Single-ascending Dose Study With a Food-Effect Cohort to Evaluate AMG 581

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetic profile of single-ascending oral doses of AMG 581 in healthy subjects and subjects diagnosed with schizophrenia or schizoaffective disorder receiving antipsychotic treatment.

This will be a placebo-controlled, single-ascending oral-dose study of AMG 581 with a food-effect cohort. Approximately 70 subjects will be enrolled. This study will enroll healthy subjects into 8 cohorts (Cohorts 1,2,3,4,5,6,8 and 9), and subjects with schizophrenia or schizoaffective disorder receiving antipsychotic medication into a single cohort (Cohort 7).

Inclusion criteria

• Provide informed consent prior to initiation of any study-related procedure
• Male and female subjects ≥ 18 to ≤ 45 years of age at the time of screening
• Non-nicotine or non-tobacco for healthy subjects
• No history of relevant medical disorders
• BMI ≥ 18.0 and ≤ 30.0
• Non-reproductive females
• Males practicing effect birth control
• Avoid tanning/direct sunlight
• Willing to consume high-fat meal
• Schizophrenia or schizoaffective disorder
• PANSS score ≤ 4 points on a few 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
• Tremor or gait disturbance
• History of hereditary shorten QT syndrome
• Malignancy or tumor (other than skin cancers)
• History of GI disease
• QTc ≥ 450 msec or ≤ 380 msec
• Creatinine clearance < 80 mL/min at screening