Long-Term, Open Label Atomoxetine Study

This study has been completed.
Sponsor:
Information provided by:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00190684
First received: September 12, 2005
Last updated: December 15, 2010
Last verified: December 2010
  Purpose

To learn about the safety and any side effects of atomoxetine when given to children and adolescents for about 5 years (long-term) and to learn whether atomoxetine can help children and adolescents with attention-deficit/hyperactivity disorder (ADHD) who take the drug for about 5 years (long-term).

Study participants can be atomoxetine naive, atomoxetine experienced whose therapy has been interrupted or, atomoxetine experienced on a known stable dose.


Condition Intervention Phase
Attention Deficit Hyperactivity Disorder
Drug: atomoxetine
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Long-Term, Open Label Safety Study of Atomoxetine Hydrochloride in Patients, 6 Years and Older With Attention-Deficit/Hyperactivity Disorder

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Categorical Changes in Vital Signs (Blood Pressure [BP], Pulse, Weight, Temperature) During the Study [ Time Frame: Baseline through 5 years ] [ Designated as safety issue: Yes ]
    Vital signs were assesed categorically using the term high for BP, high and low for pulse and temperature, or decreased for weight. For BP, high was an increase to a value above the 95th percentile of the National Institute of Health (NIH) values. For pulse, high was an increase of at least 25 beats per minute to at least 110, and low was a decrease of at least 20 beats per minute to at most 65 beats per minute. For temperature, high was an increase of at least 1 to 37.7 and low was a decrease of at least 1.3 to at most 35.6. Decrease in weight was marked by a reduction of at least 3.5%.

  • Change From Baseline to 5 Year Endpoint in BP [ Time Frame: baseline, 5 years ] [ Designated as safety issue: Yes ]
  • Change From Baseline to 5 Year Endpoint in Pulse [ Time Frame: baseline, 5 years ] [ Designated as safety issue: Yes ]
  • Change From Baseline to 5 Year Endpoint in Body Weight [ Time Frame: baseline, 5 years ] [ Designated as safety issue: Yes ]
  • Change From Baseline to 5 Year Endpoint in Height [ Time Frame: baseline, 5 years ] [ Designated as safety issue: Yes ]
  • Change From Baseline to 5 Year Endpoint in Weight, Height, and Body Mass Index (BMI) Percentile Stratified by Baseline Quartile [ Time Frame: baseline, 5 years ] [ Designated as safety issue: Yes ]
    Patients were assessed for changes in weight, height, and BMI. BMI is an estimate of body fat based on body weight divided by height squared.

  • Change From Baseline to 5 Year Endpoint in Electrocardiogram (ECG) [ Time Frame: baseline, 5 years ] [ Designated as safety issue: Yes ]
    Patients were assessed for changes in ECG. The RR interval is the time duration between two consecutive R waves of the ECG. The QRS interval is the beginning of Q to the end of the S wave. The QT interval is a measure of time between the start of the Q wave and the end of the T wave and is dependent on the heart rate. A corrected QT interval (QTc) has been corrected in order to aid interpretation. QTbz is the QT interval using Bazett's correction formula. QTfr is the QT interval using Fridericia's correction formula.QTdat is the QT interval using a data specific correction method for children.

  • Change From Baseline to 5 Year Endpoint in Heart Rate [ Time Frame: baseline, 5 years ] [ Designated as safety issue: Yes ]
    Patients were assessed for changes in heart rate using electrocardiogram.

  • Number of Patients Meeting Committee for Proprietary Medicinal Products (CPMP) Categorical QTc Interval Criteria Part I (Numerical Increase) [ Time Frame: baseline through 5 years ] [ Designated as safety issue: Yes ]
    QT interval is a measure of time between the start of the Q wave and the end of the T wave and is dependent on the heart rate. A corrected QT interval (QTc) has been corrected in order to aid interpretation. QTbz is the QT interval using Bazett's correction formula. QTfr is the QT interval using Fridericia's correction formula. QTdat is the QT interval using a data specific correction method for children.

  • Number of Patients Meeting CPMP Categorical QTc Interval Criteria Part II (Interpretation at Baseline and Endpoint) [ Time Frame: baseline through 5 years ] [ Designated as safety issue: Yes ]
    QT interval is a measure of time between the start of the Q wave and the end of the T wave and is dependent on the heart rate. A corrected QT interval (QTc) has been corrected in order to aid interpretation. QTbz is the QT interval using Bazett's correction formula. QTfr is the QT interval using Fridericia's correction formula. QTdat is the QT interval using a data specific correction method for children. For Males: Normal is <430 ms, Borderline is >=430 ms and <450 ms, Prolonged is >=450 ms. For Females: Normal is <450 ms, Borderline is >=450 ms and <470 ms, Prolonged is >=470 ms.

