Clinical trial NCT01423916: Trial to Evaluate the Effects of OPC-34712 on QT/QTc in Subjects With Schizophrenia or Schizoaffective Disorder
Official title: A Parallel-arm, Double-blind, Placebo and Positive Controlled Multiple Oral Dose Administration Trial to Evaluate the Effects of OPC-34712 on QT/QTc in Subjects With Schizophrenia or Schizoaffective Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Schizophrenia
Schizoaffective Disorder
Keywords: Schizophrenia
QTc Interval
Lead sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Sponsor class: INDUSTRY
First posted: 2011-08-26
Enrollment: 218
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to establish pharmacodynamics (PD), pharmacokinetics (PK), and adverse event (AE) profile of OPC-34712 administered to schizophrenic/schizoaffective subjects. The goals of this trial are three-fold:

* To determine the effect of OPC-34712 on the individual QT interval (QTcI) corrected for placebo
* To determine the effect of moxifloxacin on QTcI
* To examine the concentration-effect relationship of OPC-34712 and moxifloxacin on QTcI


Eligibility criteria: Inclusion Criteria:

* Male and female subjects between 18 and 55 years of age, inclusive, with a diagnosis of schizophrenia or schizoaffective disorder as defined by DSM-IV-TR criteria.
* Body mass index of 19 to 35 kg/m2.

Exclusion Criteria:

* Females who are pregnant or lactating. A negative serum pregnancy test must be confirmed prior to the first dose of trial medication for all female subjects.
* Subjects presenting with a first episode of schizophrenia or schizoaffective disorder based on the clinical judgment of the investigator.
* Subjects who have received continuous medication therapy to treat schizophrenia or schizoaffective disorder for less than 6 months prior to washout.
* Subjects with schizophrenia or schizoaffective disorder that are considered resistant/refractory to antipsychotic treatment by history, who have a history of failure to clozapine, or who are responsive only to clozapine treatment.
* Subjects with a current DSM-IV-TR Axis I diagnosis other than schizophrenia or schizoaffective disorder.
* Hospitalization for an exacerbation of schizophrenia or schizoaffective disorder within 3 months prior to randomization.
* Subjects who have a history of or who have evidence of other medical and/or neurological conditions that would expose them to an undue risk of a significant AE or interfere with assessments of safety or efficacy during the course of the trial.
* Subjects with a history of neuroleptic malignant syndrome.
* Subjects with a history of seizure disorder.
* Subjects who meet DSM-IV-TR criteria for substance dependence within 6 months prior to randomization.

Primary outcomes:
measure: Time-matched QTcI Change From Baseline (Day -1) Corrected for Placebo on Day 11 Following Brexpiprazole Treatment.
timeFrame: Day 11 (Hours 1, 2, 3, 4, 5, 6, 8, 12, 16, 24)
measure: Number of Participants With Adverse Events (AE) and Clinically Important Changes in Vital Signs, Physical Examinations, Laboratory Tests, and Standard ECGs (Electrocardiogram).
timeFrame: AEs were recorded from Screening (informed consent was signed) during the 12-day treatment period to follow-up 30 (+ 2) days post-last dose of study medication
measure: Maximum Peak Plasma Concentration (Cmax) of Brexpiprazole and Moxifloxacin.
timeFrame: Day 11
measure: Time to Maximum (Peak) Plasma Concentration (Tmax) of Brexpiprazole and Moxifloxacin.
timeFrame: Day 11
measure: Area Under the Plasma Concentration-time Curve During Dosing (AUCT).
timeFrame: Day 11
Secondary outcomes:
measure: Number of Participants Noted With Time-matched Change in Mean QTcI Change From Baseline for Assay Sensitivity of Moxifloxacin Treatment Corrected for Placebo at Day 11.
timeFrame: Baseline, Day 11
measure: Change From Baseline in Summary of Maximum QTcI on Day 11 Minus Mean QTcI on Day -1 (Baseline).
timeFrame: Baseline, Day 11
measure: Change From Baseline in Summary of Maximum QTcI on Day 11 Minus Maximum QTcI on Day -1 (Baseline).
timeFrame: Baseline, Day 11
measure: Number of Participants With QTcI Interval Between 30 and 60 Msec on Day 11.
timeFrame: Day 11
measure: Number of Participants With QTcI Interval > 60 Msec on Day 11.
timeFrame: Day 11
measure: Number Participants Noted With New Incidence of QT Interval of > 500 Msec on Day 11.
timeFrame: Day 11
measure: Number of Participants With New Incidence of ECG Morphology Abnormalities on Day 11.
timeFrame: Day 11
measure: Number of Participants With Maximum Change From Baseline to the On-treatment ECG Values on Day 11 for Heart Rate (HR), PR Interval, and QRS Interval.
timeFrame: Day 11
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Otsuka Investigational Site
state: California
city: San Diego
country: United States
facility: Otsuka Investigational Site
state: California
city: Fort Lauderdale
country: United States
facility: Otsuka Investigational Site
state: Florida
city: Overland Park
country: United States
facility: Otsuka Investigational Site
state: Kansas
city: Rockville
country: United States
facility: Otsuka Investigational Site
state: Maryland
city: St. Louis
country: United States
facility: Otsuka Investigational Site
state: Missouri
city: Philadelphia
country: United States
facility: Otsuka Investigational Site
state: Pennsylvania
city: Austin
country: United States
facility: Otsuka Investigational Site
state: Texas
Study officials:
References: