<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/NCT02972424</url>
  </required_header>
  <id_info>
    <org_study_id>2015-330</org_study_id>
    <nct_id>NCT02972424</nct_id>
  </id_info>
  <brief_title>PTH(1-34) and Pelvic Fracture Healing - a Randomized Controlled Trial</brief_title>
  <official_title>PTH(1-34) and Pelvic Fracture Healing - a Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital for Special Surgery, New York</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Weill Medical College of Cornell University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Hospital for Special Surgery, New York</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>
      In the proposed trial the investigators will recruit women and men &gt;65 years of age with&#xD;
      acute osteoporosis-related pelvic fractures and address 3 specific aims over 3 months of&#xD;
      treatment in a placebo controlled double blind study to determine if standard care and&#xD;
      teriparatide 20 mcg/day versus placebo for pelvic fractures:&#xD;
&#xD;
        1. Results in earlier evidence of cortical bridging on routine radiographs followed by&#xD;
           confirmatory Focus CT, a novel method to reduce radiation exposure from CT scans&#xD;
           (primary outcome).&#xD;
&#xD;
        2. Leads to a faster reduction in pain as assessed by both the Numeric Rating Scale and a&#xD;
           reduction in the use of narcotics (secondary outcome).&#xD;
&#xD;
        3. Leads more rapidly to improved functional outcome using a short physical performance&#xD;
           battery to assess lower extremity function (secondary outcome).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The incidence rate of pelvic fractures increases dramatically with age, from 5.4 and 3.8 per&#xD;
      10,000 person-years in women and men aged 65 to 69 years to 93.5 and 44.5 per 10,000&#xD;
      person-years in women and men aged 90 years and older, respectively. Pelvic fractures are&#xD;
      accompanied by severe pain, chronic immobility and loss of function and independence in the&#xD;
      elderly. Pelvic fractures consume substantial healthcare resources, and based on&#xD;
      administrative claims data, they are one of the most costly osteoporosis related fractures.&#xD;
      Un-healed fractures, occurring in one-third of pelvic fracture patients at 3 months, can&#xD;
      cause continued pain and impact mobility. With aging of the population, and expected&#xD;
      concomitant increase in the incidence of pelvic fractures, there is a pressing need to find&#xD;
      effective treatments that will accelerate healing. Fracture of the pubic ramus is most&#xD;
      relevant and practical for randomized double-blinded placebo controlled study as this&#xD;
      fracture is accompanied by severe pain and immobility in elderly, is associated with delayed&#xD;
      fracture healing, and is almost always treated non-operatively. The current standard of care&#xD;
      for pelvic fractures includes pain management, patient mobilization, and the prevention of&#xD;
      complications associated with comorbid conditions. The investigators hypothesize that&#xD;
      development of a successful adjunctive therapy to accelerate fracture healing would lead to&#xD;
      improved care and reduce both direct and indirect costs from pelvic fractures. In the&#xD;
      proposed trial the investigators will recruit women and men &gt;65 years of age with acute&#xD;
      osteoporosis-related pelvic fractures and address 3 specific aims over 3 months of treatment&#xD;
      in a placebo controlled double blind study to determine if standard care and teriparatide 20&#xD;
      mcg/day versus placebo for pelvic fractures:&#xD;
&#xD;
        1. Results in earlier evidence of cortical bridging on routine radiographs followed by&#xD;
           confirmatory Focus CT, a novel method to reduce radiation exposure from CT scans&#xD;
           (primary outcome).&#xD;
&#xD;
        2. Leads to a faster reduction in pain as assessed by both the Numeric Rating Scale and a&#xD;
           reduction in the use of narcotics (secondary outcome).&#xD;
&#xD;
        3. Leads more rapidly to improved functional outcome using a short physical performance&#xD;
           battery to assess lower extremity function (secondary outcome).&#xD;
&#xD;
      The investigators will extend this study with 9 months of open label TPTD to determine if any&#xD;
      potential differences between the placebo and TPTD groups during the 3 months of treatment&#xD;
      are evident and persist over time, even in patients who use TPTD after the three month&#xD;
      placebo controlled intervention. If TPTD can improve fracture healing, this study will have&#xD;
      an impact on the treatment of persons with pelvic fracture who are not surgical candidates&#xD;
      and often face severe pain, chronic immobility, and loss of function in the elderly. A&#xD;
      positive finding of accelerated healing of pelvic fractures would also encourage study of&#xD;
      TPTD for treatment of other osteoporotic fractures.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 1, 2017</start_date>
  <completion_date type="Actual">July 8, 2021</completion_date>
  <primary_completion_date type="Actual">March 8, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Evidence of Cortical Bridging for Fracture Healing</measure>
    <time_frame>3 months</time_frame>
    <description>Evidence of cortical bridging based on Focus CT,</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Pain by Numeric Rating Scale Between Baseline and Three Months</measure>
    <time_frame>3 months</time_frame>
