Relative Bioavailability of Omaveloxolone When Capsules Are Sprinkled Over and Mixed in Applesauce Compared With Administration as Intact Omaveloxolone Capsules: A Phase 1, Randomized, Open-Label, Single-Dose, Crossover Study in Healthy Adults.

Omaveloxolone (SKYCLARYS®) is approved for the treatment of Friedreich ataxia (FA) in patients aged ≥16 years in the United States and European Union (EU). The recommended dosage is 150 mg administered orally once daily as three 50-mg capsules. However, some patients with FA may have oropharyngeal dysphagia or difficulty swallowing whole capsules; therefore, alternate method(s) of administration are needed. A Phase 1 clinical study in 32 healthy volunteers evaluated the relative bioavailability, safety, and tolerability of a single dose of omaveloxolone when capsule contents were sprinkled on and mixed in applesauce compared to when taken as intact capsules. Palatability when sprinkled on and mixed in applesauce was assessed with a questionnaire. After a single 150-mg dose, the peak and overall exposures of omaveloxolone were similar irrespective of administration method, with the 90% CIs of the geometric least squares mean ratio (%) for maximum plasma concentration (Cmax), AUC0-t, and AUC0-∞ within the 80% to 125% reference intervals. Omaveloxolone was absorbed more slowly as intact capsules (median tmax, 10 h) compared with sprinkled capsule contents over applesauce (median tmax, 6 h). With chronic daily administration of omaveloxolone to treat FA, the 4-h difference in tmax is not considered clinically relevant. Sprinkled omaveloxolone capsule contents on applesauce were well tolerated, with acceptable palatability and no serious adverse events. Given the similar systemic exposure when capsules were swallowed whole, sprinkling omaveloxolone capsule contents on and mixing in applesauce is a feasible alternative method of administering omaveloxolone and has been included in both the United States and EU prescribing information.

Night shift preparation, performance, and perception: are there differences between emergency medicine nurses, residents, and faculty?

OBJECTIVE: Determine differences between faculty, residents, and nurses regarding night shift preparation, performance, recovery, and perception of emotional and physical health effects. METHODS: Survey study performed at an urban university medical center emergency department with an accredited residency program in emergency medicine. RESULTS: Forty-seven faculty, 37 residents, and 90 nurses completed the survey. There was no difference in use of physical sleep aids between groups, except nurses utilized blackout curtains more (69%) than residents (60%) and faculty (45%). Bedroom temperature preference was similar. The routine use of pharmacologic sleep aids differed: nurses and residents (both 38%) compared to faculty (13%). Residents routinely used melatonin more (79%) than did faculty (33%) and nurses (38%). Faculty preferred not to eat (45%), whereas residents (24%) preferred a full meal. The majority (>72%) in all groups drank coffee before their night shift and reported feeling tired despite their routine, with 4:00 a.m. as median nadir. Faculty reported a higher rate (41%) of falling asleep while driving compared to residents (14%) and nurses (32%), but the accident rate (3% to 6%) did not differ significantly. All had similar opinions regarding night shift-associated health effects. However, faculty reported lower level of satisfaction working night shifts, whereas nurses agreed less than the other groups regarding increased risk of drug and alcohol dependence. CONCLUSION: Faculty, residents, and nurses shared many characteristics. Faculty tended to not use pharmacologic sleep aids, not eat before their shift, fall asleep at a higher rate while driving home, and enjoy night shift work less.