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.