<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/NCT02258074</url>
  </required_header>
  <id_info>
    <org_study_id>DK099877-C</org_study_id>
    <secondary_id>U01DK099877</secondary_id>
    <nct_id>NCT02258074</nct_id>
  </id_info>
  <brief_title>The COMBINE Study: The CKD Optimal Management With BInders and NicotinamidE</brief_title>
  <acronym>COMBINE</acronym>
  <official_title>The COMBINE Study: The CKD Optimal Management With BInders and NicotinamidE</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Cleveland Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>The Cleveland Clinic</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The COMBINE clinical trial is a pilot study evaluating the effects of nicotinamide and&#xD;
      lanthanum carbonate on serum phosphate and fibroblast growth factor 23 (FGF23) in patients&#xD;
      with Chronic Kidney Disease (CKD) stages 3-4.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 2015</start_date>
  <completion_date type="Actual">September 2019</completion_date>
  <primary_completion_date type="Actual">November 2018</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>Other</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>FGF23</measure>
    <time_frame>Baseline to 12 months</time_frame>
    <description>Change from baseline to 12 months in FGF23 level.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Serum Phosphate (mg/dl)</measure>
    <time_frame>Baseline to 12 months</time_frame>
    <description>Change from Baseline to 12 months in serum phosphate level</description>
  </primary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">205</enrollment>
  <condition>Chronic Kidney Disease</condition>
  <arm_group>
    <arm_group_label>Lanthanum carbonate + nicotinamide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>One nicotinamide 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two lanthanum carbonate 500 mg capsules by mouth with each meal (3000 mg) for 12 months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Lanthanum carbonate + nicotinamide placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Two lanthanum carbonate 500 mg capsules by mouth with each meal (3000 mg) for 12 months. One Placebo (for nicotinamide) 750 mg capsule by mouth twice daily (1500 mg) for 12 months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Lanthanum carbonate placebo and nicotinamide</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>One nicotinamide 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two Placebo (for lanthanum carbonate) 500 mg capsules by mouth with each meal (3000 mg) for 12 months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Lanthanum carbonate placebo and nicotinamide placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>One Placebo (for nicotinamide) 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two Placebo (for lanthanum carbonate) 500 mg capsules by mouth with each meal (3000 mg) for 12 months.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nicotinamide</intervention_name>
    <arm_group_label>Lanthanum carbonate + nicotinamide</arm_group_label>
    <arm_group_label>Lanthanum carbonate placebo and nicotinamide</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lanthanum Carbonate</intervention_name>
    <arm_group_label>Lanthanum carbonate + nicotinamide</arm_group_label>
    <arm_group_label>Lanthanum carbonate + nicotinamide placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo (for Nicotinamide)</intervention_name>
    <description>Sugar pill manufactured to mimic Nicotinamide 750 mg capsule</description>
    <arm_group_label>Lanthanum carbonate + nicotinamide placebo</arm_group_label>
    <arm_group_label>Lanthanum carbonate placebo and nicotinamide placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo (for lanthanum carbonate)</intervention_name>
    <description>Sugar pill manufactured to mimic Lanthanum Carbonate 500 mg capsule</description>
    <arm_group_label>Lanthanum carbonate placebo and nicotinamide</arm_group_label>
    <arm_group_label>Lanthanum carbonate placebo and nicotinamide placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients with estimated glomerular filtration rate (eGFR) 20-45 ml/min/1.73m2&#xD;
&#xD;
          2. Age 18-85 years&#xD;
&#xD;
          3. Serum phosphate ≥ 2.8 mg/dL&#xD;
&#xD;
          4. Platelet count ≥ 125,000/mm3&#xD;
&#xD;
          5. Able to provide consent&#xD;
&#xD;
          6. Able to travel to study visits&#xD;
&#xD;
          7. Able to eat at least two meals a day&#xD;
&#xD;
          8. In the opinion of the site investigator, willing and able to follow the study&#xD;
             treatment regimen and comply with the site investigator's recommendations.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of allergic reaction to nicotinamide, niacin (excluding flushing),&#xD;
             multivitamin preparations, or lanthanum carbonate&#xD;
&#xD;
          2. Liver disease, defined as known cirrhosis by imaging or physician diagnosis,&#xD;
             documented alcohol use &gt; 14 drinks/week, or aspartate aminotransferase (AST), alanine&#xD;
             aminotransferase (ALT), alkaline phosphatase, or total bilirubin concentrations &gt; 2&#xD;
             times the upper limit of the local laboratory reference range&#xD;
&#xD;
          3. Creatine kinase (CK) concentrations &gt; 2 times the upper limit of the local laboratory&#xD;
             reference range&#xD;
&#xD;
          4. Major hemorrhagic event within the past six months requiring in-patient admission&#xD;
&#xD;
          5. Blood or platelet transfusion within the past six months&#xD;
&#xD;
