<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/NCT03003000</url>
  </required_header>
  <id_info>
    <org_study_id>1335.5</org_study_id>
    <secondary_id>2016-000902-12</secondary_id>
    <nct_id>NCT03003000</nct_id>
  </id_info>
  <brief_title>Ibuprofen/Caffeine Lower Back or Neck Pain Study</brief_title>
  <official_title>A Randomized, Placebo- and Active-controlled Multi-country, Multi-centre Parallel Group Study to Evaluate the Efficacy and Safety of a Fixed Dose Combination of 400 mg Ibuprofen and 100 mg Caffeine Compared to Ibuprofen 400 mg and Placebo in Patients With Acute Lower Back or Neck Pain.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <brief_summary>
    <textblock>
      To assess the efficacy and safety of a 400 mg ibuprofen/100 mg caffeine tablet in comparison&#xD;
      to a 400 mg ibuprofen tablet for the treatment of acute lower back or neck pain. To assess&#xD;
      the safety and tolerability of a 400 mg ibuprofen/100 mg caffeine tablet in comparison to a&#xD;
      400 mg ibuprofen tablet and a placebo tablet.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 20, 2016</start_date>
  <completion_date type="Actual">September 28, 2017</completion_date>
  <primary_completion_date type="Actual">September 24, 2017</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>Double</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Pain on Movement (POM) With Regard to the Worst Procedure (WP) Between Baseline and Day 2 (Morning, 2 Hours After Drug Intake)</measure>
    <time_frame>Baseline and Day 2</time_frame>
    <description>The change in pain on movement (POM) with regard to the worst procedure (WP), i.e. the procedure with the highest pain score at baseline (POMwp), between baseline (morning of Day 1, pre-dosing) and Day 2 (morning, 2 hour (h) after drug intake).&#xD;
POM was assessed by the patient at the performance of one standardized, muscle group specific movement and was measured by a numerical rating scale ranging from 0 = 'no pain'to 10 = 'worst pain possible for this condition'.&#xD;
The procedure resulting in highest POM at baseline (worst procedure, POMWP) was repeated for an individual patient. If 2 or more procedures gave the same highest POM, the patient was asked which of the procedures giving the highest POM scores he/she considered the most unpleasant.&#xD;
Change in POMwp was calculated as baseline POMwp - POMwp at Day 2 - indicating a reduction in POMwp, where the result is positive.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The Area Under the Curve (AUC) for Pain on Movement (POM) With Regard to the Worst Procedure (POMwp) Between Baseline and Day 4 (Morning) (POMwpAUC72hour (h))</measure>
    <time_frame>Baseline, Day 1, Day 2 and Day 4 (morning)</time_frame>
    <description>This is a key secondary endpoint. The area under the curve (AUC) for pain on movement (POM) with regard to the worst procedure (POMwp) between baseline and Day 4 (morning), (POMwpAUC72h ). POM was assessed by the patient at the performance of one standardized, muscle group specific movement and was measured by a numerical rating scale ranging from 0 = 'no pain'to 10 = 'worst pain possible for this condition'. A higher AUC value indicates higher POMwp</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Area Under the Curve (AUC) for the Procedure With the Highest Pain Score at Baseline (POMWP) Between Baseline and Day 6 (Morning) (POM(WP)AUC(120h))</measure>
    <time_frame>Baseline, Day 1, Day 2, Day 4 and Day 6 (morning)</time_frame>
    <description>This is a key secondary endpoint. The area under the curve for pain on movement with regard to the worst procedure between baseline and Day 6 (morning) (POM(WP)AUC(120h).&#xD;
POM was assessed by the patient at the performance of one standardized, muscle group specific movement and was measured by a numerical rating scale ranging from 0 = 'no pain'to 10 = 'worst pain possible for this condition'. A higher AUC value indicates higher POMwp.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Pressure Algometry Between Baseline and Day 2 (Morning, 2 Hour After Drug Intake)</measure>
    <time_frame>Baseline and Day 2 (morning, 2 h after drug intake)</time_frame>
    <description>Change in pressure algometry between baseline and Day 2 (morning, 2 h after drug intake).&#xD;
Pressure algometry was determined by the investigator as the pressure value (N/cm2) at a defined trigger point which is located in the area of POMWP. The measurement was performed by using a Somedic Algometer (Somedic AB, Sweden) or an equivalent calibrated and certified device. The pain reaction was determined by placing the algometer on the trigger point, i.e. an area of 1 cm² for which the patient indicated most painful tenderness. The pressure was constantly increased until the patient asked not to increase the pressure anymore. Upon this pain reaction, the corresponding pressure value was documented in the Electronic case report form (eCRF). The trigger point was to be marked with a ball pen to be able to repeat the subsequent assessment at the same position. Change in pressure was calculated as baseline pressure - pressure at Day 2, with a negative result indicating an improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Global Assessment of Efficacy by the Patient at the End of Treatment (Morning of Day 6)</measure>
    <time_frame>At the end of treatment (morning of Day 6)</time_frame>
    <description>Global assessment of efficacy by the patient at the end of treatment (morning of Day 6) is presented. The patient/investigator assessed the overall efficacy of the trial treatment on a 4-point verbal rating scale by answering the question: &quot;How would you rate the overall effect of the trial medication for relieving back or neck pain?&quot; (0 = poor; 1 = fair; 2 = good; 3 = very good).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Patients With a Decrease in POMwp of at Least 30% or 50% Between Baseline and Day 2 (Morning, 2 h After Drug Intake)</measure>
    <time_frame>Baseline and Day 2 (morning, 2 h after drug intake)</time_frame>
    <description>Number of patients with a decrease in POMwp of at least 30% or 50% between baseline and Day 2 (morning, 2 h after drug intake.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to First Meaningful POMwp Relief Within 2 h After the First Dose of Trial Medication</measure>
    <time_frame>Within 2 h after the first dose of trial medication</time_frame>
    <description>Time to event analysis of patients with first meaningful POMwp relief within 2 h after the first dose of trial medication. The percentage of observed patients with a meaningful POMwp relief within 2 h after the first dose of trial medication was reported. The procedure which resulted in the highest POM at baseline (POMwp) was repeated by the investigator 10, 20, 30, 60 and 120 min after the first dose of trial medication. The POMwp relief score (POMwpRS) was assessed by the patient at each of these time points by using a 5-point verbal rating scale (0 = no POMwp relief; 1 = little or perceptible POMwp relief; 2 = meaningful POMwp relief; 3 = a lot of POMwp relief; 4 = complete POMwp relief).&#xD;
The time to first meaningful POMWP relief was the earliest assessment time point after the first application of the trial medication at which the patient reported a score of ≥2.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">635</enrollment>
  <condition>Back Pain</condition>
  <condition>Neck Pain</condition>
  <arm_group>
    <arm_group_label>ibuprofen + caffeine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Fixed Dose Combination</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ibuprofen</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ibuprofen</intervention_name>
    <arm_group_label>ibuprofen</arm_group_label>
    <arm_group_label>ibuprofen + caffeine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>caffeine</intervention_name>
    <arm_group_label>ibuprofen + caffeine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <arm_group_label>placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Signed and dated written informed consent at Visit 1 in accordance with Good Clinical&#xD;
             Practice (GCP) and local legislation.&#xD;
&#xD;
          -  Male or female patients who are &gt;=18 years with current diagnosis of acute back pain&#xD;
             or of neck pain for at least 24 hours, but less than 21 days.&#xD;
&#xD;
          -  Acute back pain or acute neck pain resulting in Pain on Movement (POM) &gt;=5 on the 0-10&#xD;
             Numerical Rating Scale (NRS) for at least one POM procedure out of 5 standardised&#xD;
             procedures.&#xD;
&#xD;
          -  Sensitivity to algometric pressure on the painful trigger point &lt;= 25 N/cm².&#xD;
&#xD;
