Bioavailability of DHE Administered by I123 POD Device, IV Injection, and Migranal Nasal Spray in Healthy Adults

Inclusion Criteria: * Adult male and females, 18 to 55 years of age (inclusive) at the time of screening. * Subjects must be in good general health, with no significant medical history (including migraine), have no clinically significant abnormalities on physical examination at screening, and/or before administration of the initial dose of investigational product. * Subjects must have a Body Mass Index (BMI) between 18 and 32 kg/m2, inclusive. * Subjects must have clinical laboratory values within normal range as specified by the testing laboratory, or assessed as not clinically significant by the Principal Investigator. * Negative urine drug screen/alcohol breath test at screening. * Subjects who are willing to refrain from smoking for the duration of the study. Exclusion Criteria: * Subjects with a recent history of migraine and its variants including hemiplegic migraine and basilar migraine. A recent history of migraine is defined as (a) current or past history of migraine with at least 1 attack in last 6 months or (b) those receiving antimigraine prophylaxis. * Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV). * Subjects who have ingested caffeine within 48 hours before admission on Day -1. Subjects must also agree to refrain from consumption of caffeinated drinks for 48 hours before admission of Days 7 and 14 (i.e. prior to each subsequent dosing), and throughout confinement. * Subjects with ischemic heart disease or subjects who have clinical symptoms or findings consistent with coronary artery vasospasm including Prinzmetal's variant angina. * Subjects with hypertension, known peripheral arterial disease, Raynaud's phenomenon, sepsis, history of vascular surgery or severely impaired hepatic or renal function * Subjects who have previously shown hypersensitivity to ergot alkaloids or metoclopramide. * Use of any relevant prescription, over-the-counter medication (with the exception of oral contraceptives), foods (e.g. grapefruit juice) or supplements (including herbal) within 14 days of randomization \[especially those affecting the Cytochrome P450 3A4 (CYP3A4) metabolic pathway\]. * History or presence of alcoholism or drug abuse within the 2 years prior to the first investigational product administration. * Surgery within the past three months prior to the first investigational product administration as determined by the PI to be clinically relevant. * Active infection and/or use of macrolide antibiotics within 14 days prior to enrollment. * History of recurrent infections. * Any nasal congestion or physical blockage in either nostril, or deviated nasal septum as determined by nasal examination.