<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/NCT02978651</url>
  </required_header>
  <id_info>
    <org_study_id>P16 04/ / BF2.649</org_study_id>
    <secondary_id>2016-002963-32</secondary_id>
    <nct_id>NCT02978651</nct_id>
  </id_info>
  <brief_title>Pitolisant (BF2.649) in the Treatment of Excessive Daytime Sleepiness in Patients With Obstructive Sleep Apnoea Syndrome, Treated or Not by Nasal Continuous Positive Airway Pressure, But Still Complaining of Excessive Daytime Sleepiness</brief_title>
  <acronym>HAROSA IV</acronym>
  <official_title>Efficacy and Safety of Pitolisant (BF2.649) in the Treatment of Excessive Daytime Sleepiness in Patients With Obstructive Sleep Apnoea Syndrome, Treated or Not by Nasal Continuous Positive Airway Pressure, But Still Complaining of Excessive Daytime Sleepiness</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bioprojet</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Bioprojet</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The first objective of this study is to demonstrate the efficacy and safety of pitolisant&#xD;
      given at 10, 20, or 40 mg per day versus placebo during 12 weeks of the Double Blind period,&#xD;
      to treat the Excessive Daytime Sleepiness (EDS) in patients with Obstructive Sleep Apnea&#xD;
      (OSA) refusing the nasal Continuous Positive Airway Pressure (nCPAP) therapy or treated by&#xD;
      nCPAP but still complaining of EDS.&#xD;
&#xD;
      The secondary objectives of the study include assessing the long-term tolerance as well as&#xD;
      the maintenance of efficacy of pitolisant given at 10, 20 or 40 mg per day during 39 weeks of&#xD;
      Open Label Extension period.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Strategic decision of Sponsor&#xD;
  </why_stopped>
  <primary_completion_date type="Actual">January 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 (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Epworth sleepiness scale (ESS)</measure>
    <time_frame>Change from Baseline of ESS at 12 weeks and Change from Baseline of ESS at 52 weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of ESS responders</measure>
    <time_frame>at week 12 /52 versus baseline</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reduction of sleepiness and sleep episodes on the sleep diary</measure>
    <time_frame>at week 12 /52 versus baseline</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvement in vigilance according to Oxford Sleep Resistance (OSleR) test</measure>
    <time_frame>at week 12 /52 versus baseline</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>European Quality of Life Questionnaire (EQ-5D)</measure>
    <time_frame>at week 12 /52 versus baseline</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Leeds Sleep Evaluation Questionnaire (LSEQ)</measure>
    <time_frame>at week 12 /52 versus baseline</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Pichot Fatigue Scale</measure>
    <time_frame>at week 12 /52 versus baseline</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Trail Making Test parts (A and B)</measure>
    <time_frame>at week 12 /52 versus baseline</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvement in Clinical Global Impression (CGI)</measure>
    <time_frame>at week 12 /52 versus baseline</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Z-score: composite score including ESS and OSLER results</measure>
    <time_frame>at week 12 /52 versus baseline</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Excessive Daytime Sleepiness</condition>
  <condition>Obstructive Sleep Apnea</condition>
  <arm_group>
    <arm_group_label>Pitolisant (BF2.649)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Histamine H3 receptor H3R antagonist/ inverse agonist</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pitolisant (BF2.649)</intervention_name>
    <arm_group_label>Pitolisant (BF2.649)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Oral Tablet</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male and/or female outpatients aged from at least 18 years.&#xD;
&#xD;
          -  Patients complaining of EDS refusing to be treated by nCPAP therapy or having been&#xD;
             submitted to nCPAP therapy for a minimum period of 3 months, and still complaining of&#xD;
             EDS despite the efforts made beforehand to obtain an efficient nCPAP therapy.&#xD;
&#xD;
          -  Polysomnography performed (for patients submitted to nCPAP therapy - under nCPAP)&#xD;
             between V1 and V2 or during the last 12 months with Apnea-Hypopnea Index (AHI): for&#xD;
             patients without nCPAP therapy ≥ 15; for patients under nCPAP therapy less or equal to&#xD;
             10.&#xD;
&#xD;
          -  For patients submitted to nCPAP therapy: nCPAP ≥ 4 hours / day (compliance checked on&#xD;
             the clock-time counter of the CPAP machine)&#xD;
&#xD;
          -  Mini Mental State Examination (MMSE) ≥ 28&#xD;
&#xD;
          -  Beck Depression Inventory - 13 items (BDI-13) score &lt; 16 and item G (suicidal&#xD;
             ideation) of BDI-13 = 0&#xD;
&#xD;
          -  Body Mass Index (BMI) less or equal to 40 kg/m²&#xD;
&#xD;
          -  Epworth Sleepiness Scale (ESS) ≥ 12&#xD;
&#xD;
          -  Female patients with child-bearing potential using a medically accepted method of&#xD;
             birth control (i.e. oral contraceptives of normal average dosage) agreeing to continue&#xD;
             this method throughout the study, and during the month following treatment&#xD;
             discontinuation, being negative to serum pregnancy test performed at the screening&#xD;
             visit.&#xD;
&#xD;
          -  If specified by the investigator, the patient must be willing not to operate a car (if&#xD;
             sleepy at wheel) or heavy machinery for the duration of the trial or as long as the&#xD;
             investigator deems it clinically indicated. In addition, the patient should be willing&#xD;
             to maintain during the study their usual behaviors which could affect their diurnal&#xD;
             sleepiness (e.g. circadian rhythm, caffeine consumption, nocturnal sleep duration)&#xD;
&#xD;
          -  Patients having signed and dated the informed consent form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients suffering from chronic severe insomnia in accordance with the International&#xD;
             Classification of Sleep Disorders (ICSD 2005) without OSA&#xD;
&#xD;
          -  Patients with co-existing narcolepsy (ICSD 2005), judged on clinical criteria&#xD;
&#xD;
          -  Patients with sleep debt not due to OSA (according to the physician' s judgment)&#xD;
&#xD;
          -  Patients with non-respiratory sleep fragmentation (restless leg syndrome…)&#xD;
&#xD;
          -  Shift work, professional drivers&#xD;
&#xD;
          -  Refusal from the patient to stop any current therapy for EDS or predictable risk for&#xD;
             the patient to stop the therapy&#xD;
&#xD;
          -  Patients suffering from a psychiatric disease&#xD;
&#xD;
          -  Acute or chronic disease preventing the improvement assessment, e.g. severe chronic&#xD;
             obstructive pulmonary disease (COPD)&#xD;
&#xD;
          -  Current or recent (within one year) history of drug, alcohol, narcotic or other&#xD;
             substance abuse or dependence&#xD;
&#xD;
          -  Any significant serious abnormality of the cardiovascular system, e.g. recent&#xD;
             myocardial infarction, angina, hypertension or dysrhythmias (within the previous 6&#xD;
             months), Electrocardiogram Fridericia corrected QT interval higher than 450 ms,&#xD;
             history of left ventricular hypertrophy or mitral valve prolapse&#xD;
&#xD;
          -  Severe co-morbid medical or biological conditions that may jeopardize study&#xD;
             participation at the discretion of the investigator (particularly in the&#xD;
             cardiovascular system and the instable diabetes).&#xD;
&#xD;
          -  Positive serology tests (HIV, HCV and HBsAg)&#xD;
&#xD;
          -  Pregnant or breast-feeding women.&#xD;
&#xD;
          -  Women with child-bearing potential and no efficient birth-control method&#xD;
&#xD;
          -  Patients unable to understand the study protocol.&#xD;
&#xD;
          -  Patients with suspected or known hypersensitivity to study medication&#xD;
