The study was stopped due to an administrative decision not safety.

The primary purpose of this study is to evaluate the safety and tolerability of multiple oral doses of AMG 333 for 14 days in healthy subjects and migraine subjects. As part of the secondary objectives, the study will characterize the pharmacokinetic (PK) profile of AMG 333 after multiple oral doses in healthy subjects and migraine subjects, as well as characterize the effect of multiple doses of AMG 333 on increases in blood pressure (BP) induced by the cold pressor test (CPT) in healthy 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.