<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/NCT02972359</url>
  </required_header>
  <id_info>
    <org_study_id>KF7013-03</org_study_id>
    <secondary_id>2016-001164-11</secondary_id>
    <secondary_id>U1111-1180-8099</secondary_id>
    <nct_id>NCT02972359</nct_id>
  </id_info>
  <brief_title>Safety of Intravenous Neridronic Acid in CRPS</brief_title>
  <official_title>Open-label Safety Trial of Intravenous Neridronic Acid in Subjects With Complex Regional Pain Syndrome (CRPS)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Grünenthal GmbH</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Grünenthal GmbH</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this trial was to investigate the safety of intravenous neridronic acid in&#xD;
      patients with complex regional pain syndrome (CRPS).&#xD;
&#xD;
      The trial was divided into 3 periods: a 60-day enrollment period, a treatment period&#xD;
      consisting of 4 infusions over 10 days, and a follow-up period of approximately 50 weeks&#xD;
      (with visits at Week 2, Week 6, Week 12, Week 26, Week 39, and Week 52).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      At the Enrollment Visit the trial objectives, procedures, and risks were explained to the&#xD;
      participants and the informed consent form was signed. Medical history was obtained, a&#xD;
      physical examination was conducted, and other safety assessments were performed. Signs and&#xD;
      symptoms of CRPS were assessed to confirm the diagnosis of CRPS according to the Budapest&#xD;
      clinical criteria. Participants were trained to report their pain. Calcium and vitamin D&#xD;
      supplementation were initiated to ensure sufficient vitamin D levels prior to treatment.&#xD;
&#xD;
      Participants meeting all eligibility criteria received infusions of investigational medicinal&#xD;
      product (IMP) during visits on Day 1, Day 4, Day 7, and Day 10. Flexibility of ±1 day was&#xD;
      allowed for Day 4, Day 7, and Day 10 whilst ensuring a minimum period of 48 hours between&#xD;
      infusions. During the treatment period and follow-up period, pain intensity ratings were&#xD;
      captured at the site visits in a patient reported-outcome system.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 20, 2016</start_date>
  <completion_date type="Actual">January 9, 2019</completion_date>
  <primary_completion_date type="Actual">January 9, 2019</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Occurrence of Any Treatment Emergent Adverse Event (TEAE)</measure>
    <time_frame>Day 1 to Week 52</time_frame>
    <description>The primary endpoint of this trial was a binary endpoint assessing whether or not a participant experienced any TEAE.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Occurrence of Permanent Discontinuation From Treatment Due to an Adverse Event</measure>
    <time_frame>Day 1 to Day 10</time_frame>
    <description>The investigator could choose to permanently discontinue a participant from treatment if continued exposure of the participant to neridronic acid could have posed an undue risk to the participant.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the Current Pain Intensity Score</measure>
    <time_frame>Baseline to Week 12 and Week 26</time_frame>
    <description>The current Complex Regional Pain Syndrome (CRPS)-related pain intensity score was captured at each visit using an 11-point numerical rating scale where 0 = &quot;no pain&quot; and 10 = &quot;pain as bad as you can imagine&quot;, a higher score indicates more pain.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Response to Treatment, Defined as at Least 30% Decrease From Baseline in the Current Pain Intensity Score</measure>
    <time_frame>Baseline, at Week 12 and Week 26</time_frame>
    <description>Participants with at least a 30 percent decrease in the current pain intensity score were considered to have responded to treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Response to Treatment, Defined as at Least 50% Decrease From Baseline in the Current Pain Intensity Score</measure>
    <time_frame>Baseline, at Week 12 and Week 26</time_frame>
    <description>Participants with at least a 50 percent decrease in the current pain intensity score were considered to have responded to treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient Global Impression of Change (PGIC) at Week 12</measure>
    <time_frame>at Week 12</time_frame>
    <description>The Patient Global Impression of Change (PGIC) is a self-reported measure of perceived change in overall condition since the start of the study. Participants selected one of seven responses ranging from &quot;very much improved&quot; to &quot;very much worse&quot;. A response of &quot;very much improved&quot; or &quot;much improved&quot; is generally regarded as a clinically important improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient Global Impression of Change (PGIC) at Week 26</measure>
    <time_frame>at Week 26</time_frame>
    <description>The Patient Global Impression of Change (PGIC) is a self-reported measure of perceived change in overall condition since the start of the study. Participants selected one of seven responses ranging from &quot;very much improved&quot; to &quot;very much worse&quot;. A response of &quot;very much improved&quot; or &quot;much improved&quot; is generally regarded as a clinically important improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the Pain Interference Score of the Brief Pain Inventory (BPI)</measure>
    <time_frame>Baseline to Week 12 and Week 26</time_frame>
    <description>The Brief Pain Inventory (BPI) Interference Score is the mean value of 7 self-reported items in question 9 of the BPI Short Form Questionnaire. Participants rated their interference of pain with general activity, walking, work, sleep and other activities in the past 24 hours, with possible ratings from 0 (does not interfere) to 10 (completely interferes). The BPI interference Score ranges from 0 to 10, with higher values indicating greater pain interference of daily activities.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">580</enrollment>
  <condition>Complex Regional Pain Syndrome</condition>
  <arm_group>
    <arm_group_label>Neridronic acid</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Neridronic acid 100 mg administered on Day 1, Day 4, Day 7, and Day 10, resulting in a total dose of neridronic acid 400 mg.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Neridronic acid</intervention_name>
    <description>Neridronic acid administered as intravenous infusion.</description>
    <arm_group_label>Neridronic acid</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Informed consent signed.&#xD;
&#xD;
          -  Male or female participant at least 18 years of age at Visit 1.&#xD;
&#xD;
          -  A diagnosis of complex regional pain syndrome according to the clinical diagnostic&#xD;
             criteria recommended by the International Association for the Study of Pain (IASP;&#xD;
             &quot;Budapest clinical criteria&quot;), assessed at Visit 1. Signs and symptoms of CRPS must&#xD;
             apply to an affected limb (arm or leg) and must demonstrate asymmetry with respect to&#xD;
             the contralateral limb.&#xD;
&#xD;
          -  Ongoing moderate to severe chronic pain, including a baseline current pain intensity&#xD;
