First-in-Human Study to Evaluate AMG 579 in Healthy Subjects and Patients With Stable Schizophrenia

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and tolerability of AMG 579 following a single oral dose administration in healthy subjects (Part A) and in patients with schizophrenia or stable schizoaffective disorder (Part B). The study in healthy subjects (Part A) concluded, and following a protocol amendment, enrolled only patients with schizophrenia or stable schizoaffective disorder (Part B).

Official Title
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Phase I, Randomized, Placebo-Controlled, Ascending Single Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of AMG 579 in Healthy Adult Subjects and Patients With Stable Schizophrenia or Schizoaffective Disorder

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: AMG 579
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of schizophrenia (chronic, all types) or schizoaffective disorder according to Diagnostic and Statistical Manual of Mental Disorders, 4th edition Text Revision (DSM-IV-TR) criteria and by Mini International Neuropsychiatric Interview (M.I.N.I.) 6.0 for Schizophrenia and Psychotic Disorders Studies Body weight greater or equal to 50 kg and body mass index (BMI) between 18 and 38.0 kg/m2, inclusive, at screening Patient is judged by the Investigator to be likely to tolerate being off of antipsychotic medications for the duration of the trial (for patients withdrawing from or currently not taking antipsychotic medications) Clinically stable, as judged by the investigator, and in a non-acute phase for at least 12 weeks within enrollment. If patient is on antipsychotic medications, they must be on second generation oral antipsychotic therapy (eg, ziprasidone, quetiapine, olanzapine, etc) for at least 8 weeks within enrollment and at least one month within enrollment on a stable dose Exclusion Criteria: Hospitalized for psychiatric symptoms in the 3 months within enrollment Patients with evidence of mental retardation by history or clinical examination or known premorbid IQ ≤ 70 Current risk of self-harm or violence as determined by the investigator, or current risk of suicide or history of suicidal behavior within 12 months of enrollment, and/or ongoing suicidal ideation as assessed using Columbia-Suicidal Severity Rating Scale (C-SSRS) at screening (eg, any response of yes to the Suicidal Ideation questions on the C-SSRS in the past 12 months). Additional critera apply. Eligibility criteria for healthy subjects (Part A) not outlined above.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AMG 579<br> | Drug: AMG 579<br>* 3 dose levels of single oral dose administration of AMG 579 in healthy subjects (Part A), and 5 dose levels of single oral dose administration of AMG 579 in patients with schizophrenia or schizoaffective disorder (Part B)<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Matching placebo control for AMG 579 at each dose level<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse events per subject to include clinically significant changes in neurological examinations, safety laboratory tests, electrocardiograms, and vital signs |  | Up to 15 days | 
| Incidence of treatment-emergent suicidal ideation and behavior | Measured by Columbia-Suicide Severity Rating Scale (C-SSRS) | Up to 15 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak plasma and cerebrospinal fluid (CSF; cohort 4 healthy subjects only) concentration (Cmax) of AMG 579 |  | Up to 15 days | 
| Time of peak plasma and CSF (cohort 4 only healthy subjects only) concentration (tmax) of AMG 579 |  | Up to 15 days | 
| Area under the plasma and CSF (cohort 4 healthy subjects only) concentration versus time curve (AUC) of AMG 579 |  | Up to 15 days | 
| Terminal phase half-life (t1/2) in plasma and CSF (cohort 4 healthy subjects only) of AMG 579 |  | Up to 15 days | 
| Scores on Simpson Angus Scale (SAS) and Barnes Akathesia Rating Scale (BARS) |  | Up to 15 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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single dose, safety, healthy subjects, schizoaffective disorder, AMG 579