<clinical_study>
  <!-- This xml conforms to an XML Schema at:
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  <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/NCT04461353</url>
  </required_header>
  <id_info>
    <org_study_id>PUL-01</org_study_id>
    <nct_id>NCT04461353</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Orally Inhaled Aerosolized Hydroxychloroquine Sulfate in Healthy Adult Volunteers</brief_title>
  <official_title>A Phase 1 Randomized Double Blind Placebo Controlled, Single-Dose, Dose-Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Orally Inhaled Aerosolized Hydroxychloroquine Sulfate in Healthy Adult Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Pulmoquine Therapeutics, Inc</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Rockefeller University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Pulmoquine Therapeutics, Inc</source>
  <oversight_info>
    <has_dmc>Yes</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 'A Randomized Phase 1 Double Blind Placebo Controlled, Single-Dose,&#xD;
      Dose-Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Orally&#xD;
      Inhaled Aerosolized Hydroxychloroquine Sulfate in Healthy Adult Volunteers.' The primary&#xD;
      objectives are as follows:&#xD;
&#xD;
        -  To assess the safety and tolerability of AHCQ administered as a single dose by oral&#xD;
           inhalation in healthy individuals at escalating doses until either the maximum tolerated&#xD;
           dose (MTD) is identified or 1 mL of a 50 mg/mL solution is administered.&#xD;
&#xD;
        -  To determine the recommended Phase 2a dose (RP2D).&#xD;
&#xD;
      Secondary objectives:&#xD;
&#xD;
      • To characterize pharmacokinetics (PK) of single dose AHCQ in healthy individuals.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study Design:&#xD;
&#xD;
      This is a randomized, double-blind placebo-controlled Phase 1 single-dose dose-escalation&#xD;
      study to assess the safety, tolerability and PK of oral inhalation of AHCQ in healthy&#xD;
      participants.&#xD;
&#xD;
      Escalating single doses of AHCQ will be studied in healthy participants. The study drug will&#xD;
      be administered by inhalation through the mouth, and participants will be encouraged to&#xD;
      exhale through the nose. The study drug, AHCQ, will be administered starting at an initial&#xD;
      dose of 20 mg (Cohort A1, 1 mL of 20 mg/mL AHCQ solution) with a proposed subsequent doses of&#xD;
      50 mg (Cohort A2, 1 mL of 50 mg/mL AHCQ).&#xD;
&#xD;
      Number of Participants (Planned):&#xD;
&#xD;
      Two dose levels are planned to be evaluated. Each cohort will comprise 8 participants (6&#xD;
      active, 2 placebo). Therefore, 16 participants will initially be planned to be enrolled in&#xD;
      the study. Additional participants may be enrolled if one or more enrolled participants do&#xD;
      not complete the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 25, 2020</start_date>
  <completion_date type="Actual">August 17, 2020</completion_date>
  <primary_completion_date type="Actual">August 17, 2020</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>Parallel Assignment</intervention_model>
    <intervention_model_description>This is a randomized, double-blind placebo-controlled Phase 1 single-dose dose-escalation study to assess the safety, tolerability and PK of oral inhalation of AHCQ in healthy participants.&#xD;
A sentinel dose strategy will be employed and the decision to escalate to the next dose level, or deescalate or stop the study, will be based on review and analysis of all available blinded safety and tolerability data by the Safety Review Committee (SRC), which will make a recommendation to the Sponsor and the Sponsor will inform the PI of the recommendation.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidences of treatment-emergent adverse events (TEAEs) as assessed by TGSHAAV (September 2007) or CTCAE version 5.0</measure>
    <time_frame>after treatment (Day 1) through to Day 30</time_frame>
    <description>TEAEs (defined as AEs with onset after study drug administration or existing AEs that worsen in severity after study drug administration)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline in clinical laboratory test results for CBC with differential</measure>
    <time_frame>Screening and Day 8</time_frame>
    <description>Blood sample collected for CBC with differential will be assessed from baseline (at screening)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal laboratory test results for CBC with differential at Screening</measure>
    <time_frame>Screening</time_frame>
    <description>Screening blood sample collected for CBC with differential, counting the number of abnormal clinical tests</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal laboratory test results for CBC with differential - Day 8</measure>
    <time_frame>Day 8</time_frame>
    <description>Day 8 blood sample collected for CBC with differential</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes from baseline for blood glucose</measure>
    <time_frame>Screening and Day 1</time_frame>
    <description>Blood sample collected for blood glucose and measured with a glucometer</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal laboratory test results for chemistry -Screening</measure>
    <time_frame>Screening</time_frame>
    <description>Blood sample collected for chemistry panel (albumin, total protein, ALP, ALT, AST, direct and indirect bilirubin, GGT, BUN, creatinine, glucose, bicarbonate, calcium, chloride, magnesium, phosphate, potassium, sodium, and LDH)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal laboratory tests results for chemistry - Day 8</measure>
    <time_frame>Day 8</time_frame>
    <description>Blood sample collected for chemistry panel (albumin, total protein, ALP, ALT, AST, direct and indirect bilirubin, GGT, BUN, creatinine, glucose, bicarbonate, calcium, chloride, magnesium, phosphate, potassium, sodium, and LDH)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal laboratory tests results for urinalysis - Screening</measure>
    <time_frame>Screening</time_frame>
    <description>Collection of urine sample to test pH, specific gravity, protein, glucose, ketones, urobilinogen, bilirubin, leukocyte esterase, squamous cells, epithelial cells, clarity, bacteria, blood</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal laboratory tests results for urinalysis- Day 8</measure>
    <time_frame>Day 8</time_frame>
    <description>Collection of urine sample to test pH, specific gravity, protein, glucose, ketones, urobilinogen, bilirubin, leukocyte esterase, squamous cells, epithelial cells, clarity, bacteria, blood</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in vital signs from baseline (pre-dose) - respiratory rate</measure>
    <time_frame>Screening, Day 1, Day 2 and Day 8</time_frame>
    <description>The Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials (September 2007) (TGSHAAV) will be used as the primary criteria for assessment of clinical abnormalities. Mild (17-20 breaths per minute) to Potentially Life Threatening (intubation)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in vital signs from baseline (pre-dose)- temperature</measure>
    <time_frame>Screening, Day 1, Day 2 and Day 8</time_frame>
    <description>Oral temperature</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in vital signs from baseline (pre-dose) - seated blood pressure</measure>
    <time_frame>Screening, Day 1, Day 2 and Day 8</time_frame>
    <description>Systolic and diastolic blood pressure</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in vital signs from baseline (pre-dose) - pulse</measure>
    <time_frame>Screening, Day 1, Day 2 and Day 8</time_frame>
    <description>Heart rate measure by radial pulse rate (beats/min)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in vital signs from baseline (pre-dose) - O2 saturation</measure>
    <time_frame>Screening, Day 1, Day 2 and Day 8</time_frame>
    <description>O2 saturation (%), measured by pulse oximeter. Graded as per TGSHAAV (September 2007) from Moderate (pulse oximeter &lt;92%) to Potentially Life Threatening (Life-threatening airway compromise; urgent intervention indicated)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal and physical examinations findings during Screening- general appearance</measure>
    <time_frame>Screening</time_frame>
    <description>Physical exam by clinician. A directed physical examination will be conducted</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal and physical examinations findings on Day 1 - general appearance</measure>
    <time_frame>Day 1</time_frame>
    <description>Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal and physical examinations findings on Day 2- general appearance</measure>
    <time_frame>Day 2</time_frame>
    <description>Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal and physical examinations findings on Day 8- general appearance</measure>
    <time_frame>Day 8</time_frame>
    <description>Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal and physical examinations findings during Screening- neurological</measure>
    <time_frame>Screening</time_frame>
    <description>Physical exam by clinician. A directed physical examination will be conducted</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal and physical examinations findings on Day 1- neurological</measure>
    <time_frame>Day 1</time_frame>
    <description>Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal and physical examinations findings on Day 2- neurological</measure>
    <time_frame>Day 2</time_frame>
    <description>Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal and physical examinations findings on Day 8- neurological</measure>
    <time_frame>Day 8</time_frame>
    <description>Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal and physical examinations findings during Screening - heart/cardiovascular</measure>
    <time_frame>Screening</time_frame>
    <description>Physical exam by clinician. A directed physical examination will be conducted</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal and physical examinations findings on Day 1 - heart/cardiovascular</measure>
    <time_frame>Day 1 (pre-dose, within 3 hours of dose)</time_frame>
    <description>Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal and physical examinations findings on Day 2 - heart/cardiovascular</measure>
    <time_frame>Day 2</time_frame>
    <description>Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal and physical examinations findings on Day 8 - heart/cardiovascular</measure>
    <time_frame>Day 8</time_frame>
    <description>Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal and physical examinations findings during Screening - lungs</measure>
    <time_frame>Screening</time_frame>
    <description>Physical exam by clinician. A directed physical examination will be conducted</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal and physical examinations findings on Day 1 - lungs</measure>
    <time_frame>Day 1</time_frame>
    <description>Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal and physical examinations findings on Day 2 - lungs</measure>
    <time_frame>Day 2</time_frame>
    <description>Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal and physical examinations findings on Day 8 - lungs</measure>
    <time_frame>Day 8</time_frame>
    <description>Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal and physical examinations findings during Screening- abdomen</measure>
    <time_frame>Screening</time_frame>
    <description>Physical exam by clinician. A directed physical examination will be conducted</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal and physical examinations findings on Day 1 - abdomen</measure>
    <time_frame>Day 1</time_frame>
    <description>Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal and physical examinations findings on Day 2- abdomen</measure>
    <time_frame>Day 2</time_frame>
    <description>Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal and physical examinations findings on Day 8- abdomen</measure>
