Study Assessments
Primary endpoints comprised the following efficacy measures: clinical assessments and subject self-assessments. Primary endpoints compared grading of each ISR parameter following administration of elamipretide with each separate intervention versus grading of each ISR parameter following administration of elamipretide alone. For clinical assessments, 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) was used. Self-assessments were based on a questionnaire to determine how bothered the patient was following each injection of elamipretide and included parameters of pain, burning sensation, cold sensation, itching, redness, swelling, and bruising (Not at all, A little, Moderately, Very, Extremely).
Secondary endpoints consisted of PK and general safety assessments. Plasma samples were analyzed for elamipretide and its M1/M2 metabolites using a validated liquid chromatography/tandem mass spectrometry assay. The lower limits of assay quantitation were 3.0, 1.5, and 1.0ng/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 compared 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 based on severity (mild/moderate/severe) and relationship to study drug (unrelated or unlikely/possible/probably related). Injection sites were photographed at 0.5, 1, 2, 4, and 12-hours post-elamipretide-dose for qualitative purposes.