Approximately 97% of boys aged 4 to 7 years with Duchenne muscular dystrophy (DMD) were able to successfully swallow softgel capsules in 2 separate trials. There was high adherence to the oral administration over 52 weeks with no discontinuations related to difficulty swallowing capsules.
As part of enrollment criteria for the phase 3 randomized, double-blind, placebo-controlled PolarisDMD trial and the phase 2 MoveDMD trial, researchers performed a pill swallowing assessment in the boys. Patients and their caregivers were given a choice between the smaller 100 mg capsule and the larger 250 mg capsule containing the NF-κB inhibitor edasalonexent. These capsules contained a special phosphatidylcholine coating that reduces friction and eases swallowing.
In addition, patients and their caregivers were provided pill-swallowing techniques such as the use of soft foods like applesauce or bananas, motivational training, and swallowing aids. One such swallowing aid included the Medi-Straw pill swallowing straw to support intact drug administration.
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In the phase 2 trial, 32 of 33 boys (97%) with DMD who were screened were able to swallow capsules. Of the 31 patients who enrolled in the phase 2 trial, 24 boys (77%) selected the larger 250 mg capsule. Of the 7 who selected the smaller capsule, 4 boys transitioned to the larger capsule by week 24 of the study. The number of capsules per dose of treatment may have ultimately influenced the decision to switch to the larger capsule, so that a fewer number of capsules were administered per dose. Parents reported a 98% treatment compliance rate in the phase 2 trial.
In the phase 3 trial, 143 of the 148 boys (97%) screened were able to swallow capsules. Of the 131 patients who enrolled in the phase 3 trial, 81 (62%) selected the larger capsule. Of the 50 (38%) who selected the smaller capsule, 34 boys transitioned to the larger capsule by 6 months and another 3 boys transitioned by 12 months.
When assessing pill swallowing capability by age, 90% of the 48 patients who were 4 years old could swallow the capsules and 100% of the patients aged 5 or more years and older could swallow capsules. Parents reported a 92% treatment compliance rate in the phase 3 trial.
Although edasalonexent is no longer in clinical development due to failure to meet the goal in the phase 3 trial, data from these trials provided useful information regarding the capacity of oral drug administration in capsular form to young boys with DMD. The authors of this study suggested, “solid oral dosage forms (tablets and capsules) may be preferable to formulators and healthcare providers since they provide improvements compared to liquids with respect to dosing accuracy, taste making, the need for excipients, and stability.”
Considering the results of this study, the authors strongly recommend using softgel capsules to treat DMD as an alternative to liquid drug treatments in children as young as 4 years old.
It is important to note that this study did not address young adults with DMD. These young adults may present with progressive dysphagia which may negatively affect compliance with oral medication administration.
Mancini M, Shafai G, Thaler E, Donovan JM, Finkel RS. Assessing the ability of boys with Duchenne muscular dystrophy age 4–7 years to swallow softgel capsules: clinical trial experience with edasalonexent. J Clin Pharm Ther. Published online July 14, 2021. doi:10.111/jcpt.13478