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

NCT01423916 | Completed Phase 1 Results

• 1 other identifier: 331-10-242
• Study Type: interventional
• Target: 218
• Locations: 1 country
• Sites: 8

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

Conditions

Schizophrenia; Schizoaffective Disorder

Keywords

Schizophrenia; QTc Interval

Outcome Measures

Primary Outcomes (5)

• 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).

  Day 11 (Hours 1, 2, 3, 4, 5, 6, 8, 12, 16, 24)

• 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.

  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

• 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.

  Day 11

• 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.

  Day 11

• 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.

  Day 11

Secondary Outcomes (8)

• 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.

  Baseline, Day 11

• Change From Baseline in Summary of Maximum QTcI on Day 11 Minus Mean QTcI on Day -1 (Baseline).

  Baseline, Day 11

• Change From Baseline in Summary of Maximum QTcI on Day 11 Minus Maximum QTcI on Day -1 (Baseline).

  Baseline, Day 11

• Number of Participants With QTcI Interval Between 30 and 60 Msec on Day 11.

  Day 11

• Number of Participants With QTcI Interval > 60 Msec on Day 11.

  Day 11

Study Arms (4)

Arm 1 (OPC-34712, placebo)

ACTIVE COMPARATOR

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); Drug: Placebo

Arm 2 (OPC-34712, placebo)

ACTIVE COMPARATOR

Arm 2 will be administered 12 mg OPC-34712 QD for 11 days and OPC-34712 placebo for 1 day.

Drug: OPC-34712 (12mg); Drug: Placebo

Arm 3 (moxifloxacin, placebo)

ACTIVE COMPARATOR

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; Drug: Placebo

Arm 4 (moxifloxacin, placebo)

ACTIVE COMPARATOR

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; Drug: Placebo

Interventions

OPC-34712 (4mg) DRUG

Arms assigned to this intervention receive 4mg.

Arm 1 (OPC-34712, placebo)

Moxifloxacin DRUG

Arms assigned to this intervention will receive 400mg.

Arm 3 (moxifloxacin, placebo); Arm 4 (moxifloxacin, placebo)

OPC-34712 (12mg) DRUG

Arms assigned to this intervention receive 12mg.

Arm 2 (OPC-34712, placebo)

Placebo DRUG

OPC-34712 placebo

Arm 1 (OPC-34712, placebo); Arm 2 (OPC-34712, placebo); Arm 3 (moxifloxacin, placebo); Arm 4 (moxifloxacin, placebo)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead

Study Sites (8)

Otsuka Investigational Site

Long Beach, California, 90806, United States

Location

Otsuka Investigational Site

San Diego, California, 92102, United States

Location

Otsuka Investigational Site

Fort Lauderdale, Florida, 33308, United States

Location

Otsuka Investigational Site

Overland Park, Kansas, 66212, United States

Location

Otsuka Investigational Site

Rockville, Maryland, 20850, United States

Location

Otsuka Investigational Site

St Louis, Missouri, 63118, United States

Location

Otsuka Investigational Site

Philadelphia, Pennsylvania, 19139, United States

Location

Otsuka Investigational Site

Austin, Texas, 78754, United States

Location

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Interventions

Moxifloxacin

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Global Medical Affairs
• Organization: Otsuka Pharmaceutical Development and Commercialization, Inc.

800 562-3974

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2011
• First Posted: August 26, 2011
• Study Start: July 1, 2011
• Primary Completion: February 1, 2012
• Study Completion: March 1, 2012
• Last Updated: October 29, 2015
• Results First Posted: October 29, 2015

Record last verified: 2015-09

Locations

US (8)