          6. Secondary hyperparathyroidism (PTH &gt; 5 times the upper limit of normal range for the&#xD;
             laboratory) or currently taking cinacalcet (Sensipar)&#xD;
&#xD;
          7. Current, clinically significant malabsorption, as determined at the discretion of the&#xD;
             site investigator&#xD;
&#xD;
          8. Anemia (screening Hg &lt; 9.0 g/dl)&#xD;
&#xD;
          9. Serum albumin &lt; 2.5 mg/dl&#xD;
&#xD;
         10. Anticipated initiation of dialysis or kidney transplantation within 12 months as&#xD;
             assessed by and at the discretion of the site investigator.&#xD;
&#xD;
         11. Use of immunosuppressive medications (stable oral steroids ≤ 10 mg of prednisone/day&#xD;
             or inhaled steroids are exempted)&#xD;
&#xD;
         12. In the opinion of the site investigator, active abuse of alcohol or drugs&#xD;
&#xD;
         13. Recent (within the last 14 days) initiation or change in dose of treatment with 1,25&#xD;
             (OH)2 vitamin D or active vitamin D analogues (paricalcitol or hectorol). Patients on&#xD;
             stable doses of these agents initiated more than 14 days prior to screening are&#xD;
             eligible to participate.&#xD;
&#xD;
         14. Current or recent treatment (within the last 14 days) with phosphate binder or&#xD;
             niacin/nicotinamide &gt; 100 mg/day&#xD;
&#xD;
         15. Current participation in another clinical trial or other interventional research&#xD;
&#xD;
         16. Currently taking investigational drugs&#xD;
&#xD;
         17. Institutionalized individuals, including prisoners and nursing home residents&#xD;
&#xD;
         18. Malignancy requiring therapy within 2 years (basal or squamous cell skin carcinoma and&#xD;
             localized prostate cancer are exempted)&#xD;
&#xD;
             -&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael F. Flessner, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)</affiliation>
  </overall_official>
  <overall_official>
    <last_name>John W. Kusek, PhD</last_name>
    <role>Study Director</role>
    <affiliation>National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jennifer J Gassman, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Data Coordinating Center, Cleveland Clinic</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Linda F Fried, MD</last_name>
    <role>Study Chair</role>
    <affiliation>University of Pittsburgh</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California at San Diego</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92161</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Denver Nephrology Research</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80230</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>George Washington University</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20037</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NorthShore University Health System</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern University</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Utah VA</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Isakova T, Ix JH, Sprague SM, Raphael KL, Fried L, Gassman JJ, Raj D, Cheung AK, Kusek JW, Flessner MF, Wolf M, Block GA. Rationale and Approaches to Phosphate and Fibroblast Growth Factor 23 Reduction in CKD. J Am Soc Nephrol. 2015 Oct;26(10):2328-39. doi: 10.1681/ASN.2015020117. Epub 2015 May 12.</citation>
    <PMID>25967123</PMID>
  </reference>
  <results_reference>
    <citation>Ix JH, Isakova T, Larive B, Raphael KL, Raj DS, Cheung AK, Sprague SM, Fried LF, Gassman JJ, Middleton JP, Flessner MF, Block GA, Wolf M. Effects of Nicotinamide and Lanthanum Carbonate on Serum Phosphate and Fibroblast Growth Factor-23 in CKD: The COMBINE Trial. J Am Soc Nephrol. 2019 Jun;30(6):1096-1108. doi: 10.1681/ASN.2018101058. Epub 2019 May 13.</citation>
    <PMID>31085679</PMID>
  </results_reference>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>July 28, 2014</study_first_submitted>
  <study_first_submitted_qc>October 2, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 7, 2014</study_first_posted>
  <results_first_submitted>October 30, 2020</results_first_submitted>
  <results_first_submitted_qc>July 29, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">July 30, 2021</results_first_posted>
  <last_update_submitted>July 29, 2021</last_update_submitted>
  <last_update_submitted_qc>July 29, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 2, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The Cleveland Clinic</investigator_affiliation>
    <investigator_full_name>Jennifer Gassman, PhD</investigator_full_name>
    <investigator_title>Principal Investigator-Data Coordinating Center</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Renal Insufficiency, Chronic</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Niacinamide</mesh_term>
    <mesh_term>Niacin</mesh_term>
    <mesh_term>Nicotinic Acids</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>The study data will be archived in the NIDDK Data Repository.</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_info_type>Analytic Code</ipd_info_type>
    <ipd_time_frame>We anticipate that the data and documentation will be provided to the NIDDK Data Repository in March 2020 and will become available approximately six months later.</ipd_time_frame>
  </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 22, 2015</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/74/NCT02258074/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>December 7, 2015</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/74/NCT02258074/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Lanthanum Carbonate + Nicotinamide</title>