             score of greater than or equal to 4 using an 11-point Numerical Rating Scale,&#xD;
             referring to the CRPS-affected limb, at Visit 2 (prior to dosing).&#xD;
&#xD;
          -  In stable treatment and follow-up therapy for CRPS for at least 1 month prior to&#xD;
             allocation to treatment (Visit 2). Participants must have failed trials of at least 2&#xD;
             treatments for CRPS, one of which must be a pharmacologic treatment.&#xD;
&#xD;
          -  Women of child-bearing potential must have a negative urine beta-human chorionic&#xD;
             gonadotropin (β-HCG) pregnancy test at Visit 1 and must be using 2 forms of medically&#xD;
             acceptable contraception, including at least 1 highly effective method of&#xD;
             contraception with a low failure rate, defined as less than 1% per year (e.g., oral&#xD;
             contraceptives or intrauterine device), and a second medically acceptable method such&#xD;
             as use of condoms with spermicide by their male partner. A barrier method alone is not&#xD;
             acceptable. Highly effective methods of contraception must be used for at least 1&#xD;
             month prior to Visit 2 and for the duration of the trial.&#xD;
&#xD;
          -  Participants must be able to communicate meaningfully, be able to differentiate with&#xD;
             regard to location and intensity of the pain, and be able to answer the questions in&#xD;
             the questionnaires used in this trial (assistance in filling out the questionnaires&#xD;
             may be provided, if required due to motor or other impairment).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Evidence of renal impairment (estimated glomerular filtration rate [eGFR] less than 60&#xD;
             mL/min/1.73 m2 using the 2009 Chronic Kidney Disease Epidemiology Collaboration&#xD;
             [CKD-EPI] creatinine equation [Levey et al. 2009] or a urinary albumin creatinine&#xD;
             ratio greater than 150 mg/g), based on central safety laboratory data obtained prior&#xD;
             to Visit 2, or a history of chronic kidney disease. Note: a single repeat laboratory&#xD;
             test is allowed.&#xD;
&#xD;
          -  Serum calcium or magnesium outside of the central laboratory's reference range, based&#xD;
             on central safety laboratory data obtained prior to Visit 2 (a single repeat&#xD;
             laboratory test is allowed); a history of hypocalcemia or a metabolic disorder&#xD;
             anticipated to increase risk for hypocalcemia (e.g., hypoparathyroidism); concomitant&#xD;
             use of drug(s) with known potential to cause hypocalcemia (e.g., aminoglycosides).&#xD;
&#xD;
          -  Vitamin D deficiency, defined as a 25(OH)D level less than 30 ng/mL, based on central&#xD;
             safety laboratory data obtained prior to Visit 2 (up to 4 repeat laboratory tests are&#xD;
             allowed). Participants with vitamin D deficiency should receive appropriate&#xD;
             supplementation during the enrollment period. A vitamin D level of at least 30 ng/mL&#xD;
             must be documented prior to allocation to investigational medicinal product (IMP).&#xD;
&#xD;
          -  Corrected QT interval (according to Fridericia's formula; QTcF) greater than 470 ms&#xD;
             (average of 3 electrocardiograms [ECGs] obtained at Visit 1); serum potassium outside&#xD;
             the central laboratory's reference range at Visit 1; clinically unstable cardiac&#xD;
             disease, including: unstable atrial fibrillation, symptomatic bradycardia, unstable&#xD;
             congestive heart failure, active myocardial ischemia, or an indwelling pacemaker;&#xD;
             evidence of complete left bundle branch block; complete atrioventricular block;&#xD;
             history of Long QT Syndrome or a relative with this condition; or any other known risk&#xD;
             factor for torsade de pointes.&#xD;
&#xD;
          -  Participants receiving medications with a known risk of torsades de pointes within 7&#xD;
             days prior to allocation. Participants receiving selective serotonin re-uptake&#xD;
             inhibitor antidepressants (e.g., citalopram, escitalopram) or tricyclic&#xD;
             antidepressants are eligible if the QT-interval values do not meet the exclusion&#xD;
             criteria, the medication was started at least 1 month prior to allocation, the dose is&#xD;
             stable, and the dose is anticipated to remain stable until at least 4 days after the&#xD;
             last infusion of IMP.&#xD;
&#xD;
          -  Anticipated requirement for treatment with oral or intravenous bisphosphonate for&#xD;
             another condition such as osteoporosis during the trial, or administration of&#xD;
             denosumab (Prolia®) or other drugs affecting bone turnover or bone metabolism within 6&#xD;
             months prior to Visit 1.&#xD;
&#xD;
          -  History of any allergic or hypersensitivity reaction to neridronic acid or other&#xD;
             bisphosphonate, acetaminophen, or to vitamin D or calcium supplements.&#xD;
&#xD;
          -  Recent tooth extraction or other invasive dental procedure (within 3 months prior to&#xD;
             Visit 1), unhealed or infected extraction site, or significant dental/periodontal&#xD;
             disease (e.g., impacted molars, severe tooth decay, foci of infection) that may&#xD;
             predispose to need for tooth extraction or other invasive dental procedures during the&#xD;
             trial. Participants with indeterminate, suspicious or unreliable dental history, in&#xD;
             the opinion of the investigator, must undergo a dental examination prior to receiving&#xD;
             treatment.&#xD;
&#xD;
          -  Evidence of denture-related gum trauma or improperly fitting dentures causing injury.&#xD;
&#xD;
          -  Prior radiation therapy of the head or neck (within 1 year of Visit 1).&#xD;
&#xD;
          -  History of malignancy within 2 years prior to Visit 1, with the exception of basal&#xD;
             cell carcinoma.&#xD;
&#xD;
          -  Use of nerve blocks, ketamine infusions, intravenous immunoglobulin, acupuncture,&#xD;
             electromagnetic field treatment, or initiation/implementation of radiofrequency&#xD;
             ablation or other sympathectomy procedures, or peripheral nerve stimulation within 6&#xD;
             weeks prior to Visit 2.&#xD;
&#xD;
          -  Evidence of current alcohol or drug abuse, or history of alcohol or drug abuse within&#xD;
             2 years of Visit 1, based on participant history and physical examination and&#xD;
             according to the investigator's judgment.&#xD;
&#xD;
          -  Any other severe medical condition, including severe depression, or any other severe&#xD;
             mood disorder, that in the opinion of the investigator may affect efficacy or safety&#xD;
             assessments or may compromise the participant's safety during trial participation.&#xD;
&#xD;
          -  Women who are pregnant or breastfeeding.&#xD;
&#xD;
          -  Elevated aspartate aminotransferase or alanine aminotransferase greater than 2-fold&#xD;
             upper limit of normal, based on central safety laboratory data obtained at Visit 1, or&#xD;
             current evidence of chronic liver disease. Safety laboratory testing may be repeated&#xD;
