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

Study Overview
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Brief Summary
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The purpose of this study is to find out the time it takes to absorb, distribute, breakdown and remove the drug from the body, safety and tolerability of AMG 581 in healthy participants and subjects with schizophrenia.

Detailed Description
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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).

Official Title
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A Phase 1, Randomized, Double-blind, Placebo-controlled, Single-ascending Dose Study With a Food-Effect Cohort to Evaluate the Safety, Tolerability, and Pharmacokinetics of AMG 581 in Healthy Subjects and Subjects With Schizophrenia

Conditions
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Schizophrenia or Schizoaffective Disorder

Intervention / Treatment
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* Drug: AMG 581
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo<br>|
| Active Comparator: AMG 581<br> | Drug: AMG 581<br>* Active drug<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reported treatment-emergent adverse events | Number and percent of subjects experiencing adverse events | 15 days | 
| Changes in systolic/diastolic blood pressure | Summaries over time and/or changes from baseline over time in systolic and/or diastolic blood pressure | 15 days | 
| Changes in heart rate | Summaries over time and/or changes from baseline over time in heart rate | 15 days | 
| Changes in respiratory rate | Summaries over time and/or changes from baseline over time in respiratory rate | 15 days | 
| Changes in temperature | Summaries over time and/or changes from baseline over time in temperature | 15 days | 
| Changes in ECGs | Summaries over time and/or changes from baseline over time in ECGs | 15 days | 
| Scores at each study visit for Simpson Angus Scale (SAS) | Summaries over time and/or changes from baseline over time in Simpson Angus Scale (SAS) score | 15 days | 
| Scores at each study visit and summary by cohort for Barnes Akathisia Rating Scale (BARS) | Summaries over time and/or changes from baseline over time in Barnes Akathisia Rating Scale (BARS) score | 15 days | 
| Subject incidence of treatment-emergent suicidal ideation and behavior as measured by Columbia-Suicide Severity Rating Scale (C-SSRS) | Subject incidence of treatment-emergent suicidal ideation and behavior as measured by Columbia-Suicide Severity Rating Scale (C-SSRS) summarized by cohort | 15 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak plasma concentration (Cmax) | Peak plasma concentration (Cmax) | 15 days | 
| Area under the plasma concentration versus time curve (AUC) | Area under the plasma concentration versus time curve (AUC) | 15 days | 
| Median of tmax | Median of tmax | 15 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia or Schizoaffective Disorder