Back to resultsTrial to Evaluate the Effects of OPC-34712 on QT/QTc in Subjects With Schizophrenia or Schizoaffective Disorder
Primary Purpose
Schizophrenia, Schizoaffective Disorder
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
OPC-34712 (4mg)
Moxifloxacin
OPC-34712 (12mg)
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Schizophrenia focused on measuring Schizophrenia, QTc Interval
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.
Sites / Locations
- Otsuka Investigational Site
- Otsuka Investigational Site
- Otsuka Investigational Site
- Otsuka Investigational Site
- Otsuka Investigational Site
- Otsuka Investigational Site
- Otsuka Investigational Site
- Otsuka Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Active Comparator
Active Comparator
Active Comparator
Active Comparator
Arm Label
Arm 1 (OPC-34712, placebo)
Arm 2 (OPC-34712, placebo)
Arm 3 (moxifloxacin, placebo)
Arm 4 (moxifloxacin, placebo)
Arm Description
Arm 1 will be administered 4 mg OPC-34712 once daily (QD) for 11 days and OPC-34712 placebo for 1 day.
Arm 2 will be administered 12 mg OPC-34712 QD for 11 days and OPC-34712 placebo for 1 day.
Arm 3 will be administered 400 mg moxifloxacin (positive control) plus OPC-34712 placebo for 1 day and OPC-34712 placebo QD for 11 days.
Arm 4 will be administered OPC-34712 placebo QD for 11 days and 400 mg moxifloxacin (positive control) plus OPC-34712 placebo for one day.
Outcomes
Primary Outcome Measures
Time-matched QTcI Change From Baseline (Day -1) Corrected for Placebo on Day 11 Following Brexpiprazole Treatment.
Pharmacodynamics endpoint is the time-matched corrected QT interval (QTcI) change from baseline (Day -1) corrected for placebo on Day 11 following brexpiprazole treatment. The primary QT to QTc correction formula (QTcI) was determined for each participant using the participant's baseline (Day -1 placebo) ECG data. The QT correction formula QT / (RR)k was derived using log-log-linear regression, where log (QT) = a + k × log (RR) + ε to estimate the exponent (k).
Number of Participants With Adverse Events (AE) and Clinically Important Changes in Vital Signs, Physical Examinations, Laboratory Tests, and Standard ECGs (Electrocardiogram).
Clinically important changes in vital signs, physical examinations, laboratory tests and ECGs were by and large reflected in AE/SAE (which are presented in safety section) of this report.
Maximum Peak Plasma Concentration (Cmax) of Brexpiprazole and Moxifloxacin.
Pharmacokinetics endpoint is the maximum (peak) plasma concentration (Cmax) of brexpiprazole and moxifloxacin. Values for Cmax were determined directly from the observed data. Blood samples were collected on Days -1, 1, 11, and 12 at predose, and 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose or at ET.
Time to Maximum (Peak) Plasma Concentration (Tmax) of Brexpiprazole and Moxifloxacin.
Pharmacokinetics endpoint is the time to maximum (peak) plasma concentration (tmax) of brexpiprazole and moxifloxacin. Values for tmax were determined directly from the observed data. Blood samples were collected on Days -1, 1, 11, and 12 at predose, and 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose or at ET.
Area Under the Plasma Concentration-time Curve During Dosing (AUCT).
Pharmacokinetics endpoint is the area under the concentration-time curve from time zero to 24 hours (AUC0-24h) of brexpiprazole and moxifloxacin. Area under the plasma concentration-time curve during the dosing interval at steady-state (AUCT) value was estimated using the linear trapezoidal rule; the value reported represent the area under the curves to the last time point during that day. Blood samples were collected on Days -1, 1, 11, and 12 at predose, and 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose or at ET.
Secondary Outcome Measures
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.
New onset (> 450, > 480, or > 500 msec) in QTc was defined as a participant who attained a QTc > 450, > 480, > 500 msec during Day 11 but not on Day -1. The number of participants were noted with time-matched change in mean QTcI change from Baseline for assay sensitivity of moxifloxacin treatment corrected for placebo. The primary QT to QTc correction formula (QTcI) were determined for each participant using the participant's Baseline (Day -1 placebo) ECG data. The QT correction formula QT / (RR)k were derived using log-log-linear regression, where log (QT) = a + k × log (RR) + ε to estimate the exponent (k).