    <description>Leads to a faster reduction in pain as assessed by the Numeric Rating Scale of 0 (no pain) to 10 (worst pain).&#xD;
The mean reduction in pain score from 0 to 3 months is reported. Higher scores mean a greater reduction in pain.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional Outcome Using a Battery That Includes Walking Speed, Repeated Chair Stands, and Balance at 3 Months</measure>
    <time_frame>3 months</time_frame>
    <description>More rapidly improved functional outcome using a short physical performance battery to assess lower extremity function (walking speed, repeated chair stands, and balance) at 3 months. Scale is 0 to 100 with higher scores indicating better physical performance.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Physical Function at 12 Months Using a Battery That Includes Walking Speed, Repeated Chair Stands, and Balance</measure>
    <time_frame>12 months</time_frame>
    <description>More rapidly improved functional outcome using a short physical performance battery to assess lower extremity function (walking speed, repeated chair stands, and balance) at 12 months. Scale is 0 to 100 with higher scores indicating better performance.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain at 12 Months Based on the Numeric Rating Scale</measure>
    <time_frame>12 months</time_frame>
    <description>Pain at 12 months as assessed by the Numeric Rating Scale (0 to 10 where 0 means no pain and 10 worst pain)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">35</enrollment>
  <condition>Osteoporotic Fractures</condition>
  <arm_group>
    <arm_group_label>Teriparatide Prefilled Syringe</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TPTD is supplied as a sterile, colorless, clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable delivery device (pen) for subcutaneous injection. Each prefilled delivery device is filled with 2.7 mL to deliver 2.4 mL. Each mL contains 250 mcg teriparatide (corrected for acetate, chloride, and water content), 0.41 mg glacial acetic acid, 0.1 mg sodium acetate (anhydrous), 45.4 mg mannitol, 3 mg Metacresol, and Water for Injection. In addition, hydrochloric acid solution 10% and/or sodium hydroxide solution 10% may have been added to adjust the product to pH 4.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo is supplied as a sterile, colorless, clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable delivery device (pen) for subcutaneous injection. Each prefilled delivery device is filled with 2.7 mL to deliver 2.4 mL. Each mL contains 0.41 mg glacial acetic acid, 0.1 mg sodium acetate (anhydrous), 45.4 mg mannitol, 3 mg Metacresol, and Water for Injection. In addition, hydrochloric acid solution 10% and/or sodium hydroxide solution 10% may have been added to adjust the product to pH 4.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Teriparatide Prefilled Syringe</intervention_name>
    <description>TPTD 20 mcg</description>
    <arm_group_label>Teriparatide Prefilled Syringe</arm_group_label>
    <other_name>Forteo</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Matching placebo as a prefilled syringe with all inactive ingredients</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Placebo prefilled syringe</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Postmenopausal women and men &gt;65 years of age with acute pelvic fractures, occurring with&#xD;
        minimal trauma, presenting to Helen Hayes Hospital, Hospital for Special Surgery, or New&#xD;
        York Hospital (Cornell Medical). Patients that have either one or multiple pelvic fractures&#xD;
        or sacral and pelvic fractures will be included in the study. Subjects must start treatment&#xD;
        within one month of hip fracture.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Persons unable to complete the NRS and other surveys based on their mini-mental status&#xD;
             score (≤18; consistent with moderate and severe cognitive impairment)&#xD;
&#xD;
          2. Previously (prior to fracture) non-ambulatory subjects&#xD;
&#xD;
          3. Exclusion criteria related to contraindication or intolerance to TPTD:&#xD;
&#xD;
               1. Hypersensitivity to TPTD&#xD;
&#xD;
               2. Patients with increased risk of osteosarcoma: Paget's disease, history of&#xD;
                  radiation exposure&#xD;
&#xD;
               3. Patients with active hypercalcemia&#xD;
&#xD;
               4. Current hyperparathyroidism and other metabolic bone disease including&#xD;
                  osteogenesis imperfecta&#xD;
&#xD;
               5. History of multiple renal calculi or renal calculus within the last 2 years&#xD;
&#xD;
               6. Normal alkaline phosphatase levels will not be used as an entrance criterion&#xD;
                  because most fracture patients will have elevations due to the acute fracture.&#xD;
                  However, the investigators will attempt to obtain lab tests from the period prior&#xD;
                  to fracture to determine if they were normal. If unexplained elevations in&#xD;
                  alkaline phosphatase are found in labs prior to the fracture we will exclude that&#xD;
                  subject.&#xD;
&#xD;
               7. Evidence of metastatic cancer or history of bone cancer or any active cancer&#xD;
                  other than basal or squamous cell carcinoma.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>65 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jeri W Nieves, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital for Special Surgery, New York</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital for Special Surgery</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Nieves JW, Cosman F, McMahon D, Redko M, Hentschel I, Bartolotta R, Loftus M, Kazam JJ, Rotman J, Lane J. Teriparatide and pelvic fracture healing: a phase 2 randomized controlled trial. Osteoporos Int. 2022 Jan;33(1):239-250. doi: 10.1007/s00198-021-06065-4. Epub 2021 Aug 12.</citation>
