<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/NCT01732549</url>
  </required_header>
  <id_info>
    <org_study_id>8-55-58102-002</org_study_id>
    <secondary_id>2012-001038-32</secondary_id>
    <nct_id>NCT01732549</nct_id>
  </id_info>
  <brief_title>A Proof of Concept Study of Maintenance Therapy With Tasquinimod in Patients With Metastatic Castrate-resistant Prostate Cancer Who Are Not Progressing After a First Line Docetaxel Based Chemotherapy</brief_title>
  <official_title>A Randomised, Double-Blind, Placebo-Controlled Proof Of Concept Study Of Maintenance Therapy With Tasquinimod In Patients With Metastatic Castrate-Resistant Prostate Cancer Who Are Not Progressing After A First Line Docetaxel Based Chemotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ipsen</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ipsen</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to confirm that tasquinimod used as maintenance therapy is&#xD;
      active and tolerable in patients with metastatic castrate-resistant prostate cancer not&#xD;
      progressing after a first chemotherapy with docetaxel.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Development of tasquinimod in prostate cancer discontinued&#xD;
  </why_stopped>
  <start_date>January 2013</start_date>
  <completion_date type="Actual">May 2015</completion_date>
  <primary_completion_date type="Actual">February 2015</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>Time to Radiological Progression Free Survival [PFS]</measure>
    <time_frame>Every 8 weeks until disease progression documentation (approximately up to 2.5 years)</time_frame>
    <description>The time from the date of randomisation to the date of radiological progression or death due to any cause.&#xD;
Radiological progression was defined&#xD;
- Using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for soft tissue lesions (Eisenhauer, EJC 2009), as at least a 20% relative and a 5 mm absolute increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters recorded on study (including Screening or the appearance of one or more new lesions) for target Lesions.&#xD;
Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions&#xD;
- Using Prostate Cancer Clinical Working Group in March 2008 (PCWG2) criteria for bone lesions (Scher, JCO 2008). Progression was defined as appearance of 2 or more bone lesions.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Survival Based on Number of Subjects Who Died</measure>
    <time_frame>Every 3 months after study treatment stop until death (approximately up to 2.5 years)</time_frame>
    <description>Overall survival is defined as the time from randomisation to death due to any cause.&#xD;
The number of participants who died is presented since the Median was not reached for this assessment.&#xD;
Tasquinimod: Patients censored = 63, Patients at risk (t=0) = 71 Placebo: Patients censored = 67, Patients at risk (t=0) = 73</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Progression Free Survival [PFS] on Next-line Therapy (PFS 2)</measure>
    <time_frame>Every 3 months after study treatment stop (follow-up) until progression under the next line therapy (approximately up to 2.5 years)</time_frame>
    <description>The time from the date of randomisation to the date of radiological progression free survival [PFS] on next-line therapy (PFS 2) or death due to any cause.&#xD;
Radiological progression was defined&#xD;
- Using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for soft tissue lesions (Eisenhauer, EJC 2009), as at least a 20% relative and a 5 mm absolute increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters recorded on study (including Screening or the appearance of one or more new lesions) for target Lesions.&#xD;
Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions&#xD;
- Using Prostate Cancer Clinical Working Group in March 2008 (PCWG2) criteria for bone lesions (Scher, JCO 2008). Progression was defined as appearance of 2 or more bone lesions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Symptomatic PFS Based on Number of Subjects Who Had Symptomatic Progression or Death</measure>
    <time_frame>Every 8 weeks until symptomatic or radiological progression documentation (approximately up to 2.5 years)</time_frame>
    <description>Symptomatic PFS is defined as the time from the date of randomisation to the date of symptomatic progression or death due to prostate cancer, whichever occurs first [symptomatic progression as assessed by Brief Pain Inventory (BPI) and analgesic use].&#xD;
Symptomatic progression was defined by the occurrence of pain with documented disease, skeleton related adverse events.&#xD;
The median symptomatic PFS for placebo and tasquinimod groups was not reached.&#xD;
Tasquinimod: Patients censored = 48, Patients at risk (t=0) = 71 Placebo: Patients censored = 54, Patients at risk (t=0) = 73</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Further Anticancer Treatment for Prostate Cancer</measure>
    <time_frame>Every 3 months after study treatment stop until further anticancer therapy for prostate cancer (approximately up to 2.5 years)</time_frame>
    <description>Time from randomisation to further treatment for prostate cancer</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Deterioration in Functional Assessment of Cancer Therapy - Prostate (FACT-P)</measure>
    <time_frame>Up to End of Study visit (approximately up to 2.5 years)</time_frame>
    <description>End of Study visit (within 14 days of last dose of study treatment)&#xD;
Impact of tasquinimod on health related quality of life (QoL) - Analysis of time to deterioration in FACT-P&#xD;
The FACT-P measurement system is a validated collection of health related quality of life (HRQOL) questionnaires used to assess HRQOL in men with prostate cancer. It is appropriate for use with patients with any form of cancer and extensions of it have been used and validated in other chronic illness condition. The FACT-P is a self-administered 39-item scale comprising five domains: physical well-being, social/family well-being, functional well-being, emotional well-being and additional concerns. The individual subscale scores range from 0 to a high between 24 and 48 and the total score ranges between 0 and 156, with higher scores representing better Quality of Life (QoL)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline of EuroQol-5 Dimension QoL Instrument (EQ-5D) VAS Score</measure>
    <time_frame>Baseline and End-of-study Visit (approximately up to 2.5 years)</time_frame>
    <description>Baseline is defined as last measurement collected prior to the first dose of study drug. End of Study visit (within 14 days of last dose of study treatment)&#xD;
The EQ-5D, a 5-item scale useful in health resource utilisation and cost comparisons between treatment groups designed for self-completion by patients consists of two pages [EQ-5 descriptive system and EQ Visual Analogue Scale(VAS)]. The EQ-5 descriptive system comprises five dimensions: mobility, self care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, severe problems. The EQ-VAS records the respondent's self-rated health on a vertical VAS. The respondents are asked to mark health status on the day of the interview on a 10cm vertical scale with end points of 0 to100. There are notes at the both ends of the scale that the bottom rate(0) corresponds to &quot;the worst health you can imagine&quot;, and the highest rate(100) corresponds to &quot;the best health you can imagine&quot;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety Profile of Tasquinimod</measure>
    <time_frame>At regular intervals during the study treatment period and every 3 months during the follow-up until death (approximately up to 2.5 years)</time_frame>
    <description>Number of subjects reporting adverse events</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">144</enrollment>
  <condition>Metastatic Castrate Resistant Prostate Cancer</condition>
  <arm_group>