    <time_frame>Day 8</time_frame>
    <description>Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal and physical examinations findings during screening- endocrine</measure>
    <time_frame>Screening</time_frame>
    <description>Physical exam by clinician. A directed physical examination will be conducted</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal and physical examinations findings on Day 1 - endocrine</measure>
    <time_frame>Day 1</time_frame>
    <description>Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal and physical examinations findings on Day 2- endocrine</measure>
    <time_frame>Day 2</time_frame>
    <description>Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal and physical examinations findings on Day 8- endocrine</measure>
    <time_frame>Day 8</time_frame>
    <description>Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal and physical examinations findings during Screening- extremities</measure>
    <time_frame>Screening</time_frame>
    <description>Physical exam by clinician. A directed physical examination will be conducted</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal and physical examinations findings on Day 1- extremities</measure>
    <time_frame>Day 1</time_frame>
    <description>Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal and physical examinations findings on Day 2- extremities</measure>
    <time_frame>Day 2</time_frame>
    <description>Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal and physical examinations findings on Day 8- extremities</measure>
    <time_frame>Day 8</time_frame>
    <description>Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal and physical examinations findings during Screening- lymphatic</measure>
    <time_frame>Screening</time_frame>
    <description>Physical exam by clinician. A directed physical examination will be conducted</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal and physical examinations findings on Day 1- lymphatic</measure>
    <time_frame>Day 1</time_frame>
    <description>Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal and physical examinations findings on Day 2 - lymphatic</measure>
    <time_frame>Day 2</time_frame>
    <description>Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal and physical examinations findings on Day 8- lymphatic</measure>
    <time_frame>Day 8</time_frame>
    <description>Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal and physical examinations findings during screening - skin</measure>
    <time_frame>Screening</time_frame>
    <description>A directed physical examination will be conducted</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal and physical examinations findings on Day 1 - skin</measure>
    <time_frame>Day 1</time_frame>
    <description>Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal and physical examinations findings on Day 2 - skin</measure>
    <time_frame>Day 2</time_frame>
    <description>Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal and physical examinations findings on Day 8 - skin</measure>
    <time_frame>Day 8</time_frame>
    <description>Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes from baseline for pulmonary function tests (PFTs) - FEV1</measure>
    <time_frame>Screening, Day 1 at pre-dose (within 25 minutes of dose) and at +15 minutes, +1, +3 and +6 hours after study treatment, and on Day 2 and Day 8.</time_frame>
    <description>Pulmonary function testing and recording of FEV1, both actual and percent predicted</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes from baseline for pulmonary function tests (PFTs) - FVC</measure>
    <time_frame>Screening, Day 1 at pre-dose (within 25 minutes of dose) and at +15 minutes, +1, +3 and +6 hours after study treatment, and on Day 2 and Day 8.</time_frame>
    <description>Pulmonary function testing and recording of FVC, , both actual and percent predicted</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes from baseline for pulmonary function tests (PFTs) - FEV1/FVC</measure>
    <time_frame>creening, Day 1 at pre-dose (within 25 minutes of dose) and at +15 minutes, +1, +3 and +6 hours after study treatment, and on Day 2 and Day 8.</time_frame>
    <description>Pulmonary function testing and recording of FEV1/FVC</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes from baseline for ECG readings - QT interval</measure>
    <time_frame>Screening and on Day 1 pre-dose (within 3 hours of dose) and approximately +2 and +6 hours, and on Days 2 and 8.</time_frame>
    <description>The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing.&#xD;
ECG QT Interval (msec) will be the assessment parameter.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes from baseline for ECG readings - QTcB Interval</measure>
    <time_frame>Screening and on Day 1 pre-dose (within 3 hours of dose) and approximately +2 and +6 hours, and on Days 2 and 8.</time_frame>
    <description>The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing.&#xD;
ECG QTcB interval (msec) will be the assessment parameter.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes from baseline for ECG readings - QRS duration</measure>
    <time_frame>Screening and on Day 1 pre-dose (within 3 hours of dose) and approximately +2 and +6 hours, and on Days 2 and 8.</time_frame>
    <description>The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing.&#xD;
ECG QRS duration (msec) will be the assessment parameter.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes from baseline for ECG readings - PR interval</measure>
    <time_frame>Screening and on Day 1 pre-dose (within 3 hours of dose) and approximately +2 and +6 hours, and on Days 2 and 8.</time_frame>
    <description>The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing.&#xD;
ECG PR interval (msec) will be the assessment parameter.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes from baseline for ECG readings - heart rate</measure>
    <time_frame>Screening and on Day 1 pre-dose (within 3 hours of dose) and approximately +2 and +6 hours, and on Days 2 and 8.</time_frame>