             prior to Visit 2, and participants will be allowed in the trial if results of 2&#xD;
             consecutive tests, at least 3 days apart, are less than or equal to 2-fold upper limit&#xD;
             of normal.&#xD;
&#xD;
          -  Participation in another investigational drug trial within 3 months prior to Visit 1&#xD;
             or any previous trial with neridronic acid, with the exception of participants of&#xD;
             KF7013-01 who were assigned to placebo and did not receive neridronic acid.&#xD;
&#xD;
          -  Participant is engaged in litigation related to their disability from CRPS in which&#xD;
             monetary gain or loss (or other compensation) may affect their objective participation&#xD;
             in the trial.&#xD;
&#xD;
          -  Participants taking forbidden concomitant medications/therapies or not being able to&#xD;
             follow the rules of use of concomitant treatment.&#xD;
&#xD;
          -  Participants incapable of signing the informed consent.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Study Director</last_name>
    <role>Study Director</role>
    <affiliation>Grünenthal GmbH</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>US017: Cactus Clinical Research, Inc.</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85012</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US028: Quality of Life Medical and Research Centers LLC</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85712</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US045: Woodland International Research Group</name>
      <address>
        <city>Little Rock</city>
        <state>Arkansas</state>
        <zip>72211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US044: Woodland Research Northwest</name>
      <address>
        <city>Rogers</city>
        <state>Arkansas</state>
        <zip>72758</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US012: Orange County Research Institute</name>
      <address>
        <city>Anaheim</city>
        <state>California</state>
        <zip>92801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US022: Core Healthcare Group</name>
      <address>
        <city>Cerritos</city>
        <state>California</state>
        <zip>90703</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US033: Alliance Research Centers</name>
      <address>
        <city>Laguna Hills</city>
        <state>California</state>
        <zip>92653</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US027: The Helm Center for Pain Management</name>
      <address>
        <city>Laguna Woods</city>
        <state>California</state>
        <zip>92637</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US003: Samaritan Center for Medical Research</name>
      <address>
        <city>Los Gatos</city>
        <state>California</state>
        <zip>95032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US010: Catalina Research Institute, LLC</name>
      <address>
        <city>Montclair</city>
        <state>California</state>
        <zip>91763</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US014: Northern California Research</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95821</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US034: Mountain View Clinical Research, Inc.</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80209</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US032: South Lake Pain Institute</name>
      <address>
        <city>Clermont</city>
        <state>Florida</state>
        <zip>34711</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US001: Sunrise Research Institute, Inc</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33130</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US046: AMPM Research Clinic</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33169</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US035: Compass Research</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US031: Gold Coast Research, LLC</name>
      <address>
        <city>Plantation</city>
        <state>Florida</state>
        <zip>33317</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US011: Clinical Research of West Florida, Inc.</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33603</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US040: Palm Beach Research Center</name>
      <address>
        <city>West Palm Beach</city>
        <state>Florida</state>
        <zip>33409</zip>
        <country>United States</country>
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    </facility>
  </location>
  <location>
    <facility>
      <name>US026: Better Health Clinical Research Inc.</name>
      <address>
        <city>Newnan</city>
        <state>Georgia</state>
        <zip>30265</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US004: Northwestern University - Feinberg School of Medicine - Rehabilitation Institute of Chicago (RIC)</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US036: University Anesthesiologists, S.C.</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US029: Great Lakes Clinical Trials LLC</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60640</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US005: International Clinical Research Institute</name>
      <address>
        <city>Overland Park</city>
        <state>Kansas</state>
        <zip>66210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US037: St. Louis Clinical Trials, LC</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63141</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US051: Creighton University, Osteoporosis Research Center</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68122</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US002: Princeton Medical Institute</name>
      <address>
        <city>Princeton</city>
        <state>New Jersey</state>
        <zip>08540</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US049: Premier Pain Centers, LLC</name>
      <address>
        <city>Shrewsbury</city>
        <state>New Jersey</state>
        <zip>07702</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US048: Albany Medical College</name>
      <address>
        <city>Albany</city>
        <state>New York</state>
        <zip>12208</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US043: Translational Pain Research, University of Rochester</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14618</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US009: The Center for Clinical Research, LLC</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US016: North Star Medical Research, LLC</name>
      <address>
        <city>Middleburg Heights</city>
        <state>Ohio</state>
        <zip>44130</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US007: Medical Research International</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73109-4520</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US006: Abington Neurological Associates, LTD.</name>
      <address>
        <city>Willow Grove</city>
        <state>Pennsylvania</state>