Change From Baseline in Summary of Maximum QTcI on Day 11 Minus Mean QTcI on Day -1 (Baseline).
The primary QT to QTc correction formula (QTcI) were determined for each participant using the participant's Baseline (Day -1 placebo) ECG data. The QT correction formula QT / (RR)k were derived using log-log-linear regression, where log (QT) = a + k × log (RR) + ε to estimate the exponent (k). The change form Baseline in summary of maximun QTcI on Day 11 minus mean QTcI on Day -1 (Baseline) is presented here.
Change From Baseline in Summary of Maximum QTcI on Day 11 Minus Maximum QTcI on Day -1 (Baseline).
The primary QT to QTc correction formula (QTcI) were determined for each participant using the participant's Baseline (Day -1 placebo) ECG data. The QT correction formula QT / (RR)k were derived using log-log-linear regression, where log (QT) = a + k × log (RR) + ε to estimate the exponent (k). The change from Baseline in summary of maximum QTcI on Day 11 minus maximum QTcI on Day -1 (Baseline) is presented here.
Number of Participants With QTcI Interval Between 30 and 60 Msec on Day 11.
The primary QT to QTc correction formula (QTcI) were determined for each participant using the participant's Baseline (Day -1 placebo) ECG data. The QT correction formula QT / (RR)k were derived using log-log-linear regression, where log (QT) = a + k × log (RR) + ε to estimate the exponent (k). Participants with QTcI interval change between 30 to 60 msec were presented here.
Number of Participants With QTcI Interval > 60 Msec on Day 11.
The primary QT to QTc correction formula (QTcI) were determined for each participant using the participant's Baseline (Day -1 placebo) ECG data. The QT correction formula QT / (RR)k were derived using log-log-linear regression, where log (QT) = a + k × log (RR) + ε to estimate the exponent (k). Participants with QTcI interval change of > 60 msec on Day 11 were presented here.
Number Participants Noted With New Incidence of QT Interval of > 500 Msec on Day 11.
The number of participants who were noted with new incidence of QT interval of > 500 msec on Day 11 and a 12-lead ECG was used.
Number of Participants With New Incidence of ECG Morphology Abnormalities on Day 11.
Participants with incidence of ECG morphology abnormalities on Day 11 (participants who had abnormalities during Day 11 but not at Day -1) were noted. Types of abnormalities included appearance of abnormal U waves, negative T waves, elevation of ST segment, depression of ST segment, second degree heart block, third degree heart block, right bundle branch block, and left bundle branch block. ECGs were sampled at predose and approximately 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose on Days -1, 1, 11, and 12.
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.
Changes in HR with values 25% decrease from Day -1 and HR < 50 bpm and 25% increase from Day -1 and HR > 100 bpm; PR interval of greater than or equal to 25% change from Day -1 and PR > 200 msec; QRS interval of Greater than or equal to 25% change from Day -1 and > 100 msec were noted on Day 11. Maximum change from baseline to the on-treatment ECG values on Day 11 for heart rate.
Full Information
NCT ID
NCT01423916
First Posted
August 8, 2011
Last Updated
September 29, 2015
Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT01423916
Brief Title
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
2. Study Status
Record Verification Date
September 2015
Overall Recruitment Status
Completed
Study Start Date
July 2011 (undefined)
Primary Completion Date
February 2012 (Actual)
Study Completion Date
March 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia, Schizoaffective Disorder
Keywords
Schizophrenia, QTc Interval
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
218 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm 1 (OPC-34712, placebo)
Arm Type
Active Comparator
Arm Description
Arm 1 will be administered 4 mg OPC-34712 once daily (QD) for 11 days and OPC-34712 placebo for 1 day.
Arm Title
Arm 2 (OPC-34712, placebo)
Arm Type
Active Comparator
Arm Description
Arm 2 will be administered 12 mg OPC-34712 QD for 11 days and OPC-34712 placebo for 1 day.
Arm Title
Arm 3 (moxifloxacin, placebo)
Arm Type
Active Comparator
Arm Description
Arm 3 will be administered 400 mg moxifloxacin (positive control) plus OPC-34712 placebo for 1 day and OPC-34712 placebo QD for 11 days.
