<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/NCT02183688</url>
  </required_header>
  <id_info>
    <org_study_id>155.8</org_study_id>
    <nct_id>NCT02183688</nct_id>
  </id_info>
  <brief_title>Acetylsalicylic Acid (ASA) + Paracetamol + Caffeine Combination Compared With ASA + Paracetamol as Well as ASA, Paracetamol, and Caffeine in Headache Patients</brief_title>
  <official_title>A Double-blind, Randomized, Placebo-controlled Clinical Trial to Confirm the Rationale of the ASA + Paracetamol + Caffeine Combination Compared With ASA + Paracetamol as Well as ASA, Paracetamol, and Caffeine in Headache Patients</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 confirm the combination rationale for the combination of ASA + paracetamol + caffeine&#xD;
      compared with the combination of ASA + paracetamol and the individual substances ASA,&#xD;
      paracetamol, caffeine, and placebo administered orally to headache patients for two headache&#xD;
      episodes&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 1998</start_date>
  <primary_completion_date type="Actual">January 2003</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>Calculated time to 50% pain relief, based on the pain intensity evaluated on a visual analogue scale (VAS)</measure>
    <time_frame>30 min., 1, 2, 3 and 4 hours after administration of the study medication</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of patients with 50 % pain relief, evaluated on a VAS</measure>
    <time_frame>At least 2 hours after administration of the study medication</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of patients with 50 % pain relief, evaluated on a VAS</measure>
    <time_frame>At least 30 min., 1, 3, and 4 hours after administration of the study medication</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain intensity, evaluated on a VAS</measure>
    <time_frame>30 min., 1, 2, 3 and 4 hours after administration of the study medication</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ratio of weighted sum of pain intensity difference scores to maximum achievable sum of pain intensity differences (%SPIDweighted), evaluated on a VAS</measure>
    <time_frame>Up to the end of the study</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Extent of impairment of daily activities, evaluated on a 4-grade verbal scale (VRS)</measure>
    <time_frame>Before, 30 min., 1, 2, 3 and 4 hours after administration of study drug</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of headache</measure>
    <time_frame>Up to 48 hours after onset of each headache episode</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Global assessment of efficacy by the patient, evaluated on a 4-grade VRS</measure>
    <time_frame>Within 12 hours after study drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Global assessment of tolerability by the patient, evaluated on a 4-grade VRS</measure>
    <time_frame>Within 12 hours after study drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>Up to the end of the study</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Global assessment of tolerability by the investigator, evaluated on a 4-grade VRS</measure>
    <time_frame>After each administration of study drug during the treatment phase</time_frame>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">1889</enrollment>
  <condition>Migraine Disorders</condition>
  <arm_group>
    <arm_group_label>ASA + paracetamol + caffeine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>ASA + paracetamol</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>ASA</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Paracetamol</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Caffeine</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>Low dose ASA</intervention_name>
    <arm_group_label>ASA + paracetamol</arm_group_label>
    <arm_group_label>ASA + paracetamol + caffeine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>High dose ASA</intervention_name>
    <arm_group_label>ASA</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Low dose paracetamol</intervention_name>
    <arm_group_label>ASA + paracetamol</arm_group_label>
    <arm_group_label>ASA + paracetamol + caffeine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>High dose paracetamol</intervention_name>
    <arm_group_label>Paracetamol</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Caffeine</intervention_name>
    <arm_group_label>ASA + paracetamol + caffeine</arm_group_label>
