Trial to Evaluate the Effects of OPC-34712 on QT/QTc in Subjects With Schizophrenia or Schizoaffective Disorder

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier:
NCT01423916
First received: August 8, 2011
Last updated: April 9, 2012
Last verified: April 2012
  Purpose

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

Condition Intervention Phase
Schizophrenia
Schizoaffective Disorder
Drug: OPC-34712 (4mg)
Drug: Moxifloxacin
Drug: OPC-34712 (12mg)
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:

Primary Outcome Measures:
  • Change in time-matched QTcI [ Time Frame: 11 days ] [ Designated as safety issue: Yes ]
    Pharmacodynamics endpoint is the time-matched QTcI change from baseline (Day -1) corrected for placebo on Day 11 following OPC-34712 treatment.

  • Change in plasma concentration [ Time Frame: 11 days ] [ Designated as safety issue: Yes ]
    Pharmacokinetics endpoint is the maximum (peak) plasma concentration (Cmax), time to maximum (peak) plasma concentration (tmax), and the area under the concentration-time curve from time zero to 24 hours (AUC0-24h) of OPC-34712 and moxifloxacin


Secondary Outcome Measures:
  • Change in mean QTcI [ Time Frame: 11 days ] [ Designated as safety issue: Yes ]
    Time-matched change in mean QTcI change from baseline for assay sensitivity of moxifloxacin treatment corrected for placebo

  • Change in maximum QTcI minus mean QTcI [ Time Frame: 11 days ] [ Designated as safety issue: Yes ]
    Maximum QTcI on Day 11 minus mean QTcI on Day -1 (baseline)

  • Change in maximum QTcI minus maximum QTcI [ Time Frame: 11 days ] [ Designated as safety issue: Yes ]
    Maximum QTcI on Day 11 minus maximum QTcI on Day -1 (baseline)

  • Incidence of maximum change in QTcI between 30 and 60 msec [ Time Frame: 11 days ] [ Designated as safety issue: Yes ]
    Incidence of maximum change from Day -1 (baseline) in QTcI interval between 30 and 60 msec on Day 11

  • Incidence of maximum change in QTcI interval >60 msec [ Time Frame: 11 days ] [ Designated as safety issue: Yes ]
    Incidence of maximum change from Day -1 (baseline) in QTcI interval > 60 msec on Day 11

  • New incidence of maximum QTcI interval >500 msec [ Time Frame: 11 days ] [ Designated as safety issue: Yes ]
    New incidence of maximum QTcI interval > 500 msec on Day 11

  • New incidence of maximum QT interval > 500 msec on Day 11 [ Time Frame: 11 days ] [ Designated as safety issue: Yes ]
  • Change in ECG morphology [ Time Frame: 11 days ] [ Designated as safety issue: Yes ]

    ECG morphology, reviewed by an experienced cardiologist, for new incidence of the following on Day 11:

    U wave or appearance of abnormal U wave, negative T waves, elevation of ST segment, depression of ST segment, second degree heart block, third degree heart block, right bundle branch block, left bundle branch block


  • Maximum change in ECG values [ Time Frame: 11 days ] [ Designated as safety issue: Yes ]
    Maximum change from baseline to the on-treatment ECG values on Day 11 for heart rate, PR, QRS, and QT


Enrollment: 218
Study Start Date: July 2011
Study Completion Date: March 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm 1 (OPC-34712, placebo)
Arm 1 will be administered 4 mg OPC-34712 once daily (QD) for 11 days and OPC-34712 placebo for 1 day.
Drug: OPC-34712 (4mg)
Arms assigned to this intervention receive 4mg.
Drug: Placebo
OPC-34712 placebo
Active Comparator: Arm 2 (OPC-34712, placebo)
Arm 2 will be administered 12 mg OPC-34712 QD for 11 days and OPC-34712 placebo for 1 day.
Drug: OPC-34712 (12mg)
Arms assigned to this intervention receive 12mg.
Drug: Placebo
OPC-34712 placebo
Active Comparator: Arm 3 (moxifloxacin, placebo)
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.
Drug: Moxifloxacin
Arms assigned to this intervention will receive 400mg.
Drug: Placebo
OPC-34712 placebo
Active Comparator: Arm 4 (moxifloxacin, placebo)
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.
Drug: Moxifloxacin
Arms assigned to this intervention will receive 400mg.
Drug: Placebo
OPC-34712 placebo

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01423916

Locations
United States, California
Otsuka Investigational Site
Long Beach, California, United States, 90806
Otsuka Investigational Site
San Diego, California, United States, 92102
United States, Florida
Otsuka Investigational Site
Fort Lauderdale, Florida, United States, 33308
United States, Kansas
Otsuka Investigational Site
Overland Park, Kansas, United States, 66212
United States, Maryland
Otsuka Investigational Site
Rockville, Maryland, United States, 20850
United States, Missouri
Otsuka Investigational Site
St. Louis, Missouri, United States, 63118
United States, Pennsylvania
Otsuka Investigational Site
Philadelphia, Pennsylvania, United States, 19139
United States, Texas
Otsuka Investigational Site
Austin, Texas, United States, 78754
Sponsors and Collaborators
Otsuka Pharmaceutical Development & Commercialization, Inc.
  More Information

No publications provided

Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT01423916     History of Changes
Other Study ID Numbers: 331-10-242
Study First Received: August 8, 2011
Last Updated: April 9, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:
Schizophrenia
QTc Interval

Additional relevant MeSH terms:
Psychotic Disorders
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Moxifloxacin
Norgestimate, ethinyl estradiol drug combination
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Contraceptives, Oral, Combined
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 27, 2014