An Open‐Label, 2‐Period, Fixed Sequence Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Single Doses of STS101 (Dihydroergotamine Nasal Powder), with and without Concomitant Itraconazole in Healthy Adult Subjects

Abstract Dihydroergotamine (DHE) prescribing information contains a boxed warning regarding the possibility of serious and/or life‐threatening peripheral ischemia with co‐administration of strong cytochrome P450 3A4 (CYP3A4) inhibitors. The effects of the strong CYP3A4 inhibitor itraconazole on the pharmacokinetics and safety of nasally administered STS101 (DHE) were evaluated in this open‐label, 2‐period, fixed sequence study in 31 healthy participants. Following a single dose of 5.2 mg STS101, DHE exposure when co‐administered with itraconazole was 119% and 114% of that when administered alone, for the area under the plasma concentration–time curve from time 0 to infinity (AUC 0–inf ), and maximum observed plasma concentration (C max ), respectively. Co‐administration of STS101 with itraconazole was not associated with an increase in the frequency of treatment emergent adverse events compared with STS101 alone. No clinically significant findings of a single dose of 5.2 mg STS101 alone or with itraconazole were observed on nasal examinations, safety laboratory values, vital signs, or safety electrocardiograms. In this study, no clinically meaningful drug–drug interactions were seen when STS101 was co‐administered with a strong CYP3A4 inhibiting drug.