          -  Women of childbearing potential must be ready and able to use highly effective methods&#xD;
             of birth control.&#xD;
&#xD;
          -  Reliable, cooperative, and of adequate intelligence to record the requested&#xD;
             information on the analgesic questionnaires.&#xD;
&#xD;
          -  Examined by the attending physician and medically cleared to participate in the study&#xD;
&#xD;
          -  In good general health, with a body mass index (BMI) &lt; 30, and have no&#xD;
             contraindications to any of the study medication&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  History of 3 or more episodes of back or neck pain in the last 6 months excluding the&#xD;
             current episode.&#xD;
&#xD;
          -  Patients with pain at rest &gt;= 9&#xD;
&#xD;
          -  Patient with chronic back or neck pain as defined as pain for 3 weeks or longer.&#xD;
&#xD;
          -  Back or neck pain that is attributable to any identifiable cause (eg. disc prolapse,&#xD;
             spondylolisthesis, osteomalacia, inflammatory arthritis, metabolic, neurological&#xD;
             diseases or tumour)&#xD;
&#xD;
          -  Any strains of the back or neck muscles documented by clinical evaluation and&#xD;
             anamnesis that occurred 21 days to 3 months prior to the screening visit.&#xD;
&#xD;
          -  Surgery due to back or neck pain or rehabilitation due to back or neck pain in the&#xD;
             last 12 months.&#xD;
&#xD;
          -  Prior use within the last 3 days before Visit 1 or concomitant use of any anti-&#xD;
             inflammatory drugs, heparinoids, muscle relaxants or analgesics (including but not&#xD;
             limited to short-acting glucocorticoids, non-steroidal anti-inflammatory drugs&#xD;
             [NSAIDs], herbal preparations) for the same indication or other indications.&#xD;
&#xD;
          -  Spinal injections should have been discontinued in due time (investigator's judgment)&#xD;
             before patient enrollment to allow complete wash-out of the active ingredient based on&#xD;
             investigator's judgment.&#xD;
&#xD;
          -  Known severe hepatocellular insufficiency, severe renal insufficiency or Gilbert's&#xD;
             syndrome (Morbus Meulengracht)&#xD;
&#xD;
          -  Patients taking Central Nervous System (CNS) or other psychotropic drugs, or any&#xD;
             nutritional supplement known to have psychotropic effects such as St. John's Wort,&#xD;
             Chapparal, Comfrey, Germander, Gin Bu Huan, Kava, Pennyroyal Skullcap, or Valerian&#xD;
             within two months of taking the first dose of study medication. Patients who have been&#xD;
             on stable doses of these medications for at least two months will be allowed into the&#xD;
             study, as long as they maintain this dose throughout the study, and their condition is&#xD;
             judged stable by the Principal Investigator&#xD;
&#xD;
          -  Any other medical condition that would interfere with efficacy and safety assessments&#xD;
             based on investigator's judgment or any on-going clinical condition that would&#xD;
             jeopardize patient's or site personnel's safety or study compliance based on&#xD;
             investigator judgment&#xD;
&#xD;
          -  Further exclusion criteria apply&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Boehringer Ingelheim</last_name>
    <role>Study Chair</role>
    <affiliation>Boehringer Ingelheim</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Praxis Dr. Steinebach, Essen</name>
      <address>
        <city>Essen</city>
        <zip>45277</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Praxis Dr. Schaefer, 45355 Essen</name>
      <address>
        <city>Essen</city>
        <zip>45355</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Studienzentrum Bocholderstraße</name>
      <address>
        <city>Essen</city>
        <zip>45355</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Unterfrintroper Hausarztzentrum</name>
      <address>
        <city>Essen</city>
        <zip>45359</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Praxis Dr. Pabst, Gilching</name>
      <address>
        <city>Gilching</city>
        <zip>82205</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Praxis Kai Gastl</name>
      <address>
        <city>Gilching</city>
        <zip>82205</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>medicoKIT GmbH</name>
      <address>
        <city>Goch</city>
        <zip>47574</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Research Dr. Martz</name>
      <address>
        <city>Hamburg</city>
        <zip>22143</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Praxis Dr. Dahmen, 22415 Hamburg</name>
      <address>
        <city>Hamburg</city>
        <zip>22415</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Praxis Dr. Chevts, 76199 Karlsruhe</name>
      <address>
        <city>Karlsruhe</city>
        <zip>76199</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dünnwaldpraxis, Köln</name>
      <address>
        <city>Köln</city>
        <zip>51069</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Praxis Dr. Klein, Künzing</name>
      <address>
        <city>Künzing</city>
        <zip>94550</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Anästhesiologie Rheinbach</name>
      <address>
        <city>Rheinbach</city>
        <zip>53359</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Praxis Dr. Sauter</name>
      <address>
        <city>Wangen</city>
        <zip>88239</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Neurologie und Psychiatrie / Psychotherapie</name>
      <address>
        <city>Westerstede</city>
        <zip>26655</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State Healthcare Institution, City Out-Patient's Clinic #109</name>
      <address>
        <city>St. Petersburg</city>
        <zip>192283</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical Centre &quot;Reavita Med SPb&quot; LLC</name>
      <address>
        <city>St. Petersburg</city>
        <zip>194325</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City Outpatient dep.no.107;clinc.pharmacology,st.petersburg</name>
      <address>
        <city>St. Petersburg</city>
        <zip>195030</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
    <country>Russian Federation</country>
  </location_countries>
  <link>
    <url>http://trials.boehringer-ingelheim.com/</url>
    <description>Related Info</description>
  </link>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>November 17, 2016</study_first_submitted>
  <study_first_submitted_qc>December 21, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 26, 2016</study_first_posted>
  <results_first_submitted>September 27, 2018</results_first_submitted>
  <results_first_submitted_qc>March 5, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">June 7, 2019</results_first_posted>
  <last_update_submitted>March 5, 2019</last_update_submitted>
  <last_update_submitted_qc>March 5, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">June 7, 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>Neck Pain</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ibuprofen</mesh_term>
    <mesh_term>Caffeine</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>August 29, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/00/NCT03003000/SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>August 5, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/00/NCT03003000/Prot_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>This was a randomized, placebo and active-controlled, double-blind, 3-arm, parallel trial, comparing the effect of the fixed dose combination of 400 milligram (mg) ibuprofen&amp;100 mg caffeine versus 400 mg ibuprofen and placebo in patients with acute neck or back pain randomly assigned in 2:2:1 ratio respectively.</recruitment_details>
      <pre_assignment_details>All patients were screened for eligibility to participate in the trial. Patients attended specialist sites to ensure that all patients met all inclusion/exclusion criteria. Patients were not to be entered/randomised to trial treatment if any one of the specific entry criteria were not met.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Placebo</title>
          <description>Patients were administered placebo matching ibuprofen and ibuprofen/caffeine film-coated tablets orally 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.</description>
        </group>
        <group group_id="P2">
          <title>Ibuprofen</title>
          <description>Patients were administered film-coated tablets orally containing 400 mg ibuprofen 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.</description>
        </group>
        <group group_id="P3">
