Efficacy of Atomoxetine on Psychosocial Function of Children and Adolescents With Attention-Deficit/Hyperactivity Disorder (ADHD)

An Open-Label Study of the Efficacy of Atomoxetine Hydrochloride on Quality of Life of Children and Adolescents With Attention-Deficit/Hyperactivity Disorder With or Without Comorbid Conditions

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00320528

Enrollment

269

Registered

2006-05-03

Start date

2006-04-30

Completion date

2008-10-31

Last updated

2010-01-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Attention Deficit Disorder With Hyperactivity

Brief summary

This study aims to assess the effectiveness of atomoxetine on psychosocial functioning and emotional well being of children and adolescents with ADHD and to evaluate whether and in what measure the presence of comorbid conditions (internalizing and externalizing disorders) influences atomoxetine's ability to improve the quality of life of ADHD subjects.

Interventions

DRUGatomoxetine

0.5 milligrams per kilogram per day (mg/kg/day), by mouth (PO) for 1 week then 1.2 mg/kg/day, PO for 11 weeks followed by up to 1.4 mg/kg/day, PO for up to 12 additional weeks

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

6 Years to 15 Years

Healthy volunteers

Inclusion criteria

* Child or adolescent patients, male or female outpatients, who are at least 6 years of age, but must not yet have reached their 16th birthday prior to Visit 1, when informed consent is obtained * Patients must meet Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) diagnostic criteria for ADHD (any subtype) and score at least 1.5 standard deviations above the age norm for their diagnostic subtype using published norms for the Swanson, Nolan and Pelham Questionnaire: Attention-Deficit/Hyperactivity Disorder Subscale (SNAP-IV ADHD Subscale) score at both Visit 1 and 2 * Laboratory results, including serum chemistries, hematology, and urinalysis, must show no clinically significant abnormalities (clinically significant is defined as laboratory values requiring acute medical intervention, indicating a serious medical illness, or requiring further medical evaluation in the judgment of the investigator) * An electrocardiogram (ECG) must be performed to exclude cardiac diseases at the baseline/screening visit and the results must be reviewed by the investigator at Visit 2 prior to dispensing of study material * Patients and parents have been judged by the investigator to be reliable to keep appointments for clinic visits and all tests, including venipuncture, and examinations required by the protocol.

Exclusion criteria

* Patients who have a documented history of Bipolar I or II disorder, any history of psychosis or pervasive development disorder * Patients with a history of any seizure disorder (other than febrile seizures) or patients who have taken (or are currently taking) anticonvulsants for seizure control are not eligible to participate * Patients at serious suicidal risk as assessed by the investigator * Patients with significant cardiovascular disease or other conditions that could be aggravated by an increased heart rate or increased blood pressure * Patients who have any medical condition that would increase sympathetic nervous system activity markedly (for example, catecholamine-secreting neural tumor), or who are taking a medication on a daily basis (for example, albuterol, inhalation aerosols, pseudoephedrine), that has sympathomimetic activity. Such medications can be taken on an as-needed basis

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline to 12 Week Endpoint in Child Health and Illness Profile - Child Edition (CHIP-CE), Achievement Domain	Baseline, 12 Weeks	Parent-rated assessment of a child's health status and level of functioning. It consists of 76 items. The majority of items assess frequency of activities or feelings using a five-point response format (for example, 'how good is your child at making friends?' 1=never, 5=always). Standard scores (t-value) were established, with all domains and subdomains having a mean score of 50 and standard deviation of 10. Standard scores are expressed in standard deviation units. Achievement Domain Range = -3.1 to 67.7. Higher scores mean greater health or level of functioning in achievement.