        <zip>19090</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US020: Clinical Trials of South Carolina</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29406</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US038: Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37212-1050</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US019: Austin Center for Clinical Research</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78758</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US008: Pioneer Research Solutions</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77099</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US023: Axios Research, LLC</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US018: Washington Center for Pain Management</name>
      <address>
        <city>Bellevue</city>
        <state>Washington</state>
        <zip>98004</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US015: Northwest Clinical Research Center</name>
      <address>
        <city>Bellevue</city>
        <state>Washington</state>
        <zip>98007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US013: Swedish Pain Services/ Research Institute</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98122</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>DE001: Klinische Forschung Hannover-Mitte GmbH</name>
      <address>
        <city>Hannover</city>
        <zip>30159</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>DE004: Schmerzambulanz Medizinishe Hochschule Hannover</name>
      <address>
        <city>Hannover</city>
        <zip>30625</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>DE006: AmBeNet GmbH</name>
      <address>
        <city>Leipzig</city>
        <zip>04107</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>DE002: Schmerztagesklinik der Anästhesiologie Universitätsklinikum Würzburg</name>
      <address>
        <city>Würzburg</city>
        <zip>97080</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J; CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009 May 5;150(9):604-12. doi: 10.7326/0003-4819-150-9-200905050-00006. Erratum In: Ann Intern Med. 2011 Sep 20;155(6):408.</citation>
    <PMID>19414839</PMID>
  </reference>
  <verification_date>November 2019</verification_date>
  <study_first_submitted>November 21, 2016</study_first_submitted>
  <study_first_submitted_qc>November 21, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 23, 2016</study_first_posted>
  <results_first_submitted>October 15, 2019</results_first_submitted>
  <results_first_submitted_qc>October 15, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">November 4, 2019</results_first_posted>
  <last_update_submitted>November 12, 2019</last_update_submitted>
  <last_update_submitted_qc>November 12, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">November 21, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Neridronic Acid</keyword>
  <keyword>Neridronate</keyword>
  <keyword>CRPS</keyword>
  <keyword>RSD (reflex sympathetic dystrophy)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Complex Regional Pain Syndromes</mesh_term>
    <mesh_term>Reflex Sympathetic Dystrophy</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Information available on the Grünenthal Web Site</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_url>http://www.grunenthal.com/r-d-vision-mission/clinical-trials/data-sharing-clinical-trials</ipd_url>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>November 17, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/59/NCT02972359/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>May 15, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/59/NCT02972359/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The first participant was enrolled on 20 December 2016.</recruitment_details>
      <pre_assignment_details>A total of 580 participants signed an informed consent form, 318 participants hereof were allocated to treatment. Two of the allocated participants did not meet inclusion criteria/met exclusion criteria, thus 316 participants received treatment.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Neridronic Acid</title>
          <description>Neridronic acid 100 mg administered on Day 1, Day 4, Day 7, and Day 10, resulting in a total dose of neridronic acid 400 mg as intravenous infusion.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="318"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="247"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="71"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Incl. criteria not met/Exclusion met</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other reasons</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Missing</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Neridronic Acid</title>
          <description>Neridronic acid 100 mg administered on Day 1, Day 4, Day 7, and Day 10, resulting in a total dose of neridronic acid 400 mg.&#xD;
Neridronic acid: Neridronic acid administered as intravenous infusion.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="316"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="316"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="290"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="316"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="47.4" lower_limit="19" upper_limit="77"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="316"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="237"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="316"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="300"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="316"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="297"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </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>United States</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="316"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="308"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Germany</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="316"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body mass index (BMI)</title>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="316"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="28.3" spread="7.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Baseline current pain intensity 11-point NRS</title>
          <description>Measured using an 11-point Numerical rating scale (NRS) by answering the following question: &quot;Please rate your pain by selecting the one number that best describes how much pain you have right now.&quot; Scores ranged from 0 (no pain) to 10 (pain as bad as you can imagine), a higher score indicates more pain. Baseline was the score assessed before the first dose of investigational medicinal product (IMP).</description>
          <population>One participant's baseline pain assessment was missing (N=315). Full Analysis Set</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="315"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6.59" spread="1.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Baseline Pain Interference score of the Brief Pain Inventory (BPI)</title>
          <description>Participants completed the Brief Pain Inventory (BPI) Interference Scale questionnaire, which measures the impact of pain on functioning and well-being. The 7 pain interference items: general activity, walking, work, mood, enjoyment of life, relations with others, and sleep, are each rated on a 0 to 10 scale using a 24-hour recall period, with 0 indicating &quot;does not interfere&quot; and 10 indicating &quot;completely interferes&quot;. The total Pain Interference Score is calculated by adding the scores for the 7 questions and dividing by 7. This gives an interference score with a range from 0 to 10.</description>