    <arm_group_label>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;
          1. Female or male out-patients aged between 18 and 65 years&#xD;
&#xD;
          2. Diagnosis: Headache&#xD;
&#xD;
               1. Tension type headache according to international headache society (IHS) Headache&#xD;
                  Classification 2.1 (2.1.1 and 2.1.2) and/or&#xD;
&#xD;
               2. Migraine according to IHS Headache Classification 1.1, 1.2.1 or&#xD;
&#xD;
               3. Either a) or b), but cannot be distinctly classified&#xD;
&#xD;
          3. The patient normally treats his/her headache successfully with non-prescription&#xD;
             analgesics&#xD;
&#xD;
          4. He/She has been suffering from headache for 12 months at least&#xD;
&#xD;
          5. The headache first occurred before the age of 50 years&#xD;
&#xD;
          6. During the previous three months, the patient has suffered from headache twice a month&#xD;
             at least&#xD;
&#xD;
          7. Informed consent according to §§ 40, 41 of the german medicines act and Good Clinical&#xD;
             Practice (GCP)&#xD;
&#xD;
          8. The patient seems likely to comply&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. The patient treats his/her headache with prescription-only analgesics or migraine&#xD;
             remedies&#xD;
&#xD;
          2. The patient requires higher single doses of non-prescription analgesics to treat&#xD;
             his/her headache than indicated in the patient information leaflet (e.g. more than 2&#xD;
             tablets of Thomapyrin tablets)&#xD;
&#xD;
          3. The patient normally treats his/her headache with non-prescription analgesics in&#xD;
             effervescent tablet form&#xD;
&#xD;
          4. The patient normally takes his/her non-prescription analgesics immediately at the&#xD;
             onset of the first signs of a headache episode&#xD;
&#xD;
          5. Headache occurs on more than 10 days per month&#xD;
&#xD;
          6. The typical, untreated headache normally lasts less than 4 hours without treatment&#xD;
&#xD;
          7. Women with a close association between the occurrence of headache and menstruation&#xD;
             (menstrual migraine)&#xD;
&#xD;
          8. Concomitant treatment with prescription-only and/or non-prescription analgesics&#xD;
&#xD;
          9. Previous or concomitant treatment with antidepressants or antipsychotic medicines&#xD;
             (previous treatment = within the previous 4 weeks)&#xD;
&#xD;
         10. Previous or concomitant treatment with anti-rheumatic or anti-inflammatory drugs that&#xD;
             may influence the headache symptoms (previous treatment = within the previous 4 days)&#xD;
&#xD;
         11. Treatment of concomitant illnesses with drugs containing ASA (above a daily dose of&#xD;
             100 mg per day), paracetamol or caffeine (e.g. for feverish common cold, etc.)&#xD;
&#xD;
         12. Migraine prophylaxis or administration of drugs, indicated for any other reasons that&#xD;
             influence headache symptoms, e.g.&#xD;
&#xD;
             Propanolol, Metoprolol, Flunarizine, Cyclandelate, Valproic acid, Serotonin&#xD;
             antagonists (pizotifen, methysergide, lisuride), Ergotamine, Dihydroergotamine,&#xD;
             Benzodiazepines, Magnesium, Monoamine oxidase inhibitors&#xD;
&#xD;
         13. Concomitant treatments with anti-emetics&#xD;
&#xD;
         14. Drug abuse connected with the headache (defined as the administration of analgesics or&#xD;
             other drugs for the treatment of acute headache on more than 10 days per month)&#xD;
&#xD;
         15. Alcohol or drug abuse as defined by diagnostic and statistical manual of mental&#xD;
             disorders (DSM-IV)&#xD;
&#xD;
         16. Pregnancy and lactation&#xD;
&#xD;
         17. Gastrointestinal ulcers&#xD;
&#xD;
         18. Pathologically increased bleeding tendency&#xD;
&#xD;
         19. Glucose-6-phosphate dehydrogenase deficiency&#xD;
&#xD;
         20. Hypersensitivity to paracetamol, caffeine, ASA, salicylates, and other&#xD;
             anti-inflammatory/anti-rheumatic agents or other allergenic substances that are&#xD;
             relevant to the clinical trial&#xD;
&#xD;
         21. Bronchial asthma&#xD;
&#xD;
         22. Concomitant treatment with anticoagulants (e.g. coumarin derivates, heparin)&#xD;
&#xD;
         23. Clinically relevant chronic or recurrent gastrointestinal symptoms&#xD;
&#xD;
         24. Clinically relevant liver disorders&#xD;
&#xD;
