<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/NCT02245620</url>
  </required_header>
  <id_info>
    <org_study_id>SPITM-201</org_study_id>
    <nct_id>NCT02245620</nct_id>
  </id_info>
  <brief_title>A Phase 2 Study to Evaluate the Impact of MTP-131 (Bendavia™) on Skeletal Muscle Function in Elderly</brief_title>
  <acronym>MOTION</acronym>
  <official_title>A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Impact of a Single Intravenous Dose of MTP-131 (Bendavia™) on Skeletal Muscle Function in the Elderly</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Stealth BioTherapeutics Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Stealth BioTherapeutics Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This was a Phase 2, randomized, double-blind, placebo-controlled study, enrolling 41 elderly&#xD;
      subjects with previous evidence of mitochondrial dysfunction to evaluate whether the&#xD;
      administration of MTP-131 (elamipretide) will change either hand skeletal muscle energetics&#xD;
      or muscle performance in age-related skeletal muscle mitochondrial dysfunction.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This was a Phase 2, randomized, double-blind, placebo-controlled study, enrolling 41 elderly&#xD;
      subjects with previous evidence of mitochondrial dysfunction to evaluate whether the&#xD;
      administration of MTP-131 (elamipretide) will change either hand skeletal muscle energetics&#xD;
      or muscle performance in age-related skeletal muscle mitochondrial dysfunction.&#xD;
&#xD;
      Subjects were randomized 1:1 to receive either elamipretide at 0.25 mg/kg/hr intravenously at&#xD;
      a rate of 60 mL/hr for 2 hours, or placebo (lyophilized excipients without elamipretide)&#xD;
      intravenously at a rate of 60 mL/hr for 2 hours. Each treatment group went through three&#xD;
      distinct periods: Screening (up to 28 days), Treatment (1day), and Observation (7 days).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 15, 2015</start_date>
  <completion_date type="Actual">July 6, 2016</completion_date>
  <primary_completion_date type="Actual">July 6, 2016</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>Change From Baseline in ATPmax (Maximal ATP Synthetic Rate)</measure>
    <time_frame>From Baseline, Day 1 Hour 2 (2 hours after the start of infusion, or end of infusion) and Day 7</time_frame>
    <description>Maximal ATP synthetic rate (phosphorylation capacity per unit muscle volume) as determined by a muscle fatigue test.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in Phosphate/Oxygen (P/O) Ratio</measure>
    <time_frame>From Baseline, Day 1 Hour 2 (2 hours after the start of infusion, or end of infusion) and Day 7</time_frame>
    <description>As a measure of mitochondrial hand skeletal muscle energetics, mitochondrial coupling, or Phosphate/Oxygen ratio (P/O) was assessed at Baseline, Day 1 Hour 2, and Day 7.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in Nicotine Adenine Dinucleotide (NAD)</measure>
    <time_frame>From Baseline, Day 1 Hour 2 (2 hours after the start of infusion, or end of infusion) and Day 7</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in Muscle Force-Time-Integral (FTI)</measure>
    <time_frame>From Baseline to Day 1 Hour 2, Day 3, and Day 7</time_frame>
    <description>Muscle Force-Time-Integral was measured as mean change from baseline at Day 1 Hour 2, Day 3, and Day 7.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">41</enrollment>
  <condition>Skeletal Muscle Mitochondrial Dysfunction in the Elderly</condition>
  <arm_group>
    <arm_group_label>Elamipretide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Elamipretide given as an intravenous infusion of 0.25 mg/kg/hr at a rate of 60 mL/hr for 2 hours.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo (lyophilized excipients without elamipretide) given as an intravenous infusion at a rate of 60 mL/hr for 2 hours.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Elamipretide</intervention_name>
    <description>Elamipretide 0.25 mg/kg/hour administered as an intravenous infusion at the rate of 60 mL/hour for 2 hours</description>
    <arm_group_label>Elamipretide</arm_group_label>
    <other_name>MTP-131</other_name>
    <other_name>Bendavia™</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo administered as intravenous infusion at a rate of 60 mL/hour for 2 hours</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>elamipretide</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Are male and female adults aged ≥60 and ≤85 years&#xD;
&#xD;
          2. Female subjects must be post-menopausal&#xD;
&#xD;
          3. Have in vivo phosphorus-31 (31P) Magnetic Resonance Spectroscopy (MRS) and (Optical&#xD;
             Spectra Scan (OPS) determined maximum adenosine triphosphate synthetic rate (ATPmax) &lt;&#xD;
             0.70 milliMol/second (mM/sec)&#xD;
&#xD;
          4. Have in vivo 31P MRS and OPS determined P/O (Phosphate/Oxygen ratio) &lt; 1.9&#xD;
&#xD;
          5. Are ambulatory and able to perform activities of daily living without assistance&#xD;
&#xD;
