The primary purpose of this study is to determine whether AMG 333 is safe and well tolerated in healthy subjects and subjects with migraines. As part of the secondary objectives, this study will characterize the pharmacokinetic (PK) profile of AMG 333, as well as characterize the effect of AMG 333 on the cold pressor test (CPT)-induced increase in blood pressure after single oral doses in healthy subjects and subjects with migraines

This is a randomized, double-blind, placebo-controlled, ascending single-dose study evaluating AMG 333 in healthy subjects and subjects with migraines. The study will consist of 8 cohorts: 7 cohorts of healthy subjects and 1 cohort of subjects with migraines. For cohorts 1 to 7, 8 subjects each will be enrolled, and subjects will be randomized such that 6 subjects will receive AMG 333 and 2 subjects will receive placebo (3:1 ratio). In cohort 8, up to 24 subjects with migraines will be enrolled, depending on enrollment rate and emerging safety and tolerability data. These migraine subjects will be randomized to receive AMG 333 or placebo in a crossover fashion. Both healthy and migraine subjects will be monitored in house for 4 days then allowed to return home for the remainder of the 14 day observation period. Both healthy and migraine subjects will keep headache diaries.

Inclusion Criteria:

• Healthy male and female subjects with or without migraines ≥18 and ≤55 years of age at the time of screening, with no history or evidence of clinically relevant medical disorders as determined by the investigator in consultation with the Amgen physician.

Exclusion Criteria:

• History or evidence of a clinically significant disorder, condition, or disease that, in the opinion of the investigator and Amgen physician, would significantly impair pain perception (eg, history of stroke, history of neuropathy) or interfere with evaluation, procedures, or study completion.