<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/NCT03285178</url>
  </required_header>
  <id_info>
    <org_study_id>C1701-202</org_study_id>
    <nct_id>NCT03285178</nct_id>
  </id_info>
  <brief_title>A Study of the Effect of IW-1701 (Olinciguat), a Stimulator of Soluble Guanylate Cyclase (sGC), on Patients With Sickle Cell Disease (SCD)</brief_title>
  <acronym>STRONG SCD</acronym>
  <official_title>A Randomized, Placebo-controlled, Phase 2 Study to Evaluate the Safety and Pharmacodynamics of Once-daily Oral IW-1701 in Patients With Stable Sickle Cell Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cyclerion Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cyclerion Therapeutics</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>
      The primary objective of the 1701-202 STRONG SCD study is to evaluate the safety and&#xD;
      tolerability of different dose levels of IW-1701 compared with placebo when administered&#xD;
      daily for approximately 12 weeks to patients with stable SCD. Exploratory objectives include&#xD;
      evaluation of pharmacokinetic (PK) as well as evaluation of the effect of IW-1701 on symptoms&#xD;
      of SCD, health-related quality of life, and biomarkers of pharmacodynamic (PD) activity.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 22, 2017</start_date>
  <completion_date type="Actual">July 22, 2020</completion_date>
  <primary_completion_date type="Actual">July 22, 2020</primary_completion_date>
  <phase>Phase 2</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)</measure>
    <time_frame>First dose of randomized drug through 28 days after study drug discontinuation. Median number of weeks of treatment was 12.30, 11.85, 12.20, 12.20, 12.10, and 12.10, respectively, for Placebo 1, Placebo 2, Olinciguat 2 mg, 4 mg, 6 mg, and 18 mg groups.</time_frame>
    <description>An adverse event (AE) is any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. A serious AE (SAE) is defined as any AE occurring at any dose that results in any of the following: death; life-threatening; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; other important medical event. A TEAE is an event that occurs after initiation of randomized study drug through 28 days after study drug discontinuation. Events were categorized by grade: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death, and as related or unrelated to study drug. Adverse Events of special interest (AESIs) included symptomatic or Grade ≥2 hypotensive events and/or tachycardia AEs, bleeding events, pulmonary edema, and bone-related events, including fractures.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Double-Blind Treatment: Number of TEAE Events</measure>
    <time_frame>First dose of randomized drug through 28 days after study drug discontinuation. Median number of weeks of treatment was 12.30, 11.85, 12.20, 12.20, 12.10, and 12.10, respectively, for Placebo 1, Placebo 2, Olinciguat 2 mg, 4 mg, 6 mg, and 18 mg groups.</time_frame>
    <description>An AE is any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. An SAE is defined as any AE occurring at any dose that results in any of the following: death; life-threatening; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; other important medical event. A TEAE is an event that occurs after initiation of randomized study drug through 28 days after study drug discontinuation. Events were categorized by grade: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death, and as related or unrelated to study drug. If a participant had more than 1 occurrence in the same event category, only the occurrence with closest relationship to study drug was counted.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity</measure>
    <time_frame>First dose of randomized drug through 28 days after study drug discontinuation. Median number of weeks of treatment was 12.30, 11.85, 12.20, 12.20, 12.10, and 12.10, respectively, for Placebo 1, Placebo 2, Olinciguat 2 mg, 4 mg, 6 mg, and 18 mg groups.</time_frame>
    <description>An AE is any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. An SAE is defined as any AE occurring at any dose that results in any of the following: death; life-threatening; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; other important medical event. A TEAE is an event that occurs after initiation of randomized study drug through 28 days after study drug discontinuation. Events were categorized by grade: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death, and as related or unrelated to study drug. If a participant had more than 1 occurrence in the same event category, only the most severe occurrence was counted.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Double-Blind Treatment: Number of Participants With Study Drug-Related TEAEs</measure>
    <time_frame>First dose of randomized drug through 28 days after study drug discontinuation. Median number of weeks of treatment was 12.30, 11.85, 12.20, 12.20, 12.10, and 12.10, respectively, for Placebo 1, Placebo 2, Olinciguat 2 mg, 4 mg, 6 mg, and 18 mg groups.</time_frame>
    <description>An AE is any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. An SAE is defined as any AE occurring at any dose that results in any of the following: death; life-threatening; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; other important medical event. A TEAE is an event that occurs after initiation of randomized study drug through 28 days after study drug discontinuation. Events were categorized by grade: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death, and as related or unrelated to study drug. If a participant had more than 1 occurrence in the same event category, only the occurrence with closest relationship to study drug was counted.</description>
  </primary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">88</enrollment>
  <condition>Sickle Cell Disease</condition>
  <arm_group>
    <arm_group_label>IW-1701 (Olinciguat) 2 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>After a single-blind treatment with placebo once daily (QD) for 14 to 17 days of the Screening period and before the first dose of double-blind study drug on Day 1, participants received 1 mg olinciguat QD Week 1 and 2 mg olinciguat QD Weeks 2-12 under the original protocol, Amendment 1, Amendment 2, and Amendment 3.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>IW-1701 (Olinciguat) 4 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>After a single-blind treatment with placebo QD for 14 to 17 days of the Screening period and before the first dose of double-blind study drug on Day 1, participants received 2 mg olinciguat QD Week 1 and 4 mg olinciguat QD Weeks 2-12 under the original protocol, Amendment 1, Amendment 2, and Amendment 3.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>IW-1701 (Olinciguat) 6 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>After a single-blind treatment with placebo QD for 14 to 17 days of the Screening period and before the first dose of double-blind study drug on Day 1, participants received 3 mg olinciguat QD Week 1 and 6 mg olinciguat QD Weeks 2-12 under the original protocol, Amendment 1, Amendment 2, and Amendment 3.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>IW-1701 (Olinciguat) 18 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>After a single-blind treatment with placebo QD for 14 to 17 days of the Screening period and before the first dose of double-blind study drug on Day 1, participants received 6 mg olinciguat QD Days 1-7, 12 mg olinciguat QD Weeks 1-3, and 18 mg olinciguat QD Weeks 4-12 under protocol Amendment 4 and later.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>After a single-blind treatment with placebo QD for 14 to 17 days of the Screening period and before the first dose of double-blind study drug on Day 1, participants received placebo treatment QD for 12 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>IW-1701</intervention_name>
    <description>Oral Tablet</description>
    <arm_group_label>IW-1701 (Olinciguat) 18 mg</arm_group_label>
    <arm_group_label>IW-1701 (Olinciguat) 2 mg</arm_group_label>
    <arm_group_label>IW-1701 (Olinciguat) 4 mg</arm_group_label>
    <arm_group_label>IW-1701 (Olinciguat) 6 mg</arm_group_label>
