Phase I, Double-Blind,Placebo, MAD Study to Evaluate the Safety, Tolerability, PK, and PD of AMG 333 in Healthy Subjects and Migraine Subjects

This is a randomized, double-blind, placebo-controlled, ascending multiple-dose study
evaluating AMG 333 in healthy subjects and subjects with migraines. Eight healthy subjects
will be enrolled in each of cohorts 1 through 5. Study subjects will be randomized such
that 6 subjects will receive AMG 333 and 2 subjects will receive placebo (3:1 ratio) per
cohort. Likewise, 8 migraine subjects will be enrolled in cohort 6 and randomized to
receive AMG 333 or placebo (3:1 ratio). All subjects will be housed for 15 days then
allowed to return home. Migraine subjects will self-administer the headache diary at least
once daily during the screening and out-patient portions of the study, and site personnel
will administer the headache diary during the in-house period of the study. Healthy
subjects will not keep the headache diary during screening and will have the headache diary
administered by site personnel at least once daily starting on day 1 through day 14, and
will then self administer throughout their participation in the study.

Inclusion Criteria:

- Healthy male and female subjects (cohorts 1 through 5) and male and female subjects
with migraines (cohort 6), who are ≥ 18 and ≤ 55 years of age at the time of
screening, and have 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), would pose a risk to
subject safety or interfere with evaluation, procedures, or study completion.