          <title>Ibuprofen and Caffeine</title>
          <description>Patients were administered film-coated tablets orally containing 400 mg ibuprofen and 100 mg caffeine 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="126"/>
                <participants group_id="P2" count="253"/>
                <participants group_id="P3" count="256"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="121"/>
                <participants group_id="P2" count="249"/>
                <participants group_id="P3" count="251"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="5"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Non-compliant with protocol</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Refused to continue medication</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other than listed</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Treated Set (TS): The TS comprised all randomised patients who took at least 1 dose of trial medication.</population>
      <group_list>
        <group group_id="B1">
          <title>Placebo</title>
          <description>Patients were administered placebo matching ibuprofen and ibuprofen/caffeine film-coated tablets orally 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.</description>
        </group>
        <group group_id="B2">
          <title>Ibuprofen</title>
          <description>Patients were administered film-coated tablets orally containing 400 mg ibuprofen 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.</description>
        </group>
        <group group_id="B3">
          <title>Ibuprofen and Caffeine</title>
          <description>Patients were administered film-coated tablets orally containing 400 mg ibuprofen and 100 mg caffeine 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="126"/>
            <count group_id="B2" value="253"/>
            <count group_id="B3" value="256"/>
            <count group_id="B4" value="635"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <description>Age at the time of signing informed consent form is presented.</description>
          <population>TS</population>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="46.3" spread="15.00"/>
                    <measurement group_id="B2" value="45.5" spread="16.40"/>
                    <measurement group_id="B3" value="44.8" spread="17.00"/>
                    <measurement group_id="B4" value="45.4" spread="16.36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <description>Number of subjects is categorized as Male or Female.</description>
          <population>TS</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="75"/>
                    <measurement group_id="B2" value="155"/>
                    <measurement group_id="B3" value="143"/>
                    <measurement group_id="B4" value="373"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="51"/>
                    <measurement group_id="B2" value="98"/>
                    <measurement group_id="B3" value="113"/>
                    <measurement group_id="B4" value="262"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <description>Number of subjects is categorized for ethnicity data.</description>
          <population>TS</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="125"/>
                    <measurement group_id="B2" value="253"/>
                    <measurement group_id="B3" value="256"/>
                    <measurement group_id="B4" value="634"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <description>Number of subjects is categorized for race data.</description>
          <population>TS</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="125"/>
                    <measurement group_id="B2" value="249"/>
                    <measurement group_id="B3" value="251"/>
                    <measurement group_id="B4" value="625"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Pain on movement worst procedure score (0-10)</title>
          <description>POM was assessed by the patient at the performance of one standardized, muscle group specific movement and was measured by a numerical rating scale ranging from 0 = 'no pain'to 10 = 'worst pain possible for this condition'.</description>
          <population>Treated Set</population>
          <units>Unit on scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6.9" spread="1.07"/>
                    <measurement group_id="B2" value="6.8" spread="1.15"/>
                    <measurement group_id="B3" value="6.6" spread="1.15"/>
                    <measurement group_id="B4" value="6.7" spread="1.14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Pain on Movement (POM) With Regard to the Worst Procedure (WP) Between Baseline and Day 2 (Morning, 2 Hours After Drug Intake)</title>
        <description>The change in pain on movement (POM) with regard to the worst procedure (WP), i.e. the procedure with the highest pain score at baseline (POMwp), between baseline (morning of Day 1, pre-dosing) and Day 2 (morning, 2 hour (h) after drug intake).&#xD;
POM was assessed by the patient at the performance of one standardized, muscle group specific movement and was measured by a numerical rating scale ranging from 0 = 'no pain'to 10 = 'worst pain possible for this condition'.&#xD;
The procedure resulting in highest POM at baseline (worst procedure, POMWP) was repeated for an individual patient. If 2 or more procedures gave the same highest POM, the patient was asked which of the procedures giving the highest POM scores he/she considered the most unpleasant.&#xD;
Change in POMwp was calculated as baseline POMwp - POMwp at Day 2 - indicating a reduction in POMwp, where the result is positive.</description>
        <time_frame>Baseline and Day 2</time_frame>
        <population>Full analysis set (FAS): FAS comprised all patients in the TS who provided a baseline value for POMWP at Visit 1 (before drug intake) and at least 1 POMWP post-treatment value at Visit 1 (Day 1 morning, 2 h after drug intake) and at Visit 2 (Day 2, morning, 2 h after drug intake).</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Patients were administered placebo matching ibuprofen and ibuprofen/caffeine film-coated tablets orally 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.</description>
          </group>
          <group group_id="O2">
            <title>Ibuprofen</title>
            <description>Patients were administered film-coated tablets orally containing 400 mg ibuprofen 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.</description>
          </group>
          <group group_id="O3">
            <title>Ibuprofen and Caffeine</title>
            <description>Patients were administered film-coated tablets orally containing 400 mg ibuprofen and 100 mg caffeine 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Pain on Movement (POM) With Regard to the Worst Procedure (WP) Between Baseline and Day 2 (Morning, 2 Hours After Drug Intake)</title>
          <description>The change in pain on movement (POM) with regard to the worst procedure (WP), i.e. the procedure with the highest pain score at baseline (POMwp), between baseline (morning of Day 1, pre-dosing) and Day 2 (morning, 2 hour (h) after drug intake).&#xD;
POM was assessed by the patient at the performance of one standardized, muscle group specific movement and was measured by a numerical rating scale ranging from 0 = 'no pain'to 10 = 'worst pain possible for this condition'.&#xD;
The procedure resulting in highest POM at baseline (worst procedure, POMWP) was repeated for an individual patient. If 2 or more procedures gave the same highest POM, the patient was asked which of the procedures giving the highest POM scores he/she considered the most unpleasant.&#xD;
Change in POMwp was calculated as baseline POMwp - POMwp at Day 2 - indicating a reduction in POMwp, where the result is positive.</description>
          <population>Full analysis set (FAS): FAS comprised all patients in the TS who provided a baseline value for POMWP at Visit 1 (before drug intake) and at least 1 POMWP post-treatment value at Visit 1 (Day 1 morning, 2 h after drug intake) and at Visit 2 (Day 2, morning, 2 h after drug intake).</population>
          <units>Unit on scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="126"/>
                <count group_id="O2" value="253"/>
                <count group_id="O3" value="256"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.712" spread="0.1422"/>
                    <measurement group_id="O2" value="1.998" spread="0.1042"/>
                    <measurement group_id="O3" value="1.869" spread="0.1030"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Superiority of ibuprofen and caffeine versus ibuprofen as well as ibuprofen and caffeine versus placebo had to be shown to reject the overall null hypothesis that there is no difference in change in POMWP between baseline and Day 2 (morning, 2 h after drug intake) between patients treated with ibuprofen/caffeine and patients treated with placebo.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.3446</p_value>