    <other_name>Olinciguat</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Oral Tablet</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        INCLUSION CRITERIA&#xD;
&#xD;
          1. Patient is ambulatory male or female 16 to 70 years of age at the Screening Visit.&#xD;
&#xD;
          2. Patient has SCD, including homozygous hemoglobin S (HbSS), hemoglobin SC disease&#xD;
             (HbSC), heterozygous hemoglobin S-beta zero (HbSβ0)-thalassemia, or heterozygous&#xD;
             hemoglobin S-beta plus (HbSβ+)-thalassemia, documented in their medical history.&#xD;
&#xD;
          3. If patient is on medication(s) for SCD, such as hydroxyurea (HU), are on a stable&#xD;
             regimen.&#xD;
&#xD;
          4. Per medical history and/or patient recall, patient has had at least 1 and no more than&#xD;
             10 sickle cell-related pain crises in the 12 months before the Screening Visit and&#xD;
             none occurring in the 4 weeks before the Randomization Visit.&#xD;
&#xD;
          5. Patient completes daily eDiary entries for at least 10 days during the last 14 days of&#xD;
             the Run in Period as assessed at the Randomization Visit.&#xD;
&#xD;
          6. Women of childbearing potential must have a negative pregnancy test prior to&#xD;
             randomization and must agree to use protocol-specified contraception from the&#xD;
             Screening Visit through 90 days after the final dose of study drug.&#xD;
&#xD;
          7. Male patients must be surgically sterile by vasectomy (conducted ≥60 days before the&#xD;
             Screening Visit or confirmed via sperm analysis) or must agree to use&#xD;
             protocol-specified contraception and agree to refrain from sperm donation from the&#xD;
             Screening Visit through 90 days after the final dose of study drug.&#xD;
&#xD;
        EXCLUSION CRITERIA&#xD;
&#xD;
          1. Patient requires a program of prescheduled, regularly administered chronic blood&#xD;
             transfusion therapy.&#xD;
&#xD;
          2. Patient has been hospitalized for an SCD-related complication in the 4 weeks before&#xD;
             the Randomization Visit.&#xD;
&#xD;
          3. Patient has taken opioid(s) &gt;200 morphine mg equivalent/day within the 4 weeks before&#xD;
             the Randomization Visit.&#xD;
&#xD;
          4. Patient is taking aspirin ≥325 mg daily, P2Y12 inhibitors, any anticoagulant&#xD;
             medication, specific inhibitors of phosphodiesterase 5 (PDE5), nonspecific inhibitors&#xD;
             of phosphodiesterase 5 (PDE5), moderate or strong cytochrome P450 3A (CYP3A)&#xD;
             inhibitors, any supplements for the treatment of erectile dysfunction, riociguat, or&#xD;
             nitrates or nitric oxide donors in any form.&#xD;
&#xD;
          5. Patient has major concurrent illness or medical condition that in the opinion of the&#xD;
             Investigator would preclude participation in a clinical study.&#xD;
&#xD;
        NOTE: Other inclusion and exclusion criteria apply, per protocol&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>16 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Children's Hospital of Orange County</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92868</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MedStar Health Research Institute, MedStar Washington Hospital Center</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Howard University Center for Sickle Cell Disease</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20060</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Innovative Medical Research of South Florida, Inc.</name>
      <address>
        <city>Aventura</city>
        <state>Florida</state>
        <zip>33180</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Century Clinical Research, Inc.</name>
      <address>
        <city>Fort Lauderdale</city>
        <state>Florida</state>
        <zip>32117</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Foundation for Sickle Cell Disease Research</name>
      <address>
        <city>Hollywood</city>
        <state>Florida</state>
        <zip>33021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Omega Research Maitland, LLC</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32810</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Grady Memorial Hospital</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Atlanta Center for Medical Research</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30331</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Illinois at Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Healthcare Research Network II, LLC</name>
      <address>
        <city>Flossmoor</city>
        <state>Illinois</state>
        <zip>60422</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trials of SWLA, LLC</name>
      <address>
        <city>Lake Charles</city>
        <state>Louisiana</state>
        <zip>70601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Maryland Medical Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins School of Medicine Children's Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Boston Children's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Michigan-Detroit</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>33021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Healthcare Research Network</name>
      <address>
        <city>Hazelwood</city>
        <state>Missouri</state>
        <zip>63042</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hackensack University Medical Center, Pediatric Hematology and Oncology</name>
      <address>
        <city>Hackensack</city>
        <state>New Jersey</state>
        <zip>07601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jacobi Medical Center</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10461</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New York Medical College</name>
      <address>
        <city>Valhalla</city>
        <state>New York</state>
        <zip>10595</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>East Carolina University - Leo W. Jenkins Cancer Center</name>
      <address>
        <city>Greenville</city>
        <state>North Carolina</state>
        <zip>27834</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>East Carolina University Brody School of Medicine, Department of Pediatrics, Division of Pediatric Hematology</name>
      <address>
        <city>Greenville</city>
        <state>North Carolina</state>
        <zip>27834</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lynn Institute of Tulsa</name>
      <address>
        <city>Tulsa</city>
        <state>Oklahoma</state>
        <zip>74105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Clinical Trial Center LLC</name>
      <address>
        <city>Jenkintown</city>
        <state>Pennsylvania</state>
        <zip>19046</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pittsburgh Medical Center Hillman Cancer Center</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Accurate Clinical Research</name>
      <address>
        <city>Baytown</city>
        <state>Texas</state>
        <zip>77521</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>&quot;UT Health Clinical Research Unit Center for Clinical and Translational Sciences</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mays Cancer Center UT Health San Antonio</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Virginia Commonwealth University - Clinical Research Unit</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23298</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Blood Center of Wisconsin (BCW)</name>
      <address>
        <city>Wauwatosa</city>
        <state>Wisconsin</state>
        <zip>53226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hammoud Hospital University Medical Center</name>
      <address>
        <city>Sidon</city>
        <country>Lebanon</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nini Hospital</name>
      <address>
        <city>Tripoli</city>
        <country>Lebanon</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal London Hospital</name>
      <address>
        <city>London</city>
        <zip>E1 2ES</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Whittington Hospital</name>