         25. Clinically relevant pre-existing renal damage&#xD;
&#xD;
         26. Gilbert's syndrome&#xD;
&#xD;
         27. Not successfully treated hyperthyroidism&#xD;
&#xD;
         28. Simultaneous participation in another clinical trial&#xD;
&#xD;
         29. Participation in another clinical trial within 4 weeks of entering this study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <link>
    <url>http://trials.boehringer-ingelheim.com/content/dam/internet/opu/clinicaltrial/com_EN/results/155/155.8_U05-1668.pdf</url>
    <description>Related Info</description>
  </link>
  <verification_date>July 2014</verification_date>
  <study_first_submitted>July 7, 2014</study_first_submitted>
  <study_first_submitted_qc>July 7, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 8, 2014</study_first_posted>
  <last_update_submitted>July 7, 2014</last_update_submitted>
  <last_update_submitted_qc>July 7, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 8, 2014</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>Migraine Disorders</mesh_term>
    <mesh_term>Headache</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acetaminophen</mesh_term>
    <mesh_term>Caffeine</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02183688
org study id: 155.8
nct id: NCT02183688
lead sponsor: 
To confirm the combination rationale for the combination of ASA + paracetamol + caffeine
      compared with the combination of ASA + paracetamol and the individual substances ASA,
      paracetamol, caffeine, and placebo administered orally to headache patients for two headache
      episodes
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double
measure: Calculated time to 50% pain relief, based on the pain intensity evaluated on a visual analogue scale (VAS)
time frame: 30 min., 1, 2, 3 and 4 hours after administration of the study medication
measure: Percentage of patients with 50 % pain relief, evaluated on a VAS
time frame: At least 2 hours after administration of the study medication
measure: Percentage of patients with 50 % pain relief, evaluated on a VAS
time frame: At least 30 min., 1, 3, and 4 hours after administration of the study medication
measure: Pain intensity, evaluated on a VAS
time frame: 30 min., 1, 2, 3 and 4 hours after administration of the study medication
measure: Ratio of weighted sum of pain intensity difference scores to maximum achievable sum of pain intensity differences (%SPIDweighted), evaluated on a VAS
time frame: Up to the end of the study
measure: Extent of impairment of daily activities, evaluated on a 4-grade verbal scale (VRS)
time frame: Before, 30 min., 1, 2, 3 and 4 hours after administration of study drug
measure: Duration of headache
time frame: Up to 48 hours after onset of each headache episode
measure: Global assessment of efficacy by the patient, evaluated on a 4-grade VRS
time frame: Within 12 hours after study drug administration
measure: Global assessment of tolerability by the patient, evaluated on a 4-grade VRS
time frame: Within 12 hours after study drug administration
measure: Number of patients with adverse events
time frame: Up to the end of the study
measure: Global assessment of tolerability by the investigator, evaluated on a 4-grade VRS
time frame: After each administration of study drug during the treatment phase
arm group label: ASA + paracetamol + caffeine
arm group type: Experimental
arm group label: ASA + paracetamol
arm group type: Active Comparator
arm group label: ASA
arm group type: Active Comparator
arm group label: Paracetamol
arm group type: Active Comparator
arm group label: Caffeine
arm group type: Active Comparator
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Low dose ASA
arm group label: ASA + paracetamol
arm group label: ASA + paracetamol + caffeine
intervention type: Drug
intervention name: High dose ASA
arm group label: ASA
intervention type: Drug
intervention name: Low dose paracetamol
arm group label: ASA + paracetamol
arm group label: ASA + paracetamol + caffeine
intervention type: Drug
intervention name: High dose paracetamol
arm group label: Paracetamol
intervention type: Drug
intervention name: Caffeine
arm group label: ASA + paracetamol + caffeine
arm group label: Caffeine
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
url: http://trials.boehringer-ingelheim.com/content/dam/internet/opu/clinicaltrial/com_EN/results/155/155.8_U05-1668.pdf
description: Related Info
responsible party type: Sponsor
mesh term: Migraine Disorders
mesh term: Headache
mesh term: Acetaminophen
mesh term: Caffeine