Multiple Ascending Dose Study on Safety, Tolerability, and Pharmacokinetics of AMG 581 in Healthy Subjects or Subjects With Schizophrenia or Schizoaffective

Schizophrenia or Schizoaffective Disorder Clinical Trial

— MAD  

Official title:

A Phase I, Randomized, Placebo-controlled, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of AMG 581 in Healthy Subjects or Subjects With Schizophrenia or Schizoaffective Disorder on Antipsychotic Medication

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02504476
• Other study ID #: 20130259
• Status: Completed
• Phase: Phase 1
• First received: July 8, 2015
• Last updated: March 4, 2016
• Start date: August 2015
• Est. completion date: February 2016

Study information

• Verified date: March 2016
• 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 in healthy participants and subjects with schizophrenia and whether it causes any side effects.

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 information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: February 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

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
• Midazolam
Interaction

Locations

Country	Name	City	State
United States	Parexel	Glendale	California
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	39 days	No
Other	Cmax and AUC of AMG 581 prior to versus following midazolam administration	Cmax and AUC prior to versus following AMG 581 administration	36 days	No
Other	Subjective experience following administration of AMG 581	Subjective experience of study subjects following administration of AMG 581 as measured by the Bond and Lader visual analogue scales (VAS)	39 days	No
Other	Changes in psychotic symptoms following administration of AMG 581	Subjective experience of study subjects following administration of AMG 581 as measured by the Positive and Negative Syndrome Scale (PANSS) (subjects with schizophrenia or schizoaffective disorder receiving antipsychotic treatment only)	39 days	No
Other	Relationship between QTc and temperature	To explore the relationship between changes in QTc and changes in body temperature	39 days	No
Primary	Reported treatment-emergent adverse events	Number and percent of subjects experiencing adverse events	39 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	39 days	Yes
Primary	Changes in heart rate	Summaries over time and/or changes from baseline over time in heart rate	39 days	Yes
Primary	Changes in respiratory rate	Summaries over time and/or changes from baseline over time in respiratory rate	39 days	Yes
Primary	Changes in temperature	Summaries over time and/or changes from baseline over time in temperature	39 days	Yes
Primary	Changes in ECGs	Summaries over time and/or changes from baseline over time in ECGs	39 days	Yes
Primary	Maximum change from baseline in QTc in ECGs and number and percentage of subjects with maximum changes exceeding prespecified limits in each group	Subjects' maximum change from baseline in QTc and the number and percentage of subjects in each group	39 days	Yes
Primary	Maximum post-baseline QTc values and number and percentage of subjects with maximum post-baseline QTc values exceeding prespecified limits in each group	Subjects' maximum post-baseline values and the number and percentage of subjects in each group	39 days	Yes
Primary	Scores at each study visit for Simpson Angus Scale (SAS)	Summaries over time and/or changes from baseline over time in changes in Simpson Angus Scale (SAS) score	39 days	Yes
Primary	Scores at each study visit for Barnes Akathisia Rating Scale (BARS)	Summaries over time and/or changes from baseline over time in in Barnes Akathisia Rating Scale (BARS) score	39 days	Yes
Primary	Subject incidence of treatment-emergent suicidal ideation and behavior as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)	Subject incidence of treatment-emergent suicidal ideation and behavior as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) summarized by cohort	39 days	Yes
Secondary	Compare PK parameter (Cmax) between Day 1 and Day 18	Compare PK parameter (Cmax) between Day 1 and Day 18	18 days	No
Secondary	Compare PK parameter (AUC) between Day 1 and Day 18	Compare PK parameter (AUC) between Day 1 and Day 18	18 days	No
Secondary	Compare PK parameter (tmax) Compare PK parameter (tmax) between Day 1 and Day 18	Compare PK parameter (tmax) Compare PK parameter (tmax) between Day 1 and Day 18	18 days	No
Secondary	Plasma PK parameters of midazolam and 1-OH midazolam	Cmax and AUC prior to versus following AMG 581 administration	36 days	No

External Links

•   AmgenTrials clinical trials website