      <address>
        <city>London</city>
        <zip>N19 5NF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Guys and St Thomas NHS Foundation Trust - Evelina London Childrens Hospital</name>
      <address>
        <city>London</city>
        <zip>SE1 7EH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Guy's Hospital</name>
      <address>
        <city>London</city>
        <zip>SE1 9RT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hammersmith Hospital</name>
      <address>
        <city>London</city>
        <zip>W12 0NN</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Lebanon</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>September 8, 2017</study_first_submitted>
  <study_first_submitted_qc>September 13, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 15, 2017</study_first_posted>
  <results_first_submitted>June 21, 2023</results_first_submitted>
  <results_first_submitted_qc>July 19, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">July 21, 2023</results_first_posted>
  <disposition_first_submitted>July 18, 2021</disposition_first_submitted>
  <disposition_first_submitted_qc>July 19, 2023</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">July 21, 2023</disposition_first_posted>
  <last_update_submitted>July 19, 2023</last_update_submitted>
  <last_update_submitted_qc>July 19, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 21, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Sickle Cell Disease</keyword>
  <keyword>SCD</keyword>
  <keyword>Olinciguat</keyword>
  <keyword>IW-1701</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anemia, Sickle Cell</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>July 24, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/78/NCT03285178/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>May 22, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/78/NCT03285178/SAP_002.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>After a 2-week single-blind placebo Run-in, eligible participants were stratified by hydroxyurea (hydroxycarbamide [HU]) use (yes or no) and randomly assigned to double-blind study drug (olinciguat or placebo).&#xD;
Under Amendment 3 and earlier: Participants were assigned in a 1:1:1:1 ratio to placebo, 2 mg olinciguat, 4 mg olinciguat, or 6 mg olinciguat.&#xD;
Under Amendment 4 and later: Participants were assigned in a 3:1 ratio to 18 mg olinciguat or placebo.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Single-Blind Run-in: Placebo</title>
          <description>Single-blind treatment with placebo once daily (QD) for 14 to 17 days of the Screening period and before the first dose of double-blind study drug on Day 1.</description>
        </group>
        <group group_id="P2">
          <title>Double-Blind Treatment: Placebo 1</title>
          <description>Participants received placebo treatment QD for 12 weeks under the original protocol, Amendment 1, Amendment 2, and Amendment 3.</description>
        </group>
        <group group_id="P3">
          <title>Double-Blind Treatment: Placebo 2</title>
          <description>Participants received placebo treatment QD for 12 weeks under protocol Amendment 4 and later.</description>
        </group>
        <group group_id="P4">
          <title>Double-Blind Treatment: IW-1701 (Olinciguat) 2 mg</title>
          <description>Participants received 1 mg olinciguat QD Week 1 and 2 mg olinciguat QD Weeks 2-12 under the original protocol, Amendment 1, Amendment 2, and Amendment 3.</description>
        </group>
        <group group_id="P5">
          <title>Double-Blind Treatment: IW-1701 (Olinciguat) 4 mg</title>
          <description>Participants received 2 mg olinciguat QD Week 1 and 4 mg olinciguat QD Weeks 2-12 under the original protocol, Amendment 1, Amendment 2, and Amendment 3.</description>
        </group>
        <group group_id="P6">
          <title>Double-Blind Treatment: IW-1701 (Olinciguat) 6 mg</title>
          <description>Participants received 3 mg olinciguat QD Week 1 and 6 mg olinciguat QD Weeks 2-12 under the original protocol, Amendment 1, Amendment 2, and Amendment 3.</description>
        </group>
        <group group_id="P7">
          <title>Double-Blind Treatment: IW-1701 (Olinciguat) 18 mg</title>
          <description>Participants received 6 mg olinciguat QD Days 1-7, 12 mg olinciguat QD Weeks 1-3, and 18 mg olinciguat QD Weeks 4-12 under protocol Amendment 4 and later.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Single-Blind Run-In Period</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="88"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="70"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>COVID-19 Pandemic Precautions - Suspended by Institutional Review Board (IRB)</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>COVID-19 Pandemic Precautions- Suspended per Local Guidelines</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Double-Blind Treatment Period</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="10"/>
                <participants group_id="P3" count="9"/>
                <participants group_id="P4" count="8"/>
                <participants group_id="P5" count="8"/>
                <participants group_id="P6" count="11"/>
                <participants group_id="P7" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="8"/>
                <participants group_id="P3" count="6"/>
                <participants group_id="P4" count="7"/>
                <participants group_id="P5" count="6"/>
                <participants group_id="P6" count="9"/>
                <participants group_id="P7" count="21"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="3"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="2"/>
                <participants group_id="P6" count="2"/>
                <participants group_id="P7" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Randomized Mistakenly During the Run-In Period - Did Not Receive Study Drug</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="2"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="2"/>
                <participants group_id="P7" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>COVID-19</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Safety Population: Randomized participants who received at least 1 dose of study drug</population>
      <group_list>
        <group group_id="B1">
          <title>Double-Blind Treatment: Placebo 1</title>
          <description>Participants received placebo treatment QD for 12 weeks under the original protocol, Amendment 1, Amendment 2, and Amendment 3.</description>
        </group>
        <group group_id="B2">
          <title>Double-Blind Treatment: Placebo 2</title>
          <description>Participants received placebo treatment QD for 12 weeks under protocol Amendment 4 and later</description>
        </group>
        <group group_id="B3">
          <title>Double-Blind Treatment: IW-1701 (Olinciguat) 2 mg</title>
          <description>Participants received 1 mg olinciguat QD Week 1 and 2 mg olinciguat QD Weeks 2-12 under the original protocol, Amendment 1, Amendment 2, and Amendment 3.</description>
        </group>
        <group group_id="B4">
          <title>Double-Blind Treatment: IW-1701 (Olinciguat) 4 mg</title>
          <description>Participants received 2 mg olinciguat QD Week 1 and 4 mg olinciguat QD Weeks 2-12 under the original protocol, Amendment 1, Amendment 2, and Amendment 3.</description>
        </group>
        <group group_id="B5">
          <title>Double-Blind Treatment: IW-1701 (Olinciguat) 6 mg</title>
          <description>Participants received 3 mg olinciguat QD Week 1 and 6 mg olinciguat QD Weeks 2-12 under the original protocol, Amendment 1, Amendment 2, and Amendment 3.</description>
        </group>
        <group group_id="B6">
          <title>Double-Blind Treatment: IW-1701 (Olinciguat) 18 mg</title>
          <description>Participants received 6 mg olinciguat QD Days 1-7, 12 mg olinciguat QD Weeks 1-3, and 18 mg olinciguat QD Weeks 4-12 under protocol Amendment 4 and later.</description>
        </group>
        <group group_id="B7">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="9"/>
            <count group_id="B2" value="8"/>