    <arm_group_label>Tasquinimod</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1 capsule daily, taken orally with water and food (0.25 mg initially then dose escalated to 0.5 mg or 1 mg per day) until disease progression or toxicity or patient's willingness to stop.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>1 capsule daily, taken orally with water and food until disease progression or toxicity or patient's willingness to stop.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tasquinimod</intervention_name>
    <description>A patient's dose will escalate from one level to the next, once tolerability of the current dose is established. If tolerability issues arise at 0.5 or 1 mg/day, patients will have their dose reduced to 0.25 or 0.5 mg/day, respectively.</description>
    <arm_group_label>Tasquinimod</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo capsules are identical to tasquinimod capsules in appearance and excipients but exclude the active compound (tasquinimod), to be taken orally once a day with water and food</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically documented prostate cancer with evidence of metastatic disease on&#xD;
             radiological evaluation, with or without symptoms (defined according to the BPI scale,&#xD;
             with use of analgesics or narcotics)&#xD;
&#xD;
          -  Has received a first line docetaxel based chemotherapy (as a monotherapy) every 3&#xD;
             weeks schedule of administration with corticosteroids for a minimum of 6 cycles with a&#xD;
             cumulative dose ≥360 mg/m2. Any combination with investigational or non&#xD;
             investigational agent is prohibited&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1&#xD;
&#xD;
          -  Docetaxel-related adverse effects must have been resolved to NCI-CTCAE v4.03 (Common&#xD;
             Toxicity Criteria for Adverse Effects) Grade ≤1. Chemotherapy-induced alopecia and&#xD;
             Grade 2 peripheral neuropathy are allowed&#xD;
&#xD;
          -  No progressive disease at the end of docetaxel treatment defined according to RECIST&#xD;
             criteria, no new lesion(s) assessed by bone scan and no elevated prostate specific&#xD;
             antigen (PSA) for the three last tests with PSA3≤PSA2≤PSA1. The time between each PSA&#xD;
             test should be preferably at least 14 days, however, a minimum of 7 days is&#xD;
             acceptable.&#xD;
&#xD;
        Note: PSA value can be rounded to the nearest whole number if PSA&gt;10 ng/mL. If the PSA3&#xD;
        value is above the PSA2, a fourth PSA test will be performed. The PSA4 value should be&#xD;
        below or equal to PSA2&#xD;
&#xD;
          -  Last dose of docetaxel administered between 21 and 42 days before randomisation&#xD;
&#xD;
          -  Chemical or surgical castration verified by levels of serum testosterone ≤50 ng/dL&#xD;
             (1.75 nmol/L)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Has concurrent use of other anticancer agents or treatments, with the following&#xD;
             exceptions: ongoing treatment with luteinising hormone-releasing hormone agonists or&#xD;
             antagonists, denosumab or bisphosphonate (e.g., zoledronic acid) is permitted if&#xD;
             started ≥4 weeks prior to Screening. Ongoing treatment should be kept at a stable dose&#xD;
             regimen&#xD;
&#xD;
          -  Has ongoing treatment with warfarin&#xD;
&#xD;
          -  Had prior radiation therapy since starting docetaxel. Exceptions may be made for&#xD;
             palliative non-myelosuppressive radiation therapy administered more than 2 weeks prior&#xD;
             to randomisation&#xD;
&#xD;
          -  Had prior strontium, samarium or radium therapy or prior treatment with tasquinimod,&#xD;
             or any agents with antiangiogenic properties&#xD;
&#xD;
          -  Has ongoing treatment with corticosteroids at &gt;10 mg/day prednisolone equivalent&#xD;
&#xD;
          -  Has prostate cancer pain that warrants the initiation of radiotherapy or chemotherapy&#xD;
&#xD;
          -  Has known brain or epidural metastases. Patients with previous medullary cord&#xD;
             compression without any neurological deficit could be included&#xD;
&#xD;
          -  Has a history of other malignancies, except adequately treated non-melanoma skin&#xD;
             cancer or other solid tumours curatively treated, without evidence of disease for &gt;5&#xD;
             years&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ipsen Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Ipsen</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>AZ Maria Middelares</name>
      <address>
        <city>Gent</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Gent</name>
      <address>
        <city>Gent</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Leuven</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Roeselare</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Praha</city>
        <state>Hradčany</state>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Praha</city>
        <state>Libeň</state>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Brno</city>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Olomouc</city>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Prague 2</city>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Aalborg</city>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Aarhus</city>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Herlev</city>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>København</city>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Angers</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Bordeaux</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Clermont Ferrand</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Dijon</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Lille</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Besancon</name>
      <address>
        <city>Lyon</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Leon Berard</name>
      <address>
        <city>Lyon</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Edouard Herriot</name>
      <address>
        <city>Lyon</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>St Herblain</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Toulouse</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Villejuif</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Aachen</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Essen</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>München</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Nürtingen</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Tübingen</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bajcsy-Zsilinszky Kórház</name>
      <address>
        <city>Budapest</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Országos Onkológia Intézet</name>
      <address>
        <city>Budapest</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uzsoki utcai Kórház</name>
      <address>
        <city>Budapest</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Genova</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Milano</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Modena</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Pavia</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Roma</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Rozzano</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Torino</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kaunas</city>
        <country>Lithuania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Vilnius</city>
        <country>Lithuania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Gdansk</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Gdynia</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Olsztyn</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Urology and Urological Oncology Department and Clinic</name>
      <address>
        <city>Wroclaw</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wojewódzki Szpital Specjalistyczny we Wrocławiu</name>
      <address>
