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

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

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).

Study Overview

• Status: Terminated
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: AMG 579; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Glendale, California, United States, 91206
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Matching placebo control for AMG 579 at each dose level
Experimental: AMG 579	Drug: AMG 579; 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)

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: February 27, 2012
• First Submitted That Met QC Criteria: March 29, 2012
• First Posted (Estimate): April 2, 2012

Study Record Updates

• Last Update Posted (Estimate): October 10, 2012
• Last Update Submitted That Met QC Criteria: October 5, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: single dose, safety, healthy subjects, schizoaffective disorder, AMG 579
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: 20101275