Clinical trial NCT02504476: Multiple Ascending Dose Study on Safety, Tolerability, and Pharmacokinetics of AMG 581 in Healthy Subjects or Subjects With Schizophrenia or Schizoaffective
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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Schizophrenia or Schizoaffective Disorder
Keywords: Schizophrenia or Schizoaffective Disorder
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2015-07-22
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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%;

Primary outcomes:
measure: Reported treatment-emergent adverse events
timeFrame: 39 days
measure: Changes in systolic/diastolic blood pressure
timeFrame: 39 days
measure: Changes in heart rate
timeFrame: 39 days
measure: Changes in respiratory rate
timeFrame: 39 days
measure: Changes in temperature
timeFrame: 39 days
measure: Changes in ECGs
timeFrame: 39 days
measure: Maximum change from baseline in QTc in ECGs and number and percentage of subjects with maximum changes exceeding prespecified limits in each group
timeFrame: 39 days
measure: Maximum post-baseline QTc values and number and percentage of subjects with maximum post-baseline QTc values exceeding prespecified limits in each group
timeFrame: 39 days
measure: Scores at each study visit for Simpson Angus Scale (SAS)
timeFrame: 39 days
measure: Scores at each study visit for Barnes Akathisia Rating Scale (BARS)
timeFrame: 39 days
measure: Subject incidence of treatment-emergent suicidal ideation and behavior as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: 39 days
Secondary outcomes:
measure: Compare PK parameter (Cmax) between Day 1 and Day 18
timeFrame: 18 days
measure: Compare PK parameter (AUC) between Day 1 and Day 18
timeFrame: 18 days
measure: Compare PK parameter (tmax) Compare PK parameter (tmax) between Day 1 and Day 18
timeFrame: 18 days
measure: Plasma PK parameters of midazolam and 1-OH midazolam
timeFrame: 36 days
Other outcomes:
measure: AMG 581 metabolites in plasma
timeFrame: 39 days
measure: Cmax and AUC of AMG 581 prior to versus following midazolam administration
timeFrame: 36 days
measure: Subjective experience following administration of AMG 581
timeFrame: 39 days
measure: Changes in psychotic symptoms following administration of AMG 581
timeFrame: 39 days
measure: Relationship between QTc and temperature
timeFrame: 39 days
Locations:
city: Glendale
country: United States
facility: Research Site
state: California
city: Glendale
country: United States
facility: Parexel
state: California
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: