<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/NCT03765294</url>
  </required_header>
  <id_info>
    <org_study_id>ID-078-110</org_study_id>
    <secondary_id>2018-002360-96</secondary_id>
    <nct_id>NCT03765294</nct_id>
  </id_info>
  <brief_title>A Study to Investigate the Effects of ACT-541468 on Nighttime Respiratory Function in Patients With Mild to Moderate Obstructive Sleep Apnea</brief_title>
  <official_title>A Randomized, Double-blind, Placebo-controlled, 2-way Crossover Study to Investigate the Effects of ACT-541468 on Nighttime Respiratory Function in Patients With Mild to Moderate Obstructive Sleep Apnea</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Idorsia Pharmaceuticals Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Idorsia Pharmaceuticals Ltd.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is conducted to investigate the effects of ACT-541468 on nighttime respiratory&#xD;
      function in patients with mild to moderate obstructive sleep apnea&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 14, 2019</start_date>
  <completion_date type="Actual">November 5, 2019</completion_date>
  <primary_completion_date type="Actual">November 5, 2019</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>2-way cross-over</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Apnea/hypopnea index (AHI) after multiple-dose administration of ACT-541468 as measured by polysomnography (PSG)</measure>
    <time_frame>After multiple-dose administration (i.e., at Night 5) (duration: 8 hours PSG recording)</time_frame>
    <description>AHI is defined by total number of apnea (pause in respiration ≥ 10 s) plus hypopnea (reduction in airflow or tidal volume from pre-event baseline by 30% for at least 10 s accompanied by a decrease of SaO2 ≥ 4%) events, divided by total sleep time (TST, in min), then multiplied by 60, during TST</description>
  </primary_outcome>
  <other_outcome>
    <measure>AHI during TST after single-dose administration</measure>
    <time_frame>After single-dose (i.e., Night 1) administration (duration: 8 hours PSG recording)</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Mean SaO2 during TST</measure>
    <time_frame>After single-dose (i.e., Night 1) administration (duration: 8 hours PSG recording)</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>AHI during the awake, non-REM, and REM phases</measure>
    <time_frame>After single-dose (i.e., Night 1) administration (duration: 8 hours PSG recording)</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Mean SaO2 during the awake, non-REM, and REM phases</measure>
    <time_frame>After single-dose (i.e., Night 1) administration (duration: 8 hours PSG recording)</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Percentage of TST during which SaO2 is &lt; 90%, &lt; 85%, and &lt; 80%</measure>
    <time_frame>After single-dose (i.e., Night 1) administration (duration: 8 hours PSG recording)</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Change from baseline to EOP of both periods in subjective next-day performance (morning sleepiness, daytime alertness, and daytime ability to function) as assessed by VAS</measure>
    <time_frame>After single-dose (i.e., Night 1) and multiple-dose (i.e., Night 5) administration (duration: 2 x 8 hours PSG recording)</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Objective sleep parameters LPS, WASO, TST, and SEI following single- and multiple-dose administration, as measured by PSG</measure>
    <time_frame>After single-dose (i.e., Night 1) and multiple-dose (i.e., Night 5) administration (duration: 2 x 8 hours PSG recording)</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Safety profile including incidence of adverse events (AEs) and serious adverse events (SAEs)</measure>
    <time_frame>From baseline to EOS (duration: for up to 10 weeks)</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">28</enrollment>
  <condition>Obstructive Sleep Apnea</condition>
  <arm_group>
    <arm_group_label>Treatment A: ACT-541468</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>50 mg once daily from Day 1 to Day 5 of Period A</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment B: Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Matching placebo once daily from Day 1 to Day 5 of Period B</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ACT-541468</intervention_name>
    <description>Film-coated tablet for oral use</description>
    <arm_group_label>Treatment A: ACT-541468</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Film-coated tablet for oral use</description>
    <arm_group_label>Treatment B: Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Signed informed consent in a language understandable to the subject prior to any&#xD;
             study-mandated procedure.&#xD;
&#xD;
          -  Male and female subjects aged ≥ 18 years at Screening.&#xD;
&#xD;
          -  Women of childbearing potential must have a negative serum pregnancy test at Screening&#xD;
             and a negative urine pregnancy test at Screening Visit 2 and on Day 1 pre-dose of the&#xD;
             first period. They must agree to consistently and correctly use a highly effective&#xD;
             method of contraception with a failure rate of &lt; 1% per year.&#xD;
&#xD;
          -  Women of non-childbearing potential, i.e., postmenopausal, with previous bilateral&#xD;
             salpingectomy, bilateral salpingo-oophorectomy or hysterectomy, or with premature&#xD;
             ovarian failure, XY genotype, Turner syndrome, and/or uterine agenesis.&#xD;
&#xD;
          -  Diagnosis of OSA according to the International Classification of Sleep Disorders&#xD;
             documented by medical history and confirmed in a sleep laboratory in the context of&#xD;
             diagnosing OSA within the last 3 years.&#xD;
&#xD;
          -  Patient with mild to moderate intensity of OSA determined during OSA diagnosis and&#xD;
             confirmed on the screening night PSG and defined as apnea/hypopnea index (AHI) ranging&#xD;
