<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/NCT01726920</url>
  </required_header>
  <id_info>
    <org_study_id>ACH-NRP-03(04/12)</org_study_id>
    <nct_id>NCT01726920</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of a Fixed-dose Combination of Naratriptan and Naproxen in Acute Treatment of Migraine.</brief_title>
  <acronym>Copérnico</acronym>
  <official_title>A Phase III, Multicenter, National, Open, Randomized, Parallel and Comparative Study to Evaluate the Efficacy and Safety of a Fixed-dose Combination of Naratriptan 2,5 mg + Naproxen 500 mg for the Acute Treatment of Migraine.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ache Laboratorios Farmaceuticos S.A.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ache Laboratorios Farmaceuticos S.A.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine whether a fixed-dose combination of naratriptan 2,5&#xD;
      mg + naproxen 500 mg is effective and safe compared each monotherapy for the acute treatment&#xD;
      of migraine.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Due to budget limitations, the company decided to withdraw this study.&#xD;
  </why_stopped>
  <start_date>July 2014</start_date>
  <primary_completion_date type="Anticipated">December 2014</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Headache relief 2 hours after dosing, without use of rescue medication</measure>
    <time_frame>2 hours after single dose treatment</time_frame>
    <description>Participants were evaluated (self-assessment) for pain intensity by using a 4-point rating scale: 0= none, 1= mild, 2= moderate, and 3= severe.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Headache relief 4 hours after dosing, without use of rescue medication</measure>
    <time_frame>4 hours after single dose treatment</time_frame>
    <description>Participants were evaluated (self-assessment) for pain intensity by using a 4-point rating scale: 0= none, 1= mild, 2= moderate, and 3= severe</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maintenance of pain relief between 2 and 24 hours after dosing, without use of rescue medication</measure>
    <time_frame>2 to 24 hours after single dose treatment</time_frame>
    <description>Participants were evaluated (self-assessment) for pain intensity by using a 4-point rating scale: 0=none, 1=mild, 2=moderate, and 3=severe.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain-free response 2 and 4 hours after dosing, without use of rescue medication</measure>
    <time_frame>2 and 4 hours after single dose treatment</time_frame>
    <description>Participants were evaluated (self-assessment) for pain intensity by using a 4-point rating scale: 0= none, 1= mild, 2= moderate, and 3= severe.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maintenance of pain-free response between 2 and 24 hours, without use of rescue medication</measure>
    <time_frame>2 to 24 hours after single dose treatment</time_frame>
    <description>Participants were evaluated (self-assessment) for pain intensity by using a 4-point rating scale: 0= none, 1= mild, 2= moderate, and 3= severe.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Freedom from nausea, vomiting, photophobia and phonophobia 2 and 4 hours after dosing</measure>
    <time_frame>2 and 4 hours after single dose treatment</time_frame>
    <description>Participants were evaluated (self-assessment) for the presence of vomiting, nausea, photophobia and phonophobia.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maintenance of freedom from nausea, vomiting, photophobia and phonophobia between 2 and 24 hours after dosing, without use of rescue medication</measure>
    <time_frame>2 to 24 hours after single dose treatment</time_frame>
    <description>Participants were evaluated (self-assessment) for the presence of vomiting, nausea, photophobia and phonophobia.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Recurrence of pain between 2 and 24 hours after dosing, without use of rescue medication</measure>
    <time_frame>2 to 24 hours after single dose treatment</time_frame>
    <description>Participants were evaluated (self-assessment) for pain intensity by using a 4-point rating scale: 0= none, 1= mild, 2= moderate, and 3= severe.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of subjects who used rescue medication between 2 and 24 hours after dosing, at least once</measure>
    <time_frame>2 to 24 hours after single dose treatment</time_frame>
    <description>Participants were evaluated (self-assessment) about use of rescue medication.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety descriptive about occurence of adverse events, evaluation of results of general physical examination.</measure>
    <time_frame>Collection of safety data throughout the whole study period</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Migraine</condition>
  <condition>Headache</condition>
  <arm_group>
    <arm_group_label>naratriptan + naproxen</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Fixed-dose combination of naratriptan + naproxen</description>
  </arm_group>
  <arm_group>
    <arm_group_label>naratriptan</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>naproxen</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>naratriptan + naproxen</intervention_name>
