A Phase 4, Multicenter, 2-part Study Composed of a Randomized, Double-blind, Parallel-group, Placebo-controlled, Active-comparator, Dose-optimization Evaluation Followed by a 1-Year Open-label Evaluation to Assess the Safety and Efficacy of Guanfacine Hydrochloride Prolonged-release (SPD503) in Children and Adolescents Aged 6 to 17 Years With Attention-deficit/Hyperactivity Disorder
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- Shire
- 入组人数
- 396
- 试验地点
- 94
- 主要终点
- Parts A and B: Change From Baseline in the Reaction Time (RTI) Task of the Cambridge Automated Neuropsychological Test Battery (CANTAB) at Week 10
研究概览
简要总结
The main aim of this study is learn more about long-term TAK-503 treatment in children and teenagers with ADHD for whom earlier stimulant treatment did not work.
The study has two parts (A and B). In Part A, participants will take tablets of TAK-503, atomoxetine or placebo and in Part B TAK-503 tablets.
详细描述
This study will be conducted in two parts Part A and Part B. Part A is a double-blinded, double-dummy, placebo-controlled study with an atomoxetine arm as an active reference to TAK-503. Eligible participants with ADHD will be randomized in a 1:1:1 ratio among TAK-503, atomoxetine, and placebo treatment arms up to 49 weeks of double-blinded treatment. Upon completion of Part A, participants will roll over to Part B directly as per the study protocol directions for an additional 52 weeks of open-label TAK-503 treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
This study contains two parts (Part A and Part B), where Part A will be double blind, double dummy parts of the study followed by Part B as an open label part of the study.
入排标准
- 年龄范围
- 6 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Study Part A:
- •Participant is a male or female aged 6 to 17 years inclusive at the time of consent/assent.
- •Participant must meet Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for a primary diagnosis of ADHD based on a detailed psychiatric evaluation using the Kiddie-Schedule for Affective Disorders-Present and Lifetime Version (K-SADS-PL) by a trained child and adolescent psychiatrist at screening (Visit 1A).
- •Participant for whom prior stimulant therapy is not suitable, not tolerated, or shown to be ineffective as determined by investigator clinical assessment and review of the Prior Stimulant Medication Questionnaire (PSMQ) administered during screening (Visit 1A).
- •Participant has an ADHD-RS-5 total score greater than or equal to (> =) 28 at baseline (Visit 2A).
- •Participant has a baseline (Visit 2A) CGI-S score > =
- •Participant who is a female of childbearing potential (FOCP) and postmenarchal must have a negative serum beta-human chorionic gonadotropin (β-hCG) pregnancy test at screening (Visit 1A) and a negative urine pregnancy test at baseline (Visit 2A), be nonlactating, and agree to comply with any applicable contraceptive requirements described in the protocol. Female of child bearing potential is defined as any female participant who is at least aged 9 years or younger than 9 years and postmenarchal.
- •Participants parent or legally authorized representative (LAR) must provide signature of informed consent. Documentation of assent (if applicable) must be provided by the participant indicating that the participant is aware of the investigational nature of the study and the required procedures and restrictions in accordance with the International Council for Harmonisation (ICH) Good Clinical Practice (GCP) Guideline E6[R2] and applicable regulations, before completing any study-related procedures.
- •Participant and parent/LAR are willing and able to comply with all the testing and requirements defined in this protocol, including oversight of morning dosing. Specifically, the parent/LAR must be available for the duration of the study to administer the investigational medicinal product (IMP) dose each morning when the participant awakens.
- •Participant has supine and standing blood pressure (BP) measurements less than the 95th percentile for age, sex, and height at both screening (Visit 1A) and baseline (Visit 2A).
- •Participant is functioning at an age-appropriate level intellectually, as judged by the investigator.
- •Participant is able to swallow intact tablets and capsules.
- •Study Part B:
- •Female participants of child-bearing potential must have a negative serum β-hCG pregnancy test if a screening visit is conducted and/or a negative urine pregnancy test at baseline and agree to comply with any applicable contraceptive requirements of the protocol. An FOCP is defined as any female participant who is at least aged 9 years or younger than 9 years and postmenarchal.