            <p_value_desc>No adjustment for multiplicity issues was made for this comparison. The level of significance was 0.05.</p_value_desc>
            <method>Mixed effect Model Repeated Measurement</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.156</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.168</ci_lower_limit>
            <ci_upper_limit>0.480</ci_upper_limit>
            <estimate_desc>Adjusted mean change from baseline ibuprofen and caffeine - Adjusted mean change from baseline placebo. A positive result favors the treatment with ibuprofen and caffeine</estimate_desc>
            <other_analysis_desc>Mixed effect model for repeated measures analysis (MMRM) includes fixed, categorical effects of treatment, country, worst procedure site, time and interaction terms for treatment-by-time, treatment-by-stratum-by-time, treatment-by-stratum and stratum-by-time interaction, as well as the continuous fixed covariates of baseline POMwp and baseline-by-time interaction, using unstructured covariance matrix.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Superiority of ibuprofen and caffeine versus ibuprofen as well as ibuprofen and caffeine versus placebo had to be shown to reject the overall null hypothesis that there is no difference in change in POMWP between baseline and Day 2 (morning, 2 h after drug intake) between patients treated with ibuprofen/caffeine and patients treated with ibuprofen.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.3358</p_value>
            <p_value_desc>No adjustment for multiplicity issues was made for this comparison. The level of significance was 0.05.</p_value_desc>
            <method>Mixed effect Model Repeat Measurement</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.129</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.392</ci_lower_limit>
            <ci_upper_limit>0.134</ci_upper_limit>
            <estimate_desc>Adjusted mean change from baseline ibuprofen and caffeine - Adjusted mean change from baseline ibuprofen. A positive result favors the treatment with ibuprofen and caffeine</estimate_desc>
            <other_analysis_desc>Mixed effect model for repeated measures analysis (MMRM) includes fixed, categorical effects of treatment, country, worst procedure site, time and interaction terms for treatment-by-time, treatment-by-stratum-by-time, treatment-by-stratum and stratum-by-time interaction, as well as the continuous fixed covariates of baseline POMwp and baseline-by-time interaction, using unstructured covariance matrix</other_analysis_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Area Under the Curve (AUC) for Pain on Movement (POM) With Regard to the Worst Procedure (POMwp) Between Baseline and Day 4 (Morning) (POMwpAUC72hour (h))</title>
        <description>This is a key secondary endpoint. The area under the curve (AUC) for pain on movement (POM) with regard to the worst procedure (POMwp) between baseline and Day 4 (morning), (POMwpAUC72h ). POM was assessed by the patient at the performance of one standardized, muscle group specific movement and was measured by a numerical rating scale ranging from 0 = 'no pain'to 10 = 'worst pain possible for this condition'. A higher AUC value indicates higher POMwp</description>
        <time_frame>Baseline, Day 1, Day 2 and Day 4 (morning)</time_frame>
        <population>Treated Set (TS): The TS comprised all randomised patients who took at least 1 dose of trial medication.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Patients were administered placebo matching ibuprofen and ibuprofen/caffeine film-coated tablets orally 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.</description>
          </group>
          <group group_id="O2">
            <title>Ibuprofen</title>
            <description>Patients were administered film-coated tablets orally containing 400 mg ibuprofen 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.</description>
          </group>
          <group group_id="O3">
            <title>Ibuprofen and Caffeine</title>
            <description>Patients were administered film-coated tablets orally containing 400 mg ibuprofen and 100 mg caffeine 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.</description>
          </group>
        </group_list>
        <measure>
          <title>The Area Under the Curve (AUC) for Pain on Movement (POM) With Regard to the Worst Procedure (POMwp) Between Baseline and Day 4 (Morning) (POMwpAUC72hour (h))</title>
          <description>This is a key secondary endpoint. The area under the curve (AUC) for pain on movement (POM) with regard to the worst procedure (POMwp) between baseline and Day 4 (morning), (POMwpAUC72h ). POM was assessed by the patient at the performance of one standardized, muscle group specific movement and was measured by a numerical rating scale ranging from 0 = 'no pain'to 10 = 'worst pain possible for this condition'. A higher AUC value indicates higher POMwp</description>
          <population>Treated Set (TS): The TS comprised all randomised patients who took at least 1 dose of trial medication.</population>
          <units>Unit on scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="126"/>
                <count group_id="O2" value="253"/>
                <count group_id="O3" value="256"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.800" spread="0.1266"/>
                    <measurement group_id="O2" value="4.461" spread="0.0942"/>
                    <measurement group_id="O3" value="4.512" spread="0.0931"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0474</p_value>
            <p_value_desc>No adjustment for multiplicity issues was made for this comparison. The level of significance was 0.05.</p_value_desc>
            <method>ANCOVA</method>
            <method_desc>ANCOVA included treatment, country, and worst procedure site as fixed effects and baseline POMwp as a continuous covariate.</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.288</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.572</ci_lower_limit>
            <ci_upper_limit>-0.003</ci_upper_limit>
            <estimate_desc>Adjusted mean ibuprofen and caffeine - Adjusted mean placebo. A negative result favors ibuprofen and caffeine</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.6658</p_value>
            <p_value_desc>No adjustment for multiplicity issues was made for this comparison. The level of significance was 0.05.</p_value_desc>
            <method>ANCOVA</method>
            <method_desc>The ANCOVA included treatment, country, and worst procedure site as fixed effects and baseline POMwp as a continuous covariate.</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.051</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.180</ci_lower_limit>
            <ci_upper_limit>0.282</ci_upper_limit>
            <estimate_desc>Adjusted mean ibuprofen and caffeine - Adjusted mean ibuprofen. A negative result favors ibuprofen and caffeine.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Area Under the Curve (AUC) for the Procedure With the Highest Pain Score at Baseline (POMWP) Between Baseline and Day 6 (Morning) (POM(WP)AUC(120h))</title>
        <description>This is a key secondary endpoint. The area under the curve for pain on movement with regard to the worst procedure between baseline and Day 6 (morning) (POM(WP)AUC(120h).&#xD;
POM was assessed by the patient at the performance of one standardized, muscle group specific movement and was measured by a numerical rating scale ranging from 0 = 'no pain'to 10 = 'worst pain possible for this condition'. A higher AUC value indicates higher POMwp.</description>
        <time_frame>Baseline, Day 1, Day 2, Day 4 and Day 6 (morning)</time_frame>
        <population>TS</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Patients were administered placebo matching ibuprofen and ibuprofen/caffeine film-coated tablets orally 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.</description>
          </group>
          <group group_id="O2">
            <title>Ibuprofen</title>
            <description>Patients were administered film-coated tablets orally containing 400 mg ibuprofen 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.</description>
          </group>
          <group group_id="O3">
            <title>Ibuprofen and Caffeine</title>
            <description>Patients were administered film-coated tablets orally containing 400 mg ibuprofen and 100 mg caffeine 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.</description>
          </group>
        </group_list>
        <measure>
          <title>The Area Under the Curve (AUC) for the Procedure With the Highest Pain Score at Baseline (POMWP) Between Baseline and Day 6 (Morning) (POM(WP)AUC(120h))</title>
          <description>This is a key secondary endpoint. The area under the curve for pain on movement with regard to the worst procedure between baseline and Day 6 (morning) (POM(WP)AUC(120h).&#xD;
POM was assessed by the patient at the performance of one standardized, muscle group specific movement and was measured by a numerical rating scale ranging from 0 = 'no pain'to 10 = 'worst pain possible for this condition'. A higher AUC value indicates higher POMwp.</description>
          <population>TS</population>
          <units>Unit on scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="126"/>
                <count group_id="O2" value="253"/>
                <count group_id="O3" value="256"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.175" spread="0.1334"/>
                    <measurement group_id="O2" value="3.718" spread="0.0992"/>
                    <measurement group_id="O3" value="3.776" spread="0.0981"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0091</p_value>
            <p_value_desc>No adjustment for multiplicity issues was made for this comparison. The level of significance was 0.05.</p_value_desc>
            <method>ANCOVA</method>
            <method_desc>The ANCOVA included treatment, country, and worst procedure site as fixed effects and baseline POMwp as a continuous covariate.</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.399</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.698</ci_lower_limit>
            <ci_upper_limit>-0.100</ci_upper_limit>
            <estimate_desc>Adjusted mean ibuprofen and caffeine - Adjusted mean placebo. A negative result favors ibuprofen and caffeine</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.6387</p_value>
            <p_value_desc>No adjustment for multiplicity issues was made for this comparison. The level of significance was 0.05.</p_value_desc>
            <method>ANCOVA</method>
            <method_desc>The ANCOVA included treatment, country, and worst procedure site as fixed effects and baseline POMwp as a continuous covariate.</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.058</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.185</ci_lower_limit>
            <ci_upper_limit>0.302</ci_upper_limit>
            <estimate_desc>Adjusted mean ibuprofen and caffeine - Adjusted mean ibuprofen. A negative result favors ibuprofen and caffeine</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Pressure Algometry Between Baseline and Day 2 (Morning, 2 Hour After Drug Intake)</title>
        <description>Change in pressure algometry between baseline and Day 2 (morning, 2 h after drug intake).&#xD;
Pressure algometry was determined by the investigator as the pressure value (N/cm2) at a defined trigger point which is located in the area of POMWP. The measurement was performed by using a Somedic Algometer (Somedic AB, Sweden) or an equivalent calibrated and certified device. The pain reaction was determined by placing the algometer on the trigger point, i.e. an area of 1 cm² for which the patient indicated most painful tenderness. The pressure was constantly increased until the patient asked not to increase the pressure anymore. Upon this pain reaction, the corresponding pressure value was documented in the Electronic case report form (eCRF). The trigger point was to be marked with a ball pen to be able to repeat the subsequent assessment at the same position. Change in pressure was calculated as baseline pressure - pressure at Day 2, with a negative result indicating an improvement.</description>
        <time_frame>Baseline and Day 2 (morning, 2 h after drug intake)</time_frame>
        <population>TS</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Patients were administered placebo matching ibuprofen and ibuprofen/caffeine film-coated tablets orally 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.</description>
          </group>
          <group group_id="O2">
            <title>Ibuprofen</title>
            <description>Patients were administered film-coated tablets orally containing 400 mg ibuprofen 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.</description>
          </group>
          <group group_id="O3">
            <title>Ibuprofen and Caffeine</title>
            <description>Patients were administered film-coated tablets orally containing 400 mg ibuprofen and 100 mg caffeine 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Pressure Algometry Between Baseline and Day 2 (Morning, 2 Hour After Drug Intake)</title>
          <description>Change in pressure algometry between baseline and Day 2 (morning, 2 h after drug intake).&#xD;
Pressure algometry was determined by the investigator as the pressure value (N/cm2) at a defined trigger point which is located in the area of POMWP. The measurement was performed by using a Somedic Algometer (Somedic AB, Sweden) or an equivalent calibrated and certified device. The pain reaction was determined by placing the algometer on the trigger point, i.e. an area of 1 cm² for which the patient indicated most painful tenderness. The pressure was constantly increased until the patient asked not to increase the pressure anymore. Upon this pain reaction, the corresponding pressure value was documented in the Electronic case report form (eCRF). The trigger point was to be marked with a ball pen to be able to repeat the subsequent assessment at the same position. Change in pressure was calculated as baseline pressure - pressure at Day 2, with a negative result indicating an improvement.</description>
          <population>TS</population>
          <units>newton/centimeter² (N/cm^2)</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="126"/>
                <count group_id="O2" value="253"/>
                <count group_id="O3" value="256"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.734" spread="0.6107"/>
                    <measurement group_id="O2" value="-3.331" spread="0.4396"/>
                    <measurement group_id="O3" value="-3.175" spread="0.4366"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Mixed effect model for repeated measures (MMRM) includes fixed, categorical effects of treatment, country, worst procedure site, time and interaction terms for treatment-by-time as well as the continuous fixed covariates of baseline pressure algometry and baseline-by-time interaction, using unstructured covariance matrix.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.4398</p_value>
            <p_value_desc>No adjustment for multiplicity issues was made for this comparison. The level of significance was 0.05.</p_value_desc>
            <method>Mixed effect model for repeated measures</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.559</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.861</ci_lower_limit>
            <ci_upper_limit>1.979</ci_upper_limit>
            <estimate_desc>Adjusted mean change ibuprofen and caffeine - Adjusted mean change placebo. A negative result favors ibuprofen and caffeine.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>MMRM includes fixed, categorical effects of treatment, country, worst procedure site, time and interaction terms for treatment-by-time as well as the continuous fixed covariates of baseline pressure algometry and baseline-by-time interaction, using unstructured covariance matrix.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.7911</p_value>
            <p_value_desc>No adjustment for multiplicity issues was made for this comparison. The level of significance was 0.05.</p_value_desc>
            <method>Mixed effect Model Repeat Measurement</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.156</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.002</ci_lower_limit>
            <ci_upper_limit>1.314</ci_upper_limit>
            <estimate_desc>Adjusted mean change ibuprofen and caffeine - Adjusted mean change ibuprofen. A negative result favors ibuprofen and caffeine.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Global Assessment of Efficacy by the Patient at the End of Treatment (Morning of Day 6)</title>
        <description>Global assessment of efficacy by the patient at the end of treatment (morning of Day 6) is presented. The patient/investigator assessed the overall efficacy of the trial treatment on a 4-point verbal rating scale by answering the question: &quot;How would you rate the overall effect of the trial medication for relieving back or neck pain?&quot; (0 = poor; 1 = fair; 2 = good; 3 = very good).</description>
        <time_frame>At the end of treatment (morning of Day 6)</time_frame>