            <count group_id="B3" value="8"/>
            <count group_id="B4" value="8"/>
            <count group_id="B5" value="11"/>
            <count group_id="B6" value="24"/>
            <count group_id="B7" value="68"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="30.3" spread="9.43"/>
                    <measurement group_id="B2" value="31.5" spread="9.29"/>
                    <measurement group_id="B3" value="26.3" spread="10.51"/>
                    <measurement group_id="B4" value="34.5" spread="11.38"/>
                    <measurement group_id="B5" value="34.4" spread="13.34"/>
                    <measurement group_id="B6" value="32.7" spread="12.63"/>
                    <measurement group_id="B7" value="32.0" spread="11.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="7"/>
                    <measurement group_id="B5" value="6"/>
                    <measurement group_id="B6" value="14"/>
                    <measurement group_id="B7" value="44"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="5"/>
                    <measurement group_id="B6" value="10"/>
                    <measurement group_id="B7" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="8"/>
                    <measurement group_id="B5" value="10"/>
                    <measurement group_id="B6" value="15"/>
                    <measurement group_id="B7" value="53"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="9"/>
                    <measurement group_id="B7" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="8"/>
                    <measurement group_id="B5" value="10"/>
                    <measurement group_id="B6" value="22"/>
                    <measurement group_id="B7" value="60"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="1"/>
                    <measurement group_id="B7" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="1"/>
                    <measurement group_id="B7" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)</title>
        <description>An adverse event (AE) is any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. A serious AE (SAE) is defined as any AE occurring at any dose that results in any of the following: death; life-threatening; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; other important medical event. A TEAE is an event that occurs after initiation of randomized study drug through 28 days after study drug discontinuation. Events were categorized by grade: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death, and as related or unrelated to study drug. Adverse Events of special interest (AESIs) included symptomatic or Grade ≥2 hypotensive events and/or tachycardia AEs, bleeding events, pulmonary edema, and bone-related events, including fractures.</description>
        <time_frame>First dose of randomized drug through 28 days after study drug discontinuation. Median number of weeks of treatment was 12.30, 11.85, 12.20, 12.20, 12.10, and 12.10, respectively, for Placebo 1, Placebo 2, Olinciguat 2 mg, 4 mg, 6 mg, and 18 mg groups.</time_frame>
        <population>Safety Population: Randomized participants who received at least 1 dose of study drug</population>
        <group_list>
          <group group_id="O1">
            <title>Double-Blind Treatment: Placebo 1</title>
            <description>Participants received placebo treatment QD for 12 weeks under the original protocol, Amendment 1, Amendment 2, and Amendment 3.</description>
          </group>
          <group group_id="O2">
            <title>Double-Blind Treatment: Placebo 2</title>
            <description>Participants received placebo treatment QD for 12 weeks under protocol Amendment 4 and later.</description>
          </group>
          <group group_id="O3">
            <title>Double-Blind Treatment: IW-1701 (Olinciguat) 2 mg</title>
            <description>Participants received 1 mg olinciguat QD Week 1 and 2 mg olinciguat QD Weeks 2-12 under the original protocol, Amendment 1, Amendment 2, and Amendment 3.</description>
          </group>
          <group group_id="O4">
            <title>Double-Blind Treatment: IW-1701 (Olinciguat) 4 mg</title>
            <description>Participants received 2 mg olinciguat QD Week 1 and 4 mg olinciguat QD Weeks 2-12 under the original protocol, Amendment 1, Amendment 2, and Amendment 3.</description>
          </group>
          <group group_id="O5">
            <title>Double-Blind Treatment: IW-1701 (Olinciguat) 6 mg</title>
            <description>Participants received 3 mg olinciguat QD Week 1 and 6 mg olinciguat QD Weeks 2-12 under the original protocol, Amendment 1, Amendment 2, and Amendment 3.</description>
          </group>
          <group group_id="O6">
            <title>Double-Blind Treatment: IW-1701 (Olinciguat) 18 mg</title>
            <description>Participants received 6 mg olinciguat QD Days 1-7, 12 mg olinciguat QD Weeks 1-3, and 18 mg olinciguat QD Weeks 4-12 under protocol Amendment 4 and later.</description>
          </group>
        </group_list>
        <measure>
          <title>Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)</title>
          <description>An adverse event (AE) is any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. A serious AE (SAE) is defined as any AE occurring at any dose that results in any of the following: death; life-threatening; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; other important medical event. A TEAE is an event that occurs after initiation of randomized study drug through 28 days after study drug discontinuation. Events were categorized by grade: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death, and as related or unrelated to study drug. Adverse Events of special interest (AESIs) included symptomatic or Grade ≥2 hypotensive events and/or tachycardia AEs, bleeding events, pulmonary edema, and bone-related events, including fractures.</description>
          <population>Safety Population: Randomized participants who received at least 1 dose of study drug</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="8"/>
                <count group_id="O3" value="8"/>
                <count group_id="O4" value="8"/>
                <count group_id="O5" value="11"/>
                <count group_id="O6" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Participants with &gt;=1 TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="6"/>
                    <measurement group_id="O3" value="5"/>
                    <measurement group_id="O4" value="5"/>
                    <measurement group_id="O5" value="8"/>
                    <measurement group_id="O6" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with &gt;=1 Grade 3-5 TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="3"/>
                    <measurement group_id="O5" value="4"/>
                    <measurement group_id="O6" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with &gt;=1 Study Drug-Related TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="4"/>
                    <measurement group_id="O6" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with &gt;=1 SAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="3"/>
                    <measurement group_id="O5" value="4"/>
                    <measurement group_id="O6" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with &gt;=1 TEAE Leading to Study Drug Discontinuation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with &gt;=1 AESI</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Double-Blind Treatment: Number of TEAE Events</title>
        <description>An AE is any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. An SAE is defined as any AE occurring at any dose that results in any of the following: death; life-threatening; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; other important medical event. A TEAE is an event that occurs after initiation of randomized study drug through 28 days after study drug discontinuation. Events were categorized by grade: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death, and as related or unrelated to study drug. If a participant had more than 1 occurrence in the same event category, only the occurrence with closest relationship to study drug was counted.</description>
        <time_frame>First dose of randomized drug through 28 days after study drug discontinuation. Median number of weeks of treatment was 12.30, 11.85, 12.20, 12.20, 12.10, and 12.10, respectively, for Placebo 1, Placebo 2, Olinciguat 2 mg, 4 mg, 6 mg, and 18 mg groups.</time_frame>
        <population>Safety Population: Randomized participants who received at least 1 dose of study drug. Participants with &gt;=1 TEAE.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo 1</title>
            <description>Participants receiving treatment under the original protocol, Amendment 1, Amendment 2, and Amendment 3</description>
          </group>
          <group group_id="O2">
            <title>Placebo 2</title>
            <description>Participants receiving treatment under protocol Amendment 4 and later</description>
          </group>
          <group group_id="O3">
            <title>IW-1701 (Olinciguat) 2 mg</title>
            <description>Participants receiving treatment under the original protocol, Amendment 1, Amendment 2, and Amendment 3</description>
          </group>
          <group group_id="O4">
            <title>IW-1701 (Olinciguat) 4 mg</title>
            <description>Participants receiving treatment under the original protocol, Amendment 1, Amendment 2, and Amendment 3</description>
          </group>
          <group group_id="O5">
            <title>IW-1701 (Olinciguat) 6 mg</title>
            <description>Participants receiving treatment under the original protocol, Amendment 1, Amendment 2, and Amendment 3</description>
          </group>
          <group group_id="O6">
            <title>IW-1701 (Olinciguat) 18 mg</title>
            <description>Participants receiving treatment under protocol Amendment 4 and later</description>
          </group>
        </group_list>
        <measure>
          <title>Double-Blind Treatment: Number of TEAE Events</title>
          <description>An AE is any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. An SAE is defined as any AE occurring at any dose that results in any of the following: death; life-threatening; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; other important medical event. A TEAE is an event that occurs after initiation of randomized study drug through 28 days after study drug discontinuation. Events were categorized by grade: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death, and as related or unrelated to study drug. If a participant had more than 1 occurrence in the same event category, only the occurrence with closest relationship to study drug was counted.</description>
          <population>Safety Population: Randomized participants who received at least 1 dose of study drug. Participants with &gt;=1 TEAE.</population>
          <units>TEAE Events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="5"/>
                <count group_id="O5" value="8"/>
                <count group_id="O6" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26"/>
                    <measurement group_id="O2" value="29"/>
                    <measurement group_id="O3" value="36"/>
                    <measurement group_id="O4" value="30"/>
                    <measurement group_id="O5" value="39"/>
                    <measurement group_id="O6" value="101"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity</title>
        <description>An AE is any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. An SAE is defined as any AE occurring at any dose that results in any of the following: death; life-threatening; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; other important medical event. A TEAE is an event that occurs after initiation of randomized study drug through 28 days after study drug discontinuation. Events were categorized by grade: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death, and as related or unrelated to study drug. If a participant had more than 1 occurrence in the same event category, only the most severe occurrence was counted.</description>
        <time_frame>First dose of randomized drug through 28 days after study drug discontinuation. Median number of weeks of treatment was 12.30, 11.85, 12.20, 12.20, 12.10, and 12.10, respectively, for Placebo 1, Placebo 2, Olinciguat 2 mg, 4 mg, 6 mg, and 18 mg groups.</time_frame>
        <population>Safety Population: Randomized participants who received at least 1 dose of study drug</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo 1</title>
            <description>Participants receiving treatment under the original protocol, Amendment 1, Amendment 2, and Amendment 3</description>
          </group>
          <group group_id="O2">
            <title>Placebo 2</title>
            <description>Participants receiving treatment under protocol Amendment 4 and later</description>
          </group>
          <group group_id="O3">
            <title>IW-1701 (Olinciguat) 2 mg</title>
            <description>Participants receiving treatment under the original protocol, Amendment 1, Amendment 2, and Amendment 3</description>
          </group>
          <group group_id="O4">
            <title>IW-1701 (Olinciguat) 4 mg</title>
            <description>Participants receiving treatment under the original protocol, Amendment 1, Amendment 2, and Amendment 3I</description>
          </group>
          <group group_id="O5">
            <title>IW-1701 (Olinciguat) 6 mg</title>
            <description>Participants receiving treatment under the original protocol, Amendment 1, Amendment 2, and Amendment 3</description>
          </group>
          <group group_id="O6">
            <title>IW-1701 (Olinciguat) 18 mg</title>
            <description>Participants receiving treatment under protocol Amendment 4 and later</description>
          </group>
        </group_list>
        <measure>
          <title>Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity</title>
          <description>An AE is any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. An SAE is defined as any AE occurring at any dose that results in any of the following: death; life-threatening; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; other important medical event. A TEAE is an event that occurs after initiation of randomized study drug through 28 days after study drug discontinuation. Events were categorized by grade: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death, and as related or unrelated to study drug. If a participant had more than 1 occurrence in the same event category, only the most severe occurrence was counted.</description>
          <population>Safety Population: Randomized participants who received at least 1 dose of study drug</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="8"/>
                <count group_id="O3" value="8"/>
                <count group_id="O4" value="8"/>
                <count group_id="O5" value="11"/>
                <count group_id="O6" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Participants with ≥1 TEAE: Any</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="6"/>
                    <measurement group_id="O3" value="5"/>
                    <measurement group_id="O4" value="5"/>
                    <measurement group_id="O5" value="8"/>
                    <measurement group_id="O6" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with ≥1 TEAE: Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="4"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="2"/>
                    <measurement group_id="O5" value="2"/>
                    <measurement group_id="O6" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with ≥1 TEAE: Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="3"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="2"/>
                    <measurement group_id="O6" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with ≥1 TEAE: Grade 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="3"/>
                    <measurement group_id="O5" value="4"/>
                    <measurement group_id="O6" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with ≥1 TEAE: Grade 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with ≥1 TEAE: Grade 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Double-Blind Treatment: Number of Participants With Study Drug-Related TEAEs</title>
        <description>An AE is any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. An SAE is defined as any AE occurring at any dose that results in any of the following: death; life-threatening; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; other important medical event. A TEAE is an event that occurs after initiation of randomized study drug through 28 days after study drug discontinuation. Events were categorized by grade: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death, and as related or unrelated to study drug. If a participant had more than 1 occurrence in the same event category, only the occurrence with closest relationship to study drug was counted.</description>
        <time_frame>First dose of randomized drug through 28 days after study drug discontinuation. Median number of weeks of treatment was 12.30, 11.85, 12.20, 12.20, 12.10, and 12.10, respectively, for Placebo 1, Placebo 2, Olinciguat 2 mg, 4 mg, 6 mg, and 18 mg groups.</time_frame>
        <population>Safety Population: Randomized participants who received at least 1 dose of study drug</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo 1</title>
            <description>Participants receiving treatment under the original protocol, Amendment 1, Amendment 2, and Amendment 3</description>
          </group>
          <group group_id="O2">
            <title>Placebo 2</title>
            <description>Participants receiving treatment under protocol Amendment 4 and later</description>
          </group>
          <group group_id="O3">
            <title>IW-1701 (Olinciguat) 2 mg</title>
            <description>Participants receiving treatment under the original protocol, Amendment 1, Amendment 2, and Amendment 3</description>
          </group>
          <group group_id="O4">
            <title>IW-1701 (Olinciguat) 4 mg</title>
            <description>Participants receiving treatment under the original protocol, Amendment 1, Amendment 2, and Amendment 3I</description>
          </group>
          <group group_id="O5">
            <title>IW-1701 (Olinciguat) 6 mg</title>
            <description>Participants receiving treatment under the original protocol, Amendment 1, Amendment 2, and Amendment 3</description>
          </group>
          <group group_id="O6">
            <title>IW-1701 (Olinciguat) 18 mg</title>
            <description>Participants receiving treatment under protocol Amendment 4 and later</description>
          </group>
        </group_list>
        <measure>
          <title>Double-Blind Treatment: Number of Participants With Study Drug-Related TEAEs</title>
          <description>An AE is any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. An SAE is defined as any AE occurring at any dose that results in any of the following: death; life-threatening; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; other important medical event. A TEAE is an event that occurs after initiation of randomized study drug through 28 days after study drug discontinuation. Events were categorized by grade: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death, and as related or unrelated to study drug. If a participant had more than 1 occurrence in the same event category, only the occurrence with closest relationship to study drug was counted.</description>
          <population>Safety Population: Randomized participants who received at least 1 dose of study drug</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="8"/>
                <count group_id="O3" value="8"/>
                <count group_id="O4" value="8"/>
                <count group_id="O5" value="11"/>
                <count group_id="O6" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="4"/>
                    <measurement group_id="O6" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>AEs during Single-blind Run-in Period were collected from first dose of Run-in placebo up to the first dose of randomized study drug, up to 17 days. AEs during the Double-Blind Period: First dose of randomized drug through 28 days after study drug discontinuation. Median number of weeks of treatment was 12.30, 11.85, 12.20, 12.20, 12.10, and 12.10, respectively, for Placebo 1, Placebo 2, Olinciguat 2 mg, 4 mg, 6 mg, and 18 mg groups.</time_frame>
      <desc>All Cause mortality was collected for the duration of the study, mean 141.2 days.</desc>
      <group_list>
        <group group_id="E1">
          <title>Single-Blind Run-in Period: Placebo</title>
          <description>Single-blind treatment with placebo for 14 to 17 days of the Screening period and before the first dose of double-blind study drug on Day 1.</description>
        </group>
        <group group_id="E2">
          <title>Double-Blind Treatment Period: Placebo 1</title>
          <description>Participants receiving treatment under the original protocol, Amendment 1, Amendment 2, and Amendment 3</description>
        </group>
        <group group_id="E3">
          <title>Double-Blind Treatment Period: Placebo 2</title>
          <description>Participants receiving treatment under protocol Amendment 4 and later</description>
        </group>
        <group group_id="E4">
          <title>Double-Blind Treatment Period: IW-1701 (Olinciguat) 2 mg</title>
          <description>Participants receiving treatment under the original protocol, Amendment 1, Amendment 2, and Amendment 3</description>
        </group>
        <group group_id="E5">
          <title>Double-Blind Treatment Period: IW-1701 (Olinciguat) 4 mg</title>
          <description>Participants receiving treatment under the original protocol, Amendment 1, Amendment 2, and Amendment 3I</description>
        </group>
        <group group_id="E6">
          <title>Double-Blind Treatment Period: IW-1701 (Olinciguat) 6 mg</title>
          <description>Participants receiving treatment under the original protocol, Amendment 1, Amendment 2, and Amendment 3</description>
        </group>
        <group group_id="E7">
          <title>Double-Blind Treatment Period: IW-1701 (Olinciguat) 18 mg</title>
          <description>Participants receiving treatment under protocol Amendment 4 and later</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 23.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="4" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="6" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>SICKLE CELL ANAEMIA WITH CRISIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="3" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>APLASTIC ANAEMIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>IMPAIRED GASTRIC EMPTYING</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>ABDOMINAL PAIN</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>NON-CARDIAC CHEST PAIN</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>PNEUMONIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>ARTHRALGIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>INTERVERTEBRAL DISC PROTRUSION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>MENORRHAGIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>ACUTE CHEST SYNDROME</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA 23.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="5" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="6" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="20" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>SICKLE CELL ANAEMIA WITH CRISIS</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>ANAEMIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>LEUKOCYTOSIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>THROMBOCYTOPENIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>TACHYCARDIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>SINUS TACHYCARDIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Congenital, familial and genetic disorders</title>
            <event_list>
              <event>