    <description>Tablets containing naratriptan 2,5 mg + naproxen 500 mg</description>
    <arm_group_label>naratriptan + naproxen</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>naratriptan</intervention_name>
    <description>Tablets containing naratriptan 2,5 mg</description>
    <arm_group_label>naratriptan</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>naproxen</intervention_name>
    <description>Tablets containing naproxen 500 mg</description>
    <arm_group_label>naproxen</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female patient, age in the range of 18-65 years inclusive that has onset of&#xD;
             migraine before age 50;&#xD;
&#xD;
          -  Patient has at least a 3-month history of migraine with or without aura according to&#xD;
             the ICHD-II, 2004, IHS (International Headache Society) criteria;&#xD;
&#xD;
          -  Patients experienced an average migraine headache frequency of 2-6 moderate or severe&#xD;
             attacks per month in the last 03 months prior to screening visit;&#xD;
&#xD;
          -  Patients able to distinguish his/her migraine attacks from any other types of&#xD;
             headaches;&#xD;
&#xD;
          -  Patients able to understand and consent to participate in this clinical study,&#xD;
             expressed by signing the Informed Consent (IC).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of more than 6 migraine attacks/month in the last 03 months prior to screening&#xD;
             visit;&#xD;
&#xD;
          -  History of non-migraine headache frequency ≥ 15 days/month in each of the 3 months&#xD;
             prior to screening;&#xD;
&#xD;
          -  History of following migraine variants, according to the ICHD-II, 2004, IHS&#xD;
             (International Headache Society): basilar migraine, aura without headache, familial&#xD;
             hemiplegic migraine, sporadic hemiplegic migraine or aura with non-migraine headache;&#xD;
&#xD;
          -  If female of childbearing potential, has a negative urine pregnancy test at Visit 0&#xD;
             and doesn't use, or doesn't agree to use, for the duration of the study, a medically&#xD;
             acceptable form of contraception as determined by the investigator;&#xD;
&#xD;
          -  Woman in pregnancy or lactation period;&#xD;
&#xD;
          -  History of epilepsy or psychiatric condition that may affect the compliance of the&#xD;
             treatment;&#xD;
&#xD;
          -  Patients in acupuncture treatment for the symptoms of migraine attacks;&#xD;
&#xD;
          -  History or symptoms of cardiovascular disease (myocardial infarction, ischemic heart&#xD;
             disease, or with Prinzmetal's angina) or has symptoms of ischemic heart disease;&#xD;
&#xD;
          -  Suffers from peripheral vascular disease;&#xD;
&#xD;
          -  History of cerebrovascular pathology including stroke and/or transient ischemic&#xD;
             attacks;&#xD;
&#xD;
          -  History of allergic reactions to naproxen preparations, including subjects in whom&#xD;
             aspirin or other NSAID drugs induce the syndrome of asthma, rhinitis, nasal polyps or&#xD;
             urticaria;&#xD;
&#xD;
          -  Diagnosis of renal or hepatic failure;&#xD;
&#xD;
          -  Has significant (as determined by the investigator) cardiovascular risk factors that&#xD;
             may include uncontrolled high blood pressure, post-menopausal women, males over 40&#xD;
             years old, hypercholesterolemia, obesity, diabetes mellitus, smoking, or a family&#xD;
             history of cardiovascular disease in a 1st degree relative;&#xD;
&#xD;
          -  Patients who have stopped or changed the dosage of the preventive treatment of&#xD;
             migraine in the last 2 weeks prior the screening visit (V0), including the use of&#xD;
             calcium channel blockers, tricyclic antidepressants, beta blockers or serotonergic&#xD;
             medications for any other indications;&#xD;
&#xD;
          -  Use of prohibited medicine as shown in 9.3 item of this protocol;&#xD;
&#xD;
          -  Inability to understand and report the categorical scale debilitating functional of&#xD;
             study or symptoms diary;&#xD;
&#xD;
          -  Has abused, in the opinion of the Investigator, any of the following drugs, currently&#xD;
             or within the past 2 years: opioids, alcohol, barbiturates, benzodiazepine, cocaine or&#xD;
             abuse of drugs for migraine treatment including narcotics or ergotamines headache in&#xD;
             the past 03 months;&#xD;
&#xD;
          -  Hypersensitivity to naratriptan, naproxen, or any of its components;&#xD;
&#xD;
          -  Hypersensitivity to sulfonamides;&#xD;
&#xD;
          -  History of malignancy ≤ 5 years or &gt; 5 years without documentation of remission /&#xD;
             cure, for example, melanoma, leukemia, lymphoma, myeloproliferative disorders and&#xD;
             renal cell carcinoma of any duration. Exception: Subjects with basal cell skin&#xD;
             cancers, squamous cell, and cervical cancer in situ may be eligible;&#xD;
&#xD;