        <population>TS including participants with available data for global assessment of efficacy</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Patients were administered placebo matching ibuprofen and ibuprofen/caffeine film-coated tablets orally 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.</description>
          </group>
          <group group_id="O2">
            <title>Ibuprofen</title>
            <description>Patients were administered film-coated tablets orally containing 400 mg ibuprofen 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.</description>
          </group>
          <group group_id="O3">
            <title>Ibuprofen and Caffeine</title>
            <description>Patients were administered film-coated tablets orally containing 400 mg ibuprofen and 100 mg caffeine 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.</description>
          </group>
        </group_list>
        <measure>
          <title>Global Assessment of Efficacy by the Patient at the End of Treatment (Morning of Day 6)</title>
          <description>Global assessment of efficacy by the patient at the end of treatment (morning of Day 6) is presented. The patient/investigator assessed the overall efficacy of the trial treatment on a 4-point verbal rating scale by answering the question: &quot;How would you rate the overall effect of the trial medication for relieving back or neck pain?&quot; (0 = poor; 1 = fair; 2 = good; 3 = very good).</description>
          <population>TS including participants with available data for global assessment of efficacy</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="123"/>
                <count group_id="O2" value="253"/>
                <count group_id="O3" value="255"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Very good</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                    <measurement group_id="O2" value="43"/>
                    <measurement group_id="O3" value="41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Good</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46"/>
                    <measurement group_id="O2" value="115"/>
                    <measurement group_id="O3" value="116"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Fair</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35"/>
                    <measurement group_id="O2" value="57"/>
                    <measurement group_id="O3" value="66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Poor</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28"/>
                    <measurement group_id="O2" value="38"/>
                    <measurement group_id="O3" value="32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0045</p_value>
            <p_value_desc>No adjustment for multiplicity issues was made for this comparison. The level of significance was 0.05.</p_value_desc>
            <method>Regression, Logistic</method>
            <method_desc>An ordinal logistic regression model adjusting for country and worst procedure site.</method_desc>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.777</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.195</ci_lower_limit>
            <ci_upper_limit>2.642</ci_upper_limit>
            <estimate_desc>An odds ratio &gt;1 indicates better efficacy for ibuprofen and caffeine than for the comparator</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.9603</p_value>
            <p_value_desc>No adjustment for multiplicity issues was made for this comparison. The level of significance was 0.05.</p_value_desc>
            <method>Regression, Logistic</method>
            <method_desc>An ordinal logistic regression model adjusting for country and worst procedure site.</method_desc>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.008</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.732</ci_lower_limit>
            <ci_upper_limit>1.389</ci_upper_limit>
            <estimate_desc>An odds ratio &gt;1 indicates better efficacy for ibuprofen and caffeine than for the comparator</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Patients With a Decrease in POMwp of at Least 30% or 50% Between Baseline and Day 2 (Morning, 2 h After Drug Intake)</title>
        <description>Number of patients with a decrease in POMwp of at least 30% or 50% between baseline and Day 2 (morning, 2 h after drug intake.</description>
        <time_frame>Baseline and Day 2 (morning, 2 h after drug intake)</time_frame>
        <population>TS</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Patients were administered placebo matching ibuprofen and ibuprofen/caffeine film-coated tablets orally 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.</description>
          </group>
          <group group_id="O2">
            <title>Ibuprofen</title>
            <description>Patients were administered film-coated tablets orally containing 400 mg ibuprofen 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.</description>
          </group>
          <group group_id="O3">
            <title>Ibuprofen and Caffeine</title>
            <description>Patients were administered film-coated tablets orally containing 400 mg ibuprofen and 100 mg caffeine 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients With a Decrease in POMwp of at Least 30% or 50% Between Baseline and Day 2 (Morning, 2 h After Drug Intake)</title>
          <description>Number of patients with a decrease in POMwp of at least 30% or 50% between baseline and Day 2 (morning, 2 h after drug intake.</description>
          <population>TS</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="126"/>
                <count group_id="O2" value="253"/>
                <count group_id="O3" value="256"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Patients with a decrease of ≥30%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49"/>
                    <measurement group_id="O2" value="111"/>
                    <measurement group_id="O3" value="101"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Patients with a decrease of ≥50%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17"/>
                    <measurement group_id="O2" value="59"/>
                    <measurement group_id="O3" value="44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.9022</p_value>
            <p_value_desc>No adjustment for multiplicity issues was made for this comparison. The level of significance was 0.05.</p_value_desc>
            <method>likelihood-ratio test</method>
            <method_desc>The likelihood-ratio test was used to test treatment differences for patients with a decrease of ≥30%.</method_desc>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.028</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.663</ci_lower_limit>
            <ci_upper_limit>1.592</ci_upper_limit>
            <estimate_desc>An odds ratio &gt;1 indicates better efficacy for ibuprofen and caffeine than for the comparator.</estimate_desc>
            <other_analysis_desc>Results are based on the Logistic regression. Logistic regression model was adjusted for the categorical covariates country and worst procedure site.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.3129</p_value>
            <p_value_desc>No adjustment for multiplicity issues was made for this comparison. The level of significance was 0.05.</p_value_desc>
            <method>likelihood-ratio test</method>
            <method_desc>The likelihood-ratio test was used to test treatment differences for patients with a decrease of ≥30%.</method_desc>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>0.834</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.586</ci_lower_limit>
            <ci_upper_limit>1.187</ci_upper_limit>
            <estimate_desc>An odds ratio &gt;1 indicates better efficacy for ibuprofen and caffeine than for the comparator.</estimate_desc>
            <other_analysis_desc>Results are based on the Logistic regression. Logistic regression model was adjusted for the categorical covariates country and worst procedure site.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.3301</p_value>
            <p_value_desc>No adjustment for multiplicity issues was made for this comparison. The level of significance was 0.05.</p_value_desc>
            <method>likelihood-ratio test</method>
            <method_desc>The likelihood-ratio test was used to test treatment differences for patients with a decrease of ≥50%.</method_desc>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.354</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.736</ci_lower_limit>
            <ci_upper_limit>2.494</ci_upper_limit>
            <estimate_desc>An odds ratio &gt;1 indicates better efficacy for ibuprofen and caffeine than for the comparator</estimate_desc>
            <other_analysis_desc>Results are based on the Logistic regression. Logistic regression model was adjusted for the categorical covariates country and worst procedure site.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0864</p_value>