          <population>20 participants baseline pain assessment were missing. Full Analysis Set</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="296"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7.3" spread="1.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Occurrence of Any Treatment Emergent Adverse Event (TEAE)</title>
        <description>The primary endpoint of this trial was a binary endpoint assessing whether or not a participant experienced any TEAE.</description>
        <time_frame>Day 1 to Week 52</time_frame>
        <population>Safety Set</population>
        <group_list>
          <group group_id="O1">
            <title>Neridronic Acid</title>
            <description>Neridronic acid 100 mg administered on Day 1, Day 4, Day 7, and Day 10, resulting in a total dose of neridronic acid 400 mg.&#xD;
Neridronic acid: Neridronic acid administered as intravenous infusion.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Occurrence of Any Treatment Emergent Adverse Event (TEAE)</title>
          <description>The primary endpoint of this trial was a binary endpoint assessing whether or not a participant experienced any TEAE.</description>
          <population>Safety Set</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="316"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Participants with TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="277"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with serious TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with non-serious TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="275"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with unexpected TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="267"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with related TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="190"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with related serious TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with TEAE leading to IMP discont.</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with TEAE leading to trial discont.</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Occurrence of Permanent Discontinuation From Treatment Due to an Adverse Event</title>
        <description>The investigator could choose to permanently discontinue a participant from treatment if continued exposure of the participant to neridronic acid could have posed an undue risk to the participant.</description>
        <time_frame>Day 1 to Day 10</time_frame>
        <population>Safety Set</population>
        <group_list>
          <group group_id="O1">
            <title>Neridronic Acid</title>
            <description>Neridronic acid 100 mg administered on Day 1, Day 4, Day 7, and Day 10, resulting in a total dose of neridronic acid 400 mg.&#xD;
Neridronic acid: Neridronic acid administered as intravenous infusion.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Occurrence of Permanent Discontinuation From Treatment Due to an Adverse Event</title>
          <description>The investigator could choose to permanently discontinue a participant from treatment if continued exposure of the participant to neridronic acid could have posed an undue risk to the participant.</description>
          <population>Safety Set</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="316"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in the Current Pain Intensity Score</title>
        <description>The current Complex Regional Pain Syndrome (CRPS)-related pain intensity score was captured at each visit using an 11-point numerical rating scale where 0 = &quot;no pain&quot; and 10 = &quot;pain as bad as you can imagine&quot;, a higher score indicates more pain.</description>
        <time_frame>Baseline to Week 12 and Week 26</time_frame>
        <population>Full Analysis Set</population>
        <group_list>
          <group group_id="O1">
            <title>Neridronic Acid</title>
            <description>Neridronic acid 100 mg administered on Day 1, Day 4, Day 7, and Day 10, resulting in a total dose of neridronic acid 400 mg.&#xD;
Neridronic acid: Neridronic acid administered as intravenous infusion.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in the Current Pain Intensity Score</title>
          <description>The current Complex Regional Pain Syndrome (CRPS)-related pain intensity score was captured at each visit using an 11-point numerical rating scale where 0 = &quot;no pain&quot; and 10 = &quot;pain as bad as you can imagine&quot;, a higher score indicates more pain.</description>
          <population>Full Analysis Set</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="316"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline to Week 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="283"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.54" spread="2.27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="269"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.57" spread="2.45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Response to Treatment, Defined as at Least 30% Decrease From Baseline in the Current Pain Intensity Score</title>
        <description>Participants with at least a 30 percent decrease in the current pain intensity score were considered to have responded to treatment.</description>
        <time_frame>Baseline, at Week 12 and Week 26</time_frame>
        <population>Full Analysis Set</population>
        <group_list>
          <group group_id="O1">
            <title>Neridronic Acid</title>
            <description>Neridronic acid 100 mg administered on Day 1, Day 4, Day 7, and Day 10, resulting in a total dose of neridronic acid 400 mg.&#xD;
Neridronic acid: Neridronic acid administered as intravenous infusion.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Response to Treatment, Defined as at Least 30% Decrease From Baseline in the Current Pain Intensity Score</title>
          <description>Participants with at least a 30 percent decrease in the current pain intensity score were considered to have responded to treatment.</description>
          <population>Full Analysis Set</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="316"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>At least 30% pain reduction - Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="105"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At least 30% pain reduction - Week 26</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="110"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Response to Treatment, Defined as at Least 50% Decrease From Baseline in the Current Pain Intensity Score</title>
        <description>Participants with at least a 50 percent decrease in the current pain intensity score were considered to have responded to treatment.</description>
        <time_frame>Baseline, at Week 12 and Week 26</time_frame>
        <population>Full Analysis Set</population>
        <group_list>
          <group group_id="O1">
            <title>Neridronic Acid</title>
            <description>Neridronic acid 100 mg administered on Day 1, Day 4, Day 7, and Day 10, resulting in a total dose of neridronic acid 400 mg.&#xD;
Neridronic acid: Neridronic acid administered as intravenous infusion.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Response to Treatment, Defined as at Least 50% Decrease From Baseline in the Current Pain Intensity Score</title>