    <PMID>34383100</PMID>
  </results_reference>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>November 18, 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>September 17, 2021</results_first_submitted>
  <results_first_submitted_qc>July 26, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">July 27, 2022</results_first_posted>
  <last_update_submitted>July 26, 2022</last_update_submitted>
  <last_update_submitted_qc>July 26, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 27, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>pelvic fracture</keyword>
  <keyword>healing</keyword>
  <keyword>teriparatide</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fractures, Bone</mesh_term>
    <mesh_term>Osteoporotic Fractures</mesh_term>
    <mesh_term>Hip Fractures</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Teriparatide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>The investigators will make the data available for sharing 12-months after the publication of the primary paper. SAS datasets, a data dictionary, images of case report forms, SAS format library, the SAS program in which source data is recoded for analysis and data table summary descriptive statistics for data validation cross-check will be made available on an encrypted USB drive. A data sharing agreement is required.</ipd_description>
    <ipd_time_frame>12 months after publication of results for 2 years</ipd_time_frame>
    <ipd_access_criteria>Submission should be made to Nievesje@hss.edu</ipd_access_criteria>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 21, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/24/NCT02972424/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>We included men and postmenopausal women &gt;50 years of age within 1 month of acute pelvic fractures, occurring with minimal trauma. Sites included Hospital for Special Surgery, Helen Hayes Hospital or New York Presbyterian Hospital. Patients who had one or multiple pubic rami fractures (with or without sacral fractures) were included in the study. The first person was recruited into the study in May 2017 and the last person was recruited in August 2019.</recruitment_details>
      <pre_assignment_details>Participants were excluded if they were unable to provide informed consent, if they were non-ambulatory prior to the fracture, or if they had a contraindication or intolerance to teriparatide. Serum calcium level had to be within normal range, serum creatinine could not be elevated more than 1.5 times above upper normal limit for age and alkaline phosphatase levels could not be greater than 1.5 times the upper normal limit.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Teriparatide</title>
          <description>TPTD is supplied as a sterile, colorless, clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable delivery device (pen) for subcutaneous injection. Each prefilled delivery device is filled with 2.7 mL to deliver 2.4 mL. Each mL contains 250 mcg teriparatide (corrected for acetate, chloride, and water content), 0.41 mg glacial acetic acid, 0.1 mg sodium acetate (anhydrous), 45.4 mg mannitol, 3 mg Metacresol, and Water for Injection. In addition, hydrochloric acid solution 10% and/or sodium hydroxide solution 10% may have been added to adjust the product to pH 4.&#xD;
Teriparatide Prefilled Syringe: TPTD 20 mcg</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Placebo is supplied as a sterile, colorless, clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable delivery device (pen) for subcutaneous injection. Each prefilled delivery device is filled with 2.7 mL to deliver 2.4 mL. Each mL contains 0.41 mg glacial acetic acid, 0.1 mg sodium acetate (anhydrous), 45.4 mg mannitol, 3 mg Metacresol, and Water for Injection. In addition, hydrochloric acid solution 10% and/or sodium hydroxide solution 10% may have been added to adjust the product to pH 4.&#xD;
Placebo: Matching placebo as a prefilled syringe with all inactive ingredients</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>3 Month Endpoints- Blinded Portion</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="17"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
                <participants group_id="P2" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Open Label Extension 3 to 12 Months</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
                <participants group_id="P2" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Participants must have taken at least one dose of study medication for intention to treat analysis</population>
      <group_list>
        <group group_id="B1">
          <title>Teriparatide</title>
          <description>TPTD is supplied as a sterile, colorless, clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable delivery device (pen) for subcutaneous injection. Each prefilled delivery device is filled with 2.7 mL to deliver 2.4 mL. Each mL contains 250 mcg teriparatide (corrected for acetate, chloride, and water content), 0.41 mg glacial acetic acid, 0.1 mg sodium acetate (anhydrous), 45.4 mg mannitol, 3 mg Metacresol, and Water for Injection. In addition, hydrochloric acid solution 10% and/or sodium hydroxide solution 10% may have been added to adjust the product to pH 4.&#xD;