- •Participant has a supine and standing BP measurement less than the 95th percentile for age, sex, and height.
排除标准
- •Study Part A:
- •Participant has a current, controlled (requiring medication or therapy) or uncontrolled, comorbid psychiatric disorder (except oppositional defiant disorder), including but not limited to any of the following comorbid Axis I and Axis II disorders (the K-SADS-PL should be reviewed to confirm diagnosis, if necessary):
- •Post-traumatic stress disorder (PTSD)
- •Bipolar illness, psychosis, or family history in either biological parent
- •Pervasive developmental disorder
- •Obsessive-compulsive disorder (OCD)
- •Psychosis/schizophrenia
- •Serious tic disorder or a family history of Tourette's disorder
- •Participant is currently considered to be a suicide risk by the investigator; has made a previous suicide attempt; has a history of, or currently demonstrating, active suicidal ideation.
- •Participant has a substance abuse disorder as defined by DSM-5 criteria or has been suspected of a substance abuse or dependence disorder (except nicotine) within the past 6 months.
- •Participant has a clinically important abnormality on the urine drug and alcohol screen (except for the participants current ADHD stimulant, if applicable) at screening (Visit 1A).
- •Participant has been physically, sexually, and/or emotionally abused.
- •Participant has any other disorder that as judged by the investigator could contraindicate TAK-503 or confound the results of the safety and efficacy assessments.
- •Participant has any condition or illness including any clinically significant abnormal laboratory value at screening (Visit 1A) or, if the laboratory test was repeated, at baseline (Visit 2A) that, as judged by the investigator, would be an inappropriate risk to the participant and/or could confound the interpretation of study results.
- •Participant has current abnormal thyroid function, defined as abnormal thyroid-stimulating hormone and thyroxine at screening (Visit 1A). Treatment with a stable dose of thyroid medication for > = 3 months before screening will be permitted.
- •Participant has a known history or presence of: malignancy (except nonmelanoma skin cancer), pregnancy, and/or a developmental delay or abnormality associated with growth or sexual maturation delays that are not related to ADHD.
- •Children aged 6 to 12 years with a body weight less than (<) 25.0 kg or adolescents aged > = 13 years with a body weight < 34.0 kg at screening (Visit 1A) or baseline (Visit 2A).
- •Participant is significantly overweight based on the Centers for Disease Control (CDC) BMI-for-age sex-specific charts at screening (Visit 1A) or baseline (Visit 2A). For this study, significantly overweight will be defined as a BMI that is greater than the 95th percentile.
- •Participant has a known history or presence of: structural cardiac abnormalities, serious heart rhythm abnormalities, syncope, cardiac conduction problems (e.g. clinically significant heart block or QT interval prolongation), bradycardia, or exercise-related cardiac events including syncope and presyncope.
- •Participant has clinically significant electrocardiogram (ECG) findings, as judged by the investigator, at baseline (Visit 2A).
- •Participant has orthostatic hypotension* or a known history of hypertension. (*Orthostatic hypotension is defined as a sustained reduction of systolic blood pressure of at least 20 millimeter of mercury (mm Hg) or diastolic blood pressure of 10 mm Hg within 3 minutes of standing from supine.)
- •Participant has a known family history of sudden cardiac death or ventricular arrhythmia.
- •Participant is currently using any medication that violates protocol-specified washout criteria at baseline (Visit 2A), including any ADHD medication or other prohibited medications such as herbal supplements, medications that affect BP or heart rate (HR) or medications that have central nervous system (CNS) effects or affect cognitive performance, such as sedating antihistamines and decongestant sympathomimetics (inhaled bronchodilators are permitted) or a history of chronic use of sedating medications (i.e., antihistamines).
- •Participant has a medical condition except ADHD that requires treatment with any medication that affects the CNS.
- •Participant is female and pregnant or currently lactating.
- •Participant has taken another investigational product or participated in a clinical study within 30 days before screening (Visit 1A).
- •Participant does not tolerate or has a known or suspected allergy, hypersensitivity, or clinically significant intolerance to guanfacine hydrochloride, atomoxetine, or any TAK-503 or atomoxetine drug product component.
