Multiple Ascending Dose Study on Safety, Tolerability, and Pharmacokinetics of AMG 581 in Healthy Subjects or Subjects With Schizophrenia or Schizoaffective

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetic
profile of ascending multiple oral doses of AMG 581 in healthy subjects or subjects with
schizophrenia or schizoaffective disorder on antipsychotic medication. The study will also
assess the effects of AMG 581 on midazolam PK in healthy subjects or subjects with
schizophrenia or schizoaffective disorder on antipsychotic medication.

Inclusion Criteria:

- Provided informed consent prior to initiation of any study-specific
activities/procedures; -male or female subjects should be between the ages of 18 and 45
years (18-55 years for subjects with schizophrenia);-non-nicotine or non-tobacco (healthy
subjects only); - no history of relevant medical disorders; - BMI ≥ 18.0; - females of
non-reproductive potential; - males practicing effective birth control; - avoid
tanning/direct sunlight; - schizophrenia or schizoaffective disorder; PANSS score ≤ 4
points on following items (i.e. conceptual disorganization, hallucinatory behavior,
excitement, suspiciousness/persecution, hostility, depression, anxiety, disorientation,
uncooperativeness, disturbance of volition, and poor impulse control) / total score ≤ 80
points

Exclusion Criteria:

- females lactating/breastfeeding; pregnant partners of male subjects; essential tremor
or gait disturbance; - history of hereditary shorten QT syndrome; - malignancy or
tumor (other than skin cancers); - history of GI disease that could interfere with
absorption; - QTc ≥ 450 msec or ≤ 380 msec; - HbA1c ≥ 7%;