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

Primary Purpose

ADHD, Autism, Bipolar I Disorder

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Brexpiprazole
Sponsored by
Otsuka Pharmaceutical Development & Commercialization, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for ADHD focused on measuring CNS Disorders, Brexpiprazole

Eligibility Criteria

6 Years - 12 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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:

    1. Medical history
    2. Clinical laboratory determination
    3. ECGs
    4. 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 (ยฑ 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:

    1. Comply with prescribed dosage regimens and tablet ingestion, as well as the discontinuation of prohibited concomitant medications
    2. Reliably return for scheduled visits
    3. To be reliably rated on assessment scales

Exclusion Criteria:

  • Subjects with a clinical presentation or history that is consistent with delirium, dementia, amnesia, or other cognitive disorders; subjects with psychotic symptoms that are better accounted for by another general medical condition(s) other than those listed in the second inclusion criterion above, or direct effect of a substance (ie, medication, illicit drug use, etc.).
  • 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:

    1. A significant risk of committing suicide based on history and the principal investigator's clinical judgment, or routine psychiatric status examination
    2. Current suicidal behavior
    3. Imminent risk of injury; active suicidal ideation
    4. 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, โ‰ฅ 95 mmHg.
  • Subjects who have had a dose of depot antipsychotics within 6 months of screening.
  • Consumption of alcohol or grapefruit, grapefruit juice, Seville oranges, or Seville orange juice within 72 hours prior to the first dose of IMP and throughout the trial
  • Subjects who participated in a clinical trial and were exposed to IMP within the last 30 days prior to screening or who participated in more than 2 interventional clinical trials within the past year.
  • Subjects with a history of neuroleptic malignant syndrome or hypersensitivity to atypical antipsychotics.
  • Subjects with a history of true allergic (i.e. not intolerance) response to more than one class of medications.
  • Subjects with a history of allergic reaction or a known or suspected sensitivity to any substance that is contained in the IMP formula.
  • Subjects who do not tolerate venipuncture or have poor venous access that would cause difficulty for collecting blood samples.
  • Prisoners or subjects who are compulsorily detained (e.g. juvenile detention, court-mandated treatment) for any reason.
  • Inability to tolerate oral medication or swallow tablets.

Sites / Locations

  • Woodland International Research Group
  • Woodland Research Northwest, LLC
  • Alliance for Wellness dba Alliance for Research
  • New Hope Clinical Research
  • IPS Research Company
  • Cutting Edge Research Group
  • Clinical Trials of Texas, Inc.
  • Road Runner Research Ltd.
  • Aspen Clinical Research

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

10 to <13 Years of Age

6 to <10 Years of Age

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Maximum Plasma Concentration (Cmax) [PK]
The maximum plasma concentration of drug will be assessed for brexpiprazole and its major metabolite DM-3411.
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
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
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
Terminal-phase elimination half-life (tยฝ,z) [PK]
tยฝ,z will be assessed for plasma brexpiprazole and its major metabolite DM-3411 to determine drug persistence in the body
Apparent clearance of drug from plasma after extravascular administration (CL/F) [PK]
CL/F for brexpiprazole only

Secondary Outcome Measures

Treatment-Emergent Adverse Events (TEAES) [Safety]
Clinical laboratory tests [Safety]
Collect hematology, serum chemistry,and urinalysis will be assessed to determine the safety and tolerability of drug
Vital signs observed and change from baseline data (systolic and diastolic blood pressure) [Safety]
Vital signs observed and change from baseline data (heart rate) [Safety]
Vital signs observed and change from baseline data (respiratory rate) [Safety]
Vital signs observed and change from baseline data (body temperature) [Safety]
12-lead electrocardiogram (ECGs) [Safety]
Physical examinations (height) [Safety]
Height is measured in cm,and will be used to calculate Body Mass Index (BMI)
Physical examinations (weight) [Safety]
Weight is measured in kg, and will be used to calculate Body Mass Index (BMI)
Physical examinations- Body Mass Index (BMI) [Safety]
Body Mass Index (BMI) measured using height (cm) and weight (kg)
Physical examinations- review of body systems [Safety]
Subject will be examined by site staff for any notable changes
Simpson-Angus Scale (SAS) rating scale [Safety]
Will be used in analysis of Extrapyramidal Symptoms (EPS)
Abnormal Involuntary Movement Scale (AIMS) [Safety]
Will be used in analysis of Extrapyramidal Symptoms (EPS)
Barnes Akathisia Rating Scale (BARS) [Safety]
Will be used in analysis of Extrapyramidal Symptoms (EPS)
Columbia-Suicide Severity Rating Scale (C-SSRS) [Safety]

Full Information

First Posted
September 21, 2017
Last Updated
June 11, 2018
Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.
Collaborators
H. Lundbeck A/S
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1. Study Identification

Unique Protocol Identification Number
NCT03292848
Brief Title
Trial to Assess the Pharmacokinetics, Safety, Tolerability of Oral Brexpiprazole in Children (6 to <13 Years Old) With Central Nervous System Disorders
Official Title
A Phase 1, Single-dose, Sequential Cohort, Nonrandomized Crossover Trial to Assess the Pharmacokinetics, Safety, and Tolerability of Oral Brexpiprazole in Children (6 to< 13 Years Old) With Central Nervous System Disorders
Study Type
Interventional

2. Study Status

Record Verification Date
June 2018
Overall Recruitment Status
Completed
Study Start Date
October 10, 2017 (Actual)
Primary Completion Date
May 21, 2018 (Actual)
Study Completion Date
May 21, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.
Collaborators
H. Lundbeck A/S

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
A study to assess pharmacokinetics, safety and tolerability of brexpiprazole in children ages 6 to <13 years with CNS disorders.
Detailed Description
A US based nonrandomized, sequential cohort, crossover trial to assess pharmacokinetics, safety and tolerability of brexpiprazole in children ages 6 to <13 years with CNS disorders who are receiving antipsychotic treatment for their medical condition.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
ADHD, Autism, Bipolar I Disorder, Conduct Disorder, Oppositional Defiant Disorder
Keywords
CNS Disorders, Brexpiprazole

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
10 to <13 Years of Age
Arm Type
Experimental
Arm Description
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.
Arm Title
6 to <10 Years of Age
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Brexpiprazole
Other Intervention Name(s)
OPC-34712
Intervention Description
Tablet
Primary Outcome Measure Information:
Title
Maximum Plasma Concentration (Cmax) [PK]
Description
The maximum plasma concentration of drug will be assessed for brexpiprazole and its major metabolite DM-3411.
Time Frame
Up to 22 days or early termination
Title
Area under concentration-time curve (AUC) calculated from time zero to time t (AUCt) [PK]
Description
AUCt will be assessed for plasma brexpiprazole and its major metabolite DM-3411 to determine average concentration of drug over time
Time Frame
Up to 22 days or early termination
Title
AUC from time zero to infinity [PK]
Description
AUC infinity will be assessed for plasma brexpiprazole and its major metabolite DM-3411 to determine total drug exposure over time
Time Frame
Up to 22 days or early termination
Title
Time of maximum plasma concentration (tmax) [PK]
Description
The amount of time that the maximum plasma concentration of drug will be assessed for plasma brexpiprazole and its major metabolite DM-3411
Time Frame
Up to 22 days or early termination
Title
Terminal-phase elimination half-life (tยฝ,z) [PK]
Description
tยฝ,z will be assessed for plasma brexpiprazole and its major metabolite DM-3411 to determine drug persistence in the body
Time Frame
Up to 22 days or early termination
Title
Apparent clearance of drug from plasma after extravascular administration (CL/F) [PK]
Description
CL/F for brexpiprazole only
Time Frame
Up to 22 days or early termination
Secondary Outcome Measure Information:
Title
Treatment-Emergent Adverse Events (TEAES) [Safety]
Time Frame
Up to 22 days or early termination with a 21 day follow-up period
Title
Clinical laboratory tests [Safety]
Description
Collect hematology, serum chemistry,and urinalysis will be assessed to determine the safety and tolerability of drug
Time Frame
Up to 22 days or early termination
Title
Vital signs observed and change from baseline data (systolic and diastolic blood pressure) [Safety]
Time Frame
Up to 22 days or early termination
Title
Vital signs observed and change from baseline data (heart rate) [Safety]
Time Frame
Up to 22 days or early termination
Title
Vital signs observed and change from baseline data (respiratory rate) [Safety]
Time Frame
Up to 22 days or early termination
Title
Vital signs observed and change from baseline data (body temperature) [Safety]
Time Frame
Up to 22 days or early termination
Title
12-lead electrocardiogram (ECGs) [Safety]
Time Frame
Up to 22 days or early termination
Title
Physical examinations (height) [Safety]
Description
Height is measured in cm,and will be used to calculate Body Mass Index (BMI)
Time Frame
Up to 22 days or early termination
Title
Physical examinations (weight) [Safety]
Description
Weight is measured in kg, and will be used to calculate Body Mass Index (BMI)
Time Frame
Up to 22 days or early termination
Title
Physical examinations- Body Mass Index (BMI) [Safety]
Description
Body Mass Index (BMI) measured using height (cm) and weight (kg)
Time Frame
Up to 22 days or early termination
Title
Physical examinations- review of body systems [Safety]
Description
Subject will be examined by site staff for any notable changes
Time Frame
Up to 22 days or early termination
Title
Simpson-Angus Scale (SAS) rating scale [Safety]
Description
Will be used in analysis of Extrapyramidal Symptoms (EPS)
Time Frame
Up to 22 days or early termination
Title
Abnormal Involuntary Movement Scale (AIMS) [Safety]
Description
Will be used in analysis of Extrapyramidal Symptoms (EPS)
Time Frame
Up to 22 days or early termination
Title
Barnes Akathisia Rating Scale (BARS) [Safety]
Description
Will be used in analysis of Extrapyramidal Symptoms (EPS)
Time Frame
Up to 22 days or early termination
Title
Columbia-Suicide Severity Rating Scale (C-SSRS) [Safety]
Time Frame
Up to 22 days or early termination