- •Participant has a history of a seizure disorder (except for a single childhood febrile seizure episode that occurred before the age of 3 years)
- •Participant is well-controlled on his/her current ADHD medication with acceptable tolerability, and the parent/treating physician does not object to the current medication.
- •Participant has alanine transaminase (ALT) greater than (>) 2*upper limit of normal (ULN) or aspartate aminotransferase (AST) >2*ULN or bilirubin >1.5*ULN at screening.
- •Study Part B:
- •Participant failed screening, voluntarily withdrew, or was discontinued from Study Part A for protocol nonadherence, participant noncompliance, or TEAE or SAE.
- •Participant had any clinically significant TEAE during Study Part A that, as judged by the investigator, would preclude exposure to TAK-
- •Participant has a history of alcohol or other substance abuse or dependence, as defined by DSM-5 (with the exception of nicotine) within the last 6 months.
- •Participant currently uses any of the prohibited medication or other medications, including herbal supplements, that affect BP or HR or that have CNS effects or affect cognitive performance, such as sedating antihistamines and decongestant sympathomimetics (inhaled bronchodilators are permitted) or a history of chronic use of sedating medications (i.e. antihistamines) in violation of the protocol-specified washout criteria at baseline.
- •Participant has a known or suspected allergy, hypersensitivity, or clinically significant intolerance to guanfacine hydrochloride, or any components found in TAK-
- •Participant has taken any IMP except placebo in Study Part A within the 30 days before baseline of Study Part B (Visit 2B).
- •Participant is significantly overweight based on the CDC BMI-for-age sex-specific charts at screening. Significantly overweight is defined as a BMI > 95th percentile.
- •Participant is a child aged 6 to 12 years with a body weight of < 25.0 kg or an adolescent aged > = 13 years with a body weight of < 34.0 kg at screening (Visit 1B)
- •Participant has any condition or illness including clinically significant abnormal laboratory values at screening which as judged by the investigator would represent an inappropriate risk to the participant and/or confound the interpretation of study results.
- •Participant is currently considered a suicide risk as judged by the investigator, has previously made a suicide attempt, has a history of, or is currently demonstrating active suicidal ideation. Participants with intermittent passive suicidal ideation are not necessarily excluded based on the assessment of the investigator.
- •Participant has clinically significant ECG findings, as judged by the investigator, at baseline (Visit 2B).
- •Participant has a known history or presence of structural cardiac abnormalities, serious heart rhythm abnormalities, syncope, cardiac conduction problems (e.g. clinically significant heart block), exercise-related cardiac events including syncope and presyncope, or clinically significant bradycardia.
- •Participant has orthostatic hypotension or a known history of hypertension. (*Orthostatic hypotension is defined as a sustained reduction of systolic blood pressure of at least 20 mm Hg or diastolic blood pressure of 10 mm Hg within 3 minutes of standing from supine).
- •Participant has a history of a seizure disorder (except for a single childhood febrile seizure episode that occurred before the age of 3 years) or the presence of a serious tic disorder including Tourette's syndrome.
- •Participant has a medical condition except ADHD, which requires treatment with any medication that affects the CNS.
- •Participant has ALT >2*ULN or AST >2*ULN or bilirubin >1.5*ULN at screening.
研究组 & 干预措施
Part A: Atomoxetine hydrochloride
Participants who weigh less than (<) 70 kilograms (kg) at baseline will receive Atomoxetine hydrochloride capsule orally at an initial dose of 0.5 milligram per kilogram (mg/kg) which may be increased to the target dose of 1.2 mg/kg oral capsule QD during the treatment of 18 weeks. Permitted doses of Atomoxetine hydrochloride capsule will be 10, 18, 25, 40, 60, and 80 mg QD. Participants who weigh >= 70 kg at baseline will receive Atomoxetine hydrochloride at an initial dose of 40 mg oral capsule QD which may be increased to 80 mg and then to 100 mg for 18 weeks. The total dose for participants who weigh >= 70 kg at baseline will not exceed 100 mg.