    <description>The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing.&#xD;
ECG heart rate (beats/min) will be the assessment parameter.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal ECG - Screening</measure>
    <time_frame>Screening</time_frame>
    <description>The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing.&#xD;
ECG QT Interval will be the assessment parameter.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal ECG- Day 1</measure>
    <time_frame>Day 1 pre-dose (within 3 hours of dose) and +2 and +6 hours</time_frame>
    <description>The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing.&#xD;
ECG QT Interval will be the assessment parameter.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal ECG - Day 2</measure>
    <time_frame>Days 2</time_frame>
    <description>The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing.&#xD;
ECG QT Interval will be the assessment parameter.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of abnormal ECG - Day 8</measure>
    <time_frame>Days 8.</time_frame>
    <description>The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing.&#xD;
ECG QT Interval will be the assessment parameter.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>HCQ concentration in whole blood versus time profiles</measure>
    <time_frame>Day 1 pre-dose (time 0) and +2, +3, +5, and +15 minutes after dose, and also +1, +2, +4 and +6 hours post-dose completion. Day 2 (+24±4 hours post dose) and Day 8.</time_frame>
    <description>Blood samples for PK analysis will be collected via indwelling catheter or via direct venipuncture.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Severe Acute Respiratory Syndrome Coronavirus 2</condition>
  <arm_group>
    <arm_group_label>Hydroxychloroquine Sulfate</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The study drug AHCQ will be administered by inhalation through the mouth. The starting dose will be 20 mg (Cohort A1) with a proposed subsequent dose of 50 mg (Cohort A2). At each dose level 8 participants (including at least 3 female participants and 3 participants older than 50 years old) will be enrolled. Six participants will receive the active study drug and 2 participants will receive placebo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo will be administered by inhalation through the mouth. It will be administered in both Cohort A1 and Cohort A2. Six participants will receive the active study drug and 2 participants will receive placebo.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aerolized Hydroxychloroquine Sulfate</intervention_name>
    <description>sterile AHCQ 100 mg/mL for inhalation, is a clear solution packaged in clear glass vials and stored at room temperature.</description>
    <arm_group_label>Hydroxychloroquine Sulfate</arm_group_label>
    <other_name>AHCQ</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>The placebo product and diluent solution is sodium chloride inhalation solution, United States Pharmacopeia (USP) 0.9%.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Willing and able to give written informed consent.&#xD;
&#xD;
          2. Males or females aged ≥18 years old.&#xD;
&#xD;
          3. Good general health as determined by no acute illness and no clinically significant&#xD;
             abnormal findings on medical history, vital signs, laboratory tests, or physical&#xD;
             examination at screening that, in the opinion of the PI, would interfere with study&#xD;
             drug administration, jeopardize the safety of the study participant, or impact the&#xD;
             validity of the study results; participants with stable chronic illness are allowed at&#xD;
             the discretion of the PI.&#xD;
&#xD;
          4. An interpretable 12-lead ECG with a corrected QT (QTc) interval ≤450 ms, according to&#xD;
             Bazett's formula, without evidence of clinically significant abnormal findings.&#xD;
&#xD;
          5. Normal FEV1/FVC ratio, defined as any value above 0.7 or above the lower 5th&#xD;
             percentile of normal AND FEV1 &gt;80% of predicted or above the lower 5th percentile of&#xD;
             normal.&#xD;
&#xD;
          6. Pulse oximetry 02 saturation ≥95% in room air.&#xD;
&#xD;
          7. Negative test result for COVID-19 within 7 days of Day 1 AND concurrent with local&#xD;
             hospital policy:&#xD;
&#xD;
               -  A nasopharyngeal swab tested with the ID NOW COVID-19 assay (Abbot). OR&#xD;
&#xD;
               -  A negative RNA-based test result of an oropharyngeal or nasopharyngeal swab or&#xD;
                  saliva sample performed according to CLIA/CLEP.&#xD;
&#xD;
          8. Females of child-bearing potential must be non-pregnant, non-lactating, have a&#xD;
             negative urine pregnancy test at screening, and agree to use an acceptable form of&#xD;
             birth control for 200 days after the last administration of the study drug. Females&#xD;
             are considered of non-childbearing potential if they are postmenopausal (last&#xD;
             menstrual period at least 1 year before screening) or have been surgically sterilized&#xD;
             (documented hysterectomy, tubal ligation, or bilateral oophorectomy) for at least 6&#xD;
             months at screening.&#xD;
&#xD;
          9. Willing to comply with protocol-defined procedures and complete all study visits.&#xD;
&#xD;
         10. Willing to use the Inhalation System and exhale through the nose.&#xD;
&#xD;
         11. Adequate venous access in the left or right arm to allow collection of required blood&#xD;
             samples.&#xD;
&#xD;
         12. Participant understands and communicates in English.&#xD;
&#xD;
         13. Serum Potassium level ≥3.5 mEq/L, Serum Magnesium level ≥1.5 mg/dL, and Serum Calcium&#xD;
             ≥8.5 mg/dL.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Any self-reported symptoms of influenza-like or COVID-19-like illness in the 14 days&#xD;
             preceding the study visit: Fever &gt;101.4 °F, sore throat, nasal congestion, post-nasal&#xD;
             discharge, shortness of breath, gastrointestinal distress, wheezing, cough, headache,&#xD;
             or fatigue.&#xD;
&#xD;
          2. Any history of diagnosed chronic lung disease, including but not limited to asthma or&#xD;
             chronic obstructive lung disease.&#xD;
&#xD;
          3. Symptoms of seasonal allergies or use of any drugs for seasonal allergies or any&#xD;
             inhaled (oral/nasal) drugs in the 2 weeks prior to Day 1. Mild seasonal allergy&#xD;
             symptoms that have not altered sleep or activity patterns nor required use of&#xD;
             over-the-counter (OTC) or prescription medications are allowed.&#xD;
&#xD;
          4. Any close contact exposure in the past 28 days to a person who was diagnosed as having&#xD;
             COVID-19, with or without laboratory confirmation, during that close contact exposure&#xD;
             or in the ensuing 14 days OR a similar encounter with a person who was determined to&#xD;
             have suspected COVID-19, defined by that person being ordered to enter isolation for&#xD;
             that indication by a medical authority. Close contact is defined as being within&#xD;
             approximately 6 feet of a COVID-19 case for a prolonged (&gt;10 minutes) period of time&#xD;
             and can occur while caring for, living with, visiting, or sharing a healthcare waiting&#xD;
             area or room with a COVID-19 patient OR having direct contact with infectious&#xD;
             secretions of a COVID-19 patient (e.g., being coughed on), if such contact occurred&#xD;
             while not wearing the recommended personal protective equipment for that type of&#xD;
             contact [e.g., gowns, gloves, N95 respirator (or equivalent), eye protection].&#xD;
&#xD;
          5. Any participant with a history of SARS-CoV-2 infection that was confirmed by testing&#xD;
             or diagnosed without testing within 4 weeks preceding Day 1. If infection occurred&#xD;
             more than 4 weeks prior, candidates may be enrolled if they meet the rest of the&#xD;
             eligibility criteria.&#xD;
&#xD;
          6. Any participant with a history severe respiratory illness that required&#xD;
             hospitalization in the 60 days preceding Day 1 OR any participant with a history&#xD;
             severe respiratory illness that required hospitalization in the preceding 120 days&#xD;
             without full recovery.&#xD;
&#xD;
          7. Participation in another clinical study that involved treatment with an&#xD;
             investigational product or device within 30 days of screening or during the study.&#xD;
&#xD;
          8. Participants with a known history of human immunodeficiency virus (HIV) infection.&#xD;
&#xD;
          9. Known, active hepatitis A, B, or C infection.&#xD;
&#xD;
         10. History of bronchospasm in response to use of an inhalation device.&#xD;
&#xD;
         11. Use of any prescription medication (except oral contraceptives) during the 30 days&#xD;
             prior to study dosing that may affect drug absorption, metabolism and excretion,&#xD;
             prolong the QTc interval, affect drug efficacy, or increase the risk of adverse&#xD;
             reactions, unless approved by the Principal Investigator.&#xD;
&#xD;
         12. Use of any OTC product, herbal product, diet aid, hormone supplement, etc., within 7&#xD;
             days prior to dosing unless approved by the Principal Investigator.&#xD;
&#xD;
         13. Unwilling or unable to provide written informed consent.&#xD;
&#xD;
         14. Any known hypersensitivity to quinolines (e.g., hydroxychloroquine, chloroquine,&#xD;
             primaquine, quinine) or known history of glucose-6-phosphate dehydrogenase (G6PD)&#xD;
             deficiency or any contraindication to oral hydroxychloroquine.&#xD;
&#xD;
         15. Known retinopathy, fundus disease, or macular disease.&#xD;
&#xD;
         16. Diagnosis of long QT Syndrome.&#xD;
&#xD;
         17. Smoking of tobacco or non-tobacco substances, or vaping, within the last 6 months.&#xD;
&#xD;
         18. Severe obesity (body mass index [BMI] ≥35 kg/m2).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ohad S Bentur, MD, MHA</last_name>
    <role>Principal Investigator</role>
    <affiliation>Rockefeller University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The Rockefeller University</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>June 23, 2020</study_first_submitted>
  <study_first_submitted_qc>July 7, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 8, 2020</study_first_posted>
  <last_update_submitted>October 6, 2020</last_update_submitted>
  <last_update_submitted_qc>October 6, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 8, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>coronavirus</keyword>
  <keyword>COVID-19</keyword>
  <keyword>Hydroxychloroquine Sulfate</keyword>
  <keyword>Hydroxychloroquine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Coronavirus Infections</mesh_term>
    <mesh_term>Severe Acute Respiratory Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hydroxychloroquine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>There is no plan to make IPD available to other researchers.</ipd_description>
  </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/NCT04461353
org study id: PUL-01
nct id: NCT04461353
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This study is 'A Randomized Phase 1 Double Blind Placebo Controlled, Single-Dose,
      Dose-Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Orally
      Inhaled Aerosolized Hydroxychloroquine Sulfate in Healthy Adult Volunteers.' The primary
      objectives are as follows:

        -  To assess the safety and tolerability of AHCQ administered as a single dose by oral
           inhalation in healthy individuals at escalating doses until either the maximum tolerated
           dose (MTD) is identified or 1 mL of a 50 mg/mL solution is administered.

        -  To determine the recommended Phase 2a dose (RP2D).

      Secondary objectives:

      • To characterize pharmacokinetics (PK) of single dose AHCQ in healthy individuals.
Study Design:

      This is a randomized, double-blind placebo-controlled Phase 1 single-dose dose-escalation
      study to assess the safety, tolerability and PK of oral inhalation of AHCQ in healthy
      participants.

      Escalating single doses of AHCQ will be studied in healthy participants. The study drug will
      be administered by inhalation through the mouth, and participants will be encouraged to
      exhale through the nose. The study drug, AHCQ, will be administered starting at an initial
      dose of 20 mg (Cohort A1, 1 mL of 20 mg/mL AHCQ solution) with a proposed subsequent doses of
      50 mg (Cohort A2, 1 mL of 50 mg/mL AHCQ).

      Number of Participants (Planned):

      Two dose levels are planned to be evaluated. Each cohort will comprise 8 participants (6
      active, 2 placebo). Therefore, 16 participants will initially be planned to be enrolled in
      the study. Additional participants may be enrolled if one or more enrolled participants do
      not complete the study.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This is a randomized, double-blind placebo-controlled Phase 1 single-dose dose-escalation study to assess the safety, tolerability and PK of oral inhalation of AHCQ in healthy participants.
A sentinel dose strategy will be employed and the decision to escalate to the next dose level, or deescalate or stop the study, will be based on review and analysis of all available blinded safety and tolerability data by the Safety Review Committee (SRC), which will make a recommendation to the Sponsor and the Sponsor will inform the PI of the recommendation.
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Incidences of treatment-emergent adverse events (TEAEs) as assessed by TGSHAAV (September 2007) or CTCAE version 5.0
time frame: after treatment (Day 1) through to Day 30
description: TEAEs (defined as AEs with onset after study drug administration or existing AEs that worsen in severity after study drug administration)
measure: Change from baseline in clinical laboratory test results for CBC with differential
time frame: Screening and Day 8
description: Blood sample collected for CBC with differential will be assessed from baseline (at screening)
measure: Incidence of abnormal laboratory test results for CBC with differential at Screening
time frame: Screening
description: Screening blood sample collected for CBC with differential, counting the number of abnormal clinical tests
measure: Incidence of abnormal laboratory test results for CBC with differential - Day 8
time frame: Day 8
description: Day 8 blood sample collected for CBC with differential
measure: Changes from baseline for blood glucose
time frame: Screening and Day 1
description: Blood sample collected for blood glucose and measured with a glucometer
measure: Incidence of abnormal laboratory test results for chemistry -Screening
time frame: Screening
description: Blood sample collected for chemistry panel (albumin, total protein, ALP, ALT, AST, direct and indirect bilirubin, GGT, BUN, creatinine, glucose, bicarbonate, calcium, chloride, magnesium, phosphate, potassium, sodium, and LDH)
measure: Incidence of abnormal laboratory tests results for chemistry - Day 8
time frame: Day 8
description: Blood sample collected for chemistry panel (albumin, total protein, ALP, ALT, AST, direct and indirect bilirubin, GGT, BUN, creatinine, glucose, bicarbonate, calcium, chloride, magnesium, phosphate, potassium, sodium, and LDH)
measure: Incidence of abnormal laboratory tests results for urinalysis - Screening
time frame: Screening
description: Collection of urine sample to test pH, specific gravity, protein, glucose, ketones, urobilinogen, bilirubin, leukocyte esterase, squamous cells, epithelial cells, clarity, bacteria, blood
measure: Incidence of abnormal laboratory tests results for urinalysis- Day 8
time frame: Day 8
description: Collection of urine sample to test pH, specific gravity, protein, glucose, ketones, urobilinogen, bilirubin, leukocyte esterase, squamous cells, epithelial cells, clarity, bacteria, blood
measure: Changes in vital signs from baseline (pre-dose) - respiratory rate
time frame: Screening, Day 1, Day 2 and Day 8
description: The Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials (September 2007) (TGSHAAV) will be used as the primary criteria for assessment of clinical abnormalities. Mild (17-20 breaths per minute) to Potentially Life Threatening (intubation)
measure: Changes in vital signs from baseline (pre-dose)- temperature
time frame: Screening, Day 1, Day 2 and Day 8
description: Oral temperature
measure: Changes in vital signs from baseline (pre-dose) - seated blood pressure
time frame: Screening, Day 1, Day 2 and Day 8
description: Systolic and diastolic blood pressure
measure: Changes in vital signs from baseline (pre-dose) - pulse
time frame: Screening, Day 1, Day 2 and Day 8
description: Heart rate measure by radial pulse rate (beats/min)
measure: Changes in vital signs from baseline (pre-dose) - O2 saturation
time frame: Screening, Day 1, Day 2 and Day 8
description: O2 saturation (%), measured by pulse oximeter. Graded as per TGSHAAV (September 2007) from Moderate (pulse oximeter <92%) to Potentially Life Threatening (Life-threatening airway compromise; urgent intervention indicated)
measure: Incidence of abnormal and physical examinations findings during Screening- general appearance
time frame: Screening
description: Physical exam by clinician. A directed physical examination will be conducted
measure: Incidence of abnormal and physical examinations findings on Day 1 - general appearance
time frame: Day 1
description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
measure: Incidence of abnormal and physical examinations findings on Day 2- general appearance
time frame: Day 2
description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
measure: Incidence of abnormal and physical examinations findings on Day 8- general appearance
time frame: Day 8
description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
measure: Incidence of abnormal and physical examinations findings during Screening- neurological
time frame: Screening
description: Physical exam by clinician. A directed physical examination will be conducted
measure: Incidence of abnormal and physical examinations findings on Day 1- neurological
time frame: Day 1
description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
measure: Incidence of abnormal and physical examinations findings on Day 2- neurological
time frame: Day 2
description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
measure: Incidence of abnormal and physical examinations findings on Day 8- neurological
time frame: Day 8
description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
measure: Incidence of abnormal and physical examinations findings during Screening - heart/cardiovascular
time frame: Screening
description: Physical exam by clinician. A directed physical examination will be conducted
measure: Incidence of abnormal and physical examinations findings on Day 1 - heart/cardiovascular
time frame: Day 1 (pre-dose, within 3 hours of dose)
description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
measure: Incidence of abnormal and physical examinations findings on Day 2 - heart/cardiovascular
time frame: Day 2
description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
measure: Incidence of abnormal and physical examinations findings on Day 8 - heart/cardiovascular
time frame: Day 8
description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
measure: Incidence of abnormal and physical examinations findings during Screening - lungs
time frame: Screening
description: Physical exam by clinician. A directed physical examination will be conducted
measure: Incidence of abnormal and physical examinations findings on Day 1 - lungs
time frame: Day 1
description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
measure: Incidence of abnormal and physical examinations findings on Day 2 - lungs
time frame: Day 2
description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
measure: Incidence of abnormal and physical examinations findings on Day 8 - lungs
time frame: Day 8
description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
measure: Incidence of abnormal and physical examinations findings during Screening- abdomen
time frame: Screening
description: Physical exam by clinician. A directed physical examination will be conducted
measure: Incidence of abnormal and physical examinations findings on Day 1 - abdomen
time frame: Day 1
description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
measure: Incidence of abnormal and physical examinations findings on Day 2- abdomen
time frame: Day 2
description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
measure: Incidence of abnormal and physical examinations findings on Day 8- abdomen
time frame: Day 8
description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
measure: Incidence of abnormal and physical examinations findings during screening- endocrine
time frame: Screening
description: Physical exam by clinician. A directed physical examination will be conducted
measure: Incidence of abnormal and physical examinations findings on Day 1 - endocrine
time frame: Day 1
description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
measure: Incidence of abnormal and physical examinations findings on Day 2- endocrine
time frame: Day 2
description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
measure: Incidence of abnormal and physical examinations findings on Day 8- endocrine
time frame: Day 8
description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
measure: Incidence of abnormal and physical examinations findings during Screening- extremities
time frame: Screening
description: Physical exam by clinician. A directed physical examination will be conducted
measure: Incidence of abnormal and physical examinations findings on Day 1- extremities
time frame: Day 1
description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
measure: Incidence of abnormal and physical examinations findings on Day 2- extremities
time frame: Day 2
description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
measure: Incidence of abnormal and physical examinations findings on Day 8- extremities
time frame: Day 8
description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
measure: Incidence of abnormal and physical examinations findings during Screening- lymphatic
time frame: Screening
description: Physical exam by clinician. A directed physical examination will be conducted
measure: Incidence of abnormal and physical examinations findings on Day 1- lymphatic
time frame: Day 1
description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
measure: Incidence of abnormal and physical examinations findings on Day 2 - lymphatic
time frame: Day 2
description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
measure: Incidence of abnormal and physical examinations findings on Day 8- lymphatic
time frame: Day 8
description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
measure: Incidence of abnormal and physical examinations findings during screening - skin
time frame: Screening
description: A directed physical examination will be conducted
measure: Incidence of abnormal and physical examinations findings on Day 1 - skin
time frame: Day 1
description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
measure: Incidence of abnormal and physical examinations findings on Day 2 - skin
time frame: Day 2
description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
measure: Incidence of abnormal and physical examinations findings on Day 8 - skin
time frame: Day 8
description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted
measure: Changes from baseline for pulmonary function tests (PFTs) - FEV1
time frame: Screening, Day 1 at pre-dose (within 25 minutes of dose) and at +15 minutes, +1, +3 and +6 hours after study treatment, and on Day 2 and Day 8.
