Albrecht D, et al. - Via performing a 2-part, active-controlled, 3-period crossover study over 3 weeks, researchers examined and compared the safety and the pharmacokinetics of dihydroergotamine (DHE) following administration of intranasal DHE powder (STS101), intranasal DHE spray (Migranal), and intramuscular (IM) DHE injection in healthy individuals. In part 1, 15 healthy individuals with no history of migraine were administered 3 ascending dosage strengths of STS101 (1.3, 2.6, and 5.2 mg). In part 2, 1 dose each of STS101 5.2 mg, Migranal DHE Mesylate Liquid Nasal Spray 2.0 mg, and IM DHE Mesylate 1.0 mg were administered to 27 healthy individuals in a randomized order. As per outcomes, STS101 was readily absorbed, producing effective DHE plasma concentrations within 10 minutes. Relative to Migranal, STS101 achieved substantially higher C_max, AUC0-2 h and AUC0-inf, intimating it to have potentially better efficacy than Migranal. It had better variability than Migranal, thus offers improved consistency of response. Prolonged action and low recurrence were supported by the comparable AUC0-inf to IM DHE. Additionally, sufficiently low C_max was observed to avoid any significant nausea reported with IV DHE. These findings support STS101 to be easy to administer, non-injected, acute treatment for migraine, with a favorable tolerability profile. Further, it is supposed to produce rapid and consistent freedom from pain and associated migraine symptoms without recurrence.