Arm Title
Arm 4 (moxifloxacin, placebo)
Arm Type
Active Comparator
Arm Description
Arm 4 will be administered OPC-34712 placebo QD for 11 days and 400 mg moxifloxacin (positive control) plus OPC-34712 placebo for one day.
Intervention Type
Drug
Intervention Name(s)
OPC-34712 (4mg)
Intervention Description
Arms assigned to this intervention receive 4mg.
Intervention Type
Drug
Intervention Name(s)
Moxifloxacin
Intervention Description
Arms assigned to this intervention will receive 400mg.
Intervention Type
Drug
Intervention Name(s)
OPC-34712 (12mg)
Intervention Description
Arms assigned to this intervention receive 12mg.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
OPC-34712 placebo
Primary Outcome Measure Information:
Title
Time-matched QTcI Change From Baseline (Day -1) Corrected for Placebo on Day 11 Following Brexpiprazole Treatment.
Description
Pharmacodynamics endpoint is the time-matched corrected QT interval (QTcI) change from baseline (Day -1) corrected for placebo on Day 11 following brexpiprazole treatment. The primary QT to QTc correction formula (QTcI) was determined for each participant using the participant's baseline (Day -1 placebo) ECG data. The QT correction formula QT / (RR)k was derived using log-log-linear regression, where log (QT) = a + k × log (RR) + ε to estimate the exponent (k).
Time Frame
Day 11 (Hours 1, 2, 3, 4, 5, 6, 8, 12, 16, 24)
Title
Number of Participants With Adverse Events (AE) and Clinically Important Changes in Vital Signs, Physical Examinations, Laboratory Tests, and Standard ECGs (Electrocardiogram).
Description
Clinically important changes in vital signs, physical examinations, laboratory tests and ECGs were by and large reflected in AE/SAE (which are presented in safety section) of this report.
Time Frame
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
Title
Maximum Peak Plasma Concentration (Cmax) of Brexpiprazole and Moxifloxacin.
Description
Pharmacokinetics endpoint is the maximum (peak) plasma concentration (Cmax) of brexpiprazole and moxifloxacin. Values for Cmax were determined directly from the observed data. Blood samples were collected on Days -1, 1, 11, and 12 at predose, and 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose or at ET.
Time Frame
Day 11
Title
Time to Maximum (Peak) Plasma Concentration (Tmax) of Brexpiprazole and Moxifloxacin.
Description
Pharmacokinetics endpoint is the time to maximum (peak) plasma concentration (tmax) of brexpiprazole and moxifloxacin. Values for tmax were determined directly from the observed data. Blood samples were collected on Days -1, 1, 11, and 12 at predose, and 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose or at ET.
Time Frame
Day 11
Title
Area Under the Plasma Concentration-time Curve During Dosing (AUCT).
Description
Pharmacokinetics endpoint is the area under the concentration-time curve from time zero to 24 hours (AUC0-24h) of brexpiprazole and moxifloxacin. Area under the plasma concentration-time curve during the dosing interval at steady-state (AUCT) value was estimated using the linear trapezoidal rule; the value reported represent the area under the curves to the last time point during that day. Blood samples were collected on Days -1, 1, 11, and 12 at predose, and 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose or at ET.
Time Frame
Day 11
Secondary Outcome Measure Information:
Title
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.
Description
New onset (> 450, > 480, or > 500 msec) in QTc was defined as a participant who attained a QTc > 450, > 480, > 500 msec during Day 11 but not on Day -1. The number of participants were noted with time-matched change in mean QTcI change from Baseline for assay sensitivity of moxifloxacin treatment corrected for placebo. The primary QT to QTc correction formula (QTcI) were determined for each participant using the participant's Baseline (Day -1 placebo) ECG data. The QT correction formula QT / (RR)k were derived using log-log-linear regression, where log (QT) = a + k × log (RR) + ε to estimate the exponent (k).
Time Frame
Baseline, Day 11
Title
Change From Baseline in Summary of Maximum QTcI on Day 11 Minus Mean QTcI on Day -1 (Baseline).
Description
The primary QT to QTc correction formula (QTcI) were determined for each participant using the participant's Baseline (Day -1 placebo) ECG data. The QT correction formula QT / (RR)k were derived using log-log-linear regression, where log (QT) = a + k × log (RR) + ε to estimate the exponent (k). The change form Baseline in summary of maximun QTcI on Day 11 minus mean QTcI on Day -1 (Baseline) is presented here.
Time Frame
Baseline, Day 11
Title
Change From Baseline in Summary of Maximum QTcI on Day 11 Minus Maximum QTcI on Day -1 (Baseline).
Description
The primary QT to QTc correction formula (QTcI) were determined for each participant using the participant's Baseline (Day -1 placebo) ECG data. The QT correction formula QT / (RR)k were derived using log-log-linear regression, where log (QT) = a + k × log (RR) + ε to estimate the exponent (k). The change from Baseline in summary of maximum QTcI on Day 11 minus maximum QTcI on Day -1 (Baseline) is presented here.
Time Frame
Baseline, Day 11
Title
Number of Participants With QTcI Interval Between 30 and 60 Msec on Day 11.
Description
The primary QT to QTc correction formula (QTcI) were determined for each participant using the participant's Baseline (Day -1 placebo) ECG data. The QT correction formula QT / (RR)k were derived using log-log-linear regression, where log (QT) = a + k × log (RR) + ε to estimate the exponent (k). Participants with QTcI interval change between 30 to 60 msec were presented here.
Time Frame
Day 11
Title
Number of Participants With QTcI Interval > 60 Msec on Day 11.
Description
The primary QT to QTc correction formula (QTcI) were determined for each participant using the participant's Baseline (Day -1 placebo) ECG data. The QT correction formula QT / (RR)k were derived using log-log-linear regression, where log (QT) = a + k × log (RR) + ε to estimate the exponent (k). Participants with QTcI interval change of > 60 msec on Day 11 were presented here.
Time Frame
Day 11
Title
Number Participants Noted With New Incidence of QT Interval of > 500 Msec on Day 11.
Description
The number of participants who were noted with new incidence of QT interval of > 500 msec on Day 11 and a 12-lead ECG was used.
Time Frame
Day 11
Title
Number of Participants With New Incidence of ECG Morphology Abnormalities on Day 11.
Description
Participants with incidence of ECG morphology abnormalities on Day 11 (participants who had abnormalities during Day 11 but not at Day -1) were noted. Types of abnormalities included appearance of abnormal U waves, negative T waves, elevation of ST segment, depression of ST segment, second degree heart block, third degree heart block, right bundle branch block, and left bundle branch block. ECGs were sampled at predose and approximately 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose on Days -1, 1, 11, and 12.
Time Frame
Day 11
Title
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.
Description
Changes in HR with values 25% decrease from Day -1 and HR < 50 bpm and 25% increase from Day -1 and HR > 100 bpm; PR interval of greater than or equal to 25% change from Day -1 and PR > 200 msec; QRS interval of Greater than or equal to 25% change from Day -1 and > 100 msec were noted on Day 11. Maximum change from baseline to the on-treatment ECG values on Day 11 for heart rate.
Time Frame
Day 11
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
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.
Facility Information:
Facility Name
Otsuka Investigational Site
City
Long Beach
State/Province
California
ZIP/Postal Code
90806
Country
United States
Facility Name
Otsuka Investigational Site
City
San Diego
State/Province
California
ZIP/Postal Code
92102
Country
United States
Facility Name
Otsuka Investigational Site
City
Fort Lauderdale
State/Province
Florida
ZIP/Postal Code
33308
Country
United States
Facility Name
Otsuka Investigational Site
City
Overland Park
State/Province
Kansas
ZIP/Postal Code
66212
Country
United States
Facility Name
Otsuka Investigational Site
City
Rockville
State/Province
Maryland
ZIP/Postal Code
20850
Country
United States
Facility Name
Otsuka Investigational Site
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63118
Country
United States
Facility Name
Otsuka Investigational Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19139
Country
United States
Facility Name
Otsuka Investigational Site
City
Austin
State/Province
Texas
ZIP/Postal Code
78754
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Trial to Evaluate the Effects of OPC-34712 on QT/QTc in Subjects With Schizophrenia or Schizoaffective Disorder
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