Trial to Assess the Pharmacokinetics, Safety, Tolerability of Oral Brexpiprazole in Children (6 to <13 Years Old) With Central Nervous System Disorders

NCT03292848 | Completed Phase 1 FDA Drug

• 1 other identifier: 331-201-00103
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 9

Brief Summary

A study to assess pharmacokinetics, safety and tolerability of brexpiprazole in children ages 6 to \<13 years with CNS disorders.

Conditions

ADHD; Autism; Bipolar I Disorder; Conduct Disorder; Oppositional Defiant Disorder

Keywords

CNS Disorders; Brexpiprazole

Outcome Measures

Primary Outcomes (6)

• Maximum Plasma Concentration (Cmax) [PK]

  The maximum plasma concentration of drug will be assessed for brexpiprazole and its major metabolite DM-3411.

  Up to 22 days or early termination

• Area under concentration-time curve (AUC) calculated from time zero to time t (AUCt) [PK]

  AUCt will be assessed for plasma brexpiprazole and its major metabolite DM-3411 to determine average concentration of drug over time

  Up to 22 days or early termination

• AUC from time zero to infinity [PK]

  AUC infinity will be assessed for plasma brexpiprazole and its major metabolite DM-3411 to determine total drug exposure over time

  Up to 22 days or early termination

• Time of maximum plasma concentration (tmax) [PK]

  The amount of time that the maximum plasma concentration of drug will be assessed for plasma brexpiprazole and its major metabolite DM-3411

  Up to 22 days or early termination

• Terminal-phase elimination half-life (t½,z) [PK]

  t½,z will be assessed for plasma brexpiprazole and its major metabolite DM-3411 to determine drug persistence in the body

  Up to 22 days or early termination

• Apparent clearance of drug from plasma after extravascular administration (CL/F) [PK]

  CL/F for brexpiprazole only

  Up to 22 days or early termination

Secondary Outcomes (15)

• Treatment-Emergent Adverse Events (TEAES) [Safety]

  Up to 22 days or early termination with a 21 day follow-up period

• Clinical laboratory tests [Safety]

  Up to 22 days or early termination

• Vital signs observed and change from baseline data (systolic and diastolic blood pressure) [Safety]

  Up to 22 days or early termination

• Vital signs observed and change from baseline data (heart rate) [Safety]

  Up to 22 days or early termination

• Vital signs observed and change from baseline data (respiratory rate) [Safety]

  Up to 22 days or early termination

Study Arms (2)

10 to <13 Years of Age

EXPERIMENTAL

Two doses will be administered with a washout period of 14 days between the first dose of 1.5 mg the second dose of 3 mg.

Drug: Brexpiprazole

6 to <10 Years of Age

EXPERIMENTAL

Two doses will be administered with a washout period of 14 days between the first dose of 0.75 mg and the second dose of 1.5 mg.

Drug: Brexpiprazole

Interventions

Brexpiprazole DRUG

Tablet

Also known as: OPC-34712

10 to <13 Years of Age; 6 to <10 Years of Age

Eligibility Criteria

• Age: 6 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Male and female subjects between 6 and 12 years of age
• Subjects with CNS disorders including, but not limited to, ADHD, autism spectrum disorders, bipolar I disorder (subjects 10 to 12 years old only for bipolar), conduct disorder, oppositional defiant disorder, or any psychotic disorder and who are receiving antipsychotic treatment for their medical condition. Subjects' diagnoses will be determined by the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria and confirmed at screening using the Kiddie Schedule for Affective Disorders and Schizophrenia-Present and Lifetime version (K-SADS-PL).
• Subjects must be considered psychiatrically/medically appropriate for participation in a clinical trial in which they will receive two doses of an antipsychotic medication.
• Subjects with good physical health, as determined by no clinically significant deviation from normal for all of the following, prior to enrollment in the trial:
• Medical history
• Clinical laboratory determination
• ECGs
• Physical examinations
• Subjects who are within the 5th to 95th percentile for gender-specific BMI for age from the Centers for Disease Control and Prevention growth charts and weight at least 15 kg (approx. 33 lbs)
• Ability to commit to remain fully abstinent or use 2 approved methods of birth control during the trial for 21 (± 2) days following the last dose of IMP for sexually active females of childbearing potential.
• Ability, in the opinion of the PI, of the subject and the subject's legally acceptable representative or caregiver(s) to understand the nature of the trial and follow protocol requirements, including all of the following:
• Comply with prescribed dosage regimens and tablet ingestion, as well as the discontinuation of prohibited concomitant medications
• Reliably return for scheduled visits
• To be reliably rated on assessment scales

You may not qualify if:

• Subjects with a history of at least mild intellectual disability as determined by IQ \< 70, clinical evidence, or a social or school history that is suggestive of intellectual disability.
• Subjects who have any of the following:
• A significant risk of committing suicide based on history and the principal investigator's clinical judgment, or routine psychiatric status examination
• Current suicidal behavior
• Imminent risk of injury; active suicidal ideation
• Any lifetime history of suicidal behavior detected by the Children's Baseline/Screening version of the C-SSRS.
• Subjects with a lifetime history of a substance use disorder (as determined by the DSM-5 criteria), or current substance misuse including alcohol and benzodiazepines, but excluding caffeine and nicotine.
• 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. Medical conditions that are minor or well-controlled may be considered acceptable if the condition does not expose the subject to an undue risk of significant adverse event or interfere with assessments during the course of the trial.
• Subjects with insulin dependent diabetes mellitus (IDDM) are excluded. Subjects with non-IDDM may be eligible for the trial if their condition is determined to be stable.
• Subjects with epilepsy or a history of seizures (except for a single seizure episode, for instance childhood febrile seizure or post traumatic) or a history of severe head trauma or cerebrovascular disease (eg, stroke, transient ischemic attack, etc.).
• Any major surgery within 30 days prior to the first dose of IMP.
• Any history of significant bleeding or hemorrhagic tendencies.
• Blood transfusions within 30 days prior to first dose of IMP.
• Subjects with a positive drug screen for cocaine, marijuana (even if by prescription), or other illicit drugs, or alcohol are excluded and may not be retested or rescreened.
• Subjects who have supine or standing diastolic blood pressure, after resting for at least 5 minutes, ≥ 95 mmHg.

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead
• H. Lundbeck A/S: collaborator

Study Sites (9)

Woodland International Research Group

Little Rock, Arkansas, 72211, United States

Location

Woodland Research Northwest, LLC

Rogers, Arkansas, 72758, United States

Location

Alliance for Wellness dba Alliance for Research

Long Beach, California, 90807, United States

Location

New Hope Clinical Research

Charlotte, North Carolina, 28211, United States

Location

IPS Research Company

Oklahoma City, Oklahoma, 73103, United States

Location

Cutting Edge Research Group

Oklahoma City, Oklahoma, 73116, United States

Location

Clinical Trials of Texas, Inc.

San Antonio, Texas, 78229, United States

Location

Road Runner Research Ltd.

San Antonio, Texas, 78249, United States

Location

Aspen Clinical Research

Orem, Utah, 84058, United States

Location

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity; Autistic Disorder; Conduct Disorder; Oppositional Defiant Disorder; Central Nervous System Diseases

Interventions

brexpiprazole

Condition Hierarchy (Ancestors)

Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders; Autism Spectrum Disorder; Child Development Disorders, Pervasive; Nervous System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2017
• First Posted: September 26, 2017
• Study Start: October 10, 2017
• Primary Completion: May 21, 2018
• Study Completion: May 21, 2018
• Last Updated: June 12, 2018

Record last verified: 2018-06

Locations

US (9)