          <description>One nicotinamide 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two lanthanum carbonate 500 mg capsules by mouth with each meal (3000 mg) for 12 months.&#xD;
Nicotinamide&#xD;
Lanthanum Carbonate</description>
        </group>
        <group group_id="P2">
          <title>Lanthanum Carbonate + Nicotinamide Placebo</title>
          <description>Two lanthanum carbonate 500 mg capsules by mouth with each meal (3000 mg) for 12 months. One Placebo (for nicotinamide) 750 mg capsule by mouth twice daily (1500 mg) for 12 months.&#xD;
Lanthanum Carbonate&#xD;
Placebo (for Nicotinamide): Sugar pill manufactured to mimic Nicotinamide 750 mg capsule</description>
        </group>
        <group group_id="P3">
          <title>Lanthanum Carbonate Placebo and Nicotinamide</title>
          <description>One nicotinamide 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two Placebo (for lanthanum carbonate) 500 mg capsules by mouth with each meal (3000 mg) for 12 months.&#xD;
Nicotinamide&#xD;
Placebo (for lanthanum carbonate): Sugar pill manufactured to mimic Lanthanum Carbonate 500 mg capsule</description>
        </group>
        <group group_id="P4">
          <title>Lanthanum Carbonate Placebo and Nicotinamide Placebo</title>
          <description>One Placebo (for nicotinamide) 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two Placebo (for lanthanum carbonate) 500 mg capsules by mouth with each meal (3000 mg) for 12 months.&#xD;
Placebo (for Nicotinamide): Sugar pill manufactured to mimic Nicotinamide 750 mg capsule&#xD;
Placebo (for lanthanum carbonate): Sugar pill manufactured to mimic Lanthanum Carbonate 500 mg capsule</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="53"/>
                <participants group_id="P2" count="50"/>
                <participants group_id="P3" count="51"/>
                <participants group_id="P4" count="51"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="52"/>
                <participants group_id="P2" count="50"/>
                <participants group_id="P3" count="51"/>
                <participants group_id="P4" count="51"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Lanthanum Carbonate + Nicotinamide</title>
          <description>One nicotinamide 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two lanthanum carbonate 500 mg capsules by mouth with each meal (3000 mg) for 12 months.&#xD;
Nicotinamide&#xD;
Lanthanum Carbonate</description>
        </group>
        <group group_id="B2">
          <title>Lanthanum Carbonate + Nicotinamide Placebo</title>
          <description>Two lanthanum carbonate 500 mg capsules by mouth with each meal (3000 mg) for 12 months. One Placebo (for nicotinamide) 750 mg capsule by mouth twice daily (1500 mg) for 12 months.&#xD;
Lanthanum Carbonate&#xD;
Placebo (for Nicotinamide): Sugar pill manufactured to mimic Nicotinamide 750 mg capsule</description>
        </group>
        <group group_id="B3">
          <title>Lanthanum Carbonate Placebo and Nicotinamide</title>
          <description>One nicotinamide 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two Placebo (for lanthanum carbonate) 500 mg capsules by mouth with each meal (3000 mg) for 12 months.&#xD;
Nicotinamide&#xD;
Placebo (for lanthanum carbonate): Sugar pill manufactured to mimic Lanthanum Carbonate 500 mg capsule</description>
        </group>
        <group group_id="B4">
          <title>Lanthanum Carbonate Placebo and Nicotinamide Placebo</title>
          <description>One Placebo (for nicotinamide) 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two Placebo (for lanthanum carbonate) 500 mg capsules by mouth with each meal (3000 mg) for 12 months.&#xD;
Placebo (for Nicotinamide): Sugar pill manufactured to mimic Nicotinamide 750 mg capsule&#xD;
Placebo (for lanthanum carbonate): Sugar pill manufactured to mimic Lanthanum Carbonate 500 mg capsule</description>
        </group>
        <group group_id="B5">
          <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="53"/>
            <count group_id="B2" value="50"/>
            <count group_id="B3" value="51"/>
            <count group_id="B4" value="51"/>
            <count group_id="B5" value="205"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="69" spread="12"/>
                    <measurement group_id="B2" value="67" spread="13"/>
                    <measurement group_id="B3" value="70" spread="12"/>
                    <measurement group_id="B4" value="69" spread="10"/>
                    <measurement group_id="B5" value="69" spread="12"/>
                  </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="20"/>
                    <measurement group_id="B2" value="22"/>
                    <measurement group_id="B3" value="17"/>
                    <measurement group_id="B4" value="18"/>
                    <measurement group_id="B5" value="77"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="33"/>
                    <measurement group_id="B2" value="28"/>
                    <measurement group_id="B3" value="34"/>
                    <measurement group_id="B4" value="33"/>
                    <measurement group_id="B5" value="128"/>
                  </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="5"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="22"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="48"/>
                    <measurement group_id="B2" value="44"/>
                    <measurement group_id="B3" value="46"/>
                    <measurement group_id="B4" value="45"/>