          6. Had sufficient venous access for study drug administration and clinical testing.&#xD;
&#xD;
          7. Could speak and read English fluently.&#xD;
&#xD;
          8. Provided informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Had significant disease(s) or condition(s) which, in the opinion of the Investigator,&#xD;
             may have put the subject at risk because of their participation in the study or may&#xD;
             have influenced either the results of the study or the subject's ability to&#xD;
             participate in the study.&#xD;
&#xD;
          2. Had a history of rhabdomyolysis.&#xD;
&#xD;
          3. Had been hospitalized within 3 months prior to Screening for major atherosclerotic&#xD;
             events (e.g., myocardial infarction, target-vessel revascularization, coronary bypass&#xD;
             surgery or stroke) or other major medical condition (as deemed by the Primary&#xD;
             Investigator).&#xD;
&#xD;
          4. Had any metal implants that could not be removed from the body that in the opinion of&#xD;
             the Investigator were a contra-indication for undergoing the MRS procedure or any&#xD;
             other protocol-related procedure.&#xD;
&#xD;
          5. Had an implanted cardiac pacemaker or other implanted cardiac device.&#xD;
&#xD;
          6. Had a serum sodium level &lt;136 milliequivalents per litre (mEq/L) at Screening or&#xD;
             Pre-infusion.&#xD;
&#xD;
          7. Had a hemoglobin level &lt;12 g/dL at Screening or Pre-infusion.&#xD;
&#xD;
          8. Had chronic, uncontrolled hypertension as judged by the Investigator (e.g., Baseline&#xD;
             systolic blood pressure [SBP] &gt;140 mm Hg, diastolic blood pressure [DBP] &gt; 90 mm Hg)&#xD;
             or a SBP &gt;150 mm Hg or DBP &gt;95 mm Hg at the time of Screening or Baseline (if the&#xD;
             initial blood pressure [BP] reading was above these values, the reading may have been&#xD;
             repeated one time within 20 minutes of the initial reading).&#xD;
&#xD;
          9. Had a body mass index (BMI) of &lt;16 or &gt;35 kg/m2.&#xD;
&#xD;
         10. Had a creatinine clearance &lt;45 mL/min as calculated by the Cockcroft Gault equation.&#xD;
&#xD;
         11. Had a 12-lead electrocardiogram (ECG) demonstrating severe bradycardia (heart rate &lt;&#xD;
             40 bpm) or average corrected QC interval (QTc) &gt;450 ms for males and &gt; 470 ms for&#xD;
             females, and in the opinion of the Investigator was clinically significant. (If on the&#xD;
             initial ECG, QTc exceeded 450 ms for males or 470 ms for females, the ECG was to be&#xD;
             repeated 2 more times and the average of the 3 QTc values was to be used to determine&#xD;
             the subject's eligibility).&#xD;
&#xD;
         12. Had a neurologic disorder that in the opinion of the Investigator was a&#xD;
             contra-indication for enrollment into the study.&#xD;
&#xD;
         13. Had any symptoms consistent with or a current diagnosis of peripheral neuropathy, such&#xD;
             as numbness, tingling, pain, or altered sensation of hands or feet.&#xD;
&#xD;
         14. Had an active, systemic autoimmune disease other than autoimmune thyroid disease&#xD;
             (e.g., diabetes, lupus, rheumatoid arthritis) that currently required treatment or was&#xD;
             likely to require treatment during the study.&#xD;
&#xD;
         15. Subject's right hand had a history of mobility impairment, fractures, arthritis, hand&#xD;
             surgery, muscle disease or other injury that may interfere with any study procedure.&#xD;
&#xD;
         16. Had any symptoms consistent with or a current diagnosis of claustrophobia.&#xD;
&#xD;
         17. Had a history of cancer, unless subject had documentation of completed curative&#xD;
             treatment.&#xD;
&#xD;
         18. Had a history of or risk factors (e.g., significant family history, concomitant&#xD;
             medical condition) for deep vein thrombosis or pulmonary embolism.&#xD;
&#xD;
         19. Had a history of serious mental illness as judged by the Investigator.&#xD;
&#xD;
         20. Had a body temperature &gt; 37.5°C at the time of planned dosing.&#xD;
&#xD;
         21. Subjects who in the opinion of the Investigator abused alcohol or drugs.&#xD;
&#xD;
         22. Had donated or received blood or blood products within the past 30 days.&#xD;
&#xD;
         23. Investigator site personnel directly affiliated with this study and/or their immediate&#xD;
             families. Immediate family was defined as a spouse, parent, child, or sibling, whether&#xD;
             biological or legally adopted.&#xD;
&#xD;
         24. Sponsor employees and/or their immediate families. Immediate family was defined as a&#xD;
             spouse, parent, child, or sibling, whether biological or legally adopted.&#xD;
&#xD;
         25. Were currently enrolled in a clinical study involving an investigational product or&#xD;
             non-approved use of a drug or device or concurrently enrolled in any other type of&#xD;
             medical research judged to be scientifically or medically incompatible with this&#xD;
             study.&#xD;
&#xD;
         26. Had participated, within the last 30 days, in a clinical study involving an&#xD;
             investigational product. If the previous investigational product had a long half-life,&#xD;
             3 months or 5 half-lives (whichever was longer) should have passed.&#xD;
&#xD;
         27. Had previously been randomized into any study investigating elamipretide or been&#xD;
             exposed to elamipretide for any reason.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>60 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jim Carr</last_name>
    <role>Study Director</role>
    <affiliation>Stealth BioTherapeutics</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The University of Washington Medical Center</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>September 17, 2014</study_first_submitted>
  <study_first_submitted_qc>September 17, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 19, 2014</study_first_posted>
  <results_first_submitted>May 31, 2020</results_first_submitted>
  <results_first_submitted_qc>June 20, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">June 23, 2020</results_first_posted>
  <last_update_submitted>June 20, 2020</last_update_submitted>
  <last_update_submitted_qc>June 20, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 23, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Skeletal muscle dysfunction, MTP-131, Bendavia™</keyword>
  <keyword>elamipretide</keyword>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>2 subjects discontinued prematurely as per Investigator's discretion. These 2 subjects (Subject 001019 [Elamipretide group] and Subject 001063 [Placebo group]) were discontinued after randomization but prior to receiving study treatment; both were not treated due to their pre-infusion sodium levels meeting Exclusion Criteria 6.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Elamipretide</title>
          <description>Elamipretide administered as an intravenous infusion of 0.25 mg/kg/hr at a rate of 60 mL/hr for 2 hours.</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Placebo administered as intravenous infusion at a rate of 60 mL/hour for 2 hours</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="21"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
                <participants group_id="P2" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>MTP-131 (Bendavia™)</title>
          <description>MTP-131 (Bendavia™) administered as an intravenous infusion of 0.25 mg/kg/hr at a rate of 60 mL/hr for 2 hours.</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Placebo administered as intravenous infusion at a rate of 60 mL/hour for 2 hours</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="19"/>
            <count group_id="B2" value="20"/>
            <count group_id="B3" value="39"/>
          </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="67.9" spread="3.35"/>
                    <measurement group_id="B2" value="69.0" spread="3.96"/>
                    <measurement group_id="B3" value="68.5" spread="3.67"/>
                  </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="11"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="21"/>
                  </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="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="37"/>
                  </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="1"/>
                  </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="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</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>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="18"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="38"/>
                  </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="19"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body Mass index</title>
          <units>kg/m²</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="26.5" spread="4.27"/>
                    <measurement group_id="B2" value="26.1" spread="2.82"/>
                    <measurement group_id="B3" value="26.3" spread="3.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in ATPmax (Maximal ATP Synthetic Rate)</title>
        <description>Maximal ATP synthetic rate (phosphorylation capacity per unit muscle volume) as determined by a muscle fatigue test.</description>
        <time_frame>From Baseline, Day 1 Hour 2 (2 hours after the start of infusion, or end of infusion) and Day 7</time_frame>
        <population>All participants for whom Maximal ATP synthetic rate was measured at baseline and Day 1 Hour 2, and Day 7</population>
        <group_list>
          <group group_id="O1">
            <title>MTP-131 (Bendavia™)</title>
            <description>MTP-131 (Bendavia™) administered as an intravenous infusion of 0.25 mg/kg/hr at a rate of 60 mL/hr for 2 hours.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo administered as intravenous infusion at a rate of 60 mL/hour for 2 hours</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in ATPmax (Maximal ATP Synthetic Rate)</title>
