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

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

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.

Study Overview

• Status: Completed
• Conditions: Schizophrenia or Schizoaffective Disorder
• Intervention / Treatment: Drug: Placebo; Drug: AMG 581

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).

• Study Type: Interventional
• Enrollment (Actual): 70
• 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 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; Placebo
ACTIVE_COMPARATOR: AMG 581	Drug: AMG 581; Active drug

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
AMG 581 metabolites in plasma	Metabolites of AMG 581 in plasma	15 days
Subjective experience follow administration of AMG 581 as measured by the Bond and Lader visual analogue scale (VAS)	To assess the subjective experience of study subjects following administration of AMG 581 as measured by the Bond and Lader visual analogue scale (VAS)	15 days
Subjective experience follow administration of AMG 581 as measured by the Positive and Negative Syndrome Scale (PANSS)	To assess the subjective experience of study subjects following administration of AMG 581 as measured by the Positive and Negative Syndrome Scale (PANSS; subjects diagnosed with schizophrenia or schizoaffective disorder receiving antipsychotic treatment only)	15 days
Relationship between plasma concentration of AMG 581 and QTc interval	To explore the relationship between changes in QTc interval (msec) and AMG 581 plasma concentration (ng/mL)	15 days
Effect of food on plasma concentration of AMG 581	To assess the effect of a high-fat meal on the plasma concentration of AMG 581 (ng/mL) comparing median of tmax between fasted and fed conditions (yes/no)	43 days

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start: August 1, 2015
• Primary Completion (ACTUAL): October 1, 2015
• Study Completion (ACTUAL): October 1, 2015

Study Registration Dates

• First Submitted: September 16, 2015
• First Submitted That Met QC Criteria: October 1, 2015
• First Posted (ESTIMATE): October 5, 2015

Study Record Updates

• Last Update Posted (ESTIMATE): October 23, 2015
• Last Update Submitted That Met QC Criteria: October 22, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Schizophrenia or Schizoaffective Disorder
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Psychotic Disorders
• Other Study ID Numbers: 20130100