Safety and Tolerability of POD-DHE (INP104) in Migraine (STOP 301)

Open-label Study of Safety and Tolerability of Chronic Intermittent Usage for 24 or 52 Weeks of Intranasal Dihydroergotamine Mesylate (DHE) Administered Using the I123 Precision Olfactory Delivery (POD®) Device [INP104, POD-DHE] in Patients With Migraine Headache

This study consists of a 4-week screening period, a 24-week treatment period for all participants, followed by a 28-week treatment period extension (to 52 weeks in total) for a subset of at least 60 and up to 80 participants, and a 2-week post-treatment follow-up period.

This is an outpatient study in people who currently suffer a minimum of 2 migraines per month. During the study, participants will be instructed to use no more than 2 doses of the study drug INP104 within a 24-hour period, or 3 doses in a 7-day period. Participants will self-administer INP104 nasally and record their migraines in an eDiary.

Inclusion Criteria:

• Documented diagnosis of migraine with or without aura, with at least 2 attacks per month for the previous 6 months.
• Participants must be in good general health, with no significant medical history (excluding migraine).
• Participants must have the ability and willingness to attend the necessary visits at the study center.
• Participants must be able to provide the written informed consent prior to entry into the study.
• Women of childbearing potential must agree to use adequate contraception (as defined in the protocol and by study personnel) during the study and for 30 days after the last dose fo the study drug.
• Male participants and their partners must agree to use effective contraception (as defined in the protocol and by study personnel) during the study and for 30 days after the last dose of the study drug. Male participants should also refrain from sperm donation for 30 days after study completion.

Exclusion Criteria:

• Subjects with trigeminal autonomic cephalalgias (including cluster headache, hemicrania syndromes and short-lasting unilateral, neuralgiform headache attacks with conjunctival injection and tearing), hemiplegic migraine, or migraine with brainstem aura (previously referred to as basilar migraines).
• Subjects with chronic migraines, medication overuse headache or other chronic headache syndromes.
• Subjects with ischemic heart disease or subjects with clinical symptoms or findings consistent with coronary artery vasospasm, including Prinzmetal's variant angina.
• Subjects with significant risk factors for coronary artery disease (CAD) including current use of nicotine-containing products, medical history of diabetes, uncontrolled hypertension (high blood pressure), known peripheral arterial disease, Raynaud's phenomenon, sepsis or vascular surgery (within 3 months prior to study start), or severely impaired hepatic or renal (kidney) function.
• Subjects with recurrent sinusitis or epistaxis.
• Subjects with a history or presence of alcoholism or drug abuse within 2 years prior to first study drug administration.
• Women who are pregnant, or planning to get pregnant, or who are lactating while participating in the study.
• Use of any medications prohibited by protocol.
• Use of >12 days per month of triptan or ergot-based medication in the 2 months prior to screening.

Other protocol-defined inclusion/exclusion criteria may apply.