Background and objectives: Omaveloxolone (SKYCLARYS®) is approved for the treatment of Friedreich ataxia in patients 16 years of age and older in the United States. The recommended dosage is 150 mg administered orally once a day in the form of three 50 mg capsules swallowed whole. However, some patients may have oropharyngeal dysphagia or difficulty swallowing whole capsules and require an alternate method(s) of administration. A phase 1 clinical study was conducted to assess the relative bioavailability, safety, and tolerability of a single dose of omaveloxolone when administered as either intact capsules or when capsule contents are sprinkled and mixed with applesauce.
Methods: This was a randomized, phase 1, open-label, single-dose, crossover, relative bioavailability study in healthy volunteers. The study was conducted in 2 periods with a washout of at least 14 days between dosing. Serial blood samples were collected at regular intervals starting before dosing and completed at the 336-hour sample. The palatability of omaveloxolone contents sprinkled on applesauce was assessed with a questionnaire. The safety and tolerability of the study drug were assessed throughout the study.
Results: 31 out of 32 subjects completed the study. Omaveloxolone was absorbed slowly, with a median time to Cmax (tmax) of 6 hours when administered as sprinkled over applesauce, and 10 hours when administered as intact capsules. The mean (standard deviation) apparent plasma elimination half-life was similar, whether omaveloxolone was administered as intact capsules or sprinkled over applesauce: 86.9 (17.2) hours versus 90.4 (19.7) hours, respectively. Even though median tmax was earlier when omaveloxolone was administered as sprinkled over applesauce, there was considerable overlap in the range of tmax between both treatments. The study subjects found omaveloxolone administered sprinkled over applesauce to have acceptable palatability.
Conclusions: The peak and overall exposure of omaveloxolone were similar regardless of how it was administered. The difference in tmax between both methods of administration is not considered clinically relevant since omaveloxolone is chronically administered for the treatment of Friedreich ataxia. Sprinkling the contents of 150 mg omaveloxolone and mixing with applesauce appeared to be safe and well tolerated and may be used as an alternative dosing method for those who have difficulty swallowing intact capsules.
*prev. presented