Multiple Ascending Dose Study on Safety, Tolerability, and Pharmacokinetics of AMG 581 in Healthy Subjects or Subjects With Schizophrenia or Schizoaffective
- Conditions
- Schizophrenia or Schizoaffective Disorder
- Interventions
- Registration Number
- NCT02504476
- 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 in healthy participants and subjects with schizophrenia and whether it causes any side effects.
- Detailed Description
The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetic profile of ascending multiple oral doses of AMG 581 in healthy subjects or subjects with schizophrenia or schizoaffective disorder on antipsychotic medication. The study will also assess the effects of AMG 581 on midazolam PK in healthy subjects or subjects with schizophrenia or schizoaffective disorder on antipsychotic medication.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 52
- Provided informed consent prior to initiation of any study-specific activities/procedures; -male or female subjects should be between the ages of 18 and 45 years (18-55 years for subjects with schizophrenia);-non-nicotine or non-tobacco (healthy subjects only); - no history of relevant medical disorders; - BMI ≥ 18.0; - females of non-reproductive potential; - males practicing effective birth control; - avoid tanning/direct sunlight; - schizophrenia or schizoaffective disorder; PANSS score ≤ 4 points on following 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
- females lactating/breastfeeding; pregnant partners of male subjects; essential tremor or gait disturbance; - history of hereditary shorten QT syndrome; - malignancy or tumor (other than skin cancers); - history of GI disease that could interfere with absorption; - QTc ≥ 450 msec or ≤ 380 msec; - HbA1c ≥ 7%;
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description AMG 581 - Dose 1 AMG 581 - AMG 581 - Dose 2 AMG 581 - AMG 581 - Dose 3 AMG 581 - AMG 581 - Dose 4 AMG 581 - Placebo - Dose 1 AMG 581 - Placebo - Dose 1 Placebo - Placebo - Dose 2 Placebo - Placebo - Dose 3 Placebo - Placebo - Dose 4 Placebo - AMG 581/Midazolam - Drug Interaction AMG 581 - AMG 581/Midazolam - Drug Interaction Midazolam -
- Primary Outcome Measures
Name Time Method Reported treatment-emergent adverse events 39 days Number and percent of subjects experiencing adverse events
Changes in systolic/diastolic blood pressure 39 days Summaries over time and/or changes from baseline over time in systolic and/or diastolic blood pressure
Changes in heart rate 39 days Summaries over time and/or changes from baseline over time in heart rate
Maximum post-baseline QTc values and number and percentage of subjects with maximum post-baseline QTc values exceeding prespecified limits in each group 39 days Subjects' maximum post-baseline values and the number and percentage of subjects in each group
Scores at each study visit for Simpson Angus Scale (SAS) 39 days Summaries over time and/or changes from baseline over time in changes in Simpson Angus Scale (SAS) score
Scores at each study visit for Barnes Akathisia Rating Scale (BARS) 39 days Summaries over time and/or changes from baseline over time in in Barnes Akathisia Rating Scale (BARS) score
Changes in respiratory rate 39 days Summaries over time and/or changes from baseline over time in respiratory rate
Changes in temperature 39 days Summaries over time and/or changes from baseline over time in temperature
Changes in ECGs 39 days Summaries over time and/or changes from baseline over time in ECGs
Maximum change from baseline in QTc in ECGs and number and percentage of subjects with maximum changes exceeding prespecified limits in each group 39 days Subjects' maximum change from baseline in QTc and the number and percentage of subjects in each group
Subject incidence of treatment-emergent suicidal ideation and behavior as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) 39 days Subject incidence of treatment-emergent suicidal ideation and behavior as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) summarized by cohort
- Secondary Outcome Measures
Name Time Method Compare PK parameter (Cmax) between Day 1 and Day 18 18 days Compare PK parameter (Cmax) between Day 1 and Day 18
Compare PK parameter (AUC) between Day 1 and Day 18 18 days Compare PK parameter (AUC) between Day 1 and Day 18
Compare PK parameter (tmax) Compare PK parameter (tmax) between Day 1 and Day 18 18 days Compare PK parameter (tmax) Compare PK parameter (tmax) between Day 1 and Day 18
Plasma PK parameters of midazolam and 1-OH midazolam 36 days Cmax and AUC prior to versus following AMG 581 administration
Trial Locations
- Locations (2)
Research Site
🇺🇸Glendale, California, United States
Parexel
🇺🇸Glendale, California, United States