             from 5 to &lt; 30.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any circumstances or conditions, which, in the opinion of the investigator, may affect&#xD;
             full participation in the study or compliance with the protocol.&#xD;
&#xD;
          -  Pregnant or lactating women.&#xD;
&#xD;
          -  Modified Swiss Narcolepsy Scale total score &lt; 0 at Screening, or history of narcolepsy&#xD;
             or cataplexy.&#xD;
&#xD;
          -  Subjects with clinically significant abnormality on the screening night PSG as per&#xD;
             investigator judgment, including evidence of severe insomnia (i.e., sleep time &lt; 5 h)&#xD;
             periodic limb movement disorder with arousal index ≥ 10/h, restless legs syndrome,&#xD;
             circadian rhythm disorder, REM behavior disorder, parasomnia including nightmare&#xD;
             disorder, sleep terror disorder, and/or sleepwalking disorder.&#xD;
&#xD;
          -  Need for continuous positive airway pressure device or a dental appliance device&#xD;
             within the preceding 7 days prior to Screening Visit 2 and during the course of the&#xD;
             study, i.e., from Screening Visit 2 to EOS.&#xD;
&#xD;
          -  Evidence of any other clinically significant active pulmonary disease such as chronic&#xD;
             obstructive pulmonary disease (COPD) (as per Global Initiative for Obstructive Lung&#xD;
             Disease), based on investigator's judgment.&#xD;
&#xD;
          -  History of surgical intervention for obstructive sleep apnea, except nose surgery.&#xD;
&#xD;
          -  SaO2 &lt; 90% during wakefulness or mean non-apneic SaO2 (i.e., outside events of&#xD;
             apnea/hypopnea) &lt; 85% for &gt; 5 consecutive min during the screening night PSG.&#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>Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>Idorsia Pharmaceuticals Ltd.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Advanced Sleep Research</name>
      <address>
        <city>Berlin</city>
        <zip>10117</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>December 2019</verification_date>
  <study_first_submitted>December 4, 2018</study_first_submitted>
  <study_first_submitted_qc>December 4, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 5, 2018</study_first_posted>
  <last_update_submitted>December 18, 2019</last_update_submitted>
  <last_update_submitted_qc>December 18, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">December 19, 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>Apnea</mesh_term>
    <mesh_term>Sleep Apnea Syndromes</mesh_term>
    <mesh_term>Sleep Apnea, Obstructive</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/NCT03765294
org study id: ID-078-110
secondary id: 2018-002360-96
nct id: NCT03765294
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This study is conducted to investigate the effects of ACT-541468 on nighttime respiratory
      function in patients with mild to moderate obstructive sleep apnea
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: 2-way cross-over
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Apnea/hypopnea index (AHI) after multiple-dose administration of ACT-541468 as measured by polysomnography (PSG)
time frame: After multiple-dose administration (i.e., at Night 5) (duration: 8 hours PSG recording)
description: AHI is defined by total number of apnea (pause in respiration ≥ 10 s) plus hypopnea (reduction in airflow or tidal volume from pre-event baseline by 30% for at least 10 s accompanied by a decrease of SaO2 ≥ 4%) events, divided by total sleep time (TST, in min), then multiplied by 60, during TST
measure: AHI during TST after single-dose administration
time frame: After single-dose (i.e., Night 1) administration (duration: 8 hours PSG recording)
measure: Mean SaO2 during TST
time frame: After single-dose (i.e., Night 1) administration (duration: 8 hours PSG recording)
measure: AHI during the awake, non-REM, and REM phases
time frame: After single-dose (i.e., Night 1) administration (duration: 8 hours PSG recording)
measure: Mean SaO2 during the awake, non-REM, and REM phases
time frame: After single-dose (i.e., Night 1) administration (duration: 8 hours PSG recording)
measure: Percentage of TST during which SaO2 is < 90%, < 85%, and < 80%
time frame: After single-dose (i.e., Night 1) administration (duration: 8 hours PSG recording)
measure: Change from baseline to EOP of both periods in subjective next-day performance (morning sleepiness, daytime alertness, and daytime ability to function) as assessed by VAS
time frame: After single-dose (i.e., Night 1) and multiple-dose (i.e., Night 5) administration (duration: 2 x 8 hours PSG recording)
measure: Objective sleep parameters LPS, WASO, TST, and SEI following single- and multiple-dose administration, as measured by PSG
time frame: After single-dose (i.e., Night 1) and multiple-dose (i.e., Night 5) administration (duration: 2 x 8 hours PSG recording)
measure: Safety profile including incidence of adverse events (AEs) and serious adverse events (SAEs)
time frame: From baseline to EOS (duration: for up to 10 weeks)
arm group label: Treatment A: ACT-541468
arm group type: Experimental
description: 50 mg once daily from Day 1 to Day 5 of Period A
arm group label: Treatment B: Placebo
arm group type: Placebo Comparator
description: Matching placebo once daily from Day 1 to Day 5 of Period B
intervention type: Drug
intervention name: ACT-541468
description: Film-coated tablet for oral use
arm group label: Treatment A: ACT-541468
intervention type: Drug
intervention name: Placebo
description: Film-coated tablet for oral use
arm group label: Treatment B: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Clinical Trials
role: Study Director
affiliation: Idorsia Pharmaceuticals Ltd.
facility: 
country: Germany
responsible party type: Sponsor
mesh term: Apnea
mesh term: Sleep Apnea Syndromes
mesh term: Sleep Apnea, Obstructive
sharing ipd: No