          -  Participation in last one year of clinical protocols, unless it can be direct benefit&#xD;
             to patient;&#xD;
&#xD;
          -  Any finding of clinical observation (anamnesis and physical exam) laboratory&#xD;
             abnormality (eg, blood glucose, blood count), disease (for example, liver,&#xD;
             cardiovascular system, lung) or therapy that, in opinion of the investigator, may&#xD;
             endanger the patient or interfere with the endpoints of 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>
  <verification_date>March 2016</verification_date>
  <study_first_submitted>November 12, 2012</study_first_submitted>
  <study_first_submitted_qc>November 12, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 15, 2012</study_first_posted>
  <last_update_submitted>March 15, 2016</last_update_submitted>
  <last_update_submitted_qc>March 15, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">March 16, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Migraine</keyword>
  <keyword>Naratriptan</keyword>
  <keyword>Naproxen</keyword>
  <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>Naproxen</mesh_term>
    <mesh_term>Naratriptan</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/NCT01726920
org study id: ACH-NRP-03(04/12)
nct id: NCT01726920
lead sponsor: 
has dmc: Yes
The purpose of this study is to determine whether a fixed-dose combination of naratriptan 2,5
      mg + naproxen 500 mg is effective and safe compared each monotherapy for the acute treatment
      of migraine.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Headache relief 2 hours after dosing, without use of rescue medication
time frame: 2 hours after single dose treatment
description: Participants were evaluated (self-assessment) for pain intensity by using a 4-point rating scale: 0= none, 1= mild, 2= moderate, and 3= severe.
measure: Headache relief 4 hours after dosing, without use of rescue medication
time frame: 4 hours after single dose treatment
description: Participants were evaluated (self-assessment) for pain intensity by using a 4-point rating scale: 0= none, 1= mild, 2= moderate, and 3= severe
measure: Maintenance of pain relief between 2 and 24 hours after dosing, without use of rescue medication
time frame: 2 to 24 hours after single dose treatment
description: Participants were evaluated (self-assessment) for pain intensity by using a 4-point rating scale: 0=none, 1=mild, 2=moderate, and 3=severe.
measure: Pain-free response 2 and 4 hours after dosing, without use of rescue medication
time frame: 2 and 4 hours after single dose treatment
description: Participants were evaluated (self-assessment) for pain intensity by using a 4-point rating scale: 0= none, 1= mild, 2= moderate, and 3= severe.
measure: Maintenance of pain-free response between 2 and 24 hours, without use of rescue medication
time frame: 2 to 24 hours after single dose treatment
description: Participants were evaluated (self-assessment) for pain intensity by using a 4-point rating scale: 0= none, 1= mild, 2= moderate, and 3= severe.
measure: Freedom from nausea, vomiting, photophobia and phonophobia 2 and 4 hours after dosing
time frame: 2 and 4 hours after single dose treatment
description: Participants were evaluated (self-assessment) for the presence of vomiting, nausea, photophobia and phonophobia.
measure: Maintenance of freedom from nausea, vomiting, photophobia and phonophobia between 2 and 24 hours after dosing, without use of rescue medication
time frame: 2 to 24 hours after single dose treatment
description: Participants were evaluated (self-assessment) for the presence of vomiting, nausea, photophobia and phonophobia.
measure: Recurrence of pain between 2 and 24 hours after dosing, without use of rescue medication
time frame: 2 to 24 hours after single dose treatment
description: Participants were evaluated (self-assessment) for pain intensity by using a 4-point rating scale: 0= none, 1= mild, 2= moderate, and 3= severe.
measure: Proportion of subjects who used rescue medication between 2 and 24 hours after dosing, at least once
time frame: 2 to 24 hours after single dose treatment
description: Participants were evaluated (self-assessment) about use of rescue medication.
measure: Safety descriptive about occurence of adverse events, evaluation of results of general physical examination.
time frame: Collection of safety data throughout the whole study period
arm group label: naratriptan + naproxen
arm group type: Experimental
description: Fixed-dose combination of naratriptan + naproxen
arm group label: naratriptan
arm group type: Active Comparator
arm group label: naproxen
arm group type: Active Comparator
intervention type: Drug
intervention name: naratriptan + naproxen
description: Tablets containing naratriptan 2,5 mg + naproxen 500 mg
arm group label: naratriptan + naproxen
intervention type: Drug
intervention name: naratriptan
description: Tablets containing naratriptan 2,5 mg
arm group label: naratriptan
intervention type: Drug
intervention name: naproxen
description: Tablets containing naproxen 500 mg
arm group label: naproxen
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
responsible party type: Sponsor
mesh term: Migraine Disorders
mesh term: Headache
mesh term: Naproxen
mesh term: Naratriptan