Clinical trial NCT02411695: Study to Assess the Safety, Tolerability and Pharmacokinetics of Oral Brexpiprazole (OPC- 34712) in Adolescents With Schizophrenia
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Schizophrenia
Keywords: Adolescent
Otsuka,
Brexpiprazole
Lead sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Sponsor class: INDUSTRY
Collaborators: name: H. Lundbeck A/S
First posted: 2015-04-08
Enrollment: 40
Sex: ALL
Minimum age (years): 13
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Reported Adverse Events (AEs) at 30 day Follow-Up
timeFrame: 30 day Follow-Up
measure: Change from Baseline to Day 17 in Vital Signs
timeFrame: Baseline to Day 17
measure: Change from Baseline to Day 17 ECGs
timeFrame: Baseline to Day 17
measure: Change from Baseline to Day 17 Hematology
timeFrame: Baseline to Day 17
measure: Change from Baseline to Day 14 Physical examination
timeFrame: Baseline to Day 14
measure: Change from Baseline to Day 17 Body weight
timeFrame: Baseline to Day 17
measure: Change from Baseline to Day 17 Serum chemistry
timeFrame: Baseline to Day 17
measure: Change from Baseline to Day 17 Urinalysis
timeFrame: Baseline to Day 17
measure: Maximal peak steady-state plasma concentration
timeFrame: At Day 14
measure: Minimum trough steady-state plasma concentration
timeFrame: At Day 14
measure: Time to maximum peak steady-state plasma concentration
timeFrame: At Day 14
measure: Area under the concentration-time curve during the dosing interval at steady-state
timeFrame: At Day 14
measure: Terminal elimination half-life
timeFrame: At Day 14
measure: For Brex only, apparent cleanse and apparent volume of distribution
timeFrame: At Day 14
Secondary outcomes:
measure: Mean change in CGI-S score
timeFrame: Day -1 of Dose Titration Phase to Day 7 and Day 14 of Fixed Dose Phase
measure: Mean change in CGI-I score
timeFrame: Day 7 and Day 14
measure: Glycosylated haemoglobin [HbA1c]
timeFrame: Baseline to Day 17
measure: Change from Baseline to Day 17 Adrenocorticotropic hormone [ACTH]
timeFrame: Baseline to Day 17
measure: Change from Baseline to Day 17 Cortisol
timeFrame: Baseline to Day 17
measure: Change from Baseline to Day 17 Thyroid stimulating hormone [TSH]
timeFrame: Baseline to Day 17
measure: Change from Baseline to Day 17 Prothrombin time [PT]
timeFrame: Baseline to Day 17
measure: Change from Baseline to Day 17 Activated partial thromboplastin time [aPTT]
timeFrame: Baseline to Day 17
measure: Change from Baseline to Day 17 International normalized ratio [INR]
timeFrame: Baseline to Day 17
measure: For subjects with a current primary schizophrenia spectrum diagnosis, mean change in Positive and Negative Syndrom Scale (PANSS)
timeFrame: Day-1 to Day 15
measure: For subjects with a current diagnosis of bipolar spectrum disorder, mean change in Young Mania Rating Scale (YMRS)
timeFrame: Day -1 to Day 15
Other outcomes:
Locations:
city: Little Rock
country: United States
state: Arkansas
city: Culver City
country: United States
state: California
city: Orange
country: United States
state: California
city: Washington
country: United States
state: District of Columbia
city: Atlanta
country: United States
state: Georgia
city: Marlton
country: United States
state: New Jersey
city: Cincinnati
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: The Woodlands
country: United States
state: Texas
city: Orem
country: United States
state: Utah
Study officials:
affiliation: Otsuka Pharmaceutical Development & Commercialization
name: Eva Kohegyi, MD
role: STUDY_DIRECTOR
References: