measure: Vital signs measurements - Blood pressure in mm/Hg
time frame: 0-10 days
description: Incidence of changes in vital sign measurements. Descriptive statistics will be provided at each scheduled time point for each treatment group. Changes from Baseline for vital signs will be calculated for each subject.
measure: Vital signs measurements - Heart rate in beats per minute
time frame: 0-10 days
description: Incidence of changes in vital sign measurements. Descriptive statistics will be provided at each scheduled time point for each treatment group. Changes from Baseline for vital signs will be calculated for each subject.
measure: Vital signs measurements - Respiratory rate in breaths per minute
time frame: 0-10 days
description: Incidence of changes in vital sign measurements. Descriptive statistics will be provided at each scheduled time point for each treatment group. Changes from Baseline for vital signs will be calculated for each subject.
measure: Vital signs measurements - Body Temperature in ºC
time frame: 0-10 days
description: Incidence of changes in vital sign measurements. Descriptive statistics will be provided at each scheduled time point for each treatment group. Changes from Baseline for vital signs will be calculated for each subject.
measure: Global Evaluation of efficacy using 5 point categorical scale
time frame: 0-24 hours
description: Patient's global evaluation of study drug using 5 point categorical scale, response choices of 0 = poor, 1 = fair, 2 = good, 3 = very good, or 4 = excellent to be completed by the patient in response to the question "How effective do you think the study drug is as a treatment for pain?". Subjects will complete the global evaluation of study drug 24 hours after Time 0 or immediately before the first dose of rescue medication (whichever occurs first).
arm group label: Prolonged Release Group
arm group type: Experimental
description: Ibuprofen 300 mg Oral Tablet Placebo of IR tablet Placebo of PR tablet
arm group label: Immediate Release Group
arm group type: Active Comparator
description: Ibuprofen 200 mg Oral Tablet Placebo of IR tablet Placebo of PR tablet
arm group label: Placebo Group
arm group type: Placebo Comparator
description: Placebo of IR tablet Placebo of PR tablet
intervention type: Drug
intervention name: Ibuprofen 300 mg Oral Tablet
description: 2 x 300 mg tablets twice in 24 hours
arm group label: Prolonged Release Group
other name: Prolonged Release Tablet
intervention type: Drug
intervention name: Ibuprofen 200 mg Oral Tablet
description: 2 x 200 mg tablets three times in 24 hours
arm group label: Immediate Release Group
other name: Nurofen, Immediate Release Tablet
intervention type: Other
intervention name: Placebo of PR tablet
description: Up to 2 tablets four times in 24 hours
arm group label: Immediate Release Group
arm group label: Placebo Group
arm group label: Prolonged Release Group
intervention type: Other
intervention name: Placebo of IR tablet
description: Up to 2 tablets four times in 24 hours
arm group label: Immediate Release Group
arm group label: Placebo Group
arm group label: Prolonged Release Group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: No
last name: Todd Bertoch, MD
role: Principal Investigator
affiliation: JBR Clinical Research
last name: Paul Brittain, M.P.H
phone: +15128526917
email: paul.brittain@premier-research.com
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
url: https://wayback.archive-it.org/7993/20170405155045/https://www.fda.gov/ohrms/dockets/ac/02/briefing/3882B2_04_Wyeth-Ibuprophen.pdf
description: Wyeth Consumer Healthcare. (2002). Nonprescription Drug Advisory Committee (NDAC) Meeting on Risks of NSAIDs
citation: Farrar JT, Young JP Jr, LaMoreaux L, Werth JL, Poole MR. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain. 2001 Nov;94(2):149-158. doi: 10.1016/S0304-3959(01)00349-9.
PMID: 11690728
citation: Davies NM. Clinical pharmacokinetics of ibuprofen. The first 30 years. Clin Pharmacokinet. 1998 Feb;34(2):101-54. doi: 10.2165/00003088-199834020-00002.
PMID: 9515184
citation: Miles L, Hall J, Jenner B, Addis R, Hutchings S. Predicting rapid analgesic onset of ibuprofen salts compared with ibuprofen acid: Tlag, Tlow, Tmed, and a novel parameter, TCmaxRef. Curr Med Res Opin. 2018 Aug;34(8):1483-1490. doi: 10.1080/03007995.2018.1466697. Epub 2018 Apr 27.
PMID: 29667449
citation: Cooper SA, Desjardins PJ, Turk DC, Dworkin RH, Katz NP, Kehlet H, Ballantyne JC, Burke LB, Carragee E, Cowan P, Croll S, Dionne RA, Farrar JT, Gilron I, Gordon DB, Iyengar S, Jay GW, Kalso EA, Kerns RD, McDermott MP, Raja SN, Rappaport BA, Rauschkolb C, Royal MA, Segerdahl M, Stauffer JW, Todd KH, Vanhove GF, Wallace MS, West C, White RE, Wu C. Research design considerations for single-dose analgesic clinical trials in acute pain: IMMPACT recommendations. Pain. 2016 Feb;157(2):288-301. doi: 10.1097/j.pain.0000000000000375.
PMID: 26683233
citation: Singla NK, Desjardins PJ, Chang PD. A comparison of the clinical and experimental characteristics of four acute surgical pain models: dental extraction, bunionectomy, joint replacement, and soft tissue surgery. Pain. 2014 Mar;155(3):441-456. doi: 10.1016/j.pain.2013.09.002. Epub 2013 Sep 6.
PMID: 24012952
responsible party type: Sponsor
mesh term: Tooth, Impacted
mesh term: Ibuprofen
sharing ipd: No
submitted: May 12, 2022
returned: June 9, 2022
submitted: July 25, 2022
returned: August 18, 2022
submitted: November 16, 2022
returned: December 13, 2022
submitted: March 10, 2023
returned: April 3, 2023