                    <measurement group_id="B5" value="183"/>
                  </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 group_id="B4" value="0"/>
                    <measurement group_id="B5" 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="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="10"/>
                  </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 group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="9"/>
                    <measurement group_id="B4" value="16"/>
                    <measurement group_id="B5" value="52"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="35"/>
                    <measurement group_id="B2" value="32"/>
                    <measurement group_id="B3" value="37"/>
                    <measurement group_id="B4" value="32"/>
                    <measurement group_id="B5" value="136"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" 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>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="53"/>
                    <measurement group_id="B2" value="50"/>
                    <measurement group_id="B3" value="51"/>
                    <measurement group_id="B4" value="51"/>
                    <measurement group_id="B5" value="205"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Diabetes Mellitus</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                    <measurement group_id="B2" value="33"/>
                    <measurement group_id="B3" value="23"/>
                    <measurement group_id="B4" value="25"/>
                    <measurement group_id="B5" value="112"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Systolic BP</title>
          <units>mm Hg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="126.0" spread="15.0"/>
                    <measurement group_id="B2" value="129.2" spread="17.2"/>
                    <measurement group_id="B3" value="129.7" spread="15.3"/>
                    <measurement group_id="B4" value="129.3" spread="21.2"/>
                    <measurement group_id="B5" value="128.5" spread="17.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Diastolic BP</title>
          <units>mm Hg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="70.2" spread="11.1"/>
                    <measurement group_id="B2" value="71.1" spread="11.7"/>
                    <measurement group_id="B3" value="72.0" spread="12.5"/>
                    <measurement group_id="B4" value="71.5" spread="12.8"/>
                    <measurement group_id="B5" value="71.2" spread="12.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body Mass Index</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="33.2" spread="8.5"/>
                    <measurement group_id="B2" value="30.9" spread="6.3"/>
                    <measurement group_id="B3" value="32.5" spread="8.1"/>
                    <measurement group_id="B4" value="31.0" spread="6.1"/>
                    <measurement group_id="B5" value="31.9" spread="7.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>eGFR</title>
          <units>(ml/min/1.73m^2)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="32.2" spread="7.2"/>
                    <measurement group_id="B2" value="33.0" spread="7.9"/>
                    <measurement group_id="B3" value="32.1" spread="7.1"/>
                    <measurement group_id="B4" value="32.3" spread="7.0"/>
                    <measurement group_id="B5" value="32.4" spread="7.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Urine Albumin Creatinine Ratio</title>
          <units>(g/g) (range is 10th and 90th pctl)</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0.1" lower_limit="0.0" upper_limit="1.1"/>
                    <measurement group_id="B2" value="0.2" lower_limit="0.0" upper_limit="1.7"/>
                    <measurement group_id="B3" value="0.1" lower_limit="0.0" upper_limit="1.4"/>
                    <measurement group_id="B4" value="0.2" lower_limit="0.0" upper_limit="1.3"/>
                    <measurement group_id="B5" value="0.1" lower_limit="0.0" upper_limit="1.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Calcitriol Use</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="10"/>
                    <measurement group_id="B3" value="13"/>
                    <measurement group_id="B4" value="10"/>
                    <measurement group_id="B5" value="41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Serum Phosphate</title>
          <units>mg/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3.6" spread="0.5"/>
                    <measurement group_id="B2" value="3.7" spread="0.6"/>
                    <measurement group_id="B3" value="3.8" spread="0.5"/>
                    <measurement group_id="B4" value="3.6" spread="0.5"/>
                    <measurement group_id="B5" value="3.7" spread="0.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Serum FGF-23</title>
          <units>pg/ml (range is 10th to 90th pctls)</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="104.0" lower_limit="57.3" upper_limit="188.4"/>
                    <measurement group_id="B2" value="94.8" lower_limit="48.9" upper_limit="188.3"/>
                    <measurement group_id="B3" value="103.5" lower_limit="60.9" upper_limit="192.3"/>
                    <measurement group_id="B4" value="96.4" lower_limit="62.9" upper_limit="224.7"/>
                    <measurement group_id="B5" value="98.8" lower_limit="58.8" upper_limit="205.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Serum Calcium</title>
          <units>mg/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9.5" spread="0.5"/>
