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.