          <description>Maximal ATP synthetic rate (phosphorylation capacity per unit muscle volume) as determined by a muscle fatigue test.</description>
          <population>All participants for whom Maximal ATP synthetic rate was measured at baseline and Day 1 Hour 2, and Day 7</population>
          <units>mM/sec</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1 Hour 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.17" spread="0.196"/>
                    <measurement group_id="O2" value="0.12" spread="0.244"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.09" spread="0.142"/>
                    <measurement group_id="O2" value="0.06" spread="0.172"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in Phosphate/Oxygen (P/O) Ratio</title>
        <description>As a measure of mitochondrial hand skeletal muscle energetics, mitochondrial coupling, or Phosphate/Oxygen ratio (P/O) was assessed at Baseline, Day 1 Hour 2, and Day 7.</description>
        <time_frame>From Baseline, Day 1 Hour 2 (2 hours after the start of infusion, or end of infusion) and Day 7</time_frame>
        <population>All participants for whom Phosphate/Oxygen (P/O) ratio was measured at baseline and Day 1 Hour 2, and Day 7</population>
        <group_list>
          <group group_id="O1">
            <title>MTP-131 (Bendavia™)</title>
            <description>MTP-131 (Bendavia™) administered as an intravenous infusion of 0.25 mg/kg/hr at a rate of 60 mL/hr for 2 hours.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo administered as intravenous infusion at a rate of 60 mL/hour for 2 hours</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in Phosphate/Oxygen (P/O) Ratio</title>
          <description>As a measure of mitochondrial hand skeletal muscle energetics, mitochondrial coupling, or Phosphate/Oxygen ratio (P/O) was assessed at Baseline, Day 1 Hour 2, and Day 7.</description>
          <population>All participants for whom Phosphate/Oxygen (P/O) ratio was measured at baseline and Day 1 Hour 2, and Day 7</population>
          <units>ratio of phosphate to oxygen</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1 Hour 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.25" spread="0.679"/>
                    <measurement group_id="O2" value="0.26" spread="0.693"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.32" spread="0.473"/>
                    <measurement group_id="O2" value="0.51" spread="0.788"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in Nicotine Adenine Dinucleotide (NAD)</title>
        <time_frame>From Baseline, Day 1 Hour 2 (2 hours after the start of infusion, or end of infusion) and Day 7</time_frame>
        <population>All participants for whom Nicotine Adenine Dinucleotide (NAD) was measured.</population>
        <group_list>
          <group group_id="O1">
            <title>MTP-131 (Bendavia™)</title>
            <description>MTP-131 (Bendavia™) administered as an intravenous infusion of 0.25 mg/kg/hr at a rate of 60 mL/hr for 2 hours.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo administered as intravenous infusion at a rate of 60 mL/hour for 2 hours</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in Nicotine Adenine Dinucleotide (NAD)</title>
          <population>All participants for whom Nicotine Adenine Dinucleotide (NAD) was measured.</population>
          <units>millimolar</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1 Hour 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.04" spread="0.169"/>
                    <measurement group_id="O2" value="0.01" spread="0.213"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.11" spread="0.215"/>
                    <measurement group_id="O2" value="0.09" spread="0.263"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in Muscle Force-Time-Integral (FTI)</title>
        <description>Muscle Force-Time-Integral was measured as mean change from baseline at Day 1 Hour 2, Day 3, and Day 7.</description>
        <time_frame>From Baseline to Day 1 Hour 2, Day 3, and Day 7</time_frame>
        <population>All participants for whom Muscle Force-Time-Integral (FTI) was measured.</population>
        <group_list>
          <group group_id="O1">
            <title>MTP-131 (Bendavia™)</title>
            <description>MTP-131 (Bendavia™) administered as an intravenous infusion of 0.25 mg/kg/hr at a rate of 60 mL/hr for 2 hours.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo administered as intravenous infusion at a rate of 60 mL/hour for 2 hours</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in Muscle Force-Time-Integral (FTI)</title>
          <description>Muscle Force-Time-Integral was measured as mean change from baseline at Day 1 Hour 2, Day 3, and Day 7.</description>
          <population>All participants for whom Muscle Force-Time-Integral (FTI) was measured.</population>
          <units>Newton/second</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1 Hour 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.43" spread="0.882"/>