干预措施: Atomoxetine hydrochloride (Drug)
Part A: Placebo
Participants aged 6 to 12 years will receive a dose of 1 to 4 mg tablet of placebo matched to TAK-503 and aged 13 to 17 years will receive a dose of 5 to 7 mg tablets of placebo matched to TAK-503 orally QD for 18 weeks. Participants who weigh < 70 kg at baseline will receive placebo matched to Atomoxetine hydrochloride oral capsule at an initial dose of 0.5 mg/kg which may be increased to the target dose of 1.2 mg/kg QD oral capsule during the treatment of 18 weeks. Permitted doses of placebo matched to Atomoxetine hydrochloride will be 10, 18, 25, 40, 60, and 80 mg QD and participants who weigh >= 70 kg will receive placebo matched to Atomoxetine hydrochloride at an initial dose of 40 mg QD capsule orally which may be increased to 80 mg and then to 100 mg.
干预措施: Placebo (Other)
Part A: Guanfacine hydrochloride (TAK-503)
Participants randomized to TAK-503 will receive initial dose of 1 milligram (mg), and up titrated with weekly incremental dose of 1 mg until an optimal dose is reached. Participants aged 6 to 12 years will receive a dose of 1 to 4 mg and aged 13 to 17 years will receive a dose of 5 to 7 mg TAK-503 oral tablet once daily (QD) for 18 weeks.
干预措施: Guanfacine hydrochloride (TAK-503) (Drug)
Part B: Guanfacine hydrochloride (TAK-503)
Participants from Part A will roll over into Part B directly after 18 weeks and will receive TAK-503 at an initial dose of 1 mg, and up titrated with weekly incremental dose of 1 mg until an optimal dose is reached. Participants aged 6 to 12 years will receive a dose of 1 to 4 mg and aged 13 to 17 years will receive a dose of 5 to 7 mg TAK-503 oral tablet QD for 52 weeks of Part B.
干预措施: Guanfacine hydrochloride (TAK-503) (Drug)
结局指标
主要结局
Parts A and B: Change From Baseline in the Reaction Time (RTI) Task of the Cambridge Automated Neuropsychological Test Battery (CANTAB) at Week 10
时间窗: Baseline, Week 10
The neurocognitive function effects of TAK-503 on adolescents and children diagnosed with ADHD will be evaluated using the CANTAB cognitive assessments. The RTI task of CANTAB involves elements of decision-making and attention as measured by choice accuracy as well as motor responses, by measuring motor and mental response speeds, and assesses movement time, reaction time, response accuracy, and impulsivity. This outcome measure will be assessed at Week 10 in both Part A and Part B of the study.
Part A: Change from Baseline in the Reaction Time (RTI) Task of the Cambridge Automated Neuropsychological Test Battery (CANTAB) at Week 18
时间窗: Baseline, Week 18
The neurocognitive function effects of TAK-503 on adolescents and children diagnosed with ADHD will be evaluated using the CANTAB cognitive assessments. The RTI task of CANTAB involves elements of decision-making and attention as measured by choice accuracy as well as motor responses, by measuring motor and mental response speeds, and assesses movement time, reaction time, response accuracy, and impulsivity. This outcome measure will be assessed at Week 18 in Part A of the study.
Part B: Change From Baseline in the Reaction Time (RTI) Task of the Cambridge Automated Neuropsychological Test Battery (CANTAB) at Week 49
时间窗: Baseline, Week 49
The neurocognitive function effects of TAK-503 on adolescents and children diagnosed with ADHD will be evaluated using the CANTAB cognitive assessments. The RTI task of CANTAB involves elements of decision-making and attention as measured by choice accuracy as well as motor responses, by measuring motor and mental response speeds, and assesses movement time, reaction time, response accuracy, and impulsivity. This outcome measure will be assessed at Week 49 in Part B of the study.
Part A: Change From Baseline in the Cambridge Neuropsychological Test Automated Battery (CANTAB) Reaction Time (RTI) Task at Week 18
时间窗: At Baseline, Week 18
The neurocognitive function effects of TAK-503 on adolescents and children were evaluated using CANTAB assessments. The RTI task of CANTAB measured motor, mental response speeds and assessed movement time, reaction time, response accuracy and impulsivity. In CANTAB RTI task, a yellow dot appeared in one of circles (five circles for five-choice variant) and participant must react as soon as possible, releasing the button at bottom of screen and selecting the circle in which the dot appeared. Time taken from yellow dot appearing, to the participants releasing press-pad was defined as reaction time. Movement time was defined as time taken from the participant releasing the press-pad to touching the screen. Times for this assessment were calculated for correct trials and measured in milliseconds (msec) ranging from 100 to 5100, with a higher time indicating worse performance of the task. Negative change from baseline indicates improvement in reaction speed.
