Study Assessments
The primary endpoints of this study comprised the following efficacy measures: clinical assessments and subject self-assessments. Specifically, the primary endpoints consisted of comparisons of the grading of each ISR parameter following administration of elamipretide with each separate intervention versus the grading of each ISR parameter following administration of elamipretide alone. For clinical assessments, the clinical staff used a standard procedure adapted from the Division of Aids Table for Grading the Severity of Adult and Pediatric Adverse Events to score pain, erythema, induration/swelling, and pruritus using a 4-point scale based on severity (1 = mild, 2 = moderate, 3 = severe, and 4 = potentially life threatening). The self-assessments were based on a questionnaire to determine how bothered the patient was following each injection of elamipretide and included the following parameters: pain, burning sensation, cold sensation, itching, redness, swelling, and bruising (Not at all, A little, Moderately, Very, Extremely).
The secondary endpoints of this study consisted of PK and general safety assessments. Plasma samples were analyzed for elamipretide and its M1 and M2 metabolites using a validated liquid chromatography/tandem mass spectrometry assay. The lower limits of assay quantitation were 3.0, 1.5, and 1.0 ng/mL for elamipretide, M1, and M2, respectively. Maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from time zero to 6 hours (AUC0-6h) were calculated using Phoenix™ WinNonlin® software.
Safety assessments consisted of comparison of treatment-emergent adverse events (TEAEs) reported following administration of elamipretide with each separate intervention versus TEAEs reported following administration of elamipretide alone. Safety measurements for determination of TEAEs included routine clinical laboratory tests, 12-lead ECG, physical examination, and vital signs. TEAEs were graded with respect to severity (mild, moderate, or severe) and relationship to study drug (unrelated or unlikely, possible, or probably related). Injection sites were photographed at 0.5, 1, 2, 4, and 12 hours post-elamipretide-dose for qualitative purposes.