Clinical trial NCT02567370: Single-ascending Dose Study With a Food-Effect Cohort to Evaluate AMG 581
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
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: 2015-10-05
Enrollment: 70
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, safety and tolerability of AMG 581 in healthy participants and subjects with schizophrenia.

Detailed 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).

Eligibility criteria: 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

Primary outcomes:
measure: Reported treatment-emergent adverse events
timeFrame: 15 days
measure: Changes in systolic/diastolic blood pressure
timeFrame: 15 days
measure: Changes in heart rate
timeFrame: 15 days
measure: Changes in respiratory rate
timeFrame: 15 days
measure: Changes in temperature
timeFrame: 15 days
measure: Changes in ECGs
timeFrame: 15 days
measure: Scores at each study visit for Simpson Angus Scale (SAS)
timeFrame: 15 days
measure: Scores at each study visit and summary by cohort for Barnes Akathisia Rating Scale (BARS)
timeFrame: 15 days
measure: Subject incidence of treatment-emergent suicidal ideation and behavior as measured by Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: 15 days
Secondary outcomes:
measure: Peak plasma concentration (Cmax)
timeFrame: 15 days
measure: Area under the plasma concentration versus time curve (AUC)
timeFrame: 15 days
measure: Median of tmax
timeFrame: 15 days
Other outcomes:
measure: AMG 581 metabolites in plasma
timeFrame: 15 days
measure: Subjective experience follow administration of AMG 581 as measured by the Bond and Lader visual analogue scale (VAS)
timeFrame: 15 days
measure: Subjective experience follow administration of AMG 581 as measured by the Positive and Negative Syndrome Scale (PANSS)
timeFrame: 15 days
measure: Relationship between plasma concentration of AMG 581 and QTc interval
timeFrame: 15 days
measure: Effect of food on plasma concentration of AMG 581
timeFrame: 43 days
Locations:
city: Glendale
country: United States
facility: Research Site
state: California
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: