<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/NCT02227888</url>
  </required_header>
  <id_info>
    <org_study_id>N91115-1PK-02</org_study_id>
    <nct_id>NCT02227888</nct_id>
  </id_info>
  <brief_title>PK Study of N91115 in Cystic Fibrosis Patients</brief_title>
  <acronym>SNO3</acronym>
  <official_title>A Phase 1, Open-Label Study Evaluating the Pharmacokinetics of N91115 in Cystic Fibrosis Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nivalis Therapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Nivalis Therapeutics, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This Phase 1 study in F508del-CFTR homozygous CF patients is being conducted to assess the&#xD;
      pharmacokinetics and absorption dynamics of N91115 compared with healthy subjects in order to&#xD;
      identify an initial starting dose for Phase 2 trials.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open-label pharmacokinetic (PK) study of twice daily doses of 50 mg of N91115&#xD;
      administered for 14 days in F508del-CFTR homozygous CF patients. Six patients are planned for&#xD;
      enrollment. Each patient will undergo screening (Day 28 to Day 3) and, if eligible, will&#xD;
      return to the clinical site on Day 1 or optionally on Day 1. Eligibility will be reconfirmed&#xD;
      and the patient will be admitted to a clinical research unit (CRU). Patients will stay&#xD;
      overnight from Day 1 to Day 2 and will be discharged on Day 2 after all procedures and&#xD;
      assessments are completed. Patients will return to the CRU as outpatients on Days 4, 7, 11,&#xD;
      14, and 15 for PK sample collection and other assessments. They will receive an oral dose of&#xD;
      investigational medicinal product (IMP), N91115, twice daily on Days 1 through 14 and will be&#xD;
      followed for PK through Day 15. Telephone calls to assess safety and ensure compliance with&#xD;
      dosing will be made on days that patients do not make clinic visits (Days 3, 5, 6, 8, 9, 10,&#xD;
      12, and 13). Follow-up safety calls will then be made on Day 21 (adverse events) and Day 28&#xD;
      (serious adverse events only). Participation of an individual patient may last approximately&#xD;
      56 days from the time of screening until the end-of-study (Day 28) follow-up call.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">January 2015</completion_date>
  <primary_completion_date type="Actual">January 2015</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pharmacokinetics</measure>
    <time_frame>14 Days</time_frame>
    <description>To assess the pharmacokinetics of N91115 after twice daily (q 12 h) doses given for 14 days by measuring plasma and urine concentrations of N91115 and its primary metabolite.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety of dosing twice per day over 14 days</measure>
    <time_frame>14 Days</time_frame>
    <description>To assess the safety of 14 twice daily (q 12 h) doses of N91115 in F508del-CFTR homozygous CF patients by monitoring, 12 lead ECG, Adverse events, Clinical safety laboratory tests (hematology, clinical chemistry, and urinalysis), Concomitant medications, Abbreviated physical examinations, Hemoglobin oxygen saturation (O2 Sat) by pulse oximetry, Spirometry, Telemetry, Vital signs, Weight</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Cystic Fibrosis</condition>
  <arm_group>
    <arm_group_label>N91115</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Every 12 hour oral dosing of 50 mg N91115 for 14 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>N91115</intervention_name>
    <description>S nitrosoglutathione reductase inhibitor</description>
    <arm_group_label>N91115</arm_group_label>
    <other_name>Cavosonstat</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Confirmed diagnosis of CF, homozygous for the F508del-CFTR mutation&#xD;
&#xD;
          2. Weight ≥ 40 kg at screening&#xD;
&#xD;
          3. FEV1 ≥ 40% of predicted normal for age, gender, and height (Hankinson standards) pre&#xD;
             or post-bronchodilator value, at screening&#xD;
&#xD;
          4. Hematology, clinical chemistry, and urinalysis results with no clinically significant&#xD;
             abnormalities that would interfere with the study assessments at screening&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of any illness or condition that in the opinion of the investigator could&#xD;
             confound the results of the study or pose additional risk when administered IMP&#xD;
&#xD;
          2. Any acute infection, including acute upper or lower respiratory infections and&#xD;
             pulmonary exacerbations that require treatment or hospitalizations within 4 weeks of&#xD;
             Study Day 1&#xD;
&#xD;
          3. Any change in chronic therapies for CF lung disease (e.g., Ibuprofen, Pulmozyme®,&#xD;
             hypertonic saline, Azithromycin, TOBI®, Cayston®) within 4 weeks of Study Day 1&#xD;
&#xD;
          4. History, including the screening assessment, of ventricular tachycardia or ventricular&#xD;
             arrhythmias&#xD;
&#xD;
          5. History, including the screening assessment, of prolonged QT and/or QTcF (Fridericia's&#xD;
             correction) interval (&gt; 450 msec)&#xD;
&#xD;
          6. History of solid organ or hematological transplantation&#xD;
&#xD;
          7. History of alcohol abuse or drug addiction (including cannabis, cocaine, and opioids)&#xD;
             in the year prior to screening&#xD;
&#xD;
          8. Use of continuous (24 hr/day) or nocturnal supplemental oxygen&#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>Steven Shoemaker, MD</last_name>
    <role>Study Director</role>
    <affiliation>Nivalis Therapeutics, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Alabama @ Birmingham</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's CO</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Jewish Health</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80206</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2016</verification_date>
  <study_first_submitted>August 26, 2014</study_first_submitted>
  <study_first_submitted_qc>August 26, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 28, 2014</study_first_posted>
  <last_update_submitted>November 3, 2016</last_update_submitted>
  <last_update_submitted_qc>November 3, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 6, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>CF</keyword>
  <keyword>F508Del</keyword>
  <keyword>Cavosonstat</keyword>
  <keyword>N91115</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cystic Fibrosis</mesh_term>
    <mesh_term>Fibrosis</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02227888
org study id: N91115-1PK-02
nct id: NCT02227888
lead sponsor: 
has dmc: No
This Phase 1 study in F508del-CFTR homozygous CF patients is being conducted to assess the
      pharmacokinetics and absorption dynamics of N91115 compared with healthy subjects in order to
      identify an initial starting dose for Phase 2 trials.
This is an open-label pharmacokinetic (PK) study of twice daily doses of 50 mg of N91115
      administered for 14 days in F508del-CFTR homozygous CF patients. Six patients are planned for
      enrollment. Each patient will undergo screening (Day 28 to Day 3) and, if eligible, will
      return to the clinical site on Day 1 or optionally on Day 1. Eligibility will be reconfirmed
      and the patient will be admitted to a clinical research unit (CRU). Patients will stay
      overnight from Day 1 to Day 2 and will be discharged on Day 2 after all procedures and
      assessments are completed. Patients will return to the CRU as outpatients on Days 4, 7, 11,
      14, and 15 for PK sample collection and other assessments. They will receive an oral dose of
      investigational medicinal product (IMP), N91115, twice daily on Days 1 through 14 and will be
      followed for PK through Day 15. Telephone calls to assess safety and ensure compliance with
      dosing will be made on days that patients do not make clinic visits (Days 3, 5, 6, 8, 9, 10,
      12, and 13). Follow-up safety calls will then be made on Day 21 (adverse events) and Day 28
      (serious adverse events only). Participation of an individual patient may last approximately
      56 days from the time of screening until the end-of-study (Day 28) follow-up call.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Pharmacokinetics
time frame: 14 Days
description: To assess the pharmacokinetics of N91115 after twice daily (q 12 h) doses given for 14 days by measuring plasma and urine concentrations of N91115 and its primary metabolite.
measure: Safety of dosing twice per day over 14 days
time frame: 14 Days
description: To assess the safety of 14 twice daily (q 12 h) doses of N91115 in F508del-CFTR homozygous CF patients by monitoring, 12 lead ECG, Adverse events, Clinical safety laboratory tests (hematology, clinical chemistry, and urinalysis), Concomitant medications, Abbreviated physical examinations, Hemoglobin oxygen saturation (O2 Sat) by pulse oximetry, Spirometry, Telemetry, Vital signs, Weight
arm group label: N91115
arm group type: Experimental
description: Every 12 hour oral dosing of 50 mg N91115 for 14 days
intervention type: Drug
intervention name: N91115
description: S nitrosoglutathione reductase inhibitor
arm group label: N91115
other name: Cavosonstat
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Steven Shoemaker, MD
role: Study Director
affiliation: Nivalis Therapeutics, Inc.
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Cystic Fibrosis
mesh term: Fibrosis