                <sub_title>PYLORIC STENOSIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>PERIORBITAL SWELLING</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>VISION BLURRED</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>DIARRHOEA</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>ABDOMINAL PAIN</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>NAUSEA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>VOMITING</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>ABDOMINAL PAIN UPPER</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>DYSPEPSIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>TOOTHACHE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>GASTROOESOPHAGEAL REFLUX DISEASE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>CONSTIPATION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>ABDOMINAL DISCOMFORT</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>ABDOMINAL DISTENSION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>HYPOAESTHESIA ORAL</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>IMPAIRED GASTRIC EMPTYING</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>FATIGUE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>SUPRAPUBIC PAIN</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>NON-CARDIAC CHEST PAIN</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>PYREXIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>CHILLS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>EARLY SATIETY</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>VESSEL PUNCTURE SITE PAIN</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>PAIN</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>INFLUENZA LIKE ILLNESS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>INFUSION SITE EXTRAVASATION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>PERIPHERAL SWELLING</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>HYPERBILIRUBINAEMIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>DRUG HYPERSENSITIVITY</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>URINARY TRACT INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>BRONCHITIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>GINGIVITIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>GASTROENTERITIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>PNEUMONIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>SEPSIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>EAR INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>MUMPS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>NASOPHARYNGITIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>UPPER RESPIRATORY TRACT INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>ALANINE AMINOTRANSFERASE INCREASED</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>ASPARTATE AMINOTRANSFERASE INCREASED</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>AMYLASE INCREASED</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>BLOOD PRESSURE INCREASED</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>GAMMA-GLUTAMYLTRANSFERASE INCREASED</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>BLOOD BILIRUBIN INCREASED</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>WEIGHT INCREASED</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>INTERNATIONAL NORMALISED RATIO INCREASED</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>DECREASED APPETITE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>HYPERKALAEMIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>HYPOMAGNESAEMIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>BACK PAIN</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>ARTHRALGIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>INTERVERTEBRAL DISC PROTRUSION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>MUSCULAR WEAKNESS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>PAIN IN EXTREMITY</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="5" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>MUSCULOSKELETAL PAIN</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>MUSCULOSKELETAL CHEST PAIN</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>JOINT STIFFNESS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>OSTEONECROSIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>MUSCLE SPASMS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>HEADACHE</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="6" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>DYSGEUSIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>TRIGEMINAL NEURALGIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>DIZZINESS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>HYPOAESTHESIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>PARAESTHESIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>SOMNOLENCE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Product Issues</title>
            <event_list>
              <event>
                <sub_title>DEVICE MALFUNCTION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>INSOMNIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>ANXIETY</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>PROTEINURIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>RENAL PAIN</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>GENITAL DISCOLOURATION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>MENORRHAGIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>DYSMENORRHOEA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>OVARIAN CYST</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>NASAL CONGESTION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>PARANASAL SINUS DISCOMFORT</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>RHINORRHOEA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>THROAT IRRITATION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>DYSPNOEA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>HYPOXIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>UPPER-AIRWAY COUGH SYNDROME</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>OROPHARYNGEAL PAIN</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>ACUTE PULMONARY OEDEMA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>COUGH</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>WHEEZING</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>HYPERHIDROSIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>SKIN REACTION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>PRURITUS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>RASH</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>RASH MACULO-PAPULAR</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>INGROWING NAIL</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>DRY SKIN</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>PAIN OF SKIN</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>SKIN ULCER</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>HYPOTENSION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="88"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>PI may publish or disclose the results of the study 24 months after final data lock provided that sponsor can review the publication prior to public release, sponsor can request removal of confidential information of sponsor (not including results of trial), and sponsor can request a publication delay in order to protect potentially patentable information. Furthermore, if a publication committee is developing an initial publication, PI is to delay disclosure until that publication is published.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Senior Medical Director</name_or_title>
      <organization>Cyclerion Therapeutics, Inc.</organization>
      <phone>1-857-327-8778</phone>
      <email>info@cyclerion.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03285178
org study id: C1701-202
nct id: NCT03285178
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The primary objective of the 1701-202 STRONG SCD study is to evaluate the safety and
      tolerability of different dose levels of IW-1701 compared with placebo when administered
      daily for approximately 12 weeks to patients with stable SCD. Exploratory objectives include
      evaluation of pharmacokinetic (PK) as well as evaluation of the effect of IW-1701 on symptoms
      of SCD, health-related quality of life, and biomarkers of pharmacodynamic (PD) activity.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
time frame: First dose of randomized drug through 28 days after study drug discontinuation. Median number of weeks of treatment was 12.30, 11.85, 12.20, 12.20, 12.10, and 12.10, respectively, for Placebo 1, Placebo 2, Olinciguat 2 mg, 4 mg, 6 mg, and 18 mg groups.
description: An adverse event (AE) is any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. A serious AE (SAE) is defined as any AE occurring at any dose that results in any of the following: death; life-threatening; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; other important medical event. A TEAE is an event that occurs after initiation of randomized study drug through 28 days after study drug discontinuation. Events were categorized by grade: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death, and as related or unrelated to study drug. Adverse Events of special interest (AESIs) included symptomatic or Grade ≥2 hypotensive events and/or tachycardia AEs, bleeding events, pulmonary edema, and bone-related events, including fractures.
measure: Double-Blind Treatment: Number of TEAE Events
time frame: First dose of randomized drug through 28 days after study drug discontinuation. Median number of weeks of treatment was 12.30, 11.85, 12.20, 12.20, 12.10, and 12.10, respectively, for Placebo 1, Placebo 2, Olinciguat 2 mg, 4 mg, 6 mg, and 18 mg groups.
description: An AE is any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. An SAE is defined as any AE occurring at any dose that results in any of the following: death; life-threatening; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; other important medical event. A TEAE is an event that occurs after initiation of randomized study drug through 28 days after study drug discontinuation. Events were categorized by grade: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death, and as related or unrelated to study drug. If a participant had more than 1 occurrence in the same event category, only the occurrence with closest relationship to study drug was counted.
measure: Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity
time frame: First dose of randomized drug through 28 days after study drug discontinuation. Median number of weeks of treatment was 12.30, 11.85, 12.20, 12.20, 12.10, and 12.10, respectively, for Placebo 1, Placebo 2, Olinciguat 2 mg, 4 mg, 6 mg, and 18 mg groups.
description: An AE is any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. An SAE is defined as any AE occurring at any dose that results in any of the following: death; life-threatening; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; other important medical event. A TEAE is an event that occurs after initiation of randomized study drug through 28 days after study drug discontinuation. Events were categorized by grade: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death, and as related or unrelated to study drug. If a participant had more than 1 occurrence in the same event category, only the most severe occurrence was counted.
measure: Double-Blind Treatment: Number of Participants With Study Drug-Related TEAEs
time frame: First dose of randomized drug through 28 days after study drug discontinuation. Median number of weeks of treatment was 12.30, 11.85, 12.20, 12.20, 12.10, and 12.10, respectively, for Placebo 1, Placebo 2, Olinciguat 2 mg, 4 mg, 6 mg, and 18 mg groups.
description: An AE is any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. An SAE is defined as any AE occurring at any dose that results in any of the following: death; life-threatening; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; other important medical event. A TEAE is an event that occurs after initiation of randomized study drug through 28 days after study drug discontinuation. Events were categorized by grade: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death, and as related or unrelated to study drug. If a participant had more than 1 occurrence in the same event category, only the occurrence with closest relationship to study drug was counted.
arm group label: IW-1701 (Olinciguat) 2 mg
arm group type: Experimental
description: After a single-blind treatment with placebo once daily (QD) for 14 to 17 days of the Screening period and before the first dose of double-blind study drug on Day 1, participants received 1 mg olinciguat QD Week 1 and 2 mg olinciguat QD Weeks 2-12 under the original protocol, Amendment 1, Amendment 2, and Amendment 3.
arm group label: IW-1701 (Olinciguat) 4 mg
arm group type: Experimental
description: After a single-blind treatment with placebo QD for 14 to 17 days of the Screening period and before the first dose of double-blind study drug on Day 1, participants received 2 mg olinciguat QD Week 1 and 4 mg olinciguat QD Weeks 2-12 under the original protocol, Amendment 1, Amendment 2, and Amendment 3.
arm group label: IW-1701 (Olinciguat) 6 mg
arm group type: Experimental
description: After a single-blind treatment with placebo QD for 14 to 17 days of the Screening period and before the first dose of double-blind study drug on Day 1, participants received 3 mg olinciguat QD Week 1 and 6 mg olinciguat QD Weeks 2-12 under the original protocol, Amendment 1, Amendment 2, and Amendment 3.
arm group label: IW-1701 (Olinciguat) 18 mg
arm group type: Experimental
description: After a single-blind treatment with placebo QD for 14 to 17 days of the Screening period and before the first dose of double-blind study drug on Day 1, participants received 6 mg olinciguat QD Days 1-7, 12 mg olinciguat QD Weeks 1-3, and 18 mg olinciguat QD Weeks 4-12 under protocol Amendment 4 and later.
arm group label: Placebo
arm group type: Placebo Comparator
description: After a single-blind treatment with placebo QD for 14 to 17 days of the Screening period and before the first dose of double-blind study drug on Day 1, participants received placebo treatment QD for 12 weeks.
intervention type: Drug
intervention name: IW-1701
description: Oral Tablet
arm group label: IW-1701 (Olinciguat) 18 mg
arm group label: IW-1701 (Olinciguat) 2 mg
arm group label: IW-1701 (Olinciguat) 4 mg
arm group label: IW-1701 (Olinciguat) 6 mg
other name: Olinciguat
intervention type: Drug
intervention name: Placebo
description: Oral Tablet
arm group label: Placebo
criteria: 
gender: All
minimum age: 16 Years
maximum age: 70 Years
healthy volunteers: No
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country: Lebanon
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Anemia, Sickle Cell
sharing ipd: No
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reported events: 
certain agreements: 
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