        <city>Wroclaw</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clinic Vllarroel</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital del Mar</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Valle de Hebrón</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Elche</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Sabadell</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Valencia</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Leeds</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Guy's &amp; St Thomas NHS Foundation</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Royal Marsden NHS Trust</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University College Hospitals London</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Sutton</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>Czechia</country>
    <country>Denmark</country>
    <country>France</country>
    <country>Germany</country>
    <country>Hungary</country>
    <country>Italy</country>
    <country>Lithuania</country>
    <country>Poland</country>
    <country>Spain</country>
    <country>United Kingdom</country>
  </location_countries>
  <removed_countries>
    <country>Czech Republic</country>
  </removed_countries>
  <verification_date>November 2019</verification_date>
  <study_first_submitted>October 24, 2012</study_first_submitted>
  <study_first_submitted_qc>November 19, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 26, 2012</study_first_posted>
  <results_first_submitted>April 29, 2016</results_first_submitted>
  <results_first_submitted_qc>August 9, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">October 3, 2016</results_first_posted>
  <last_update_submitted>November 21, 2019</last_update_submitted>
  <last_update_submitted_qc>November 21, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">November 22, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prostatic Neoplasms</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The study was performed as a multicentre study at 51 investigational sites (of which 44 randomised patients) in Belgium, Czech Republic, Denmark, France, Germany, Hungary, Italy, Lithuania, Poland, Spain and United Kingdom (UK)</recruitment_details>
      <pre_assignment_details>A total of 219 patients were screened and 144 patients were randomised.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Tasquinimod</title>
          <description>1 capsule daily, taken orally with water and food (0.25 mg initially then dose escalated to 0.5 mg and then to 1 mg per day) until disease progression.&#xD;
Tasquinimod: Patients received initially an oral dose of 0.25 mg/day of tasquinimod, starting on Day 1, for at least 2 weeks. Once tolerability of the 0.25 mg/day dose was established, patients received a dose increase to 0.5 mg/day for at least 2 weeks, and then increased to 1 mg/day of study treatment. Patients showing poor tolerability for the escalated doses of tasquinimod were allowed to continue study treatment at the highest individually tolerated dose</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>1 capsule daily, taken orally with water and food until disease progression&#xD;
Placebo: Patients received Placebo capsules (identical to tasquinimod capsules) to be taken orally once a day with water and food</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="71"/>
                <participants group_id="P2" count="73"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Ongoing in Treatment Period:Data Cut-off</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Withdrawn During Treatment:Data Cut-off</title>
              <participants_list>
                <participants group_id="P1" count="59">Withdrawn during treatment period 59 (AE 13, Consent withdrawn 13, Disease progression 31, Other 2)</participants>
                <participants group_id="P2" count="61">Withdrawn during treatment period 61 (AE 3, Consent withdrawn 6, Disease progression 46, Other 6)</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>Ongoing Treatment Period:Final Analysis</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Withdrawn During Treatment:Final Analysi</title>
              <participants_list>
                <participants group_id="P1" count="71"/>
                <participants group_id="P2" count="73"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="71"/>
                <participants group_id="P2" count="73"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Consent withdrawn</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Disease progression</title>
              <participants_list>
                <participants group_id="P1" count="37"/>
                <participants group_id="P2" count="50"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="14"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>ITT population: All randomised patients. Patients were allocated to the treatment they were randomised to. Patients randomised that have been actually dead before randomisation were not retained in the intention to treat (ITT) population</population>
      <group_list>
        <group group_id="B1">
          <title>Tasquinimod</title>
          <description>1 capsule daily, taken orally with water and food (0.25 mg initially then dose escalated to 0.5 mg and then to 1 mg per day) until disease progression.&#xD;
Tasquinimod: Patients received initially an oral dose of 0.25 mg/day of tasquinimod, starting on Day 1, for at least 2 weeks. Once tolerability of the 0.25 mg/day dose was established, patients received a dose increase to 0.5 mg/day for at least 2 weeks, and then increased to 1 mg/day of study treatment. Patients showing poor tolerability for the escalated doses of tasquinimod were allowed to continue study treatment at the highest individually tolerated dose</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>1 capsule daily, taken orally with water and food until disease progression&#xD;
Placebo: Patients received Placebo capsules (identical to tasquinimod capsules) to be taken orally once a day with water and food</description>
        </group>
        <group group_id="B3">
          <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="71"/>
            <count group_id="B2" value="73"/>
            <count group_id="B3" value="144"/>
          </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="69.6" spread="7.18"/>
                    <measurement group_id="B2" value="69.6" spread="5.57"/>
                    <measurement group_id="B3" value="69.6" spread="6.39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age, Customized</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>18 to ≤ 65 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>66 to ≤ 75 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="40"/>
                    <measurement group_id="B2" value="45"/>
                    <measurement group_id="B3" value="85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt; 75 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="24"/>
                  </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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="71"/>
                    <measurement group_id="B2" value="73"/>
                    <measurement group_id="B3" value="144"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Black/African American</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Caucasian/White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="52"/>
                    <measurement group_id="B2" value="58"/>
                    <measurement group_id="B3" value="110"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Multiple Race</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Missing</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Czech Republic</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Belgium</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hungary</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Denmark</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Poland</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Italy</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>United Kingdom</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>France</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lithuania</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Germany</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Spain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight</title>
