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Completed

NCT Number: NCT02504476

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

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.

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Key information

Conditions

Schizophrenia or Schizoaffective Disorder Mental Disorders Psychotic Disorders Schizophrenia Schizophrenia Spectrum and Other Psychotic Disorders

Age range

18 year–45 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Parexel, Glendale, California, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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%;

Treatment and study plan

AMG 581

Drug

Active drug

Placebo

Drug

Placebo

midazolam

Drug

Interaction

Primary outcomes

  1. Reported treatment-emergent adverse events

    Time frame: 39 days

    Number and percent of subjects experiencing adverse events

  2. Changes in systolic/diastolic blood pressure

    Time frame: 39 days

    Summaries over time and/or changes from baseline over time in systolic and/or diastolic blood pressure

  3. Changes in heart rate

    Time frame: 39 days

    Summaries over time and/or changes from baseline over time in heart rate

  4. Changes in respiratory rate

    Time frame: 39 days

    Summaries over time and/or changes from baseline over time in respiratory rate

  5. Changes in temperature

    Time frame: 39 days

    Summaries over time and/or changes from baseline over time in temperature

  6. Changes in ECGs

    Time frame: 39 days

    Summaries over time and/or changes from baseline over time in ECGs

  7. Maximum change from baseline in QTc in ECGs and number and percentage of subjects with maximum changes exceeding prespecified limits in each group

    Time frame: 39 days

    Subjects' maximum change from baseline in QTc and the number and percentage of subjects in each group

  8. Maximum post-baseline QTc values and number and percentage of subjects with maximum post-baseline QTc values exceeding prespecified limits in each group

    Time frame: 39 days

    Subjects' maximum post-baseline values and the number and percentage of subjects in each group

  9. Scores at each study visit for Simpson Angus Scale (SAS)

    Time frame: 39 days

    Summaries over time and/or changes from baseline over time in changes in Simpson Angus Scale (SAS) score

  10. Scores at each study visit for Barnes Akathisia Rating Scale (BARS)

    Time frame: 39 days

    Summaries over time and/or changes from baseline over time in in Barnes Akathisia Rating Scale (BARS) score

  11. Subject incidence of treatment-emergent suicidal ideation and behavior as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)

    Time frame: 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 outcomes

  1. Compare PK parameter (Cmax) between Day 1 and Day 18

    Time frame: 18 days

    Compare PK parameter (Cmax) between Day 1 and Day 18

  2. Compare PK parameter (AUC) between Day 1 and Day 18

    Time frame: 18 days

    Compare PK parameter (AUC) between Day 1 and Day 18

  3. Compare PK parameter (tmax) Compare PK parameter (tmax) between Day 1 and Day 18

    Time frame: 18 days

    Compare PK parameter (tmax) Compare PK parameter (tmax) between Day 1 and Day 18

  4. Plasma PK parameters of midazolam and 1-OH midazolam

    Time frame: 36 days

    Cmax and AUC prior to versus following AMG 581 administration

Other outcomes

  1. AMG 581 metabolites in plasma

    Time frame: 39 days

    Metabolites of AMG 581 in plasma

  2. Cmax and AUC of AMG 581 prior to versus following midazolam administration

    Time frame: 36 days

    Cmax and AUC prior to versus following AMG 581 administration

  3. Subjective experience following administration of AMG 581

    Time frame: 39 days

    Subjective experience of study subjects following administration of AMG 581 as measured by the Bond and Lader visual analogue scales (VAS)

  4. Changes in psychotic symptoms following administration of AMG 581

    Time frame: 39 days

    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)

  5. Relationship between QTc and temperature

    Time frame: 39 days

    To explore the relationship between changes in QTc and changes in body temperature

Sponsors and collaborators

Lead sponsor

Amgen

Industry

Registry information

Official study 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

Acronym: MAD

Important dates

Study start
2015
Primary completion
2016
Study completion
2016
First posted
Jul 22, 2015
Registry last updated
Mar 7, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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