Clinical trial NCT01568203: First-in-Human Study to Evaluate AMG 579 in Healthy Subjects and Patients With Stable Schizophrenia
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Schizophrenia
Keywords: single dose, safety, healthy subjects, schizoaffective disorder, AMG 579
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2012-04-02
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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).


Eligibility criteria: 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.

Primary outcomes:
measure: Number of adverse events per subject to include clinically significant changes in neurological examinations, safety laboratory tests, electrocardiograms, and vital signs
timeFrame: Up to 15 days
measure: Incidence of treatment-emergent suicidal ideation and behavior
timeFrame: Up to 15 days
Secondary outcomes:
measure: Peak plasma and cerebrospinal fluid (CSF; cohort 4 healthy subjects only) concentration (Cmax) of AMG 579
timeFrame: Up to 15 days
measure: Time of peak plasma and CSF (cohort 4 only healthy subjects only) concentration (tmax) of AMG 579
timeFrame: Up to 15 days
measure: Area under the plasma and CSF (cohort 4 healthy subjects only) concentration versus time curve (AUC) of AMG 579
timeFrame: Up to 15 days
measure: Terminal phase half-life (t1/2) in plasma and CSF (cohort 4 healthy subjects only) of AMG 579
timeFrame: Up to 15 days
measure: Scores on Simpson Angus Scale (SAS) and Barnes Akathesia Rating Scale (BARS)
timeFrame: Up to 15 days
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Research Site
state: California
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: