Study to Assess the Safety, Tolerability and Pharmacokinetics of Oral Brexpiprazole (OPC- 34712) in Adolescents With Schizophrenia

A Phase 1, Multicenter, Open-label, Dose-Escalation Trial to Assess the Safety, Tolerability and Pharmacokinetics of Oral Brexpiprazole (OPC- 34712) in Adolescents With Schizophrenia

The purpose of this study is to assess the safety, tolerability and pharmacokinetics (PK) of oral brexpipirazole in adolescent subjects with schizophrenia or Other Related Psychiatric Disorders.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Brexpiprazole (OPC-34712)

Detailed Description

Schizophrenia is a severely delibitating mental illness that affects approximately 1% of the world population. The onset of schizophrenia symptoms typically peaks in late adolescence and early adulthood. In a minority of cases, the initial episode may occur during childhood or early adolescence. Patients who experience this "early-onset schizophrenia" exhibit symptoms that are more severe and follow a more chronic course; adolescents with schizophrenia may never achieve full remission of the initial episode. The prognosis for early-onset schizophrenia tends to be poor, and cognitive impairment is greater compared with individuals whose onset of schizophrenia occurs later in life. Several antipsychotics have been investigated for the treatment of adolescent schizophrenia, however, there is a particular challenge because developing bodies are more sensitive to side effects of antipsychotics, particularly with respect to weight gain. In order to enroll a population that includes the younger ages, adolescents with other related psychiatric disorders are also included in this study.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
  • California
    • Culver City, California, United States, 90230
    • Orange, California, United States, 92858
  • District of Columbia
    • Washington, District of Columbia, United States, 20016
  • Georgia
    • Atlanta, Georgia, United States, 30331
  • New Jersey
    • Marlton, New Jersey, United States, 08053
  • Ohio
    • Cincinnati, Ohio, United States, 45219
    • Cleveland, Ohio, United States, 44106
  • Texas
    • The Woodlands, Texas, United States, 77381
  • Utah
    • Orem, Utah, United States, 84058

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 11 years to 15 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female subjects 13 to 17 years of age, inclusive, at the time of informed consent.
• Subjects with a current diagnosis of primary schizophrenia spectrum or bipolar spectrum disorder, as defined by DSM-IV-TR criteria, and confirmed by K-SADS-PL.
• No psychiatric hospitalizations within the past 12 weeks.
• Subjects require treatment with antipsychotic medications.
• Subjects who have received previous outpatient antipsychotic treatment at an adequate dose for an adequate duration (at least 6 weeks) and who showed a previous good response to such antipsychotic treatment (other than clozapine) in the last 12 months.
• Subjects with a body weight at Screening greater than or equal to 30 kg.

Exclusion Criteria:

• Sexually active females of childbearing potential and male subjects who are not practicing two different methods of birth control with their partner (or abstinence) during the trial and for 30 days after the last dose of trial medication
• Females who are breast-feeding and/or who have a positive pregnancy test result prior to receiving trial drug.
• Subjects who have received continuous medication therapy to treat schizophrenia and schizophrenia spectrum diagnosis for less than six months prior to first dose of study medication AND subjects who have received continuous medication therapy to treat bipolar and bipolar spectrum disorder for less than two months in the past three years; or subjects who require more than one antipsychotic..
• Subjects with a current DSM-IV-TR diagnosis other than schizophrenia spectrum , bipolar spectrum, including any Axis I or Axis II (DSM-IV-TR) disorder.
• Subjects with a clinical presentation and/or history of any neurodevelopmental disorder
• Subjects who have met DSM-IV-TR criteria for substance abuse or dependence within the past 180 days.
• Subjects who currently have clinically significant neurological, hepatic, renal, metabolic, hematological, immunological, cardiovascular, pulmonary, or gastrointestinal disorders such as any history of myocardial infarction, congestive heart failure, HIV seropositive status/acquired immunodeficiency syndrome, or chronic hepatitis B or C.
• Subjects with IDDM (ie, any subjects using insulin) are excluded. Subjects with non-IDDM may be eligible for the trial if their condition is stable.
• Subjects with epilepsy or a history of seizures.
• Any major surgery or blood transfusion within 30 days prior to first dose of trial medication.
• Subjects with a positive drug screen for cocaine or other illicit drugs, or alcohol are excluded and may not be retested or re-screened.
• Prohibited concomitant medications used within the exclusionary period prior to Day 1 of the Dose Escalation Phase or anticipated need for such medications during the trial.
• Subjects who participated in a clinical trial and were exposed to IMP within the last 30 days or who participated in more than two interventional clinical trials within the past year.
• Subjects with a history of true allergic response (ie, not intolerance) to more than one class of medications.
• Inability to tolerate oral medication or swallow tablets.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; 0.5 mg, Brexpipraxzole (OPC-34712)	Drug: Brexpiprazole (OPC-34712); Subjects who are deemed eligible for the trial will be assigned to a dosing cohort and will enter a Dose Titration Phase during which they will receive a starting dose of brexpiprazole for 2 to 10 days based on their assigned titration schedule. The Dose Titration Phase may be extended up to a maximum of 14 days, based on the observed safety and tolerability profile of the previous cohort's Dose Titration Phase. Following the Dose Titration Phase, subjects will enter the Fixed Dose Phase and will be administered the assigned dose for that cohort for 14 days.
Experimental: Cohort 2; 1mg, Brexpipraxzole (OPC-34712)	Drug: Brexpiprazole (OPC-34712); Subjects who are deemed eligible for the trial will be assigned to a dosing cohort and will enter a Dose Titration Phase during which they will receive a starting dose of brexpiprazole for 2 to 10 days based on their assigned titration schedule. The Dose Titration Phase may be extended up to a maximum of 14 days, based on the observed safety and tolerability profile of the previous cohort's Dose Titration Phase. Following the Dose Titration Phase, subjects will enter the Fixed Dose Phase and will be administered the assigned dose for that cohort for 14 days.
Experimental: Cohort 3; 2mg, Brexpipraxzole (OPC-34712)	Drug: Brexpiprazole (OPC-34712); Subjects who are deemed eligible for the trial will be assigned to a dosing cohort and will enter a Dose Titration Phase during which they will receive a starting dose of brexpiprazole for 2 to 10 days based on their assigned titration schedule. The Dose Titration Phase may be extended up to a maximum of 14 days, based on the observed safety and tolerability profile of the previous cohort's Dose Titration Phase. Following the Dose Titration Phase, subjects will enter the Fixed Dose Phase and will be administered the assigned dose for that cohort for 14 days.
Experimental: Cohort 4; 3 mg, Brexpipraxzole (OPC-34712)	Drug: Brexpiprazole (OPC-34712); Subjects who are deemed eligible for the trial will be assigned to a dosing cohort and will enter a Dose Titration Phase during which they will receive a starting dose of brexpiprazole for 2 to 10 days based on their assigned titration schedule. The Dose Titration Phase may be extended up to a maximum of 14 days, based on the observed safety and tolerability profile of the previous cohort's Dose Titration Phase. Following the Dose Titration Phase, subjects will enter the Fixed Dose Phase and will be administered the assigned dose for that cohort for 14 days.
Experimental: Cohort 5; 4mg, Brexpipraxzole (OPC-34712)	Drug: Brexpiprazole (OPC-34712); Subjects who are deemed eligible for the trial will be assigned to a dosing cohort and will enter a Dose Titration Phase during which they will receive a starting dose of brexpiprazole for 2 to 10 days based on their assigned titration schedule. The Dose Titration Phase may be extended up to a maximum of 14 days, based on the observed safety and tolerability profile of the previous cohort's Dose Titration Phase. Following the Dose Titration Phase, subjects will enter the Fixed Dose Phase and will be administered the assigned dose for that cohort for 14 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reported Adverse Events (AEs) at 30 day Follow-Up		30 day Follow-Up
Change from Baseline to Day 17 in Vital Signs		Baseline to Day 17
Change from Baseline to Day 17 ECGs		Baseline to Day 17
Change from Baseline to Day 17 Hematology		Baseline to Day 17
Change from Baseline to Day 14 Physical examination		Baseline to Day 14
Change from Baseline to Day 17 Body weight		Baseline to Day 17
Change from Baseline to Day 17 Serum chemistry	Including Prolactin concentrations	Baseline to Day 17
Change from Baseline to Day 17 Urinalysis		Baseline to Day 17
Maximal peak steady-state plasma concentration		At Day 14
Minimum trough steady-state plasma concentration		At Day 14
Time to maximum peak steady-state plasma concentration		At Day 14
Area under the concentration-time curve during the dosing interval at steady-state		At Day 14
Terminal elimination half-life		At Day 14
For Brex only, apparent cleanse and apparent volume of distribution		At Day 14

Secondary Outcome Measures

Outcome Measure	Time Frame
Mean change in CGI-S score	Day -1 of Dose Titration Phase to Day 7 and Day 14 of Fixed Dose Phase
Mean change in CGI-I score	Day 7 and Day 14
Glycosylated haemoglobin [HbA1c]	Baseline to Day 17
Change from Baseline to Day 17 Adrenocorticotropic hormone [ACTH]	Baseline to Day 17
Change from Baseline to Day 17 Cortisol	Baseline to Day 17
Change from Baseline to Day 17 Thyroid stimulating hormone [TSH]	Baseline to Day 17
Change from Baseline to Day 17 Prothrombin time [PT]	Baseline to Day 17
Change from Baseline to Day 17 Activated partial thromboplastin time [aPTT]	Baseline to Day 17
Change from Baseline to Day 17 International normalized ratio [INR]	Baseline to Day 17
For subjects with a current primary schizophrenia spectrum diagnosis, mean change in Positive and Negative Syndrom Scale (PANSS)	Day-1 to Day 15
For subjects with a current diagnosis of bipolar spectrum disorder, mean change in Young Mania Rating Scale (YMRS)	Day -1 to Day 15

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Collaborators: H. Lundbeck A/S
• Investigators: Study Director: Eva Kohegyi, MD, Otsuka Pharmaceutical Development & Commercialization

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Actual): January 1, 2017
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: May 30, 2014
• First Submitted That Met QC Criteria: April 2, 2015
• First Posted (Estimate): April 8, 2015

Study Record Updates

• Last Update Posted (Actual): February 15, 2017
• Last Update Submitted That Met QC Criteria: February 14, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Adolescent; Brexpiprazole; Otsuka,
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Serotonin Agents; Dopamine Agonists; Dopamine Agents; Brexpiprazole
• Other Study ID Numbers: 331-10-233

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No