Secondary

Measure	Time frame	Description
Change From Baseline to 12 Week Endpoint in Clinical Global Impressions-ADHD-Severity (CGI-ADHD-S)	Baseline, 12 Weeks	Measures severity of the patient's overall severity of ADHD symptoms (1=normal, not at all ill; 7=among the most extremely ill patients).
Change From Baseline to 12 Week Endpoint in CHIP-CE Satisfaction, Comfort, Resilience and Risk Avoidance Domains	Baseline, 12 Weeks	Parent-rated assessment of a child's health status and level of functioning. It consists of 76 items. The majority of items assess frequency of activities or feelings using a five-point response format (for example, 'how good is your child at making friends?' 1=never, 5=always). Standard scores (t-value) were established, with all domains having a mean score of 50 and standard deviation of 10. Satisfaction range=-25.7 to 66.3; Comfort=-28.6 to 67.2; Resilience=-36.3 to 71.8; Risk Avoidance=-23.5 to 62.5. Higher scores mean greater health or level of functioning in that domain.
Change From Baseline to 12 Week Endpoint in Pediatric Anxiety Rating Scale (PARS)	Baseline, 12 Weeks	The Pediatric Anxiety Rating Scale (PARS) is used to rate the severity of anxiety in children and adolescents, ages 6 to 17 years. The total score for the PARS is derived by summing 5 of the 7 severity/impairment/interference items (2,3,5,6,7). The total score ranges from 0 (none) to 25 (extreme severity). Items 1 (overall number of anxiety symptoms) and 4 (overall severity of physical symptoms) are not included in the total score calculation.
Change From Baseline to 12 Week Endpoint in Children's Depression Rating Scale-Revised (CDRS-R)	Baseline, 12 Weeks	Measures presence and severity of depression. Consists of 17 items scored on a 1-5 or 1-7 scale. A rating of 1 indicates normal, thus the minimum score is 17. The maximum score is 113. In general, scores below 20 indicate an absence of depression; scores of 20 or 30 indicate borderline depression; scores of 40 to 60 indicate moderate depression.
Change From Baseline to 12 Week Endpoint in the Attention-Deficit/Hyperactivity Disorder (ADHD) Subscales of 18-Item Swanson, Nolan and Pelham Rating Scale (SNAP-IV)	Baseline, 12 Weeks	Items from the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) criteria for ADHD are included for the two subsets of symptoms: inattention (items #1-#9: total score=0-27) and hyperactivity/impulsivity (items #11-#19: total score=0-27). The SNAP-IV is based on a 0 (not at all) to 3 (very much) rating scale. Total combined type (inattention plus hyperactivity/impulsivity) subscale scores range from 0 to 54.
Change From Baseline to 12 Week Endpoint in Adolescent Symptom Inventory-4: Parent Checklist (ASI-4)	Baseline, 12 Weeks	Parent-completed ASI-4 contains 120 items on 18 emotional and behavioral disorders in adolescents (12-18 years old). Item score range:0 (no symptoms) to 3 (maximum impairment). Categories: A=ADHD (0-54); B=Conduct (0-60); C=Oppositional Defiant (0-24); D=Generalized Anxiety (0-18); E=Specific Phobia/Panic Attack/Obsessions/Compulsions/Somatization (0-30); F=Social Phobia (0-6); G=Separation Anxiety (0-24); H=Schizoid Personality (0-9); I=Schizophrenia (0-6); J=Enuresis (0-18); K=Major Depressive (0-42); L=Bipolar (0-27); M=Anorexia (0-12); N=Bulimia (0-12); O=Substance Abuse (0-18).
Change From Baseline to 12 Week Endpoint in Child Symptom Inventory-4: Parent Checklist (CSI-4)	Baseline, 12 Weeks	The CSI-4 contains 97 items that screen for 15 emotional and behavioral disorders in children between 5 and 12 years old. Item score range:0 (no symptoms) to 3 (maximum impairment). Categories: A=ADHD (0-54); B=Conduct (0-60); C=Oppositional Defiant (0-24); D=Generalized Anxiety (0-18); E=Specific Phobia/Panic Attack/Obsessions/Compulsions/Somatization (0-30); F=Social Phobia (0-6); G=Separation Anxiety (0-24); H=Schizoid Personality (0-9); I=Schizophrenia (0-6); J=Enuresis (0-18).
Change From Baseline to 12 Week Endpoint in Conners' Teacher Rating Scale-Revised: Short Form (CTRS-R:S)	Baseline, 12 Weeks	A 28-item rating scale (0 \[not at all/never\] to 3 \[very much true/very often\]) completed by the teacher to assess problem behaviors related to ADHD. Subscale total scores range from 0 to 15 for Oppositional and Cognitive Problems, 0 to 21 for Hyperactivity, and 0 to 36 for ADHD Index.
Change From Baseline to 12 Week Endpoint in SNAP-IV Oppositional Scale	Baseline, 12 Weeks	Items are included from the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) criteria for Oppositional Defiant Disorder. The SNAP-IV is based on a 0 (not at all) to 3 (very much) rating scale. Total subscale scores range from 0 to 24.

Countries

Italy

Participant flow

Pre-assignment details

Study Period I was a 3-day screening period. Study Period II was 12 weeks long. Study Period III was an optional additional 12 week open-label extension. Results are presented for Period II (patients who received at least one dose of study drug).

Participants by arm

Arm	Count
Pure ADHD Attention-Deficit/Hyperactivity Disorder (ADHD) alone. Received atomoxetine: 0.5 milligrams per kilogram per day (mg/kg/day), by mouth (PO) for 1 week then 1.2 mg/kg/day, PO for 11 weeks followed by up to 1.4 mg/kg/day, PO for up to 12 additional weeks	97
ADHD+Internalizing Disorders Attention-Deficit/Hyperactivity Disorder (ADHD) plus internalizing disorders. Received atomoxetine: 0.5 milligrams per kilogram per day (mg/kg/day), by mouth (PO) for 1 week then 1.2 mg/kg/day, PO for 11 weeks followed by up to 1.4 mg/kg/day, PO for up to 12 additional weeks	38
ADHD+Externalizing Disorders Attention-Deficit/Hyperactivity Disorder (ADHD) plus externalizing disorders. Received atomoxetine: 0.5 milligrams per kilogram per day (mg/kg/day), by mouth (PO) for 1 week then 1.2 mg/kg/day, PO for 11 weeks followed by up to 1.4 mg/kg/day, PO for up to 12 additional weeks	128
Total	263

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Study Period II	Adverse Event	3	4	8
Study Period II	Entry Criteria Exclusion	0	2	2
Study Period II	Parent/Caregiver Decision	8	3	11
Study Period II	Withdrawal by Subject	0	1	1
Study Period III	Adverse Event	1	0	0
Study Period III	Atomoxetine Commercially Available	68	25	90
Study Period III	Lack of Efficacy	2	0	0
Study Period III	Lost to Follow-up	1	0	0
Study Period III	Parent/Caregiver Decision	14	3	11
Study Period III	Physician Decision	0	1	2
Study Period III	Protocol Violation	0	1	0
Study Period III	Sponsor Decision	0	0	1
Study Period III	Withdrawal by Subject	1	1	2

Baseline characteristics

Characteristic	Pure ADHD	Total	ADHD+Externalizing Disorders	ADHD+Internalizing Disorders
Age Continuous	10.12 years STANDARD_DEVIATION 2.51	10.11 years STANDARD_DEVIATION 2.51	10.00 years STANDARD_DEVIATION 2.57	10.42 years STANDARD_DEVIATION 2.41
Child Health and Illness Profile - Child Edition (CHIP-CE) - Achievement Domain Achievement Domain (N=96, N=33, N=121)	29.27 T-Score STANDARD_DEVIATION 7.89	27.40 T-Score STANDARD_DEVIATION 7.86	25.83 T-Score STANDARD_DEVIATION 7.6	27.72 T-Score STANDARD_DEVIATION 7.73
Child Health and Illness Profile - Child Edition (CHIP-CE) - Achievement Domain Comfort Domain (N=96, N=35, N=122)	51.31 T-Score STANDARD_DEVIATION 9.4	47.51 T-Score STANDARD_DEVIATION 10.26	44.74 T-Score STANDARD_DEVIATION 9.38	46.76 T-Score STANDARD_DEVIATION 12.28
Child Health and Illness Profile - Child Edition (CHIP-CE) - Achievement Domain Resilience Domain (N=96, N=34, N=123)	39.34 T-Score STANDARD_DEVIATION 10.15	34.89 T-Score STANDARD_DEVIATION 11.65	31.40 T-Score STANDARD_DEVIATION 11.85	34.96 T-Score STANDARD_DEVIATION 10.89
Child Health and Illness Profile - Child Edition (CHIP-CE) - Achievement Domain Risk Avoidance (N=96, N=33, N=121)	32.03 T-Score STANDARD_DEVIATION 9.7	27.38 T-Score STANDARD_DEVIATION 12.01	22.85 T-Score STANDARD_DEVIATION 12	30.48 T-Score STANDARD_DEVIATION 12.29
Child Health and Illness Profile - Child Edition (CHIP-CE) - Achievement Domain Satisfaction Domain (N=96, N=24, N=122)	39.26 T-Score STANDARD_DEVIATION 13.89	34.34 T-Score STANDARD_DEVIATION 14.91	31.69 T-Score STANDARD_DEVIATION 14.78	30.11 T-Score STANDARD_DEVIATION 14.83
Children's Depression Rating Scale-Revised (CDRS-R)	37.93 units on a scale STANDARD_DEVIATION 12.26	41.26 units on a scale STANDARD_DEVIATION 13.35	43.06 units on a scale STANDARD_DEVIATION 13.69	43.76 units on a scale STANDARD_DEVIATION 13.48
Clinical Global Impression-Attention Deficit Hyperactivity Disorder-Severity Scale (CGI-ADHD-S)	4.64 units on a scale STANDARD_DEVIATION 0.79	4.85 units on a scale STANDARD_DEVIATION 0.8	4.98 units on a scale STANDARD_DEVIATION 0.78	4.97 units on a scale STANDARD_DEVIATION 0.79
Conners' Teacher Rating Scale-Revised:Short Form (CTRS-R:S) ADHD Index	22.14 units on a scale STANDARD_DEVIATION 6.86	23.70 units on a scale STANDARD_DEVIATION 6.52	25.18 units on a scale STANDARD_DEVIATION 6.07	22.94 units on a scale STANDARD_DEVIATION 6.01
Conners' Teacher Rating Scale-Revised:Short Form (CTRS-R:S) Cognitive Problems	7.86 units on a scale STANDARD_DEVIATION 3.73	7.88 units on a scale STANDARD_DEVIATION 3.67	7.96 units on a scale STANDARD_DEVIATION 3.61	7.68 units on a scale STANDARD_DEVIATION 3.8
Conners' Teacher Rating Scale-Revised:Short Form (CTRS-R:S) Hyperactivity	11.38 units on a scale STANDARD_DEVIATION 6.09	13.05 units on a scale STANDARD_DEVIATION 5.74	14.67 units on a scale STANDARD_DEVIATION 5.15	12.03 units on a scale STANDARD_DEVIATION 5.21
Conners' Teacher Rating Scale-Revised:Short Form (CTRS-R:S) Oppositional	5.97 units on a scale STANDARD_DEVIATION 4.93	7.10 units on a scale STANDARD_DEVIATION 5.05	8.62 units on a scale STANDARD_DEVIATION 4.83	4.97 units on a scale STANDARD_DEVIATION 4.66
Pediatric Anxiety Rating Scale (PARS)	2.50 units on a scale STANDARD_DEVIATION 2.67	4.28 units on a scale STANDARD_DEVIATION 4.76	4.67 units on a scale STANDARD_DEVIATION 5.12	7.50 units on a scale STANDARD_DEVIATION 5.68
Race/Ethnicity African	3 participants	3 participants	0 participants	0 participants
Race/Ethnicity Caucasian	90 participants	250 participants	124 participants	36 participants
Race/Ethnicity East Asian	2 participants	2 participants	0 participants	0 participants
Race/Ethnicity Hispanic	1 participants	5 participants	2 participants	2 participants
Race/Ethnicity Native American	1 participants	3 participants	2 participants	0 participants
Region of Enrollment Italy	97 participants	263 participants	128 participants	38 participants
Sex: Female, Male Female	14 Participants	26 Participants	9 Participants	3 Participants
Sex: Female, Male Male	83 Participants	237 Participants	119 Participants	35 Participants
Swanson, Nolan, and Pelham Rating Scale Revised (SNAP-IV) Combined Type Subscale (N=97, N=38, N=127)	37.48 units on a scale STANDARD_DEVIATION 7.78	40.58 units on a scale STANDARD_DEVIATION 7.2	42.91 units on a scale STANDARD_DEVIATION 5.51	40.68 units on a scale STANDARD_DEVIATION 7.87
Swanson, Nolan, and Pelham Rating Scale Revised (SNAP-IV) Hyperactivity/Impulsivity Subscale (N=97, N=38, N=	17.21 units on a scale STANDARD_DEVIATION 6.1	19.42 units on a scale STANDARD_DEVIATION 5.19	21.04 units on a scale STANDARD_DEVIATION 3.48	19.66 units on a scale STANDARD_DEVIATION 5.54
Swanson, Nolan, and Pelham Rating Scale Revised (SNAP-IV) Inattention Subscale (N=97, N=38, N=127)	20.28 units on a scale STANDARD_DEVIATION 4.19	21.16 units on a scale STANDARD_DEVIATION 3.85	21.87 units on a scale STANDARD_DEVIATION 3.48	21.03 units on a scale STANDARD_DEVIATION 3.72
Swanson, Nolan, and Pelham Rating Scale Revised (SNAP-IV) Oppositional Subscale (N=97, N=38, N=127)	10.15 units on a scale STANDARD_DEVIATION 4.54	14.27 units on a scale STANDARD_DEVIATION 5.51	17.99 units on a scale STANDARD_DEVIATION 3.57	12.32 units on a scale STANDARD_DEVIATION 4.67

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	76 / 97	29 / 38	94 / 128
serious Total, serious adverse events	1 / 97	0 / 38	2 / 128

Outcome results

Primary

Change From Baseline to 12 Week Endpoint in Child Health and Illness Profile - Child Edition (CHIP-CE), Achievement Domain

Parent-rated assessment of a child's health status and level of functioning. It consists of 76 items. The majority of items assess frequency of activities or feelings using a five-point response format (for example, 'how good is your child at making friends?' 1=never, 5=always). Standard scores (t-value) were established, with all domains and subdomains having a mean score of 50 and standard deviation of 10. Standard scores are expressed in standard deviation units. Achievement Domain Range = -3.1 to 67.7. Higher scores mean greater health or level of functioning in achievement.