          <description>Participants with at least a 50 percent decrease in the current pain intensity score were considered to have responded to treatment.</description>
          <population>Full Analysis Set</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="316"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>At least 50% pain reduction - Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At least 50% pain reduction - Week 26</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Patient Global Impression of Change (PGIC) at Week 12</title>
        <description>The Patient Global Impression of Change (PGIC) is a self-reported measure of perceived change in overall condition since the start of the study. Participants selected one of seven responses ranging from &quot;very much improved&quot; to &quot;very much worse&quot;. A response of &quot;very much improved&quot; or &quot;much improved&quot; is generally regarded as a clinically important improvement.</description>
        <time_frame>at Week 12</time_frame>
        <population>Full Analysis Set; 286 out of 316 participants attended the visit at Week 12 and were asked to complete the PGIC questionnaire.</population>
        <group_list>
          <group group_id="O1">
            <title>Neridronic Acid</title>
            <description>Neridronic acid 100 mg administered on Day 1, Day 4, Day 7, and Day 10, resulting in a total dose of neridronic acid 400 mg.&#xD;
Neridronic acid: Neridronic acid administered as intravenous infusion.</description>
          </group>
        </group_list>
        <measure>
          <title>Patient Global Impression of Change (PGIC) at Week 12</title>
          <description>The Patient Global Impression of Change (PGIC) is a self-reported measure of perceived change in overall condition since the start of the study. Participants selected one of seven responses ranging from &quot;very much improved&quot; to &quot;very much worse&quot;. A response of &quot;very much improved&quot; or &quot;much improved&quot; is generally regarded as a clinically important improvement.</description>
          <population>Full Analysis Set; 286 out of 316 participants attended the visit at Week 12 and were asked to complete the PGIC questionnaire.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="286"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Very Much Improved</title>
                  <measurement_list>
                    <measurement group_id="O1" value="31"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Much Improved</title>
                  <measurement_list>
                    <measurement group_id="O1" value="71"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Minimally Improved</title>
                  <measurement_list>
                    <measurement group_id="O1" value="98"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No Change</title>
                  <measurement_list>
                    <measurement group_id="O1" value="45"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Minimally Worse</title>
                  <measurement_list>
                    <measurement group_id="O1" value="23"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Much Worse</title>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Very Much Worse</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Missing</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Patient Global Impression of Change (PGIC) at Week 26</title>
        <description>The Patient Global Impression of Change (PGIC) is a self-reported measure of perceived change in overall condition since the start of the study. Participants selected one of seven responses ranging from &quot;very much improved&quot; to &quot;very much worse&quot;. A response of &quot;very much improved&quot; or &quot;much improved&quot; is generally regarded as a clinically important improvement.</description>
        <time_frame>at Week 26</time_frame>
        <population>Full Analysis Set; 273 out of 316 participants attended the visit at Week 26 and were asked to complete the PGIC questionnaire.</population>
        <group_list>
          <group group_id="O1">
            <title>Neridronic Acid</title>
            <description>Neridronic acid 100 mg administered on Day 1, Day 4, Day 7, and Day 10, resulting in a total dose of neridronic acid 400 mg.&#xD;
Neridronic acid: Neridronic acid administered as intravenous infusion.</description>
          </group>
        </group_list>
        <measure>
          <title>Patient Global Impression of Change (PGIC) at Week 26</title>
          <description>The Patient Global Impression of Change (PGIC) is a self-reported measure of perceived change in overall condition since the start of the study. Participants selected one of seven responses ranging from &quot;very much improved&quot; to &quot;very much worse&quot;. A response of &quot;very much improved&quot; or &quot;much improved&quot; is generally regarded as a clinically important improvement.</description>
          <population>Full Analysis Set; 273 out of 316 participants attended the visit at Week 26 and were asked to complete the PGIC questionnaire.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="273"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Very Much Improved</title>
                  <measurement_list>
                    <measurement group_id="O1" value="38"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Much Improved</title>
                  <measurement_list>
                    <measurement group_id="O1" value="58"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Minimally Improved</title>
                  <measurement_list>
                    <measurement group_id="O1" value="84"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No Change</title>
                  <measurement_list>
                    <measurement group_id="O1" value="52"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Minimally Worse</title>
                  <measurement_list>
                    <measurement group_id="O1" value="25"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Much Worse</title>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Very Much Worse</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Missing</title>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in the Pain Interference Score of the Brief Pain Inventory (BPI)</title>
        <description>The Brief Pain Inventory (BPI) Interference Score is the mean value of 7 self-reported items in question 9 of the BPI Short Form Questionnaire. Participants rated their interference of pain with general activity, walking, work, sleep and other activities in the past 24 hours, with possible ratings from 0 (does not interfere) to 10 (completely interferes). The BPI interference Score ranges from 0 to 10, with higher values indicating greater pain interference of daily activities.</description>
        <time_frame>Baseline to Week 12 and Week 26</time_frame>
        <population>Full Analysis Set</population>
        <group_list>
          <group group_id="O1">
            <title>Neridronic Acid</title>
            <description>Neridronic acid 100 mg administered on Day 1, Day 4, Day 7, and Day 10, resulting in a total dose of neridronic acid 400 mg.&#xD;
Neridronic acid: Neridronic acid administered as intravenous infusion.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in the Pain Interference Score of the Brief Pain Inventory (BPI)</title>
          <description>The Brief Pain Inventory (BPI) Interference Score is the mean value of 7 self-reported items in question 9 of the BPI Short Form Questionnaire. Participants rated their interference of pain with general activity, walking, work, sleep and other activities in the past 24 hours, with possible ratings from 0 (does not interfere) to 10 (completely interferes). The BPI interference Score ranges from 0 to 10, with higher values indicating greater pain interference of daily activities.</description>
          <population>Full Analysis Set</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="316"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline to Week 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="264"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.2" spread="2.49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 26</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="251"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.1" spread="2.64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Day 1 to Week 52</time_frame>
      <desc>318 participants were allocated to treatment. Two participants did not meet inclusion criteria/met exclusion criteria, thus 316 participants were treated (Safety Set).&#xD;
Participants were questioned about possible adverse events with non-leading questions before administration of the IMP and at regular intervals thereafter. All adverse events reported spontaneously by participants at any time point were also documented.&#xD;
Treatment emergent adverse events are reported.</desc>
      <group_list>
        <group group_id="E1">
          <title>Neridronic Acid</title>
          <description>Neridronic acid 100 mg administered on Day 1, Day 4, Day 7, and Day 10, resulting in a total dose of neridronic acid 400 mg.&#xD;
Neridronic acid: Neridronic acid administered as intravenous infusion.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (21.1)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="316"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="27" subjects_at_risk="316"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Angina unstable</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="316"/>
              </event>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="316"/>
              </event>
              <event>
                <sub_title>Stress cardiomyopathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="316"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="316"/>
              </event>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="316"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="316"/>
              </event>
              <event>
                <sub_title>Condition aggravated</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="316"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholecystitis acute</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="316"/>
              </event>
              <event>
                <sub_title>Liver disorder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="316"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="316"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="316"/>
              </event>
              <event>
                <sub_title>Procedural pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="316"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="316"/>
              </event>
              <event>
                <sub_title>Osteoarthritis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="316"/>
              </event>
              <event>
                <sub_title>Rotator cuff syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="316"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Loss of consciousness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="316"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="316"/>
              </event>
              <event>
                <sub_title>Transient ischaemic attack</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="316"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Delirium</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="316"/>
              </event>
              <event>
                <sub_title>Suicidal ideation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="316"/>
              </event>
              <event>
                <sub_title>Suicide attempt</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="316"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Cystocele</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="316"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Leg amputation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="316"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (21.1)</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="275" subjects_at_risk="316"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="46" subjects_affected="34" subjects_at_risk="316"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="39" subjects_affected="32" subjects_at_risk="316"/>
              </event>
              <event>
                <sub_title>Condition aggravated</sub_title>
                <counts group_id="E1" events="44" subjects_affected="30" subjects_at_risk="316"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="37" subjects_affected="28" subjects_at_risk="316"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="19" subjects_affected="18" subjects_at_risk="316"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="70" subjects_affected="52" subjects_at_risk="316"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="31" subjects_affected="27" subjects_at_risk="316"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="30" subjects_affected="25" subjects_at_risk="316"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="30" subjects_affected="25" subjects_at_risk="316"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" events="20" subjects_affected="17" subjects_at_risk="316"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="96" subjects_affected="65" subjects_at_risk="316"/>
              </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>The sponsor reserves the right to review any proposed presentation of the results of this trial before they are submitted for publication or public disclosure. Neither party (e.g., the sponsor, the coordinating investigator) has the right to prohibit publication or public disclosure unless it can be shown to affect possible patent rights.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Due to the open-label, uncontrolled nature of the trial and the concomitant use of pain medication, the effect of neridronic acid on pain intensity and the side effect profile of neridronic acid have to be interpreted with care.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Clinical Trial Helpdesk</name_or_title>
      <organization>Grünenthal GmbH</organization>
      <phone>+49 241 569 ext 3223</phone>
      <email>clinical-trials@grunenthal.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/NCT02972359
org study id: KF7013-03
secondary id: 2016-001164-11
secondary id: U1111-1180-8099
nct id: NCT02972359
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The aim of this trial was to investigate the safety of intravenous neridronic acid in
      patients with complex regional pain syndrome (CRPS).

