Single-Ascending Dose Study of AMG 333 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.