  • Number of Participants With Abnormal Laboratory Analytes During the Study [ Time Frame: baseline through 5 years ] [ Designated as safety issue: Yes ]
    Standard reference ranges from Covance Laboratories were used in the determination of abnormal high and low values based on age and gender, where appropriate. Aspartate aminotransferase (AST); serum glutamic oxaloacetic transaminase (SGOT); units/liter (U/L); alanine aminotransferase (ALT); serum glutamic pyruvic transaminase (SGPT); millimoles/liter (mmol/L); grams/liter (g/L); micromoles/liter (umol/L); millimoles/liter-iron (mmol/L-Fe); trillion/liter (TI/L)or 10^12 units/liter; Giga/liter (GI/L)or 10^9 units/liter; femtoliters (fL); urinalysis (UA)

  • Number of Participants in Each Tanner Stage (Pubic Hair) by Age Group [ Time Frame: 1 year through 5 years ] [ Designated as safety issue: Yes ]

    Tanner Stage:

    I: no pubic hair at all (prepubertal Dominic state) II: small amount of long, downy hair with slight pigmentation at the base of the penis and scrotum (males) or on the labia majora (females) III: hair becomes more coarse and curly, and begins to extend laterally IV: adult-like hair quality, extending across pubis but sparing medial thighs V: hair extends to medial surface of the thighs

    Age Groups:

    1. age<11.0 (female) and age<12 (male)
    2. 11=<age<12 (female) or 12<=age<13 (male)
    3. 12=<age<15 (female) or 13=<age<15 (male)
    4. age>=15 (female and male)


Secondary Outcome Measures:
  • Change From Baseline to 5 Year Endpoint in Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator Administered and Scored (ADHDRS-IV-Parent:Inv) Total Score and Subscale Scores [ Time Frame: baseline, 5 years ] [ Designated as safety issue: No ]
    Measures the 18 symptoms contained in the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR) diagnosis of ADHD. Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often). Total scores range from 0 to 54. Hyperactive/Impulsive and Inattention Subscales consisted of 9 items each, for total subscale score range of 0 to 27. ADHD Index Subscale consisted of 12 items, for total score range of 0 to 36.

  • Change From Baseline to 5 Year Endpoint in Clinical Global Impressions-Attention-Deficit/Hyperactivity Disorder-Severity (CGI-ADHD-S) Score [ Time Frame: baseline, 5 years ] [ Designated as safety issue: No ]
    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 5 Year Endpoint in Conners' Parent Rating Scale-Revised: Short Form (CPRS-R:S) Subscale Scores [ Time Frame: baseline, 5 years ] [ Designated as safety issue: No ]
    A 27-item rating scale (0 [not at all/never] to 3 [very much true/very often]) completed by the parent to assess problem behaviors related to ADHD. Subscales: Oppositional, Cognitive Problems, Hyperactivity, and ADHD Index. Subscale total scores range from 0 to 18 for all subscales except ADHD Index which ranges from 0 to 36.

  • Change From Baseline to 5 Year Endpoint in the Stroop Word Color Test [ Time Frame: baseline, 5 years ] [ Designated as safety issue: No ]
    Only patients who took the Stroop Color Word Test in a previous atomoxetine study were required to complete the Stroop in this study. Stroop measures inhibition of dominant response and interference control. Patients were given tasks of recognition (colors), reading (where a word represents a color), and interference (reading words written in different colors). There were 100 items for each of the three categories and if they made it through 100 words with time remaining, they would repeat the list. Only a small number of patients had Stroop tests in this study, so no analysis was done.


Enrollment: 1553
Study Start Date: August 2000
Study Completion Date: October 2009
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Atomoxetine
Atomoxetine-naive patients will have an acute titration to a stable dose, atomoxetine experienced patients whose therapy has been interrupted with be rapidly titrated to their previously established stable dose, and atomoxetine patients on a known stable dose may continue treatment at that dose.
Drug: atomoxetine
0.5-1.8 mg/kg/day, by mouth (PO), for up to 5 years
Other Names:
  • LY139603
  • Strattera

  Eligibility

Ages Eligible for Study:   6 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must be at least 6 years old but less than 18 years old when enrolled in first atomoxetine study
  • Must meet the study criteria for ADHD
  • Must be willing to have blood drawn and to complete other test required for this study

Exclusion Criteria:

  • allergic to more than 1 kind of medicine or have had multiple bad reactions to any drug
  • taking certain medicines that could interact with atomoxetine
  • plan to move too far away from a doctor participating in this study in the next 5 years
  • current or past history of any of the following: alcohol or drug abuse within the past 3 months, bipolar I or II disorder, high blood pressure, organic brain disease or seizures, psychosis, other disorders or conditions diagnosed by a doctor that might make you unsuitable to participate in this study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00190684

  Show 100 Study Locations
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-619-4559 Mon-Fri 9 AM - 5 PM Eastern Time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
  More Information

Additional Information:
No publications provided by Eli Lilly and Company

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Chief Medical Officer, Eli Lilly
ClinicalTrials.gov Identifier: NCT00190684     History of Changes
Other Study ID Numbers: 4331, B4Z-MC-LYAI
Study First Received: September 12, 2005
Results First Received: October 1, 2010
Last Updated: December 15, 2010
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Attention Deficit Disorder with Hyperactivity
Hyperkinesis
Attention Deficit and Disruptive Behavior Disorders
Mental Disorders Diagnosed in Childhood
Mental Disorders
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Atomoxetine
Adrenergic Uptake Inhibitors
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Neurotransmitter Uptake Inhibitors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 21, 2014