Teriparatide Prefilled Syringe: TPTD 20 mcg</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Placebo is supplied as a sterile, colorless, clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable delivery device (pen) for subcutaneous injection. Each prefilled delivery device is filled with 2.7 mL to deliver 2.4 mL. Each mL contains 0.41 mg glacial acetic acid, 0.1 mg sodium acetate (anhydrous), 45.4 mg mannitol, 3 mg Metacresol, and Water for Injection. In addition, hydrochloric acid solution 10% and/or sodium hydroxide solution 10% may have been added to adjust the product to pH 4.&#xD;
Placebo: Matching placebo as a prefilled syringe with all inactive ingredients</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="18"/>
            <count group_id="B2" value="15"/>
            <count group_id="B3" value="33"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="81.6" spread="8.1"/>
                    <measurement group_id="B2" value="81.0" spread="11.5"/>
                    <measurement group_id="B3" value="81.4" spread="9.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="28"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="5"/>
                  </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>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="33"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="32"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body mass index (kg/m^2)</title>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="22.1" spread="3.5"/>
                    <measurement group_id="B2" value="22.5" spread="5.5"/>
                    <measurement group_id="B3" value="22.3" spread="4.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>history of fracture</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>multiple rami fractures</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>displaced fractures</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>sacral fractures</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Evidence of Cortical Bridging for Fracture Healing</title>
        <description>Evidence of cortical bridging based on Focus CT,</description>
        <time_frame>3 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Teriparatide</title>
            <description>TPTD is supplied as a sterile, colorless, clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable delivery device (pen) for subcutaneous injection. Each prefilled delivery device is filled with 2.7 mL to deliver 2.4 mL. Each mL contains 250 mcg teriparatide (corrected for acetate, chloride, and water content), 0.41 mg glacial acetic acid, 0.1 mg sodium acetate (anhydrous), 45.4 mg mannitol, 3 mg Metacresol, and Water for Injection. In addition, hydrochloric acid solution 10% and/or sodium hydroxide solution 10% may have been added to adjust the product to pH 4.&#xD;
Teriparatide Prefilled Syringe: TPTD 20 mcg</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo is supplied as a sterile, colorless, clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable delivery device (pen) for subcutaneous injection. Each prefilled delivery device is filled with 2.7 mL to deliver 2.4 mL. Each mL contains 0.41 mg glacial acetic acid, 0.1 mg sodium acetate (anhydrous), 45.4 mg mannitol, 3 mg Metacresol, and Water for Injection. In addition, hydrochloric acid solution 10% and/or sodium hydroxide solution 10% may have been added to adjust the product to pH 4.&#xD;
Placebo: Matching placebo as a prefilled syringe with all inactive ingredients</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Evidence of Cortical Bridging for Fracture Healing</title>
          <description>Evidence of cortical bridging based on Focus CT,</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Pain by Numeric Rating Scale Between Baseline and Three Months</title>
        <description>Leads to a faster reduction in pain as assessed by the Numeric Rating Scale of 0 (no pain) to 10 (worst pain).&#xD;
The mean reduction in pain score from 0 to 3 months is reported. Higher scores mean a greater reduction in pain.</description>
        <time_frame>3 months</time_frame>
        <population>participants with a 3 month visit</population>
        <group_list>
          <group group_id="O1">
            <title>Teriparatide</title>
            <description>TPTD is supplied as a sterile, colorless, clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable delivery device (pen) for subcutaneous injection. Each prefilled delivery device is filled with 2.7 mL to deliver 2.4 mL. Each mL contains 250 mcg teriparatide (corrected for acetate, chloride, and water content), 0.41 mg glacial acetic acid, 0.1 mg sodium acetate (anhydrous), 45.4 mg mannitol, 3 mg Metacresol, and Water for Injection. In addition, hydrochloric acid solution 10% and/or sodium hydroxide solution 10% may have been added to adjust the product to pH 4.&#xD;
Teriparatide Prefilled Syringe: TPTD 20 mcg</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo is supplied as a sterile, colorless, clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable delivery device (pen) for subcutaneous injection. Each prefilled delivery device is filled with 2.7 mL to deliver 2.4 mL. Each mL contains 0.41 mg glacial acetic acid, 0.1 mg sodium acetate (anhydrous), 45.4 mg mannitol, 3 mg Metacresol, and Water for Injection. In addition, hydrochloric acid solution 10% and/or sodium hydroxide solution 10% may have been added to adjust the product to pH 4.&#xD;
Placebo: Matching placebo as a prefilled syringe with all inactive ingredients</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Pain by Numeric Rating Scale Between Baseline and Three Months</title>
          <description>Leads to a faster reduction in pain as assessed by the Numeric Rating Scale of 0 (no pain) to 10 (worst pain).&#xD;
The mean reduction in pain score from 0 to 3 months is reported. Higher scores mean a greater reduction in pain.</description>
          <population>participants with a 3 month visit</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="17"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.94" spread="3.42"/>
                    <measurement group_id="O2" value="2.78" spread="3.14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Functional Outcome Using a Battery That Includes Walking Speed, Repeated Chair Stands, and Balance at 3 Months</title>
        <description>More rapidly improved functional outcome using a short physical performance battery to assess lower extremity function (walking speed, repeated chair stands, and balance) at 3 months. Scale is 0 to 100 with higher scores indicating better physical performance.</description>
        <time_frame>3 months</time_frame>
        <population>All persons completing 3 month visit to provide data.</population>
        <group_list>
          <group group_id="O1">
            <title>Teriparatide</title>
            <description>TPTD is supplied as a sterile, colorless, clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable delivery device (pen) for subcutaneous injection. Each prefilled delivery device is filled with 2.7 mL to deliver 2.4 mL. Each mL contains 250 mcg teriparatide (corrected for acetate, chloride, and water content), 0.41 mg glacial acetic acid, 0.1 mg sodium acetate (anhydrous), 45.4 mg mannitol, 3 mg Metacresol, and Water for Injection. In addition, hydrochloric acid solution 10% and/or sodium hydroxide solution 10% may have been added to adjust the product to pH 4.&#xD;
Teriparatide Prefilled Syringe: TPTD 20 mcg</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo is supplied as a sterile, colorless, clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable delivery device (pen) for subcutaneous injection. Each prefilled delivery device is filled with 2.7 mL to deliver 2.4 mL. Each mL contains 0.41 mg glacial acetic acid, 0.1 mg sodium acetate (anhydrous), 45.4 mg mannitol, 3 mg Metacresol, and Water for Injection. In addition, hydrochloric acid solution 10% and/or sodium hydroxide solution 10% may have been added to adjust the product to pH 4.&#xD;
Placebo: Matching placebo as a prefilled syringe with all inactive ingredients</description>
          </group>
        </group_list>
        <measure>
          <title>Functional Outcome Using a Battery That Includes Walking Speed, Repeated Chair Stands, and Balance at 3 Months</title>
          <description>More rapidly improved functional outcome using a short physical performance battery to assess lower extremity function (walking speed, repeated chair stands, and balance) at 3 months. Scale is 0 to 100 with higher scores indicating better physical performance.</description>
          <population>All persons completing 3 month visit to provide data.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="74.2" spread="3.6"/>
                    <measurement group_id="O2" value="59.9" spread="4.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Physical Function at 12 Months Using a Battery That Includes Walking Speed, Repeated Chair Stands, and Balance</title>
        <description>More rapidly improved functional outcome using a short physical performance battery to assess lower extremity function (walking speed, repeated chair stands, and balance) at 12 months. Scale is 0 to 100 with higher scores indicating better performance.</description>
        <time_frame>12 months</time_frame>
        <population>Participants providing 12 month data and taking study drug during extension</population>
        <group_list>
          <group group_id="O1">
            <title>Teriparatide</title>
            <description>TPTD is supplied as a sterile, colorless, clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable delivery device (pen) for subcutaneous injection. Each prefilled delivery device is filled with 2.7 mL to deliver 2.4 mL. Each mL contains 250 mcg teriparatide (corrected for acetate, chloride, and water content), 0.41 mg glacial acetic acid, 0.1 mg sodium acetate (anhydrous), 45.4 mg mannitol, 3 mg Metacresol, and Water for Injection. In addition, hydrochloric acid solution 10% and/or sodium hydroxide solution 10% may have been added to adjust the product to pH 4.&#xD;
Teriparatide Prefilled Syringe: TPTD 20 mcg</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo is supplied as a sterile, colorless, clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable delivery device (pen) for subcutaneous injection. Each prefilled delivery device is filled with 2.7 mL to deliver 2.4 mL. Each mL contains 0.41 mg glacial acetic acid, 0.1 mg sodium acetate (anhydrous), 45.4 mg mannitol, 3 mg Metacresol, and Water for Injection. In addition, hydrochloric acid solution 10% and/or sodium hydroxide solution 10% may have been added to adjust the product to pH 4.&#xD;
Placebo: Matching placebo as a prefilled syringe with all inactive ingredients</description>
          </group>
        </group_list>
        <measure>
          <title>Physical Function at 12 Months Using a Battery That Includes Walking Speed, Repeated Chair Stands, and Balance</title>
          <description>More rapidly improved functional outcome using a short physical performance battery to assess lower extremity function (walking speed, repeated chair stands, and balance) at 12 months. Scale is 0 to 100 with higher scores indicating better performance.</description>
          <population>Participants providing 12 month data and taking study drug during extension</population>
          <units>score on a scale 0-100</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="70.0" spread="3.3"/>
                    <measurement group_id="O2" value="64.9" spread="4.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pain at 12 Months Based on the Numeric Rating Scale</title>
        <description>Pain at 12 months as assessed by the Numeric Rating Scale (0 to 10 where 0 means no pain and 10 worst pain)</description>
        <time_frame>12 months</time_frame>
        <population>Participants who completed 12 month visit</population>
        <group_list>
          <group group_id="O1">
            <title>Teriparatide</title>
            <description>TPTD is supplied as a sterile, colorless, clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable delivery device (pen) for subcutaneous injection. Each prefilled delivery device is filled with 2.7 mL to deliver 2.4 mL. Each mL contains 250 mcg teriparatide (corrected for acetate, chloride, and water content), 0.41 mg glacial acetic acid, 0.1 mg sodium acetate (anhydrous), 45.4 mg mannitol, 3 mg Metacresol, and Water for Injection. In addition, hydrochloric acid solution 10% and/or sodium hydroxide solution 10% may have been added to adjust the product to pH 4.&#xD;
Teriparatide Prefilled Syringe: TPTD 20 mcg</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo is supplied as a sterile, colorless, clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable delivery device (pen) for subcutaneous injection. Each prefilled delivery device is filled with 2.7 mL to deliver 2.4 mL. Each mL contains 0.41 mg glacial acetic acid, 0.1 mg sodium acetate (anhydrous), 45.4 mg mannitol, 3 mg Metacresol, and Water for Injection. In addition, hydrochloric acid solution 10% and/or sodium hydroxide solution 10% may have been added to adjust the product to pH 4.&#xD;
Placebo: Matching placebo as a prefilled syringe with all inactive ingredients</description>
          </group>
        </group_list>
        <measure>
          <title>Pain at 12 Months Based on the Numeric Rating Scale</title>
          <description>Pain at 12 months as assessed by the Numeric Rating Scale (0 to 10 where 0 means no pain and 10 worst pain)</description>
          <population>Participants who completed 12 month visit</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.5" spread="0.4"/>
                    <measurement group_id="O2" value="1.9" spread="0.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>One year</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Teriparatide for 3 Months Then Open Label for 9 Months</title>
          <description>TPTD is supplied as a sterile, colorless, clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable delivery device (pen) for subcutaneous injection. Each prefilled delivery device is filled with 2.7 mL to deliver 2.4 mL. Each mL contains 250 mcg teriparatide (corrected for acetate, chloride, and water content), 0.41 mg glacial acetic acid, 0.1 mg sodium acetate (anhydrous), 45.4 mg mannitol, 3 mg Metacresol, and Water for Injection. In addition, hydrochloric acid solution 10% and/or sodium hydroxide solution 10% may have been added to adjust the product to pH 4.&#xD;
Teriparatide Prefilled Syringe: TPTD 20 mcg</description>
        </group>
        <group group_id="E2">
          <title>Placebo for 3 Months</title>
          <description>Placebo is supplied as a sterile, colorless, clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable delivery device (pen) for subcutaneous injection. Each prefilled delivery device is filled with 2.7 mL to deliver 2.4 mL. Each mL contains 0.41 mg glacial acetic acid, 0.1 mg sodium acetate (anhydrous), 45.4 mg mannitol, 3 mg Metacresol, and Water for Injection. In addition, hydrochloric acid solution 10% and/or sodium hydroxide solution 10% may have been added to adjust the product to pH 4.&#xD;
Placebo: Matching placebo as a prefilled syringe with all inactive ingredients</description>
        </group>
        <group group_id="E3">
          <title>Open Label Teriparatide Following Placebo</title>
          <description>TPTD is supplied as a sterile, colorless, clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable delivery device (pen) for subcutaneous injection. Each prefilled delivery device is filled with 2.7 mL to deliver 2.4 mL. Each mL contains 250 mcg teriparatide (corrected for acetate, chloride, and water content), 0.41 mg glacial acetic acid, 0.1 mg sodium acetate (anhydrous), 45.4 mg mannitol, 3 mg Metacresol, and Water for Injection. In addition, hydrochloric acid solution 10% and/or sodium hydroxide solution 10% may have been added to adjust the product to pH 4.&#xD;
Teriparatide Prefilled Syringe: TPTD 20 mcg</description>
        </group>
      </group_list>
      <serious_events>
        <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="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>hyponatremia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>cardiac</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>dysphagia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>ulcer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>orthopedic procedure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <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="12" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="17"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>nausea vomiting diarrhea</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="18"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="17"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>UTI</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>muscle or joint pain</sub_title>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Fracture</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="17"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>bruising, blotching, squamous cell excision</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Social circumstances</title>
