FIH: Single-ascending Dose Study With a Food-Effect Cohort to Evaluate AMG 581
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo
|
Drug: Placebo
Placebo
|
| Active Comparator: AMG 581
|
Drug: AMG 581
Active drug
|
Outcome Measures
Primary Outcome Measures
- Reported treatment-emergent adverse events [15 days]
Number and percent of subjects experiencing adverse events
- Changes in systolic/diastolic blood pressure [15 days]
Summaries over time and/or changes from baseline over time in systolic and/or diastolic blood pressure
- Changes in heart rate [15 days]
Summaries over time and/or changes from baseline over time in heart rate
- Changes in respiratory rate [15 days]
Summaries over time and/or changes from baseline over time in respiratory rate
- Changes in temperature [15 days]
Summaries over time and/or changes from baseline over time in temperature
- Changes in ECGs [15 days]
Summaries over time and/or changes from baseline over time in ECGs
- 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
- 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
Secondary Outcome Measures
- 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 tmax [15 days]
Median of tmax
Other Outcome Measures
- AMG 581 metabolites in plasma [15 days]
Metabolites of AMG 581 in plasma
- Subjective experience follow administration of AMG 581 as measured by the Bond and Lader visual analogue scale (VAS) [15 days]
To assess the subjective experience of study subjects following administration of AMG 581 as measured by the Bond and Lader visual analogue scale (VAS)
- Subjective experience follow administration of AMG 581 as measured by the Positive and Negative Syndrome Scale (PANSS) [15 days]
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)
- Relationship between plasma concentration of AMG 581 and QTc interval [15 days]
To explore the relationship between changes in QTc interval (msec) and AMG 581 plasma concentration (ng/mL)
- Effect of food on plasma concentration of AMG 581 [43 days]
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)
Eligibility Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Site | Glendale | California | United States | 91206 |
Sponsors and Collaborators
- Amgen
Investigators
- Study Director: MD, Amgen
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 20130100