                    <measurement group_id="O2" value="0.10" spread="0.728"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.46" spread="1.036"/>
                    <measurement group_id="O2" value="0.24" spread="0.948"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.83" spread="1.485"/>
                    <measurement group_id="O2" value="0.44" spread="1.114"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>36 days</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Elamipretide</title>
          <description>Elamipretide given as an intravenous infusion of 0.25 mg/kg/hr at a rate of 60 mL/hr for 2 hours.&#xD;
Elamipretide: Elamipretide 0.25 mg/kg/hour administered as an intravenous infusion at the rate of 60 mL/hour for 2 hours</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Placebo (lyophilized excipients without elamipretide) given as an intravenous infusion at a rate of 60 mL/hr for 2 hours.&#xD;
Placebo: Placebo administered as intravenous infusion at a rate of 60 mL/hour for 2 hours</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>2</frequency_threshold>
        <default_vocab>MedDRA (19.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title vocab="MedDRA 19.0">Nausea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Vessel puncture site bruise</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Herpes zoster</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title vocab="MedDRA 19.0">Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Sinus congestion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Jim Carr, Pharm.D. Chief Clinical Development Officer</name_or_title>
      <organization>Stealth BioTherapeutics, Inc</organization>
      <phone>1-617-600-6888</phone>
      <email>jim.carr@stealthbt.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02245620
org study id: SPITM-201
nct id: NCT02245620
lead sponsor: 
has dmc: No
This was a Phase 2, randomized, double-blind, placebo-controlled study, enrolling 41 elderly
      subjects with previous evidence of mitochondrial dysfunction to evaluate whether the
      administration of MTP-131 (elamipretide) will change either hand skeletal muscle energetics
      or muscle performance in age-related skeletal muscle mitochondrial dysfunction.
This was a Phase 2, randomized, double-blind, placebo-controlled study, enrolling 41 elderly
      subjects with previous evidence of mitochondrial dysfunction to evaluate whether the
      administration of MTP-131 (elamipretide) will change either hand skeletal muscle energetics
      or muscle performance in age-related skeletal muscle mitochondrial dysfunction.

      Subjects were randomized 1:1 to receive either elamipretide at 0.25 mg/kg/hr intravenously at
      a rate of 60 mL/hr for 2 hours, or placebo (lyophilized excipients without elamipretide)
      intravenously at a rate of 60 mL/hr for 2 hours. Each treatment group went through three
      distinct periods: Screening (up to 28 days), Treatment (1day), and Observation (7 days).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change From Baseline in ATPmax (Maximal ATP Synthetic Rate)
time frame: From Baseline, Day 1 Hour 2 (2 hours after the start of infusion, or end of infusion) and Day 7
description: Maximal ATP synthetic rate (phosphorylation capacity per unit muscle volume) as determined by a muscle fatigue test.
measure: Mean Change From Baseline in Phosphate/Oxygen (P/O) Ratio
time frame: From Baseline, Day 1 Hour 2 (2 hours after the start of infusion, or end of infusion) and Day 7
description: As a measure of mitochondrial hand skeletal muscle energetics, mitochondrial coupling, or Phosphate/Oxygen ratio (P/O) was assessed at Baseline, Day 1 Hour 2, and Day 7.
measure: Mean Change From Baseline in Nicotine Adenine Dinucleotide (NAD)
time frame: From Baseline, Day 1 Hour 2 (2 hours after the start of infusion, or end of infusion) and Day 7
measure: Mean Change From Baseline in Muscle Force-Time-Integral (FTI)
time frame: From Baseline to Day 1 Hour 2, Day 3, and Day 7
description: Muscle Force-Time-Integral was measured as mean change from baseline at Day 1 Hour 2, Day 3, and Day 7.
arm group label: Elamipretide
arm group type: Experimental
description: Elamipretide given as an intravenous infusion of 0.25 mg/kg/hr at a rate of 60 mL/hr for 2 hours.
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo (lyophilized excipients without elamipretide) given as an intravenous infusion at a rate of 60 mL/hr for 2 hours.
intervention type: Drug
intervention name: Elamipretide
description: Elamipretide 0.25 mg/kg/hour administered as an intravenous infusion at the rate of 60 mL/hour for 2 hours
arm group label: Elamipretide
other name: MTP-131
other name: Bendavia™
intervention type: Drug
intervention name: Placebo
description: Placebo administered as intravenous infusion at a rate of 60 mL/hour for 2 hours
arm group label: Placebo
other name: elamipretide
criteria: 
gender: All
minimum age: 60 Years
maximum age: 85 Years
healthy volunteers: No
last name: Jim Carr
role: Study Director
affiliation: Stealth BioTherapeutics
facility: 
country: United States
responsible party type: Sponsor
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 