            <event_list>
              <event>
                <sub_title>fatigue, loss of apatite, lethargy</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="17"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>This trial had several limitations. The first is that we were underpowered to find an effect of TPTD on radiographic evidence of fracture healing due to a halt in supply of study medication, therefore, our findings should be considered exploratory. Recruitment was difficult; we screened 363 patients to recruit 35 subjects. It is also difficult to retain an older cohort with multiple underlying comorbidities. We only assessed healing at one time point.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Jeri W. Nieves</name_or_title>
      <organization>Hospital for Special Surgery</organization>
      <phone>2126061604</phone>
      <email>nievesje@hss.edu</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/NCT02972424
org study id: 2015-330
nct id: NCT02972424
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
In the proposed trial the investigators will recruit women and men >65 years of age with
      acute osteoporosis-related pelvic fractures and address 3 specific aims over 3 months of
      treatment in a placebo controlled double blind study to determine if standard care and
      teriparatide 20 mcg/day versus placebo for pelvic fractures:

        1. Results in earlier evidence of cortical bridging on routine radiographs followed by
           confirmatory Focus CT, a novel method to reduce radiation exposure from CT scans
           (primary outcome).

        2. Leads to a faster reduction in pain as assessed by both the Numeric Rating Scale and a
           reduction in the use of narcotics (secondary outcome).

        3. Leads more rapidly to improved functional outcome using a short physical performance
           battery to assess lower extremity function (secondary outcome).
The incidence rate of pelvic fractures increases dramatically with age, from 5.4 and 3.8 per
      10,000 person-years in women and men aged 65 to 69 years to 93.5 and 44.5 per 10,000
      person-years in women and men aged 90 years and older, respectively. Pelvic fractures are
      accompanied by severe pain, chronic immobility and loss of function and independence in the
      elderly. Pelvic fractures consume substantial healthcare resources, and based on
      administrative claims data, they are one of the most costly osteoporosis related fractures.
      Un-healed fractures, occurring in one-third of pelvic fracture patients at 3 months, can
      cause continued pain and impact mobility. With aging of the population, and expected
      concomitant increase in the incidence of pelvic fractures, there is a pressing need to find
      effective treatments that will accelerate healing. Fracture of the pubic ramus is most
      relevant and practical for randomized double-blinded placebo controlled study as this
      fracture is accompanied by severe pain and immobility in elderly, is associated with delayed
      fracture healing, and is almost always treated non-operatively. The current standard of care
      for pelvic fractures includes pain management, patient mobilization, and the prevention of
      complications associated with comorbid conditions. The investigators hypothesize that
      development of a successful adjunctive therapy to accelerate fracture healing would lead to
      improved care and reduce both direct and indirect costs from pelvic fractures. In the
      proposed trial the investigators will recruit women and men >65 years of age with acute
      osteoporosis-related pelvic fractures and address 3 specific aims over 3 months of treatment
      in a placebo controlled double blind study to determine if standard care and teriparatide 20
      mcg/day versus placebo for pelvic fractures:

        1. Results in earlier evidence of cortical bridging on routine radiographs followed by
           confirmatory Focus CT, a novel method to reduce radiation exposure from CT scans
           (primary outcome).

        2. Leads to a faster reduction in pain as assessed by both the Numeric Rating Scale and a
           reduction in the use of narcotics (secondary outcome).

        3. Leads more rapidly to improved functional outcome using a short physical performance
           battery to assess lower extremity function (secondary outcome).

      The investigators will extend this study with 9 months of open label TPTD to determine if any
      potential differences between the placebo and TPTD groups during the 3 months of treatment
      are evident and persist over time, even in patients who use TPTD after the three month
      placebo controlled intervention. If TPTD can improve fracture healing, this study will have
      an impact on the treatment of persons with pelvic fracture who are not surgical candidates
      and often face severe pain, chronic immobility, and loss of function in the elderly. A
      positive finding of accelerated healing of pelvic fractures would also encourage study of
      TPTD for treatment of other osteoporotic fractures.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Number of Participants With Evidence of Cortical Bridging for Fracture Healing
time frame: 3 months
description: Evidence of cortical bridging based on Focus CT,
measure: Change in Pain by Numeric Rating Scale Between Baseline and Three Months
time frame: 3 months
description: Leads to a faster reduction in pain as assessed by the Numeric Rating Scale of 0 (no pain) to 10 (worst pain).
The mean reduction in pain score from 0 to 3 months is reported. Higher scores mean a greater reduction in pain.
measure: Functional Outcome Using a Battery That Includes Walking Speed, Repeated Chair Stands, and Balance at 3 Months
time frame: 3 months
description: More rapidly improved functional outcome using a short physical performance battery to assess lower extremity function (walking speed, repeated chair stands, and balance) at 3 months. Scale is 0 to 100 with higher scores indicating better physical performance.
measure: Physical Function at 12 Months Using a Battery That Includes Walking Speed, Repeated Chair Stands, and Balance
time frame: 12 months
description: More rapidly improved functional outcome using a short physical performance battery to assess lower extremity function (walking speed, repeated chair stands, and balance) at 12 months. Scale is 0 to 100 with higher scores indicating better performance.
measure: Pain at 12 Months Based on the Numeric Rating Scale
time frame: 12 months
description: Pain at 12 months as assessed by the Numeric Rating Scale (0 to 10 where 0 means no pain and 10 worst pain)
arm group label: Teriparatide Prefilled Syringe
arm group type: Experimental
description: TPTD is supplied as a sterile, colorless, clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable delivery device (pen) for subcutaneous injection. Each prefilled delivery device is filled with 2.7 mL to deliver 2.4 mL. Each mL contains 250 mcg teriparatide (corrected for acetate, chloride, and water content), 0.41 mg glacial acetic acid, 0.1 mg sodium acetate (anhydrous), 45.4 mg mannitol, 3 mg Metacresol, and Water for Injection. In addition, hydrochloric acid solution 10% and/or sodium hydroxide solution 10% may have been added to adjust the product to pH 4.
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo is supplied as a sterile, colorless, clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable delivery device (pen) for subcutaneous injection. Each prefilled delivery device is filled with 2.7 mL to deliver 2.4 mL. Each mL contains 0.41 mg glacial acetic acid, 0.1 mg sodium acetate (anhydrous), 45.4 mg mannitol, 3 mg Metacresol, and Water for Injection. In addition, hydrochloric acid solution 10% and/or sodium hydroxide solution 10% may have been added to adjust the product to pH 4.
intervention type: Drug
intervention name: Teriparatide Prefilled Syringe
description: TPTD 20 mcg
arm group label: Teriparatide Prefilled Syringe
other name: Forteo
intervention type: Drug
intervention name: Placebo
description: Matching placebo as a prefilled syringe with all inactive ingredients
arm group label: Placebo
other name: Placebo prefilled syringe
criteria: 
gender: All
minimum age: 65 Years
maximum age: N/A
healthy volunteers: No
last name: Jeri W Nieves, PhD
role: Principal Investigator
affiliation: Hospital for Special Surgery, New York
facility: 
country: United States
citation: Nieves JW, Cosman F, McMahon D, Redko M, Hentschel I, Bartolotta R, Loftus M, Kazam JJ, Rotman J, Lane J. Teriparatide and pelvic fracture healing: a phase 2 randomized controlled trial. Osteoporos Int. 2022 Jan;33(1):239-250. doi: 10.1007/s00198-021-06065-4. Epub 2021 Aug 12.
PMID: 34383100
responsible party type: Sponsor
mesh term: Fractures, Bone
mesh term: Osteoporotic Fractures
mesh term: Hip Fractures
mesh term: Teriparatide
sharing ipd: Yes
ipd description: The investigators will make the data available for sharing 12-months after the publication of the primary paper. SAS datasets, a data dictionary, images of case report forms, SAS format library, the SAS program in which source data is recoded for analysis and data table summary descriptive statistics for data validation cross-check will be made available on an encrypted USB drive. A data sharing agreement is required.
ipd time frame: 12 months after publication of results for 2 years
ipd access criteria: Submission should be made to Nievesje@hss.edu
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: This trial had several limitations. The first is that we were underpowered to find an effect of TPTD on radiographic evidence of fracture healing due to a halt in supply of study medication, therefore, our findings should be considered exploratory. Recruitment was difficult; we screened 363 patients to recruit 35 subjects. It is also difficult to retain an older cohort with multiple underlying comorbidities. We only assessed healing at one time point.
point of contact: 