          <units>kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="83.7" spread="12.57"/>
                    <measurement group_id="B2" value="83.4" spread="15.09"/>
                    <measurement group_id="B3" value="83.6" spread="13.86"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI</title>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="27.67" spread="3.543"/>
                    <measurement group_id="B2" value="28.01" spread="4.399"/>
                    <measurement group_id="B3" value="27.84" spread="3.987"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Hispanic or Latino</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not Hispanic or Latino</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="52"/>
                    <measurement group_id="B2" value="55"/>
                    <measurement group_id="B3" value="107"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Missing</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>ECOG Performance Status Score</title>
          <description>Eastern Co-operative Oncology Group (ECOG) Score: 0=Fully active, able to carry on all pre-disease performance without restriction, 1=Restricted in physically strenuous activity, but ambulatory &amp; able to carry out work of a light or sedentary nature, e.g. light house work, office work, 2=Ambulatory &amp; capable of all self-care but unable to carry out any work activities. Up &amp; about more than 50% of waking hours, 3=Capable of limited self-care,confined to bed or chair more than 50% of waking hours, 4=Completely disabled. Cannot carry on any self care. Totally confined to bed or chair, 5=Dead</description>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>0 (Normal Activity)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="39"/>
                    <measurement group_id="B2" value="31"/>
                    <measurement group_id="B3" value="70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>1 (Restricted Activity)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="32"/>
                    <measurement group_id="B2" value="38"/>
                    <measurement group_id="B3" value="70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Missing</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Eastern Europe</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Western Europe</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="53"/>
                    <measurement group_id="B2" value="57"/>
                    <measurement group_id="B3" value="110"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Time to Radiological Progression Free Survival [PFS]</title>
        <description>The time from the date of randomisation to the date of radiological progression or death due to any cause.&#xD;
Radiological progression was defined&#xD;
- Using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for soft tissue lesions (Eisenhauer, EJC 2009), as at least a 20% relative and a 5 mm absolute increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters recorded on study (including Screening or the appearance of one or more new lesions) for target Lesions.&#xD;
Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions&#xD;
- Using Prostate Cancer Clinical Working Group in March 2008 (PCWG2) criteria for bone lesions (Scher, JCO 2008). Progression was defined as appearance of 2 or more bone lesions.</description>
        <time_frame>Every 8 weeks until disease progression documentation (approximately up to 2.5 years)</time_frame>
        <population>Intention to treat (ITT) Population</population>
        <group_list>
          <group group_id="O1">
            <title>Tasquinimod</title>
            <description>1 capsule daily, taken orally with water and food (0.25 mg initially then dose escalated to 0.5 mg and then to 1 mg per day) until disease progression.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>1 capsule daily, taken orally with water and food until disease progression</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Radiological Progression Free Survival [PFS]</title>
          <description>The time from the date of randomisation to the date of radiological progression or death due to any cause.&#xD;
Radiological progression was defined&#xD;
- Using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for soft tissue lesions (Eisenhauer, EJC 2009), as at least a 20% relative and a 5 mm absolute increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters recorded on study (including Screening or the appearance of one or more new lesions) for target Lesions.&#xD;
Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions&#xD;
- Using Prostate Cancer Clinical Working Group in March 2008 (PCWG2) criteria for bone lesions (Scher, JCO 2008). Progression was defined as appearance of 2 or more bone lesions.</description>
          <population>Intention to treat (ITT) Population</population>
          <units>weeks</units>
          <param>Median</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="71"/>
                <count group_id="O2" value="73"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31.7" lower_limit="24.3" upper_limit="53.7"/>
                    <measurement group_id="O2" value="22.7" lower_limit="16.1" upper_limit="25.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Stratified[a]</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>=0.0315</p_value>
            <p_value_desc>Log-rank test adjusting for presence (or absence) of visceral metastases, opioid analgesic use and region (Eastern Europe, Western Europe). Two-sided p-value.</p_value_desc>
            <method>Log Rank</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Unstratified[b]</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>=0.0344</p_value>
            <method>Log Rank</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival Based on Number of Subjects Who Died</title>
        <description>Overall survival is defined as the time from randomisation to death due to any cause.&#xD;
The number of participants who died is presented since the Median was not reached for this assessment.&#xD;
Tasquinimod: Patients censored = 63, Patients at risk (t=0) = 71 Placebo: Patients censored = 67, Patients at risk (t=0) = 73</description>
        <time_frame>Every 3 months after study treatment stop until death (approximately up to 2.5 years)</time_frame>
        <population>ITT Population</population>
        <group_list>
          <group group_id="O1">
            <title>Tasquinimod</title>
            <description>1 capsule daily, taken orally with water and food (0.25 mg initially then dose escalated to 0.5 mg and then to 1 mg per day) until disease progression</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>1 capsule daily, taken orally with water and food until disease progression</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival Based on Number of Subjects Who Died</title>
          <description>Overall survival is defined as the time from randomisation to death due to any cause.&#xD;
The number of participants who died is presented since the Median was not reached for this assessment.&#xD;
Tasquinimod: Patients censored = 63, Patients at risk (t=0) = 71 Placebo: Patients censored = 67, Patients at risk (t=0) = 73</description>
          <population>ITT Population</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="71"/>
                <count group_id="O2" value="73"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Stratified[a]</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>=0.4430</p_value>
            <method>Log Rank</method>
            <method_desc>Adjusting for presence (or absence) of visceral metastases, opioid analgesic use and region (Eastern Europe, Western Europe). One-sided p-value</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Progression Free Survival [PFS] on Next-line Therapy (PFS 2)</title>
        <description>The time from the date of randomisation to the date of radiological progression free survival [PFS] on next-line therapy (PFS 2) or death due to any cause.&#xD;