Part A: Change From Baseline in the CANTAB RTI Task at Week 49
时间窗: At Baseline, Week 49
The neurocognitive function effects of TAK-503 on adolescents and children were evaluated using CANTAB assessments. The RTI task of CANTAB measured motor, mental response speeds and assessed movement time, reaction time, response accuracy and impulsivity. In CANTAB RTI task, a yellow dot appeared in one of circles (five circle for five-choice variant) and participant must react as soon as possible, releasing the button at bottom of screen and selecting the circle in which the dot appeared. Time taken from yellow dot appearing, to the participants releasing press-pad was defined as reaction time. Movement time was defined as time taken from the participant releasing the press-pad to touching the screen. Times for this assessment were calculated for correct trials and measured in msec ranging from 100 to 5100, with a higher time indicating worse performance of the task. Negative change from baseline indicates improvement in reaction speed.
Part B: Change From Baseline in the CANTAB RTI Task at Week 49
时间窗: At Baseline, Week 49
The neurocognitive function effects of TAK-503 on adolescents and children were evaluated using CANTAB assessments. The RTI task of CANTAB measured motor, mental response speeds and assessed movement time, reaction time, response accuracy and impulsivity. In CANTAB RTI task, a yellow dot appeared in one of circles (five circle for five-choice variant) and participant must react as soon as possible, releasing the button at bottom of screen and selecting the circle in which the dot appeared. Time taken from yellow dot appearing, to the participants releasing press-pad was defined as reaction time. Movement time was defined as time taken from the participant releasing the press-pad to touching the screen. Times for this assessment were calculated for correct trials and measured in msec ranging from 100 to 5100, with a higher time indicating worse performance of the task. Negative change from baseline indicates improvement in reaction speed.
次要结局
- Parts A and B: Tanner Stage at Specified Time Points(Part A: Baseline, Week 10, Week 18 Part B: Baseline, Week 10, Week 49)
- Parts A and B: Conners 3 Parent Short Form (C3PS) Total Score(Part A: Baseline, Week 10, Week 18 Part B: Baseline, Week 10, Week 23, Week 36 and Week 49)
- Parts A and B: Change From Baseline in the Spatial Working Memory (SWM) Task of the Cambridge Automated Neuropsychological Test Battery (CANTAB) at Specified Time Points(Part A: Baseline, Week 10, Week 18 Part B: Baseline, Week 10, Week 49)
- Parts A and B: Change From Baseline in the Stop Signal Task (SST) Task of the Cambridge Automated Neuropsychological Test Battery (CANTAB) at Specified Time Points(Part A: Baseline, Week 10, Week 18 Part B: Baseline, Week 10, Week 49)
- Parts A and B: Change From Baseline in the Delayed Matching to Sample (DMS) Task of the Cambridge Automated Neuropsychological Test Battery (CANTAB) at Specified Time Points(Part A: Baseline, Week 10, Week 18 Part B: Baseline, Week 10, Week 49)
- Parts A and B: Number of Participants With Clinically Significant Changes in Vital signs, ECG, Physical Examination(Part A: From start of study drug administration up to Week 18; Part B: From start of study drug administration up to follow up (Week 53))
- Parts A and B: Udvalg for Kliniske Undersøgelser (UKU) Side Effect Rating Scale(Part A: Baseline, Week 10, Week 18 Part B: Baseline, Week 10, Week 23, Week 36, Week 49, Week 50, Week 51 and Week 52)
- Parts A and B: Child Health and Illness Profile - Child Edition: Parent Report Form (CHIP-CE:PRF)(Part A: Baseline, Week 10, Week 18 Part B: Baseline, Week 10, Week 23, Week 36 and Week 49)
- Parts A and B: Change From Baseline in the Rapid Visual Information Processing (RVP) Task of the Cambridge Automated Neuropsychological Test Battery (CANTAB) at Specified Time Points(Part A: Baseline, Week 10, Week 18 Part B: Baseline, Week 10, Week 49)
- Parts A and B: Columbia- Suicide Severity Rating Scale (CSSRS)(Part A: Baseline (from start of study drug administration) up to Week 18; Part B: Baseline (from start of study drug administration) to Week 52)
- Parts A and B: Pediatric Daytime Sleepiness Scale (PDSS)(Part A: Baseline, Week 10, Week 18 Part B: Baseline, Week 10, Week 23, Week 36 and Week 49)
- Parts A and B: Number of Participants With Treatment-emergent Adverse Events (TEAEs)(Part A: From start of study drug administration up to Week 18; Part B: From start of study drug administration up to follow up (Week 53))
- Parts A and B: Brief Psychiatric Rating Scale for Children (BPRS-C)(Part A: Baseline, Week 10, Week 18 Part B: Baseline, Week 10, Week 23, Week 36 and Week 49)
- Parts A and B: ADHD-Rating Scale-5 (ADHD-RS-5) Total Score and Subscales(Part A: Baseline, Week 1, Week 10, Week 18 Part B: Baseline, Week 10, Week 23, Week 36 and Week 49)
- Parts A and B: Clinical Global Impression-Improvement (CGI-I)(Part A: Week 1, Week 10, Week 18 Part B: Week 10, Week 23, Week 36 and Week 49)
- Part B: Change From Baseline in the RVP Task of the CANTAB: Probability of Hit(Baseline, Week 49)
- Part A: Change From Baseline in the Rapid Visual Information Processing (RVP) Task of the CANTAB: Mean Response Latency(Baseline, Weeks 18 and 49)
- Part B: Change From Baseline in the RVP Task of the CANTAB: Mean Response Latency(Baseline, Week 49)
- Part A: Change From Baseline in the RVP Task of the CANTAB: A'(Baseline, Weeks 18 and 49)
- Part B: Change From Baseline in the RVP Task of the CANTAB: A'(Baseline, Week 49)
- Part A: Change From Baseline in the RVP Task of the CANTAB: Probability of Hit(Baseline, Weeks 18 and 49)
- Part A: Change From Baseline in the Spatial Working Memory (SWM) Task of the CANTAB(Baseline, Weeks 18 and 49)
- Part B: Change From Baseline in the SWM Task of the CANTAB(Baseline, Week 49)
- Part A: Change From Baseline in the Stop Signal Task (SST) Task of the CANTAB: Stop Signal Reaction Time and Median Reaction Time(Baseline, Weeks 18 and 49)
- Part B: Change From Baseline in the SST Task of the CANTAB: Stop Signal Reaction Time and Median Reaction Time(Baseline, Week 49)
- Part A: Change From Baseline in the SST Task of the CANTAB: Direction Error (Go Trials), Direction Error (Stop Trials) and Missed Trials(Baseline, Weeks 18 and 49)
- Part B: Change From Baseline in the SST Task of the CANTAB: Direction Error (Go Trials), Direction Error (Stop Trials) and Missed Trials(Baseline, Week 49)
- Part A: Change From Baseline in the Delayed Matching to Sample (DMS) Task of the CANTAB: Percentage of Correct Responses(Baseline, Weeks 18 and 49)
- Part B: Change From Baseline in the DMS Task of the CANTAB: Percentage of Correct Responses(Baseline, Week 49)
- Part A: Change From Baseline in the DMS Task of the CANTAB: Mean Correct Latency(Baseline, Week 18 and 49)
- Part B: Change From Baseline in the DMS Task of the CANTAB: Mean Correct Latency(Baseline, Week 49)
- Part A: Change From Baseline in the DMS Task of the CANTAB: Mean Choices to Correct(Baseline, Weeks 18 and 49)
- Part B: Change From Baseline in the DMS Task of the CANTAB: Mean Choices to Correct(Baseline, Week 49)
- Parts A and B: Sexual Maturation Assessed Using Tanner Stage(Part A: Baseline, Weeks 18 and 49; Part B: Baseline, Week 49)