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 (ยฑ 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 Exclusion Criteria: Subjects with a clinical presentation or history that is consistent with delirium, dementia, amnesia, or other cognitive disorders; subjects with psychotic symptoms that are better accounted for by another general medical condition(s) other than those listed in the second inclusion criterion above, or direct effect of a substance (ie, medication, illicit drug use, etc.). 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, โ‰ฅ 95 mmHg. Subjects who have had a dose of depot antipsychotics within 6 months of screening. Consumption of alcohol or grapefruit, grapefruit juice, Seville oranges, or Seville orange juice within 72 hours prior to the first dose of IMP and throughout the trial Subjects who participated in a clinical trial and were exposed to IMP within the last 30 days prior to screening or who participated in more than 2 interventional clinical trials within the past year. Subjects with a history of neuroleptic malignant syndrome or hypersensitivity to atypical antipsychotics. Subjects with a history of true allergic (i.e. not intolerance) response to more than one class of medications. Subjects with a history of allergic reaction or a known or suspected sensitivity to any substance that is contained in the IMP formula. Subjects who do not tolerate venipuncture or have poor venous access that would cause difficulty for collecting blood samples. Prisoners or subjects who are compulsorily detained (e.g. juvenile detention, court-mandated treatment) for any reason. Inability to tolerate oral medication or swallow tablets.
Facility Information:
Facility Name
Woodland International Research Group
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72211
Country
United States
Facility Name
Woodland Research Northwest, LLC
City
Rogers
State/Province
Arkansas
ZIP/Postal Code
72758
Country
United States
Facility Name
Alliance for Wellness dba Alliance for Research
City
Long Beach
State/Province
California
ZIP/Postal Code
90807
Country
United States
Facility Name
New Hope Clinical Research
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28211
Country
United States
Facility Name
IPS Research Company
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73103
Country
United States
Facility Name
Cutting Edge Research Group
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73116
Country
United States
Facility Name
Clinical Trials of Texas, Inc.
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Road Runner Research Ltd.
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78249
Country
United States
Facility Name
Aspen Clinical Research
City
Orem
State/Province
Utah
ZIP/Postal Code
84058
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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