Radiological progression was defined&#xD;
- Using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for soft tissue lesions (Eisenhauer, EJC 2009), as at least a 20% relative and a 5 mm absolute increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters recorded on study (including Screening or the appearance of one or more new lesions) for target Lesions.&#xD;
Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions&#xD;
- Using Prostate Cancer Clinical Working Group in March 2008 (PCWG2) criteria for bone lesions (Scher, JCO 2008). Progression was defined as appearance of 2 or more bone lesions.</description>
        <time_frame>Every 3 months after study treatment stop (follow-up) until progression under the next line therapy (approximately up to 2.5 years)</time_frame>
        <population>ITT Population</population>
        <group_list>
          <group group_id="O1">
            <title>Tasquinimod</title>
            <description>1 capsule daily, taken orally with water and food (0.25 mg initially then dose escalated to 0.5 mg and then to 1 mg per day) until disease progression</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>1 capsule daily, taken orally with water and food until disease progression</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Progression Free Survival [PFS] on Next-line Therapy (PFS 2)</title>
          <description>The time from the date of randomisation to the date of radiological progression free survival [PFS] on next-line therapy (PFS 2) or death due to any cause.&#xD;
Radiological progression was defined&#xD;
- Using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for soft tissue lesions (Eisenhauer, EJC 2009), as at least a 20% relative and a 5 mm absolute increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters recorded on study (including Screening or the appearance of one or more new lesions) for target Lesions.&#xD;
Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions&#xD;
- Using Prostate Cancer Clinical Working Group in March 2008 (PCWG2) criteria for bone lesions (Scher, JCO 2008). Progression was defined as appearance of 2 or more bone lesions.</description>
          <population>ITT Population</population>
          <units>weeks</units>
          <param>Median</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="71"/>
                <count group_id="O2" value="73"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.3" lower_limit="7.1" upper_limit="30.7"/>
                    <measurement group_id="O2" value="24.1" lower_limit="12.6" upper_limit="NA">The data for this maximum confidence interval (CI) is not evaluable (NE), listed as Not Available (NA).&#xD;
Patients censored = 44 Patients at risk (t=0) = 47</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Stratified[a]</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.5219</p_value>
            <method>Log Rank</method>
            <method_desc>Adjusting for presence (or absence) of visceral metastases, opioid analgesic use and region (Eastern Europe, Western Europe). One-sided p-value</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Symptomatic PFS Based on Number of Subjects Who Had Symptomatic Progression or Death</title>
        <description>Symptomatic PFS is defined as the time from the date of randomisation to the date of symptomatic progression or death due to prostate cancer, whichever occurs first [symptomatic progression as assessed by Brief Pain Inventory (BPI) and analgesic use].&#xD;
Symptomatic progression was defined by the occurrence of pain with documented disease, skeleton related adverse events.&#xD;
The median symptomatic PFS for placebo and tasquinimod groups was not reached.&#xD;
Tasquinimod: Patients censored = 48, Patients at risk (t=0) = 71 Placebo: Patients censored = 54, Patients at risk (t=0) = 73</description>
        <time_frame>Every 8 weeks until symptomatic or radiological progression documentation (approximately up to 2.5 years)</time_frame>
        <population>ITT Population</population>
        <group_list>
          <group group_id="O1">
            <title>Tasquinimod</title>
            <description>1 capsule daily, taken orally with water and food (0.25 mg initially then dose escalated to 0.5 mg and then to 1 mg per day) until disease progression.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>1 capsule daily, taken orally with water and food until disease progression</description>
          </group>
        </group_list>
        <measure>
          <title>Symptomatic PFS Based on Number of Subjects Who Had Symptomatic Progression or Death</title>
          <description>Symptomatic PFS is defined as the time from the date of randomisation to the date of symptomatic progression or death due to prostate cancer, whichever occurs first [symptomatic progression as assessed by Brief Pain Inventory (BPI) and analgesic use].&#xD;
Symptomatic progression was defined by the occurrence of pain with documented disease, skeleton related adverse events.&#xD;
The median symptomatic PFS for placebo and tasquinimod groups was not reached.&#xD;
Tasquinimod: Patients censored = 48, Patients at risk (t=0) = 71 Placebo: Patients censored = 54, Patients at risk (t=0) = 73</description>
          <population>ITT Population</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="71"/>
                <count group_id="O2" value="73"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23"/>
                    <measurement group_id="O2" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Stratified[a]</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>=0.5442</p_value>
            <method>Log Rank</method>
            <method_desc>Adjusting for presence (or absence) of visceral metastases, opioid analgesic use and region (Eastern Europe, Western Europe). One-sided p-value</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Further Anticancer Treatment for Prostate Cancer</title>
        <description>Time from randomisation to further treatment for prostate cancer</description>
        <time_frame>Every 3 months after study treatment stop until further anticancer therapy for prostate cancer (approximately up to 2.5 years)</time_frame>
        <population>ITT population</population>
        <group_list>
          <group group_id="O1">
            <title>Tasquinimod</title>
            <description>1 capsule daily, taken orally with water and food (0.25 mg initially then dose escalated to 0.5 mg and then to 1 mg per day) until disease progression.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>1 capsule daily, taken orally with water and food until disease progression</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Further Anticancer Treatment for Prostate Cancer</title>
          <description>Time from randomisation to further treatment for prostate cancer</description>
          <population>ITT population</population>
          <units>weeks</units>
          <param>Median</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="71"/>
                <count group_id="O2" value="73"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="42.3" lower_limit="32.0" upper_limit="58.0"/>
                    <measurement group_id="O2" value="29.0" lower_limit="23.1" upper_limit="39.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Stratified[a]</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>=0.1120</p_value>
            <method>Log Rank</method>
            <method_desc>Adjusting for presence (or absence) of visceral metastases, opioid analgesic use and region (Eastern Europe, Western Europe). One-sided p-value</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Deterioration in Functional Assessment of Cancer Therapy - Prostate (FACT-P)</title>
        <description>End of Study visit (within 14 days of last dose of study treatment)&#xD;
Impact of tasquinimod on health related quality of life (QoL) - Analysis of time to deterioration in FACT-P&#xD;
