Study Design
This was a Phase 1, open-label, 4-week, 6-part, crossover study. After a
screening period (up to 28 days), ten eligible subjects received SC
elamipretide 60mg (0.75mL) to alternating abdominal quadrants on each of
six occasions with or without potential ISR interventions. The first
treatment arm (Arm 1) started on Day 1 with SC administration of
elamipretide only, followed by the remaining treatment arms (Arms 2-6)
with the following interventions sequentially. On Day 3, Arm 2 received
mometasone furoate 0.1% ointment applied once to an area
~8cm in diameter and covered with a hydrocolloid
occlusive dressing (DuoDERM® Extra Thin) prior to SC
elamipretide administration 1 week later on Day 10. Arm 3 received ice
application to an area ~10cm in diameter around the
injection site 5 minutes before and 5 minutes after elamipretide
administration on Day 12. Arm 4 received tacrolimus 0.1% ointment
applied to an area ~10cm in diameter around the
injection site 15 minutes before elamipretide administration on Day 14.
Arm 5 received doxepin 5% cream applied to an area
~10cm in diameter around the injection site 15 minutes
before elamipretide administration on Day 16. Arm 6 received
diphenhydramine 50mg orally taken 2 hours prior to elamipretide
administration on Day 18. All treatments were administered by and/or
under investigative staff supervision, ensuring compliance. Drug classes
and/or mechanisms of action of ISR interventions are summarized in Table
1. All patients participated in all arms of the study; therefore,
randomization and blinding were not applicable.
For each treatment arm, blood samples for determining elamipretide
plasma concentrations and metabolites were collected pre-dose and at
0.25, 0.5, 1, 2, 4, and 6-hours after elamipretide administration. Vital
signs were recorded pre-dose and at 0.5 and 6 hours after elamipretide
administration. ISR clinical and self-assessments were performed before
and at 0.5, 1, 2, 4, 6, 12, 24, and 48 hours after elamipretide
administration. Injection sites were photographed at 0.5, 1, 2, 4, and
12 hours after elamipretide administration.
This study was conducted in accordance with international ethics
guidelines, including the Declaration of Helsinki, Council for
International Organizations of Medical Sciences International Ethical
Guidelines, International Conference on Harmonisation Good Clinical
Practice guidelines, and all applicable laws and regulations. The
protocol was approved by the institutional review boards and all
participants provided written informed consent prior to entering the
trial.