Single-ascending Dose Study With a Food-Effect Cohort to Evaluate AMG 581 (FIH)
Primary Purpose
Schizophrenia or Schizoaffective Disorder
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
AMG 581
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Schizophrenia or Schizoaffective Disorder focused on measuring Schizophrenia or Schizoaffective Disorder
Eligibility Criteria
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
Sites / Locations
- Research Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Active Comparator
Arm Label
Placebo
AMG 581
Arm Description
Outcomes
Primary Outcome Measures
Reported treatment-emergent adverse events
Number and percent of subjects experiencing adverse events
Changes in systolic/diastolic blood pressure
Summaries over time and/or changes from baseline over time in systolic and/or diastolic blood pressure
Changes in heart rate
Summaries over time and/or changes from baseline over time in heart rate
Changes in respiratory rate
Summaries over time and/or changes from baseline over time in respiratory rate
Changes in temperature
Summaries over time and/or changes from baseline over time in temperature
Changes in ECGs
Summaries over time and/or changes from baseline over time in ECGs
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
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
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
Secondary Outcome Measures
Peak plasma concentration (Cmax)
Peak plasma concentration (Cmax)
Area under the plasma concentration versus time curve (AUC)
Area under the plasma concentration versus time curve (AUC)
Median of tmax
Median of tmax
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02567370
Brief Title
Single-ascending Dose Study With a Food-Effect Cohort to Evaluate AMG 581
Acronym
FIH
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2015
Overall Recruitment Status
Completed
Study Start Date
August 2015 (undefined)
Primary Completion Date
October 2015 (Actual)
Study Completion Date
October 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen
4. Oversight
Data Monitoring Committee
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia or Schizoaffective Disorder
Keywords
Schizophrenia or Schizoaffective Disorder
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
70 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Title
AMG 581
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
AMG 581
Intervention Description
Active drug
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Reported treatment-emergent adverse events
Description
Number and percent of subjects experiencing adverse events
Time Frame
15 days
Title
Changes in systolic/diastolic blood pressure
Description
Summaries over time and/or changes from baseline over time in systolic and/or diastolic blood pressure
Time Frame
15 days
Title
Changes in heart rate
Description
Summaries over time and/or changes from baseline over time in heart rate
Time Frame
15 days
Title
Changes in respiratory rate
Description
Summaries over time and/or changes from baseline over time in respiratory rate
Time Frame
15 days
Title
Changes in temperature
Description
Summaries over time and/or changes from baseline over time in temperature
Time Frame
15 days
Title
Changes in ECGs
Description
Summaries over time and/or changes from baseline over time in ECGs
Time Frame
15 days
Title
Scores at each study visit for Simpson Angus Scale (SAS)
Description
Summaries over time and/or changes from baseline over time in Simpson Angus Scale (SAS) score
Time Frame
15 days
Title
Scores at each study visit and summary by cohort for Barnes Akathisia Rating Scale (BARS)
Description
Summaries over time and/or changes from baseline over time in Barnes Akathisia Rating Scale (BARS) score
Time Frame
15 days
Title
Subject incidence of treatment-emergent suicidal ideation and behavior as measured by Columbia-Suicide Severity Rating Scale (C-SSRS)
Description
Subject incidence of treatment-emergent suicidal ideation and behavior as measured by Columbia-Suicide Severity Rating Scale (C-SSRS) summarized by cohort
Time Frame
15 days
Secondary Outcome Measure Information:
Title
Peak plasma concentration (Cmax)
Description
Peak plasma concentration (Cmax)
Time Frame
15 days
Title
Area under the plasma concentration versus time curve (AUC)
Description
Area under the plasma concentration versus time curve (AUC)
Time Frame
15 days
Title
Median of tmax
Description
Median of tmax
Time Frame
15 days
Other Pre-specified Outcome Measures:
Title
AMG 581 metabolites in plasma
Description
Metabolites of AMG 581 in plasma
Time Frame
15 days
Title
Subjective experience follow administration of AMG 581 as measured by the Bond and Lader visual analogue scale (VAS)
Description
To assess the subjective experience of study subjects following administration of AMG 581 as measured by the Bond and Lader visual analogue scale (VAS)
Time Frame
15 days
Title
Subjective experience follow administration of AMG 581 as measured by the Positive and Negative Syndrome Scale (PANSS)
Description
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)
Time Frame
15 days
Title
Relationship between plasma concentration of AMG 581 and QTc interval
Description
To explore the relationship between changes in QTc interval (msec) and AMG 581 plasma concentration (ng/mL)
Time Frame
15 days
Title
Effect of food on plasma concentration of AMG 581
Description
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)
Time Frame
43 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Glendale
State/Province
California
ZIP/Postal Code
91206
Country
United States
12. IPD Sharing Statement
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website
Learn more about this trial
Single-ascending Dose Study With a Food-Effect Cohort to Evaluate AMG 581
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