A Randomized, Controlled, Open-Label Study of the Long-Term Impact on Functioning using Atomoxetine Hydrochloride Compared to Other Early Standard Care in the Treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in Treatment-Naïve Children and Adolescents. (ADHD-LIFE Study) - (ADHD-LIFE Study)

• Register: EUCTR
• Last refreshed on: 8 October 2021
• Main ID: EUCTR2006-005512-27-FR
• Date of registration: 29/12/2006
• Prospective Registration: Yes
• Primary sponsor: Eli Lilly and Company
• Public title: A Randomized, Controlled, Open-Label Study of the Long-Term Impact on Functioning using Atomoxetine Hydrochloride Compared to Other Early Standard Care in the Treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in Treatment-Naïve Children and Adolescents. (ADHD-LIFE Study) - (ADHD-LIFE Study)
• Scientific title: A Randomized, Controlled, Open-Label Study of the Long-Term Impact on Functioning using Atomoxetine Hydrochloride Compared to Other Early Standard Care in the Treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in Treatment-Naïve Children and Adolescents. (ADHD-LIFE Study) - (ADHD-LIFE Study)
• Date of first enrolment: 12/03/2007
• Target sample size: 400
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-005512-27
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: Double blind: Parallel group: yes; Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other: yes; Other specify the comparator: Standard of care
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, France, Ireland, Italy, Netherlands, Norway, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Patients are eligible to be included in the study only if they meet all of the following criteria:
[1] Patients must be at least 6 years of age, but must not have reached their 17th birthday at Visit 1.
[2] Patients must meet the Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition Text Revision™ (DSM-IV-TR™) diagnostic criteria for ADHD. For the purposes of this study the diagnosis of ADHD will be confirmed during Visit 1 by administering the K-SADS-PL. Patients must also have an ADHD-RS-IV Parent:Inv score at least 1.5 standard deviations above the age norm for their diagnostic subtype at both Visit 1 and Visit 2. In addition, they must have a CGI-ADHD-S score ?4 at both Visit 1 and Visit 2.
[3] Patients must be pharmacological naive at Visit 1. Pharmacological naive is defined as not having received more than seven consecutive days of any dose of pharmacotherapy for ADHD during the patient’s lifetime and having not received more than two consecutive days of any dose of pharmacotherapy for ADHD within 30 days before Visit 1.
[4] Patients must be able to swallow capsules.
[5] Patients must be of normal intelligence as assessed by the investigator (that is, without a general impairment of intelligence and likely, in the investigator’s judgment, to achieve a score of ?80 on an IQ test). The administration of a formal IQ test is not an entry requirement for this study. Specific learning disabilities are not considered general impairments of intelligence.
[6] Patients and parents/legal guardians have been judged by the investigator to be reliable to keep appointments for clinic visits and all tests and examinations required by the protocol.
[7] Patients and parents must be able to communicate adequately with the investigator and site personnel.
[8] This inclusion criterion applies to females of child-bearing potential only.
Test negative for pregnancy at the time of entry (Visit 1) based on a urine pregnancy test. If local law, an ERB and/or regulatory bodies have different requirements then these requirements take precedence.
[9] Each patient (and/or legally authorized patient representative where required by local law) must understand the nature of the study and must sign an ICD.

Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
[10] Patients who weigh less than 20 kg at study entry (Visit 1).
[11] Patients who have a documented history of bipolar disorder, any history of psychosis or pervasive development disorder (autistic spectrum disorder). If the investigator believes that such a diagnosis has previously been made in error, he/she should contact Lilly and discuss the case history with the Lilly physician responsible for the study prior to allowing the patient to enter the study.
[12] 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.
[13] Patients at serious suicidal risk as assessed by the investigator. (This evaluation must include the items a, b, c, d and e of K- SADS-PL’s depression module, and there can not be a score of 3 in any of these items).
[14] Patients with a history of alcohol or drug abuse within the past 3 months (excessive or compulsive use as judged by the investigator), or who are currently using alcohol, drugs of abuse, or any prescribed or over-the-counter medication in a manner which the investigator considers indicative of abuse
[15] Patients with significant prior or current medical conditions (for example human immunodeficiency virus (HIV+), surgically corrected congenital heart defects, or malignancy.
[16] Patients who have a 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 that has sympathomimetic activity (for example, albuterol, inhalation aerosols, pseudoephedrine). Such medications can be taken on an occasional basis.
[17] Patients with a history of hyperthyroidism or hypothyroidism will be excluded. However, patients who were previously diagnosed with hyperthyroidism or hypothyroidism, who have been treated with a stable dose of thyroid supplement for at least the past 3 months, and who are clinically and chemically euthyroid will be allowed to participate in the study.
[18] Patients with acute closed angle glaucoma.
[19] Use of monoamine oxidase inhibitors (MAOIs) during the 2 weeks (14 days) prior to Visit 2.
[20] Current or past history of hypertension. For the purposes of this protocol, hypertension will be defined as average systolic or diastolic blood pressure measured on at least 2 separate occasions, greater than or equal to the 95th percentile for age and sex defined by the National Heart and Lung Institute (National High Blood Pressure Education Program Working Group on Hypertension Control in Children and Adolescents 1996). The accuracy of historical diagnoses will be determined by the investigator.
[21] Patients with cardiovascular disease, prolonged QT interval or other conditions that could be aggravated by an increased heart rate or increased blood pressure.
[22] Pregnant or breastfeeding females are excluded from the study.
[23] Sexually active females who do not use a medically acceptable method of contraception are also excluded from the study. For this study, medically acceptable methods of contraception include barrier methods (condom or diaphragm with spermicidal agent) or oral contraception. The rhythm method (abstinence during predicted times of ovulation with unprotected intercourse at other times) or coitus interruptus prior to ejaculation by the male partner are not acceptable means of contraception.
[24] Pati