                    <measurement group_id="B2" value="9.5" spread="0.5"/>
                    <measurement group_id="B3" value="9.5" spread="0.5"/>
                    <measurement group_id="B4" value="9.5" spread="0.5"/>
                    <measurement group_id="B5" value="9.5" spread="0.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Intact PTH</title>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="121.4" spread="88.7"/>
                    <measurement group_id="B2" value="123.2" spread="75.8"/>
                    <measurement group_id="B3" value="115.6" spread="80.4"/>
                    <measurement group_id="B4" value="124.6" spread="94.7"/>
                    <measurement group_id="B5" value="121.2" spread="84.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Urine Phosphorus</title>
          <units>mg/24 hrs</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="657.4" spread="265.2"/>
                    <measurement group_id="B2" value="658.5" spread="267.9"/>
                    <measurement group_id="B3" value="712.8" spread="235.0"/>
                    <measurement group_id="B4" value="644.4" spread="245.2"/>
                    <measurement group_id="B5" value="668.1" spread="252.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Phosphorus/Creatinine Ratio</title>
          <units>mg/g</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="447.0" spread="146.1"/>
                    <measurement group_id="B2" value="451.6" spread="120.9"/>
                    <measurement group_id="B3" value="487.4" spread="126.4"/>
                    <measurement group_id="B4" value="462.9" spread="130.7"/>
                    <measurement group_id="B5" value="462.1" spread="131.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>FGF23</title>
        <description>Change from baseline to 12 months in FGF23 level.</description>
        <time_frame>Baseline to 12 months</time_frame>
        <population>Adults with CKD</population>
        <group_list>
          <group group_id="O1">
            <title>Lanthanum Carbonate + Nicotinamide</title>
            <description>One nicotinamide 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two lanthanum carbonate 500 mg capsules by mouth with each meal (3000 mg) for 12 months.&#xD;
Nicotinamide&#xD;
Lanthanum Carbonate</description>
          </group>
          <group group_id="O2">
            <title>Lanthanum Carbonate + Nicotinamide Placebo</title>
            <description>Two lanthanum carbonate 500 mg capsules by mouth with each meal (3000 mg) for 12 months. One Placebo (for nicotinamide) 750 mg capsule by mouth twice daily (1500 mg) for 12 months.&#xD;
Lanthanum Carbonate&#xD;
Placebo (for Nicotinamide): Sugar pill manufactured to mimic Nicotinamide 750 mg capsule</description>
          </group>
          <group group_id="O3">
            <title>Lanthanum Carbonate Placebo and Nicotinamide</title>
            <description>One nicotinamide 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two Placebo (for lanthanum carbonate) 500 mg capsules by mouth with each meal (3000 mg) for 12 months.&#xD;
Nicotinamide&#xD;
Placebo (for lanthanum carbonate): Sugar pill manufactured to mimic Lanthanum Carbonate 500 mg capsule</description>
          </group>
          <group group_id="O4">
            <title>Lanthanum Carbonate Placebo and Nicotinamide Placebo</title>
            <description>One Placebo (for nicotinamide) 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two Placebo (for lanthanum carbonate) 500 mg capsules by mouth with each meal (3000 mg) for 12 months.&#xD;
Placebo (for Nicotinamide): Sugar pill manufactured to mimic Nicotinamide 750 mg capsule&#xD;
Placebo (for lanthanum carbonate): Sugar pill manufactured to mimic Lanthanum Carbonate 500 mg capsule</description>
          </group>
        </group_list>
        <measure>
          <title>FGF23</title>
          <description>Change from baseline to 12 months in FGF23 level.</description>
          <population>Adults with CKD</population>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="53"/>
                <count group_id="O2" value="50"/>
                <count group_id="O3" value="51"/>
                <count group_id="O4" value="51"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value=".047" lower_limit="-.056" upper_limit=".151"/>
                    <measurement group_id="O2" value="-.003" lower_limit="-.109" upper_limit=".104"/>
                    <measurement group_id="O3" value=".193" lower_limit=".085" upper_limit=".303"/>
                    <measurement group_id="O4" value=".138" lower_limit=".033" upper_limit=".233"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Serum Phosphate (mg/dl)</title>
        <description>Change from Baseline to 12 months in serum phosphate level</description>
        <time_frame>Baseline to 12 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Lanthanum Carbonate + Nicotinamide</title>
            <description>One nicotinamide 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two lanthanum carbonate 500 mg capsules by mouth with each meal (3000 mg) for 12 months.&#xD;
Nicotinamide&#xD;
Lanthanum Carbonate</description>
          </group>
          <group group_id="O2">
            <title>Lanthanum Carbonate + Nicotinamide Placebo</title>
            <description>Two lanthanum carbonate 500 mg capsules by mouth with each meal (3000 mg) for 12 months. One Placebo (for nicotinamide) 750 mg capsule by mouth twice daily (1500 mg) for 12 months.&#xD;
Lanthanum Carbonate&#xD;
Placebo (for Nicotinamide): Sugar pill manufactured to mimic Nicotinamide 750 mg capsule</description>
