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

Schizophrenia or Schizoaffective Disorder Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02567370
• Other study ID #: 20130100
• Status: Completed
• Phase: Phase 1
• First received: September 16, 2015
• Last updated: October 22, 2015
• Start date: August 2015
• Est. completion date: October 2015

Study information

• Verified date: October 2015
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: October 2015
• Est. primary completion date: October 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Psychotic Disorders
• Schizophrenia
• Schizophrenia or Schizoaffective Disorder

Intervention

Drug:
• AMG 581
Active drug
• Placebo
Placebo

Locations

Country	Name	City	State
United States	Research Site	Glendale	California

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	AMG 581 metabolites in plasma	Metabolites of AMG 581 in plasma	15 days	No
Other	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	No
Other	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	No
Other	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	No
Other	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	No
Primary	Reported treatment-emergent adverse events	Number and percent of subjects experiencing adverse events	15 days	Yes
Primary	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	Yes
Primary	Changes in heart rate	Summaries over time and/or changes from baseline over time in heart rate	15 days	Yes
Primary	Changes in respiratory rate	Summaries over time and/or changes from baseline over time in respiratory rate	15 days	Yes
Primary	Changes in temperature	Summaries over time and/or changes from baseline over time in temperature	15 days	Yes
Primary	Changes in ECGs	Summaries over time and/or changes from baseline over time in ECGs	15 days	Yes
Primary	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	Yes
Primary	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	Yes
Primary	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	Yes
Secondary	Peak plasma concentration (Cmax)	Peak plasma concentration (Cmax)	15 days	No
Secondary	Area under the plasma concentration versus time curve (AUC)	Area under the plasma concentration versus time curve (AUC)	15 days	No
Secondary	Median of tmax	Median of tmax	15 days	No

External Links

•   AmgenTrials clinical trials website