description: Pulmonary function testing and recording of FEV1, both actual and percent predicted
measure: Changes from baseline for pulmonary function tests (PFTs) - FVC
time frame: Screening, Day 1 at pre-dose (within 25 minutes of dose) and at +15 minutes, +1, +3 and +6 hours after study treatment, and on Day 2 and Day 8.
description: Pulmonary function testing and recording of FVC, , both actual and percent predicted
measure: Changes from baseline for pulmonary function tests (PFTs) - FEV1/FVC
time frame: creening, Day 1 at pre-dose (within 25 minutes of dose) and at +15 minutes, +1, +3 and +6 hours after study treatment, and on Day 2 and Day 8.
description: Pulmonary function testing and recording of FEV1/FVC
measure: Changes from baseline for ECG readings - QT interval
time frame: Screening and on Day 1 pre-dose (within 3 hours of dose) and approximately +2 and +6 hours, and on Days 2 and 8.
description: The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing.
ECG QT Interval (msec) will be the assessment parameter.
measure: Changes from baseline for ECG readings - QTcB Interval
time frame: Screening and on Day 1 pre-dose (within 3 hours of dose) and approximately +2 and +6 hours, and on Days 2 and 8.
description: The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing.
ECG QTcB interval (msec) will be the assessment parameter.
measure: Changes from baseline for ECG readings - QRS duration
time frame: Screening and on Day 1 pre-dose (within 3 hours of dose) and approximately +2 and +6 hours, and on Days 2 and 8.
description: The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing.
ECG QRS duration (msec) will be the assessment parameter.
measure: Changes from baseline for ECG readings - PR interval
time frame: Screening and on Day 1 pre-dose (within 3 hours of dose) and approximately +2 and +6 hours, and on Days 2 and 8.
description: The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing.
ECG PR interval (msec) will be the assessment parameter.
measure: Changes from baseline for ECG readings - heart rate
time frame: Screening and on Day 1 pre-dose (within 3 hours of dose) and approximately +2 and +6 hours, and on Days 2 and 8.
description: The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing.
ECG heart rate (beats/min) will be the assessment parameter.
measure: Incidence of abnormal ECG - Screening
time frame: Screening
description: The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing.
ECG QT Interval will be the assessment parameter.
measure: Incidence of abnormal ECG- Day 1
time frame: Day 1 pre-dose (within 3 hours of dose) and +2 and +6 hours
description: The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing.
ECG QT Interval will be the assessment parameter.
measure: Incidence of abnormal ECG - Day 2
time frame: Days 2
description: The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing.
ECG QT Interval will be the assessment parameter.
measure: Incidence of abnormal ECG - Day 8
time frame: Days 8.
description: The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing.
ECG QT Interval will be the assessment parameter.
measure: HCQ concentration in whole blood versus time profiles
time frame: Day 1 pre-dose (time 0) and +2, +3, +5, and +15 minutes after dose, and also +1, +2, +4 and +6 hours post-dose completion. Day 2 (+24±4 hours post dose) and Day 8.
description: Blood samples for PK analysis will be collected via indwelling catheter or via direct venipuncture.
arm group label: Hydroxychloroquine Sulfate
arm group type: Active Comparator
description: The study drug AHCQ will be administered by inhalation through the mouth. The starting dose will be 20 mg (Cohort A1) with a proposed subsequent dose of 50 mg (Cohort A2). At each dose level 8 participants (including at least 3 female participants and 3 participants older than 50 years old) will be enrolled. Six participants will receive the active study drug and 2 participants will receive placebo.
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo will be administered by inhalation through the mouth. It will be administered in both Cohort A1 and Cohort A2. Six participants will receive the active study drug and 2 participants will receive placebo.
intervention type: Drug
intervention name: Aerolized Hydroxychloroquine Sulfate
description: sterile AHCQ 100 mg/mL for inhalation, is a clear solution packaged in clear glass vials and stored at room temperature.
arm group label: Hydroxychloroquine Sulfate
other name: AHCQ
intervention type: Other
intervention name: Placebo
description: The placebo product and diluent solution is sodium chloride inhalation solution, United States Pharmacopeia (USP) 0.9%.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Ohad S Bentur, MD, MHA
role: Principal Investigator
affiliation: Rockefeller University
facility: 
country: United States
responsible party type: Sponsor
mesh term: Coronavirus Infections
mesh term: Severe Acute Respiratory Syndrome
mesh term: Hydroxychloroquine
sharing ipd: No
ipd description: There is no plan to make IPD available to other researchers.