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

Primary Purpose

Schizophrenia or Schizoaffective Disorder

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
AMG 581
Placebo
Midazolam
Sponsored by
Amgen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Schizophrenia or Schizoaffective Disorder focused on measuring Schizophrenia or Schizoaffective Disorder

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesAccepts Healthy Volunteers

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%;

Sites / Locations

  • Research Site
  • Parexel

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm Type

Active Comparator

Active Comparator

Active Comparator

Active Comparator

Placebo Comparator

Placebo Comparator

Placebo Comparator

Placebo Comparator

Other

Arm Label

AMG 581 - Dose 1

AMG 581 - Dose 2

AMG 581 - Dose 3

AMG 581 - Dose 4

Placebo - Dose 1

Placebo - Dose 2

Placebo - Dose 3

Placebo - Dose 4

AMG 581/Midazolam - Drug Interaction

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
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
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
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
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
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

Secondary Outcome Measures

Compare PK parameter (Cmax) between Day 1 and Day 18
Compare PK parameter (Cmax) between Day 1 and Day 18
Compare PK parameter (AUC) between Day 1 and Day 18
Compare PK parameter (AUC) between Day 1 and Day 18
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
Plasma PK parameters of midazolam and 1-OH midazolam
Cmax and AUC prior to versus following AMG 581 administration

Full Information

First Posted
July 8, 2015
Last Updated
March 4, 2016
Sponsor
Amgen
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1. Study Identification

Unique Protocol Identification Number
NCT02504476
Brief Title
Multiple Ascending Dose Study on Safety, Tolerability, and Pharmacokinetics of AMG 581 in Healthy Subjects or Subjects With Schizophrenia or Schizoaffective
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2016
Overall Recruitment Status
Completed
Study Start Date
August 2015 (undefined)
Primary Completion Date
February 2016 (Actual)
Study Completion Date
February 2016 (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 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.

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
52 (Actual)

8. Arms, Groups, and Interventions

Arm Title
AMG 581 - Dose 1
Arm Type
Active Comparator
Arm Title
AMG 581 - Dose 2
Arm Type
Active Comparator
Arm Title
AMG 581 - Dose 3
Arm Type
Active Comparator
Arm Title
AMG 581 - Dose 4
Arm Type
Active Comparator
Arm Title
Placebo - Dose 1
Arm Type
Placebo Comparator
Arm Title
Placebo - Dose 2
Arm Type
Placebo Comparator
Arm Title
Placebo - Dose 3
Arm Type
Placebo Comparator
Arm Title
Placebo - Dose 4
Arm Type
Placebo Comparator
Arm Title
AMG 581/Midazolam - Drug Interaction
Arm Type
Other
Intervention Type
Drug
Intervention Name(s)
AMG 581
Intervention Description
Active drug
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Intervention Type
Drug
Intervention Name(s)
Midazolam
Intervention Description
Interaction
Primary Outcome Measure Information:
Title
Reported treatment-emergent adverse events
Description
Number and percent of subjects experiencing adverse events
Time Frame
39 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
39 days
Title
Changes in heart rate
Description
Summaries over time and/or changes from baseline over time in heart rate
Time Frame
39 days
Title
Changes in respiratory rate
Description
Summaries over time and/or changes from baseline over time in respiratory rate
Time Frame
39 days
Title
Changes in temperature
Description
Summaries over time and/or changes from baseline over time in temperature
Time Frame
39 days
Title
Changes in ECGs
Description
Summaries over time and/or changes from baseline over time in ECGs
Time Frame
39 days
Title
Maximum change from baseline in QTc in ECGs and number and percentage of subjects with maximum changes exceeding prespecified limits in each group
Description
Subjects' maximum change from baseline in QTc and the number and percentage of subjects in each group
Time Frame
39 days
Title
Maximum post-baseline QTc values and number and percentage of subjects with maximum post-baseline QTc values exceeding prespecified limits in each group
Description
Subjects' maximum post-baseline values and the number and percentage of subjects in each group
Time Frame
39 days
Title
Scores at each study visit for Simpson Angus Scale (SAS)
Description
Summaries over time and/or changes from baseline over time in changes in Simpson Angus Scale (SAS) score
Time Frame
39 days
Title
Scores at each study visit for Barnes Akathisia Rating Scale (BARS)
Description
Summaries over time and/or changes from baseline over time in in Barnes Akathisia Rating Scale (BARS) score
Time Frame
39 days
Title
Subject incidence of treatment-emergent suicidal ideation and behavior as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)
Description
Subject incidence of treatment-emergent suicidal ideation and behavior as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) summarized by cohort
Time Frame
39 days
Secondary Outcome Measure Information:
Title
Compare PK parameter (Cmax) between Day 1 and Day 18
Description
Compare PK parameter (Cmax) between Day 1 and Day 18
Time Frame
18 days
Title
Compare PK parameter (AUC) between Day 1 and Day 18
Description
Compare PK parameter (AUC) between Day 1 and Day 18
Time Frame
18 days
Title
Compare PK parameter (tmax) Compare PK parameter (tmax) between Day 1 and Day 18
Description
Compare PK parameter (tmax) Compare PK parameter (tmax) between Day 1 and Day 18
Time Frame
18 days
Title
Plasma PK parameters of midazolam and 1-OH midazolam
Description
Cmax and AUC prior to versus following AMG 581 administration
Time Frame
36 days
Other Pre-specified Outcome Measures:
Title
AMG 581 metabolites in plasma
Description
Metabolites of AMG 581 in plasma
Time Frame
39 days
Title
Cmax and AUC of AMG 581 prior to versus following midazolam administration
Description
Cmax and AUC prior to versus following AMG 581 administration
Time Frame
36 days
Title
Subjective experience following administration of AMG 581
Description
Subjective experience of study subjects following administration of AMG 581 as measured by the Bond and Lader visual analogue scales (VAS)
Time Frame
39 days
Title
Changes in psychotic symptoms following administration of AMG 581
Description
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)
Time Frame
39 days
Title
Relationship between QTc and temperature
Description
To explore the relationship between changes in QTc and changes in body temperature
Time Frame
39 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: - 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%;
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
Facility Name
Parexel
City
Glendale
State/Province
California
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website

Learn more about this trial

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

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