&#xD;
          -  Patients with a dominant arm deficiency impeding the achievement of the tests&#xD;
&#xD;
          -  Patients using a prohibited medication.&#xD;
&#xD;
          -  Congenital galactose poisoning, glucose and galactose malabsorption, deficit in&#xD;
             lactase.&#xD;
&#xD;
          -  Patients participating in another study or being in a follow-up period for another&#xD;
             study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Laboratoire du sommeil Clinique de Physiologie, Sommeil et Exercice Pôle Thorax et Vaisseaux CHU de Grenoble</name>
      <address>
        <city>Grenoble</city>
        <zip>38043</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Gui de Chauliac, CHU Montpellier, Unité des Troubles du Sommeil et de l'Eveil</name>
      <address>
        <city>Montpellier</city>
        <zip>34295</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>November 2016</verification_date>
  <study_first_submitted>November 29, 2016</study_first_submitted>
  <study_first_submitted_qc>November 29, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 1, 2016</study_first_posted>
  <last_update_submitted>November 22, 2017</last_update_submitted>
  <last_update_submitted_qc>November 22, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">November 24, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>EDS</keyword>
  <keyword>OSA</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Apnea</mesh_term>
    <mesh_term>Sleep Apnea Syndromes</mesh_term>
    <mesh_term>Sleep Apnea, Obstructive</mesh_term>
    <mesh_term>Disorders of Excessive Somnolence</mesh_term>
    <mesh_term>Sleepiness</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT02978651
org study id: P16 04/ / BF2.649
secondary id: 2016-002963-32
nct id: NCT02978651
lead sponsor: 
has dmc: Yes
The first objective of this study is to demonstrate the efficacy and safety of pitolisant
      given at 10, 20, or 40 mg per day versus placebo during 12 weeks of the Double Blind period,
      to treat the Excessive Daytime Sleepiness (EDS) in patients with Obstructive Sleep Apnea
      (OSA) refusing the nasal Continuous Positive Airway Pressure (nCPAP) therapy or treated by
      nCPAP but still complaining of EDS.

      The secondary objectives of the study include assessing the long-term tolerance as well as
      the maintenance of efficacy of pitolisant given at 10, 20 or 40 mg per day during 39 weeks of
      Open Label Extension period.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Epworth sleepiness scale (ESS)
time frame: Change from Baseline of ESS at 12 weeks and Change from Baseline of ESS at 52 weeks
measure: Percentage of ESS responders
time frame: at week 12 /52 versus baseline
measure: Reduction of sleepiness and sleep episodes on the sleep diary
time frame: at week 12 /52 versus baseline
measure: Improvement in vigilance according to Oxford Sleep Resistance (OSleR) test
time frame: at week 12 /52 versus baseline
measure: European Quality of Life Questionnaire (EQ-5D)
time frame: at week 12 /52 versus baseline
measure: Leeds Sleep Evaluation Questionnaire (LSEQ)
time frame: at week 12 /52 versus baseline
measure: The Pichot Fatigue Scale
time frame: at week 12 /52 versus baseline
measure: Trail Making Test parts (A and B)
time frame: at week 12 /52 versus baseline
measure: Improvement in Clinical Global Impression (CGI)
time frame: at week 12 /52 versus baseline
measure: Z-score: composite score including ESS and OSLER results
time frame: at week 12 /52 versus baseline
arm group label: Pitolisant (BF2.649)
arm group type: Experimental
description: Histamine H3 receptor H3R antagonist/ inverse agonist
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo
intervention type: Drug
intervention name: Pitolisant (BF2.649)
arm group label: Pitolisant (BF2.649)
intervention type: Drug
intervention name: Placebo Oral Tablet
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: No
facility: 
facility: 
country: France
responsible party type: Sponsor
mesh term: Apnea
mesh term: Sleep Apnea Syndromes
mesh term: Sleep Apnea, Obstructive
mesh term: Disorders of Excessive Somnolence
mesh term: Sleepiness
sharing ipd: No