The FACT-P measurement system is a validated collection of health related quality of life (HRQOL) questionnaires used to assess HRQOL in men with prostate cancer. It is appropriate for use with patients with any form of cancer and extensions of it have been used and validated in other chronic illness condition. The FACT-P is a self-administered 39-item scale comprising five domains: physical well-being, social/family well-being, functional well-being, emotional well-being and additional concerns. The individual subscale scores range from 0 to a high between 24 and 48 and the total score ranges between 0 and 156, with higher scores representing better Quality of Life (QoL)</description>
        <time_frame>Up to End of Study visit (approximately up to 2.5 years)</time_frame>
        <population>ITT population</population>
        <group_list>
          <group group_id="O1">
            <title>Tasquinimod</title>
            <description>1 capsule daily, taken orally with water and food (0.25 mg initially then dose escalated to 0.5 mg and then to 1 mg per day) until disease progression.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>1 capsule daily, taken orally with water and food until disease progression</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Deterioration in Functional Assessment of Cancer Therapy - Prostate (FACT-P)</title>
          <description>End of Study visit (within 14 days of last dose of study treatment)&#xD;
Impact of tasquinimod on health related quality of life (QoL) - Analysis of time to deterioration in FACT-P&#xD;
The FACT-P measurement system is a validated collection of health related quality of life (HRQOL) questionnaires used to assess HRQOL in men with prostate cancer. It is appropriate for use with patients with any form of cancer and extensions of it have been used and validated in other chronic illness condition. The FACT-P is a self-administered 39-item scale comprising five domains: physical well-being, social/family well-being, functional well-being, emotional well-being and additional concerns. The individual subscale scores range from 0 to a high between 24 and 48 and the total score ranges between 0 and 156, with higher scores representing better Quality of Life (QoL)</description>
          <population>ITT population</population>
          <units>weeks</units>
          <param>Median</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="71"/>
                <count group_id="O2" value="73"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.1" lower_limit="8.1" upper_limit="13.1"/>
                    <measurement group_id="O2" value="15.7" lower_limit="10.6" upper_limit="16.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Stratified[a]</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>=0.2491</p_value>
            <method>Log Rank</method>
            <method_desc>Adjusting for presence (or absence) of visceral metastases, opioid analgesic use (or not) &amp; region (Eastern Europe, Western Europe). One-sided p-value</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline of EuroQol-5 Dimension QoL Instrument (EQ-5D) VAS Score</title>
        <description>Baseline is defined as last measurement collected prior to the first dose of study drug. End of Study visit (within 14 days of last dose of study treatment)&#xD;
The EQ-5D, a 5-item scale useful in health resource utilisation and cost comparisons between treatment groups designed for self-completion by patients consists of two pages [EQ-5 descriptive system and EQ Visual Analogue Scale(VAS)]. The EQ-5 descriptive system comprises five dimensions: mobility, self care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, severe problems. The EQ-VAS records the respondent's self-rated health on a vertical VAS. The respondents are asked to mark health status on the day of the interview on a 10cm vertical scale with end points of 0 to100. There are notes at the both ends of the scale that the bottom rate(0) corresponds to &quot;the worst health you can imagine&quot;, and the highest rate(100) corresponds to &quot;the best health you can imagine&quot;</description>
        <time_frame>Baseline and End-of-study Visit (approximately up to 2.5 years)</time_frame>
        <population>ITT population</population>
        <group_list>
          <group group_id="O1">
            <title>Tasquinimod</title>
            <description>1 capsule daily, taken orally with water and food (0.25 mg initially then dose escalated to 0.5 mg and then to 1 mg per day) until disease progression.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>1 capsule daily, taken orally with water and food until disease progression</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline of EuroQol-5 Dimension QoL Instrument (EQ-5D) VAS Score</title>
          <description>Baseline is defined as last measurement collected prior to the first dose of study drug. End of Study visit (within 14 days of last dose of study treatment)&#xD;
The EQ-5D, a 5-item scale useful in health resource utilisation and cost comparisons between treatment groups designed for self-completion by patients consists of two pages [EQ-5 descriptive system and EQ Visual Analogue Scale(VAS)]. The EQ-5 descriptive system comprises five dimensions: mobility, self care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, severe problems. The EQ-VAS records the respondent's self-rated health on a vertical VAS. The respondents are asked to mark health status on the day of the interview on a 10cm vertical scale with end points of 0 to100. There are notes at the both ends of the scale that the bottom rate(0) corresponds to &quot;the worst health you can imagine&quot;, and the highest rate(100) corresponds to &quot;the best health you can imagine&quot;</description>
          <population>ITT population</population>
          <units>Score on scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="39"/>
                <count group_id="O2" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-9.0" lower_limit="-74" upper_limit="63"/>
                    <measurement group_id="O2" value="-3.5" lower_limit="-55" upper_limit="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Safety Profile of Tasquinimod</title>
        <description>Number of subjects reporting adverse events</description>
        <time_frame>At regular intervals during the study treatment period and every 3 months during the follow-up until death (approximately up to 2.5 years)</time_frame>
        <population>Safety Population: All patients who received at least one dose of study treatment. Patients were allocated to the treatment they actually received</population>
        <group_list>
          <group group_id="O1">
            <title>Tasquinimod</title>
            <description>1 capsule daily, taken orally with water and food (0.25 mg initially then dose escalated to 0.5 mg and then to 1 mg per day) until disease progression.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>1 capsule daily, taken orally with water and food until disease progression</description>
          </group>
        </group_list>
        <measure>
          <title>Safety Profile of Tasquinimod</title>
          <description>Number of subjects reporting adverse events</description>
          <population>Safety Population: All patients who received at least one dose of study treatment. Patients were allocated to the treatment they actually received</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="71"/>
                <count group_id="O2" value="70"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Any Treatment Emergent Adverse Event (TEAEs)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="69"/>
                    <measurement group_id="O2" value="66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Intensity of TEAEs [Grade 3-5 (severe)]</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36"/>
                    <measurement group_id="O2" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Intensity of TEAEs [Grade 5]</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Intensity of TEAEs [Grade 4]</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Intensity of TEAEs [Grade 3]</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32"/>
                    <measurement group_id="O2" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Intensity of TEAEs [Grade 2 (moderate)]</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28"/>
                    <measurement group_id="O2" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Intensity of TEAEs [Grade 1 (mild)]</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Causality of TEAEs [Drug Related]</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="54"/>
                    <measurement group_id="O2" value="38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Causality of TEAEs [Not Drug Related]</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                    <measurement group_id="O2" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAEs Leading to Drug Withdrawal</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAEs leading to Dose Reduction</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAEs leading to Drug Interruption</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33"/>
                    <measurement group_id="O2" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAEs Leading to Death</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious Adverse Event (SAEs)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24"/>
                    <measurement group_id="O2" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Drug Related SAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>At regular intervals during the study treatment period and every 3 months during the follow-up until death (approximately up to 2.5 years)</time_frame>
      <desc>Non-SAE details: A summary of common (incidence &gt;5%) TEAEs is presented</desc>
      <group_list>
        <group group_id="E1">
          <title>Tasquinimod</title>
          <description>1 capsule daily, taken orally with water and food (0.25 mg initially then dose escalated to 0.5 mg and then to 1 mg per day) until disease progression.&#xD;
Tasquinimod: Patients received initially an oral dose of 0.25 mg/day of tasquinimod, starting on Day 1, for at least 2 weeks. Once tolerability of the 0.25 mg/day dose was established, patients received a dose increase to 0.5 mg/day for at least 2 weeks, and then increased to 1 mg/day of study treatment. Patients showing poor tolerability for the escalated doses of tasquinimod were allowed to continue study treatment at the highest individually tolerated dose</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>1 capsule daily, taken orally with water and food until disease progression&#xD;
Placebo: Patients received Placebo capsules (identical to tasquinimod capsules) to be taken orally once a day with water and food</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 17.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="24" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Myocardial ischaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Arteriosclerosis coronary artery</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Cardiac failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Pericarditis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Dacryostenosis acquired</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Ileus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Large intestine perforation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Proctitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
              </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="71"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Disease progression</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>General physical health deterioration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Biliary cyst</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
              </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="1" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Appendicitis perforated</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Erysipelas</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Pyelonephritis acute</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Facial bones fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Laceration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Spinal fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
              </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="2" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Fluid retention</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Chondrocalcinosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Lumbar spinal stenosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Basal cell carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Metastases to central nervous system</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Loss of consciousness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Movement disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Polyneuropathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Delirium</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Urinary retention</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Renal failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Ureteric stenosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Urethral stenosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Urinary tract pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Prostatic obstruction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Interstitial lung disease</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Deep vein thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Circulatory collapse</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 17.1</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="69" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="66" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="23" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Influenza like illness</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Cystitis</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="70"/>
              </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="26" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="70"/>
              </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="18" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Musculoskeletal chest pain</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Spinal pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Urinary retention</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Onycholysis</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="70"/>
              </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>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>The study was terminated early due to the stop of the project as decided by sponsor. The trial included number of planned patients &amp; number of events(PFS)were met to draw conclusions. Only follow-up of patients were discontinued earlier than planned.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Medical Director, Oncology</name_or_title>
      <organization>Ipsen</organization>
      <phone>clinical.trials@ipsen.com</phone>
      <email>clinical.trials@ipsen.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/NCT01732549
org study id: 8-55-58102-002
secondary id: 2012-001038-32
nct id: NCT01732549
lead sponsor: 
has dmc: Yes
The purpose of this study is to confirm that tasquinimod used as maintenance therapy is
      active and tolerable in patients with metastatic castrate-resistant prostate cancer not
      progressing after a first chemotherapy with docetaxel.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Time to Radiological Progression Free Survival [PFS]
time frame: Every 8 weeks until disease progression documentation (approximately up to 2.5 years)
description: The time from the date of randomisation to the date of radiological progression or death due to any cause.
Radiological progression was defined
- Using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for soft tissue lesions (Eisenhauer, EJC 2009), as at least a 20% relative and a 5 mm absolute increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters recorded on study (including Screening or the appearance of one or more new lesions) for target Lesions.
Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions
- Using Prostate Cancer Clinical Working Group in March 2008 (PCWG2) criteria for bone lesions (Scher, JCO 2008). Progression was defined as appearance of 2 or more bone lesions.
measure: Overall Survival Based on Number of Subjects Who Died
time frame: Every 3 months after study treatment stop until death (approximately up to 2.5 years)
description: Overall survival is defined as the time from randomisation to death due to any cause.
The number of participants who died is presented since the Median was not reached for this assessment.
Tasquinimod: Patients censored = 63, Patients at risk (t=0) = 71 Placebo: Patients censored = 67, Patients at risk (t=0) = 73
measure: Time to Progression Free Survival [PFS] on Next-line Therapy (PFS 2)
time frame: Every 3 months after study treatment stop (follow-up) until progression under the next line therapy (approximately up to 2.5 years)
description: The time from the date of randomisation to the date of radiological progression free survival [PFS] on next-line therapy (PFS 2) or death due to any cause.
Radiological progression was defined
- Using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for soft tissue lesions (Eisenhauer, EJC 2009), as at least a 20% relative and a 5 mm absolute increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters recorded on study (including Screening or the appearance of one or more new lesions) for target Lesions.
Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions
- Using Prostate Cancer Clinical Working Group in March 2008 (PCWG2) criteria for bone lesions (Scher, JCO 2008). Progression was defined as appearance of 2 or more bone lesions.
measure: Symptomatic PFS Based on Number of Subjects Who Had Symptomatic Progression or Death
time frame: Every 8 weeks until symptomatic or radiological progression documentation (approximately up to 2.5 years)
description: Symptomatic PFS is defined as the time from the date of randomisation to the date of symptomatic progression or death due to prostate cancer, whichever occurs first [symptomatic progression as assessed by Brief Pain Inventory (BPI) and analgesic use].
Symptomatic progression was defined by the occurrence of pain with documented disease, skeleton related adverse events.
The median symptomatic PFS for placebo and tasquinimod groups was not reached.
Tasquinimod: Patients censored = 48, Patients at risk (t=0) = 71 Placebo: Patients censored = 54, Patients at risk (t=0) = 73
measure: Time to Further Anticancer Treatment for Prostate Cancer
time frame: Every 3 months after study treatment stop until further anticancer therapy for prostate cancer (approximately up to 2.5 years)
description: Time from randomisation to further treatment for prostate cancer
measure: Time to Deterioration in Functional Assessment of Cancer Therapy - Prostate (FACT-P)
time frame: Up to End of Study visit (approximately up to 2.5 years)
description: End of Study visit (within 14 days of last dose of study treatment)
Impact of tasquinimod on health related quality of life (QoL) - Analysis of time to deterioration in FACT-P
The FACT-P measurement system is a validated collection of health related quality of life (HRQOL) questionnaires used to assess HRQOL in men with prostate cancer. It is appropriate for use with patients with any form of cancer and extensions of it have been used and validated in other chronic illness condition. The FACT-P is a self-administered 39-item scale comprising five domains: physical well-being, social/family well-being, functional well-being, emotional well-being and additional concerns. The individual subscale scores range from 0 to a high between 24 and 48 and the total score ranges between 0 and 156, with higher scores representing better Quality of Life (QoL)
measure: Change From Baseline of EuroQol-5 Dimension QoL Instrument (EQ-5D) VAS Score
time frame: Baseline and End-of-study Visit (approximately up to 2.5 years)
description: Baseline is defined as last measurement collected prior to the first dose of study drug. End of Study visit (within 14 days of last dose of study treatment)
The EQ-5D, a 5-item scale useful in health resource utilisation and cost comparisons between treatment groups designed for self-completion by patients consists of two pages [EQ-5 descriptive system and EQ Visual Analogue Scale(VAS)]. The EQ-5 descriptive system comprises five dimensions: mobility, self care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, severe problems. The EQ-VAS records the respondent's self-rated health on a vertical VAS. The respondents are asked to mark health status on the day of the interview on a 10cm vertical scale with end points of 0 to100. There are notes at the both ends of the scale that the bottom rate(0) corresponds to "the worst health you can imagine", and the highest rate(100) corresponds to "the best health you can imagine"
measure: Safety Profile of Tasquinimod
time frame: At regular intervals during the study treatment period and every 3 months during the follow-up until death (approximately up to 2.5 years)
description: Number of subjects reporting adverse events
arm group label: Tasquinimod
arm group type: Experimental
description: 1 capsule daily, taken orally with water and food (0.25 mg initially then dose escalated to 0.5 mg or 1 mg per day) until disease progression or toxicity or patient's willingness to stop.
arm group label: Placebo
arm group type: Placebo Comparator
description: 1 capsule daily, taken orally with water and food until disease progression or toxicity or patient's willingness to stop.
intervention type: Drug
intervention name: Tasquinimod
description: A patient's dose will escalate from one level to the next, once tolerability of the current dose is established. If tolerability issues arise at 0.5 or 1 mg/day, patients will have their dose reduced to 0.25 or 0.5 mg/day, respectively.
arm group label: Tasquinimod
intervention type: Drug
intervention name: Placebo
description: Placebo capsules are identical to tasquinimod capsules in appearance and excipients but exclude the active compound (tasquinimod), to be taken orally once a day with water and food
arm group label: Placebo
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ipsen Medical Director
role: Study Director
affiliation: Ipsen
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country: Belgium
country: Czechia
country: Denmark
country: France
country: Germany
country: Hungary
country: Italy
country: Lithuania
country: Poland
country: Spain
country: United Kingdom
country: Czech Republic
responsible party type: Sponsor
mesh term: Prostatic Neoplasms
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The study was terminated early due to the stop of the project as decided by sponsor. The trial included number of planned patients & number of events(PFS)were met to draw conclusions. Only follow-up of patients were discontinued earlier than planned.
point of contact: 