            <p_value_desc>No adjustment for multiplicity issues was made for this comparison. The level of significance was 0.05.</p_value_desc>
            <method>likelihood-ratio test</method>
            <method_desc>The likelihood-ratio test was used to test treatment differences for patients with a decrease of ≥50%.</method_desc>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>0.680</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.437</ci_lower_limit>
            <ci_upper_limit>1.057</ci_upper_limit>
            <estimate_desc>An odds ratio &gt;1 indicates better efficacy for ibuprofen and caffeine than for the comparator</estimate_desc>
            <other_analysis_desc>Results are based on the Logistic regression. Logistic regression model was adjusted for the categorical covariates country and worst procedure site.</other_analysis_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to First Meaningful POMwp Relief Within 2 h After the First Dose of Trial Medication</title>
        <description>Time to event analysis of patients with first meaningful POMwp relief within 2 h after the first dose of trial medication. The percentage of observed patients with a meaningful POMwp relief within 2 h after the first dose of trial medication was reported. The procedure which resulted in the highest POM at baseline (POMwp) was repeated by the investigator 10, 20, 30, 60 and 120 min after the first dose of trial medication. The POMwp relief score (POMwpRS) was assessed by the patient at each of these time points by using a 5-point verbal rating scale (0 = no POMwp relief; 1 = little or perceptible POMwp relief; 2 = meaningful POMwp relief; 3 = a lot of POMwp relief; 4 = complete POMwp relief).&#xD;
The time to first meaningful POMWP relief was the earliest assessment time point after the first application of the trial medication at which the patient reported a score of ≥2.</description>
        <time_frame>Within 2 h after the first dose of trial medication</time_frame>
        <population>TS</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Patients were administered placebo matching ibuprofen and ibuprofen/caffeine film-coated tablets orally 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.</description>
          </group>
          <group group_id="O2">
            <title>Ibuprofen</title>
            <description>Patients were administered film-coated tablets orally containing 400 mg ibuprofen 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.</description>
          </group>
          <group group_id="O3">
            <title>Ibuprofen and Caffeine</title>
            <description>Patients were administered film-coated tablets orally containing 400 mg ibuprofen and 100 mg caffeine 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to First Meaningful POMwp Relief Within 2 h After the First Dose of Trial Medication</title>
          <description>Time to event analysis of patients with first meaningful POMwp relief within 2 h after the first dose of trial medication. The percentage of observed patients with a meaningful POMwp relief within 2 h after the first dose of trial medication was reported. The procedure which resulted in the highest POM at baseline (POMwp) was repeated by the investigator 10, 20, 30, 60 and 120 min after the first dose of trial medication. The POMwp relief score (POMwpRS) was assessed by the patient at each of these time points by using a 5-point verbal rating scale (0 = no POMwp relief; 1 = little or perceptible POMwp relief; 2 = meaningful POMwp relief; 3 = a lot of POMwp relief; 4 = complete POMwp relief).&#xD;
The time to first meaningful POMWP relief was the earliest assessment time point after the first application of the trial medication at which the patient reported a score of ≥2.</description>
          <population>TS</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="126"/>
                <count group_id="O2" value="253"/>
                <count group_id="O3" value="256"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>0 to ≤10 min</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.6"/>
                    <measurement group_id="O2" value="0.8"/>
                    <measurement group_id="O3" value="0.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;10 to ≤20 min</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.6"/>
                    <measurement group_id="O2" value="2.0"/>
                    <measurement group_id="O3" value="1.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;20 to ≤30 min</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.6"/>
                    <measurement group_id="O2" value="2.4"/>
                    <measurement group_id="O3" value="2.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;30 to ≤60 min</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.6"/>
                    <measurement group_id="O2" value="9.1"/>
                    <measurement group_id="O3" value="5.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;60 to &lt;=120</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.7"/>
                    <measurement group_id="O2" value="8.3"/>
                    <measurement group_id="O3" value="10.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;120 min</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.9384</p_value>
            <p_value_desc>No adjustment for multiplicity issues was made for this comparison. The level of significance was 0.05.</p_value_desc>
            <method>Log Rank</method>
            <method_desc>p-value based on a stratified log-rank test</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.3534</p_value>
            <p_value_desc>No adjustment for multiplicity issues was made for this comparison. The level of significance was 0.05.</p_value_desc>
            <method>Log Rank</method>
            <method_desc>p-value based on a stratified log-rank test</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From first drug administration until 24 hour after last intake of trial medication, up to 7 days.</time_frame>
      <desc>Treated Set (TS) (The TS comprised all randomised patients who took at least 1 dose of trial medication) was used for adverse event reporting.</desc>
      <group_list>
        <group group_id="E1">
          <title>Placebo</title>
          <description>Patients were administered placebo matching ibuprofen and ibuprofen/caffeine film-coated tablets orally 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.</description>
        </group>
        <group group_id="E2">
          <title>Ibuprofen</title>
          <description>Patients were administered film-coated tablets orally containing 400 mg ibuprofen 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.</description>
        </group>
        <group group_id="E3">
          <title>Ibuprofen and Caffeine</title>
          <description>Patients were administered film-coated tablets orally containing 400 mg ibuprofen and 100 mg caffeine 3 times daily with intervals of 6 to 8 hours (while awake) on Day 1 until the morning of Day 6.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="126"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="253"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="126"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="253"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="256"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="126"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="253"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="256"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Boehringer Ingelheim, Call Centre</name_or_title>
      <organization>Boehringer Ingelheim</organization>
      <phone>1-800-243-0127</phone>
      <email>clintriage.rdg@boehringer-ingelheim.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03003000
org study id: 1335.5
secondary id: 2016-000902-12
nct id: NCT03003000
lead sponsor: 
To assess the efficacy and safety of a 400 mg ibuprofen/100 mg caffeine tablet in comparison
      to a 400 mg ibuprofen tablet for the treatment of acute lower back or neck pain. To assess
      the safety and tolerability of a 400 mg ibuprofen/100 mg caffeine tablet in comparison to a
      400 mg ibuprofen tablet and a placebo tablet.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double
measure: Change in Pain on Movement (POM) With Regard to the Worst Procedure (WP) Between Baseline and Day 2 (Morning, 2 Hours After Drug Intake)
time frame: Baseline and Day 2
description: The change in pain on movement (POM) with regard to the worst procedure (WP), i.e. the procedure with the highest pain score at baseline (POMwp), between baseline (morning of Day 1, pre-dosing) and Day 2 (morning, 2 hour (h) after drug intake).