- Parts A and B: Change From Baseline in Weight(Part A: Baseline, Weeks 18 and 49; Part B: Baseline, Week 49)
- Parts A and B: Change From Baseline in Height(Part A: Baseline, Weeks 18 and 49; Part B: Baseline, Week 49)
- Parts A and B: Change From Baseline in Body Mass Index (BMI)(Part A: Baseline, Weeks 18 and 49; Part B: Baseline, Week 49)
- Parts A and B: Number of Participants With Clinically Significant Changes in Vital Signs: Pulse Rate, Blood Pressure (BP), Temperature, and Respiratory Rate(Part A: From start of study drug administration up to Week 52; Part B: From start of study drug administration up to follow-up (Week 53))
- Parts A and B: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG)(Part A: From start of study drug administration up to Week 52; Part B: From start of study drug administration up to follow-up (Week 53))
- Parts A and B: Number of Participants With Treatment-emergent Adverse Events (TEAEs)(Part A: From start of study drug administration up to Week 52; Part B: From start of study drug administration up to follow-up (Week 53))
- Part A: Psychiatric Symptoms Assessed Using Brief Psychiatric Rating Scale for Children (BPRS-C): Total Score(Baseline, Weeks 18 and 49)
- Part B: Psychiatric Symptoms Assessed Using BPRS-C: Total Score(Baseline, Weeks 23, 36 and 49)
- Parts A and B: Number of Participants With Suicidal Ideation (SI) or Behavior Assessed Using Columbia- Suicide Severity Rating Scale (CSSRS)(Baseline up to Week 52)
- Parts A and B: Number of Participants With Side Effects Assessed Using Udvalg for Kliniske Undersøgelser (UKU) Side Effect Rating Scale: Asthenia or Lassitude or Increased Fatigability(Part A: Baseline, Weeks 18 and 49; Part B: Baseline, Weeks 23, 36, 49, 50, 51 and 52)
- Parts A and B: Number of Participants With Side Effects Assessed Using UKU Side Effect Rating Scale: Sleepiness or Sedation(Part A: Baseline, Weeks 18 and 49; Part B: Baseline, Weeks 23, 36, 49, 50, 51 and 52)
- Parts A and B: Number of Participants With Side Effects Assessed Using UKU Side Effect Rating Scale: Increased Duration of Sleep(Part A: Baseline, Weeks 18 and 49; Part B: Baseline, Weeks 23, 36, 49, 50, 51 and 52)
- Parts A and B: Number of Participants With Side Effects Assessed Using UKU Side Effect Rating Scale: Orthostatic Dizziness(Part A: Baseline, Weeks 18 and 49; Part B: Baseline, Weeks 23, 36, 49, 50, 51 and 52)
- Part A: Sedative Effects Assessed Using Pediatric Daytime Sleepiness Scale (PDSS): Total Score(Baseline, Weeks 18 and 49)
- Part B: Sedative Effects Assessed Using PDSS: Total Score(Baseline, Weeks 23, 36 and 49)
- Parts A and B: Symptoms Assessed Using ADHD-Rating Scale-5 (ADHD-RS-5): Total Score(Part A: Baseline, Weeks 18 and 49; Part B: Baseline, Week 49)
- Parts A and B: Symptoms Assessed Using ADHD-RS-5: Inattention Subscale Score(Part A: Baseline, Weeks 18 and 49; Part B: Baseline, Week 49)
- Parts A and B: Symptoms Assessed Using ADHD-RS-5: Hyperactivity-Impulsivity Subscale Score(Part A: Baseline, Weeks 18 and 49; Part B: Baseline, Week 49)
- Parts A and B: Number of Participants Assessed for Severity of Mental Illness Using Clinical Global Impression-Improvement (CGI-I)(Part A: Baseline, Weeks 1, 18 and 49; Part B: Baseline, Weeks 23, 36 and 49)
- Parts A and B: Participants Functioning and Well-being Assessed Using Child Health and Illness Profile - Child Edition: Parent Report Form (CHIP-CE:PRF): Global Score(Part A: Baseline, Weeks 18 and 49; Part B: Baseline, Weeks 23, 36 and 49)
- Parts A and B: Behavioral, Social, and Academic Issues Assessed Using Conners 3 Parent Short Form (C3PS): Total Score(Part A: Baseline, Weeks 18 and 49; Part B: Baseline, Weeks 23, 36 and 49)