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

Phase 1
Completed
Conditions
Schizophrenia or Schizoaffective Disorder
Interventions
Drug: Placebo
Registration Number
NCT02567370
Lead Sponsor
Amgen
Brief Summary

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

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).

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
70
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlacebo-
AMG 581AMG 581-
Primary Outcome Measures
NameTimeMethod
Changes in heart rate15 days

Summaries over time and/or changes from baseline over time in heart rate

Changes in respiratory rate15 days

Summaries over time and/or changes from baseline over time in respiratory rate

Scores at each study visit for Simpson Angus Scale (SAS)15 days

Summaries over time and/or changes from baseline over time in Simpson Angus Scale (SAS) score

Reported treatment-emergent adverse events15 days

Number and percent of subjects experiencing adverse events

Scores at each study visit and summary by cohort for Barnes Akathisia Rating Scale (BARS)15 days

Summaries over time and/or changes from baseline over time in Barnes Akathisia Rating Scale (BARS) score

Subject incidence of treatment-emergent suicidal ideation and behavior as measured by Columbia-Suicide Severity Rating Scale (C-SSRS)15 days

Subject incidence of treatment-emergent suicidal ideation and behavior as measured by Columbia-Suicide Severity Rating Scale (C-SSRS) summarized by cohort

Changes in temperature15 days

Summaries over time and/or changes from baseline over time in temperature

Changes in ECGs15 days

Summaries over time and/or changes from baseline over time in ECGs

Changes in systolic/diastolic blood pressure15 days

Summaries over time and/or changes from baseline over time in systolic and/or diastolic blood pressure

Secondary Outcome Measures
NameTimeMethod
Peak plasma concentration (Cmax)15 days

Peak plasma concentration (Cmax)

Area under the plasma concentration versus time curve (AUC)15 days

Area under the plasma concentration versus time curve (AUC)

Median of tmax15 days

Median of tmax

Trial Locations

Locations (1)

Research Site

🇺🇸

Glendale, California, United States

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