A Phase 2 Study to Evaluate the Impact of MTP-131 (Bendavia™) on Skeletal Muscle Function in Elderly
Condition: Skeletal Muscle Mitochondrial Dysfunction in the Elderly
Intervention: Elamipretide; Placebo
Intervention description: Elamipretide 0.25 mg/kg/hour administered as an intravenous infusion at the rate of 60 mL/hour for 2 hours; Placebo administered as intravenous infusion at a rate of 60 mL/hour for 2 hours
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 41.0
Sex: All
Minimum age: 60 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: Skeletal muscle dysfunction, MTP-131, Bendavia™; elamipretide

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Are male and female adults aged ≥60 and ≤85 years

          2. Female subjects must be post-menopausal

          3. Have in vivo phosphorus-31 (31P) Magnetic Resonance Spectroscopy (MRS) and (Optical
             Spectra Scan (OPS) determined maximum adenosine triphosphate synthetic rate (ATPmax) <
             0.70 milliMol/second (mM/sec)

          4. Have in vivo 31P MRS and OPS determined P/O (Phosphate/Oxygen ratio) < 1.9

          5. Are ambulatory and able to perform activities of daily living without assistance

          6. Had sufficient venous access for study drug administration and clinical testing.

          7. Could speak and read English fluently.

          8. Provided informed consent.

        Exclusion Criteria:

          1. Had significant disease(s) or condition(s) which, in the opinion of the Investigator,
             may have put the subject at risk because of their participation in the study or may
             have influenced either the results of the study or the subject's ability to
             participate in the study.

          2. Had a history of rhabdomyolysis.

          3. Had been hospitalized within 3 months prior to Screening for major atherosclerotic
             events (e.g., myocardial infarction, target-vessel revascularization, coronary bypass
             surgery or stroke) or other major medical condition (as deemed by the Primary
             Investigator).

          4. Had any metal implants that could not be removed from the body that in the opinion of
             the Investigator were a contra-indication for undergoing the MRS procedure or any
             other protocol-related procedure.

          5. Had an implanted cardiac pacemaker or other implanted cardiac device.

          6. Had a serum sodium level <136 milliequivalents per litre (mEq/L) at Screening or
             Pre-infusion.

          7. Had a hemoglobin level <12 g/dL at Screening or Pre-infusion.

          8. Had chronic, uncontrolled hypertension as judged by the Investigator (e.g., Baseline
             systolic blood pressure [SBP] >140 mm Hg, diastolic blood pressure [DBP] > 90 mm Hg)
             or a SBP >150 mm Hg or DBP >95 mm Hg at the time of Screening or Baseline (if the
             initial blood pressure [BP] reading was above these values, the reading may have been
             repeated one time within 20 minutes of the initial reading).

          9. Had a body mass index (BMI) of <16 or >35 kg/m2.

         10. Had a creatinine clearance <45 mL/min as calculated by the Cockcroft Gault equation.

         11. Had a 12-lead electrocardiogram (ECG) demonstrating severe bradycardia (heart rate <
             40 bpm) or average corrected QC interval (QTc) >450 ms for males and > 470 ms for
             females, and in the opinion of the Investigator was clinically significant. (If on the
             initial ECG, QTc exceeded 450 ms for males or 470 ms for females, the ECG was to be
             repeated 2 more times and the average of the 3 QTc values was to be used to determine
             the subject's eligibility).

         12. Had a neurologic disorder that in the opinion of the Investigator was a
             contra-indication for enrollment into the study.

         13. Had any symptoms consistent with or a current diagnosis of peripheral neuropathy, such
             as numbness, tingling, pain, or altered sensation of hands or feet.

         14. Had an active, systemic autoimmune disease other than autoimmune thyroid disease
             (e.g., diabetes, lupus, rheumatoid arthritis) that currently required treatment or was
             likely to require treatment during the study.

         15. Subject's right hand had a history of mobility impairment, fractures, arthritis, hand
             surgery, muscle disease or other injury that may interfere with any study procedure.

         16. Had any symptoms consistent with or a current diagnosis of claustrophobia.

         17. Had a history of cancer, unless subject had documentation of completed curative
             treatment.

         18. Had a history of or risk factors (e.g., significant family history, concomitant
             medical condition) for deep vein thrombosis or pulmonary embolism.

         19. Had a history of serious mental illness as judged by the Investigator.

         20. Had a body temperature > 37.5°C at the time of planned dosing.

         21. Subjects who in the opinion of the Investigator abused alcohol or drugs.

         22. Had donated or received blood or blood products within the past 30 days.

         23. Investigator site personnel directly affiliated with this study and/or their immediate
             families. Immediate family was defined as a spouse, parent, child, or sibling, whether
             biological or legally adopted.

         24. Sponsor employees and/or their immediate families. Immediate family was defined as a
             spouse, parent, child, or sibling, whether biological or legally adopted.

         25. Were currently enrolled in a clinical study involving an investigational product or
             non-approved use of a drug or device or concurrently enrolled in any other type of
             medical research judged to be scientifically or medically incompatible with this
             study.

         26. Had participated, within the last 30 days, in a clinical study involving an
             investigational product. If the previous investigational product had a long half-life,
             3 months or 5 half-lives (whichever was longer) should have passed.

         27. Had previously been randomized into any study investigating elamipretide or been
             exposed to elamipretide for any reason.