Study Design
This was a Phase 1, open-label, 4-week, 6-part, crossover study. After a
screening period (up to 28 days), a total of ten eligible subjects
received SC elamipretide 60 mg (0.75 mL) to alternating quadrants of the
abdomen on each of six occasions with or without potential ISR
interventions. The first treatment arm (Arm 1) started on Day 1 with the
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 ~8 cm 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 ~10 cm 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 ~10 cm in diameter around
the injection site 15 minutes before elamipretide administration on Day
14. Arm 5 received doxepin 5% cream applied to an area
~10 cm in diameter around the injection site 15 minutes
before elamipretide administration on Day 16. Arm 6 received
diphenhydramine 50 mg orally taken 2 hours prior to elamipretide
administration on Day 18. All treatments were administered by and/or
under the supervision of investigative staff, ensuring compliance. The
drug classes and/or mechanisms of action of these ISR interventions are
summarized in Table 1. All patients participated in all arms of the
study and therefore, randomization and blinding were not applicable.
For each treatment arm, blood samples for the determination of plasma
concentrations of elamipretide and its 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.