          </group>
          <group group_id="O3">
            <title>Lanthanum Carbonate Placebo and Nicotinamide</title>
            <description>One nicotinamide 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two Placebo (for lanthanum carbonate) 500 mg capsules by mouth with each meal (3000 mg) for 12 months.&#xD;
Nicotinamide&#xD;
Placebo (for lanthanum carbonate): Sugar pill manufactured to mimic Lanthanum Carbonate 500 mg capsule</description>
          </group>
          <group group_id="O4">
            <title>Lanthanum Carbonate Placebo and Nicotinamide Placebo</title>
            <description>One Placebo (for nicotinamide) 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two Placebo (for lanthanum carbonate) 500 mg capsules by mouth with each meal (3000 mg) for 12 months.&#xD;
Placebo (for Nicotinamide): Sugar pill manufactured to mimic Nicotinamide 750 mg capsule&#xD;
Placebo (for lanthanum carbonate): Sugar pill manufactured to mimic Lanthanum Carbonate 500 mg capsule</description>
          </group>
        </group_list>
        <measure>
          <title>Serum Phosphate (mg/dl)</title>
          <description>Change from Baseline to 12 months in serum phosphate level</description>
          <units>mg/dl</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="53"/>
                <count group_id="O2" value="50"/>
                <count group_id="O3" value="51"/>
                <count group_id="O4" value="51"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.06" lower_limit="-0.08" upper_limit="0.20"/>
                    <measurement group_id="O2" value="0.06" lower_limit="-0.09" upper_limit="0.21"/>
                    <measurement group_id="O3" value="0.12" lower_limit="-0.03" upper_limit="0.27"/>
                    <measurement group_id="O4" value="0.12" lower_limit="-0.01" upper_limit="0.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>1 year</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Lanthanum Carbonate + Nicotinamide</title>
          <description>One nicotinamide 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two lanthanum carbonate 500 mg capsules by mouth with each meal (3000 mg) for 12 months.&#xD;
Nicotinamide&#xD;
Lanthanum Carbonate</description>
        </group>
        <group group_id="E2">
          <title>Lanthanum Carbonate + Nicotinamide Placebo</title>
          <description>Two lanthanum carbonate 500 mg capsules by mouth with each meal (3000 mg) for 12 months. One Placebo (for nicotinamide) 750 mg capsule by mouth twice daily (1500 mg) for 12 months.&#xD;
Lanthanum Carbonate&#xD;
Placebo (for Nicotinamide): Sugar pill manufactured to mimic Nicotinamide 750 mg capsule</description>
        </group>
        <group group_id="E3">
          <title>Lanthanum Carbonate Placebo and Nicotinamide</title>
          <description>One nicotinamide 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two Placebo (for lanthanum carbonate) 500 mg capsules by mouth with each meal (3000 mg) for 12 months.&#xD;
Nicotinamide&#xD;
Placebo (for lanthanum carbonate): Sugar pill manufactured to mimic Lanthanum Carbonate 500 mg capsule</description>
        </group>
        <group group_id="E4">
          <title>Lanthanum Carbonate Placebo and Nicotinamide Placebo</title>
          <description>One Placebo (for nicotinamide) 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two Placebo (for lanthanum carbonate) 500 mg capsules by mouth with each meal (3000 mg) for 12 months.&#xD;
Placebo (for Nicotinamide): Sugar pill manufactured to mimic Nicotinamide 750 mg capsule&#xD;
Placebo (for lanthanum carbonate): Sugar pill manufactured to mimic Lanthanum Carbonate 500 mg capsule</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="53"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="53"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="50"/>
                <counts group_id="E3" subjects_affected="14" subjects_at_risk="51"/>
                <counts group_id="E4" subjects_affected="14" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiovascular Hospitalizations</sub_title>
                <counts group_id="E1" events="12" subjects_affected="8" subjects_at_risk="53"/>
                <counts group_id="E2" events="5" subjects_affected="4" subjects_at_risk="50"/>
                <counts group_id="E3" events="6" subjects_affected="4" subjects_at_risk="51"/>
                <counts group_id="E4" events="12" subjects_affected="6" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Endocrine</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="53"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>GI Hospitalizations</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="53"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="50"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatic Hospitalizations</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="53"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infection-related Hospitalizations</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="53"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="50"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="51"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Injury</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="53"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Musculoskeletal</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="53"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="51"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Malignancy</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="53"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Nervous System</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="53"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Reached ESRD (dialysis or transplant)</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="53"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="51"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Renal Hospitalizations</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="53"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="50"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Respiratory</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="53"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Surgical and Medical Procedures</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="53"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="51"/>
              </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="33" subjects_at_risk="53"/>
                <counts group_id="E2" subjects_affected="29" subjects_at_risk="50"/>
                <counts group_id="E3" subjects_affected="30" subjects_at_risk="51"/>
                <counts group_id="E4" subjects_affected="26" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Bruising</sub_title>
                <counts group_id="E1" events="57" subjects_affected="20" subjects_at_risk="53"/>
                <counts group_id="E2" events="32" subjects_affected="16" subjects_at_risk="50"/>
                <counts group_id="E3" events="55" subjects_affected="21" subjects_at_risk="51"/>
                <counts group_id="E4" events="47" subjects_affected="18" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Bleeding</sub_title>
                <counts group_id="E1" events="18" subjects_affected="10" subjects_at_risk="53"/>
                <counts group_id="E2" events="21" subjects_affected="13" subjects_at_risk="50"/>
                <counts group_id="E3" events="22" subjects_affected="10" subjects_at_risk="51"/>
                <counts group_id="E4" events="14" subjects_affected="7" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Platelets &lt; 100,000</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="53"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E4" events="4" subjects_affected="2" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Creatine Kinase &gt; 800 U/L</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="53"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea (severe)</sub_title>
                <counts group_id="E1" events="20" subjects_affected="11" subjects_at_risk="53"/>
                <counts group_id="E2" events="15" subjects_affected="9" subjects_at_risk="50"/>
                <counts group_id="E3" events="9" subjects_affected="4" subjects_at_risk="51"/>
                <counts group_id="E4" events="4" subjects_affected="4" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Heartburn (severe)</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="53"/>
                <counts group_id="E2" events="5" subjects_affected="3" subjects_at_risk="50"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E4" events="6" subjects_affected="4" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Diarrhea (severe)</sub_title>
                <counts group_id="E1" events="22" subjects_affected="12" subjects_at_risk="53"/>
                <counts group_id="E2" events="8" subjects_affected="5" subjects_at_risk="50"/>
                <counts group_id="E3" events="14" subjects_affected="8" subjects_at_risk="51"/>
                <counts group_id="E4" events="15" subjects_affected="7" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Liver Function Abnormalities</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="53"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Hives</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="53"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="50"/>
                <counts group_id="E3" events="13" subjects_affected="9" subjects_at_risk="51"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Serum Phosphate &gt;= 5.9 mg/dl</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="53"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="50"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Serum Phosphate &lt; 1.5 mg/dl</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="53"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Flushing</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="53"/>
                <counts group_id="E2" events="14" subjects_affected="5" subjects_at_risk="50"/>
                <counts group_id="E3" events="7" subjects_affected="4" subjects_at_risk="51"/>
                <counts group_id="E4" events="8" subjects_affected="4" subjects_at_risk="51"/>
              </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>
    <point_of_contact>
      <name_or_title>Jennifer J. Gassman, PhD</name_or_title>
      <organization>Cleveland Clinic Foundation</organization>
      <phone>216-444-9938</phone>
      <email>gassmaj@ccf.org</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/NCT02258074
org study id: DK099877-C
secondary id: U01DK099877
nct id: NCT02258074
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The COMBINE clinical trial is a pilot study evaluating the effects of nicotinamide and
      lanthanum carbonate on serum phosphate and fibroblast growth factor 23 (FGF23) in patients
      with Chronic Kidney Disease (CKD) stages 3-4.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: Triple (Participant, Care Provider, Investigator)
measure: FGF23
time frame: Baseline to 12 months
description: Change from baseline to 12 months in FGF23 level.
measure: Serum Phosphate (mg/dl)
time frame: Baseline to 12 months
description: Change from Baseline to 12 months in serum phosphate level
arm group label: Lanthanum carbonate + nicotinamide
arm group type: Experimental
description: One nicotinamide 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two lanthanum carbonate 500 mg capsules by mouth with each meal (3000 mg) for 12 months.
arm group label: Lanthanum carbonate + nicotinamide placebo
arm group type: Placebo Comparator
description: Two lanthanum carbonate 500 mg capsules by mouth with each meal (3000 mg) for 12 months. One Placebo (for nicotinamide) 750 mg capsule by mouth twice daily (1500 mg) for 12 months.
arm group label: Lanthanum carbonate placebo and nicotinamide
arm group type: Active Comparator
description: One nicotinamide 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two Placebo (for lanthanum carbonate) 500 mg capsules by mouth with each meal (3000 mg) for 12 months.
arm group label: Lanthanum carbonate placebo and nicotinamide placebo
arm group type: Placebo Comparator
description: One Placebo (for nicotinamide) 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two Placebo (for lanthanum carbonate) 500 mg capsules by mouth with each meal (3000 mg) for 12 months.
intervention type: Drug
intervention name: Nicotinamide
arm group label: Lanthanum carbonate + nicotinamide
arm group label: Lanthanum carbonate placebo and nicotinamide
intervention type: Drug
intervention name: Lanthanum Carbonate
arm group label: Lanthanum carbonate + nicotinamide
arm group label: Lanthanum carbonate + nicotinamide placebo
intervention type: Drug
intervention name: Placebo (for Nicotinamide)
description: Sugar pill manufactured to mimic Nicotinamide 750 mg capsule
arm group label: Lanthanum carbonate + nicotinamide placebo
arm group label: Lanthanum carbonate placebo and nicotinamide placebo
intervention type: Drug
intervention name: Placebo (for lanthanum carbonate)
description: Sugar pill manufactured to mimic Lanthanum Carbonate 500 mg capsule
arm group label: Lanthanum carbonate placebo and nicotinamide
arm group label: Lanthanum carbonate placebo and nicotinamide placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Michael F. Flessner, MD, PhD
role: Study Director
affiliation: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
last name: John W. Kusek, PhD
role: Study Director
affiliation: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
last name: Jennifer J Gassman, Ph.D.
role: Principal Investigator
affiliation: Data Coordinating Center, Cleveland Clinic
last name: Linda F Fried, MD
role: Study Chair
affiliation: University of Pittsburgh
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
citation: Isakova T, Ix JH, Sprague SM, Raphael KL, Fried L, Gassman JJ, Raj D, Cheung AK, Kusek JW, Flessner MF, Wolf M, Block GA. Rationale and Approaches to Phosphate and Fibroblast Growth Factor 23 Reduction in CKD. J Am Soc Nephrol. 2015 Oct;26(10):2328-39. doi: 10.1681/ASN.2015020117. Epub 2015 May 12.
PMID: 25967123
citation: Ix JH, Isakova T, Larive B, Raphael KL, Raj DS, Cheung AK, Sprague SM, Fried LF, Gassman JJ, Middleton JP, Flessner MF, Block GA, Wolf M. Effects of Nicotinamide and Lanthanum Carbonate on Serum Phosphate and Fibroblast Growth Factor-23 in CKD: The COMBINE Trial. J Am Soc Nephrol. 2019 Jun;30(6):1096-1108. doi: 10.1681/ASN.2018101058. Epub 2019 May 13.
PMID: 31085679
responsible party type: Principal Investigator
investigator affiliation: The Cleveland Clinic
investigator full name: Jennifer Gassman, PhD
investigator title: Principal Investigator-Data Coordinating Center
mesh term: Kidney Diseases
mesh term: Renal Insufficiency, Chronic
mesh term: Niacinamide
mesh term: Niacin
mesh term: Nicotinic Acids
sharing ipd: Yes
ipd description: The study data will be archived in the NIDDK Data Repository.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Clinical Study Report (CSR)
ipd info type: Analytic Code
ipd time frame: We anticipate that the data and documentation will be provided to the NIDDK Data Repository in March 2020 and will become available approximately six months later.
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 