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Attention Deficit Hyperactivity Disorder
MedDRA version: 8.1 Level: LLT Classification code 10003735 Term: Attention deficit-hyperactivity disorder

Intervention(s)

Trade Name: Strattera
Product Name: Atomoxetine Hydrochloride
Product Code: LY139603
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Atomoxetine Hydrochloride

Primary Outcome(s)

Main Objective: The primary objective is to test the hypothesis that atomoxetine given at individually titrated doses for 6 months is superior to other early standard therapy in improving quality of life as measured by the mean change in the achievement domain of the Child Health and Illness Profile – Child Edition, Parent Report Form (CHIP-CE PRF), in pharmacologically naïve children and adolescents with Attention-Deficit/Hyperactivity Disorder (ADHD).

Primary end point(s): 6.1. Primary Outcome Variable, Quality of Life Measure
The Child Health and Illness Profile (CHIP) is a validated, generic health-status survey developed to assess the overall health of children and adolescents. There is a parent-rated version for children (CHIP-CE PRF) and 2 self-rating versions, one for children and one for adolescents. The Child Edition (CHIP-CE CRF) is for ages 6 to 11 and the Adolescent Edition (CHIP-AE) is for ages 12 and older. The Parent Report Form for Children (CHIP-CE PRF) will be rated by the parents of both children and adolescents in this study. The parent-rated version has been selected as the primary outcome measure while the self-rated versions constitute secondary outcome measures in this study.
Scores from the CHIP are reported at the domain level and as a profile-type. “Average”’ health on the CHIP domains is within 0.6 of a standard deviation of the mean of 50. That is, average/good health is in the range from 44 to 56 points (+/- 6 points, since the CHIP standard deviation is 10). A score of 43 or below indicates poor health in that domain. A score of 57 or higher indicates excellent health. The achievement domain describes the developmentally appropriate role functioning in school and with peers. It includes academic performance (5 items) and peer relations (5 items) sub domains.
The CHIP instruments were developed and validated by Drs. Barbara Starfield, Anne Riley and their colleagues at the Johns Hopkins Bloomberg School of Public Health (Riley et al. 1998, Starfield et al. 2000, Riley et al. 2004a, Riley et al. 2004b, Rajmil et al. 2003). The CHIP-CE PRF has already been shown to be sensitive to changes in patients with ADHD (B4Z-BP-LYBS study).
6.1.1. Child Health and Illness Profile – Child Edition – Parent Report Form (CHIP–CE PRF)
The CHIP-CE, Parent Report Form (CHIP-CE PRF), will be rated by the parents of both children and adolescents at Visits 2, 4, 5, 6, 7, 10 and at early discontinuation The CHIP-CE PRF, is a parent rated assessment of a child’s health status and level of functioning. It consists of 76 items and takes approximately 20 minutes to complete. It is a validated and comprehensive measure of a child’s functioning and examines the following domains: Satisfaction, Comfort, Risk Avoidance, Resilience, and Achievement. 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).
The total score will be calculated by summing the domain raw means and dividing by 5 (the number of domains).

Secondary Objective: The secondary objectives of the study are as follows:
• to compare atomoxetine with other early standard therapy at 4 months in patients with ADHD as measured by mean change in the achievement domain of the CHIP-CE PRF
• to compare atomoxetine with other early standard therapy at 4 and 6 months in patients with ADHD as measured by change in the CHIP-CE PRF total score and domains (satisfaction, comfort, resilience and risk avoidance)
• to compare atomoxetine with other early standard therapy at 4 months and 6 months in patients with Attention-Deficit/Hyperactivity Disorder (ADHD) in the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P)
• to compare atomoxetine with other early standard therapy at 4 months and 6 months in patients with Attention-Deficit/Hyperactivity Disorder (ADHD) as measured by the ADHD-RS-IV Parent:Inv

Secondary ID(s)

B4Z-EW-LYDY

Ethics review

Status: Approved
Approval date: 12/03/2007
Contact:

Results

• Results available: Yes
• Date Posted: 03/01/2017
• Date Completed: 03/07/2009
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2006-005512-27/results