POM was assessed by the patient at the performance of one standardized, muscle group specific movement and was measured by a numerical rating scale ranging from 0 = 'no pain'to 10 = 'worst pain possible for this condition'.
The procedure resulting in highest POM at baseline (worst procedure, POMWP) was repeated for an individual patient. If 2 or more procedures gave the same highest POM, the patient was asked which of the procedures giving the highest POM scores he/she considered the most unpleasant.
Change in POMwp was calculated as baseline POMwp - POMwp at Day 2 - indicating a reduction in POMwp, where the result is positive.
measure: The Area Under the Curve (AUC) for Pain on Movement (POM) With Regard to the Worst Procedure (POMwp) Between Baseline and Day 4 (Morning) (POMwpAUC72hour (h))
time frame: Baseline, Day 1, Day 2 and Day 4 (morning)
description: This is a key secondary endpoint. The area under the curve (AUC) for pain on movement (POM) with regard to the worst procedure (POMwp) between baseline and Day 4 (morning), (POMwpAUC72h ). POM was assessed by the patient at the performance of one standardized, muscle group specific movement and was measured by a numerical rating scale ranging from 0 = 'no pain'to 10 = 'worst pain possible for this condition'. A higher AUC value indicates higher POMwp
measure: The Area Under the Curve (AUC) for the Procedure With the Highest Pain Score at Baseline (POMWP) Between Baseline and Day 6 (Morning) (POM(WP)AUC(120h))
time frame: Baseline, Day 1, Day 2, Day 4 and Day 6 (morning)
description: This is a key secondary endpoint. The area under the curve for pain on movement with regard to the worst procedure between baseline and Day 6 (morning) (POM(WP)AUC(120h).
POM was assessed by the patient at the performance of one standardized, muscle group specific movement and was measured by a numerical rating scale ranging from 0 = 'no pain'to 10 = 'worst pain possible for this condition'. A higher AUC value indicates higher POMwp.
measure: Change in Pressure Algometry Between Baseline and Day 2 (Morning, 2 Hour After Drug Intake)
time frame: Baseline and Day 2 (morning, 2 h after drug intake)
description: Change in pressure algometry between baseline and Day 2 (morning, 2 h after drug intake).
Pressure algometry was determined by the investigator as the pressure value (N/cm2) at a defined trigger point which is located in the area of POMWP. The measurement was performed by using a Somedic Algometer (Somedic AB, Sweden) or an equivalent calibrated and certified device. The pain reaction was determined by placing the algometer on the trigger point, i.e. an area of 1 cm² for which the patient indicated most painful tenderness. The pressure was constantly increased until the patient asked not to increase the pressure anymore. Upon this pain reaction, the corresponding pressure value was documented in the Electronic case report form (eCRF). The trigger point was to be marked with a ball pen to be able to repeat the subsequent assessment at the same position. Change in pressure was calculated as baseline pressure - pressure at Day 2, with a negative result indicating an improvement.
measure: Global Assessment of Efficacy by the Patient at the End of Treatment (Morning of Day 6)
time frame: At the end of treatment (morning of Day 6)
description: Global assessment of efficacy by the patient at the end of treatment (morning of Day 6) is presented. The patient/investigator assessed the overall efficacy of the trial treatment on a 4-point verbal rating scale by answering the question: "How would you rate the overall effect of the trial medication for relieving back or neck pain?" (0 = poor; 1 = fair; 2 = good; 3 = very good).
measure: Number of Patients With a Decrease in POMwp of at Least 30% or 50% Between Baseline and Day 2 (Morning, 2 h After Drug Intake)
time frame: Baseline and Day 2 (morning, 2 h after drug intake)
description: Number of patients with a decrease in POMwp of at least 30% or 50% between baseline and Day 2 (morning, 2 h after drug intake.
measure: Time to First Meaningful POMwp Relief Within 2 h After the First Dose of Trial Medication
time frame: Within 2 h after the first dose of trial medication
description: Time to event analysis of patients with first meaningful POMwp relief within 2 h after the first dose of trial medication. The percentage of observed patients with a meaningful POMwp relief within 2 h after the first dose of trial medication was reported. The procedure which resulted in the highest POM at baseline (POMwp) was repeated by the investigator 10, 20, 30, 60 and 120 min after the first dose of trial medication. The POMwp relief score (POMwpRS) was assessed by the patient at each of these time points by using a 5-point verbal rating scale (0 = no POMwp relief; 1 = little or perceptible POMwp relief; 2 = meaningful POMwp relief; 3 = a lot of POMwp relief; 4 = complete POMwp relief).
The time to first meaningful POMWP relief was the earliest assessment time point after the first application of the trial medication at which the patient reported a score of ≥2.
arm group label: ibuprofen + caffeine
arm group type: Experimental
description: Fixed Dose Combination
arm group label: ibuprofen
arm group type: Active Comparator
arm group label: placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: ibuprofen
arm group label: ibuprofen
arm group label: ibuprofen + caffeine
intervention type: Drug
intervention name: caffeine
arm group label: ibuprofen + caffeine
intervention type: Drug
intervention name: placebo
arm group label: placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Boehringer Ingelheim
role: Study Chair
affiliation: Boehringer Ingelheim
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country: Germany
country: Russian Federation
url: http://trials.boehringer-ingelheim.com/
description: Related Info
responsible party type: Sponsor
mesh term: Neck Pain
mesh term: Ibuprofen
mesh term: Caffeine
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 