      The trial was divided into 3 periods: a 60-day enrollment period, a treatment period
      consisting of 4 infusions over 10 days, and a follow-up period of approximately 50 weeks
      (with visits at Week 2, Week 6, Week 12, Week 26, Week 39, and Week 52).
At the Enrollment Visit the trial objectives, procedures, and risks were explained to the
      participants and the informed consent form was signed. Medical history was obtained, a
      physical examination was conducted, and other safety assessments were performed. Signs and
      symptoms of CRPS were assessed to confirm the diagnosis of CRPS according to the Budapest
      clinical criteria. Participants were trained to report their pain. Calcium and vitamin D
      supplementation were initiated to ensure sufficient vitamin D levels prior to treatment.

      Participants meeting all eligibility criteria received infusions of investigational medicinal
      product (IMP) during visits on Day 1, Day 4, Day 7, and Day 10. Flexibility of ±1 day was
      allowed for Day 4, Day 7, and Day 10 whilst ensuring a minimum period of 48 hours between
      infusions. During the treatment period and follow-up period, pain intensity ratings were
      captured at the site visits in a patient reported-outcome system.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With Occurrence of Any Treatment Emergent Adverse Event (TEAE)
time frame: Day 1 to Week 52
description: The primary endpoint of this trial was a binary endpoint assessing whether or not a participant experienced any TEAE.
measure: Number of Participants With Occurrence of Permanent Discontinuation From Treatment Due to an Adverse Event
time frame: Day 1 to Day 10
description: The investigator could choose to permanently discontinue a participant from treatment if continued exposure of the participant to neridronic acid could have posed an undue risk to the participant.
measure: Change From Baseline in the Current Pain Intensity Score
time frame: Baseline to Week 12 and Week 26
description: The current Complex Regional Pain Syndrome (CRPS)-related pain intensity score was captured at each visit using an 11-point numerical rating scale where 0 = "no pain" and 10 = "pain as bad as you can imagine", a higher score indicates more pain.
measure: Number of Participants With Response to Treatment, Defined as at Least 30% Decrease From Baseline in the Current Pain Intensity Score
time frame: Baseline, at Week 12 and Week 26
description: Participants with at least a 30 percent decrease in the current pain intensity score were considered to have responded to treatment.
measure: Number of Participants With Response to Treatment, Defined as at Least 50% Decrease From Baseline in the Current Pain Intensity Score
time frame: Baseline, at Week 12 and Week 26
description: Participants with at least a 50 percent decrease in the current pain intensity score were considered to have responded to treatment.
measure: Patient Global Impression of Change (PGIC) at Week 12
time frame: at Week 12
description: The Patient Global Impression of Change (PGIC) is a self-reported measure of perceived change in overall condition since the start of the study. Participants selected one of seven responses ranging from "very much improved" to "very much worse". A response of "very much improved" or "much improved" is generally regarded as a clinically important improvement.
measure: Patient Global Impression of Change (PGIC) at Week 26
time frame: at Week 26
description: The Patient Global Impression of Change (PGIC) is a self-reported measure of perceived change in overall condition since the start of the study. Participants selected one of seven responses ranging from "very much improved" to "very much worse". A response of "very much improved" or "much improved" is generally regarded as a clinically important improvement.
measure: Change in the Pain Interference Score of the Brief Pain Inventory (BPI)
time frame: Baseline to Week 12 and Week 26
description: The Brief Pain Inventory (BPI) Interference Score is the mean value of 7 self-reported items in question 9 of the BPI Short Form Questionnaire. Participants rated their interference of pain with general activity, walking, work, sleep and other activities in the past 24 hours, with possible ratings from 0 (does not interfere) to 10 (completely interferes). The BPI interference Score ranges from 0 to 10, with higher values indicating greater pain interference of daily activities.
arm group label: Neridronic acid
arm group type: Experimental
description: Neridronic acid 100 mg administered on Day 1, Day 4, Day 7, and Day 10, resulting in a total dose of neridronic acid 400 mg.
intervention type: Drug
intervention name: Neridronic acid
description: Neridronic acid administered as intravenous infusion.
arm group label: Neridronic acid
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Study Director
role: Study Director
affiliation: Grünenthal GmbH
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country: Germany
country: United States
citation: Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J; CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009 May 5;150(9):604-12. doi: 10.7326/0003-4819-150-9-200905050-00006. Erratum In: Ann Intern Med. 2011 Sep 20;155(6):408.
PMID: 19414839
responsible party type: Sponsor
mesh term: Complex Regional Pain Syndromes
mesh term: Reflex Sympathetic Dystrophy
mesh term: Syndrome
sharing ipd: Yes
ipd description: Information available on the Grünenthal Web Site
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Clinical Study Report (CSR)
ipd url: http://www.grunenthal.com/r-d-vision-mission/clinical-trials/data-sharing-clinical-trials
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Due to the open-label, uncontrolled nature of the trial and the concomitant use of pain medication, the effect of neridronic acid on pain intensity and the side effect profile of neridronic acid have to be interpreted with care.
point of contact: 