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Attention Deficit Hyperactivity DisorderPhase 4EMDNCT01127646

A Study in Attention Deficit Hyperactivity Disorder in Children and Adolescents

A Phase 4 study testing Atomoxetine and Osmotic-release oral system methylphenidate in people with Attention Deficit Hyperactivity Disorder, run by Eli Lilly and Company at 14 sites in 3 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The main purpose of the study is to help to understand the effect on children and adolescents who are stable on treatment with atomoxetine or osmotic-release oral system (OROS) methylphenidate for attention-deficit/hyperactivity disorder (ADHD) of not taking the medication for a maximum of 6 days over a 28-day study… Read more about this study

Who is it for?
Ages 6 to 16 years
Conditions the study is for
Attention Deficit Hyperactivity Disorder
What is being tested?
Atomoxetine and Osmotic-release oral system methylphenidate
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
23 participants
Where
14 sitesin 3 countries
Study dates
Jun 2010to May 2011
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 6 to 16 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • Patients must meet the Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition Text Revision (DSM-IV-TR) diagnostic criteria for attention-deficit/hyperactivity disorder (ADHD), confirmed at screening by administering the Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children-Present and Lifetime Version.
  • Patients must have an Attention-Deficit/Hyperactivity Disorder Rating Scale - IV - Parent Version: Investigator Administered and Scored, total score of less than or equal to 20 at screening and baseline.
  • Patients must have a Clinical Global Impression-Attention-Deficit/Hyperactivity Disorder-Improvement score of 1 ("very much better") or 2 ("much better") at screening and baseline.
  • Patients must have been taking either atomoxetine or osmotic-release oral system methylphenidate for the treatment of ADHD between 3 and a maximum of 15 months prior to screening.
  • Patients must have been receiving the same dose of atomoxetine or osmotic-release oral system methylphenidate as monotherapy in a single daily dose during the 4 weeks prior to screening.
  • For females of child-bearing potential only: Test negative for pregnancy at the time of entry based on a urine pregnancy test
  • Signed informed consent document (ICD)

Who cannot join

  • Patients who weigh less than 20 kilograms (kg) or more than 70 kg at study entry
  • Documented history of bipolar disorder, any history of psychosis or pervasive development disorder.
  • Patients with a history of any seizure disorder or patients who have taken anticonvulsant treatment for seizure control.
  • Patients at serious suicidal risk.
  • History of severe allergies to more than one class of medications or have had multiple adverse drug reactions.
  • Patients with acute or unstable medical conditions including cardiovascular disease and hypertension.
Show all 9Show fewer
  • Patients taking excluded concomitant medications or likely to begin structured psychotherapy for ADHD.
  • Patients who are currently enrolled in, or discontinued within the last 30 days from a clinical trial.
  • Sexually active females who do not use a medically acceptable method of contraception.

Trial locations and contacts

14 sites in 3 countries.

14 sites in 3 countries

Spain5 sites
  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

    Barcelona, 08022

  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

    Donostia / San Sebastian, 20009

  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

    Esplugues de Llobregat, 08950

  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

    Palma de Mallorca, 07198

  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

    Sabadell, 08201

Other trials in Spain

Sweden5 sites
  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

    Gothenburg, 41118

  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

    Handen, 13645

  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

    Malmö, 205 02

  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

    Stockholm, 116 21

  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

    Uppsala, 75185

Other trials in Sweden

Netherlands4 sites
  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

    Arnhem, 6800 TA

  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

    Capelle aan den IJssel, 2908 LP

  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

    Maastricht, 6229 HX

  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

    Rotterdam, 3075 EA

Other trials in Netherlands

About this study

Official title: Assessing the Effect of Missing Doses (Off-Days) of Daily Medication in Patients Stable on Pharmacotherapy for ADHD Receiving Atomoxetine or OROS Methylphenidate: A Parallel Matched Group Clinical Study (On/Off Study)

The main purpose of the study is to help to understand the effect on children and adolescents who are stable on treatment with atomoxetine or osmotic-release oral system (OROS) methylphenidate for attention-deficit/hyperactivity disorder (ADHD) of not taking the medication for a maximum of 6 days over a 28-day study treatment period.

Read the detailed description

The present study is designed to assess the effect of missed doses of daily medication (off-days). On the off-days the patient will take a placebo (sugar pill). Over the 4 weeks of the actual study there will be 6 random off-days of study medicine and neither the caregiver, patient nor study doctor will know which days are the missing days.

To cover all aspects of the patients' lives and notably their school time, aside from investigator's assessments, evaluations will also be performed on a daily basis by those involved in their day-to-day life: parents, teachers (on school days) and the patients themselves, using an electronic diary.

Being tested
Atomoxetine, Osmotic-release oral system methylphenidate, Placebo
Medical subject headings
Attention Deficit Disorder with Hyperactivity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AtomoxetineDrug

    Also called Strattera, LY139603

    25-80 milligrams (mg) administered orally, once daily.

  • Osmotic-release oral system methylphenidateDrug

    18-54 mg administered orally, once daily.

  • PlaceboDrug

    Administered orally, once daily for random nonconsecutive 6 days during 4-week treatment period.

Study groups in NCT01127646
Study groupRoleWhat they receive
AtomoxetineExperimentalParticipants received 25-80 milligrams (mg) of atomoxetine orally, once daily during the run-in period for up to 7 days. The run-in period was followed by the 4-week on/off period in which participants received 25-80 mg of atomoxetine orally, once daily for 4 weeks, except for the off-days, where participants received 1 or 2 oral once daily placebo doses per week, with 6 nonconsecutive, double-blinded placebo doses in total over the 4-week on/off period. The on/off period was followed by a run-out period in which participants received 25-80 mg of atomoxetine orally, once daily for 1-5 days.
Receives: Drug: Atomoxetine; Drug: Placebo
Osmotic-release oral system methylphenidateActive comparatorParticipants received 18-54 mg of osmotic-release oral system (OROS) methylphenidate orally, once daily during the run-in period for up to 7 days. The run-in period was followed by the 4-week on/off period in which participants received 18-54 mg of OROS methylphenidate orally, once daily for 4 weeks, except for the off-days, where participants received 1 or 2 oral once daily placebo doses per week, with 6 nonconsecutive, double-blinded placebo doses in total over the 4-week on/off period. The on/off period was followed by a run-out period in which participants received 18-54 mg of OROS methylphenidate orally, once daily for 1-5 days.
Receives: Drug: Osmotic-release oral system methylphenidate; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Daily Parent Report of Evening and Morning Behavior-Revised (DPREMB-R) Scale Mean Total Score (On-Days Versus Off-Days) During the 4-Week Treatment Period

    Parent-completed 11-item questionnaire; measures difficulty level of and 8 common evening behaviors (such as, sit through dinner) and 3 common morning behaviors (such as, get out of bed). Each item is scored on a 4-point Likert scale ranging from 0 (no difficulty) to 3 (a lot of difficulty). Total score (evening+morning) range is 0 to 33. Higher scores indicate greater difficulty in evening and morning behavior. DPREMB-R total score between days without missing doses (on-days) and days with missing doses (off-days) was not analyzed due to the insufficient sample size.

    Measured: Baseline through 4 weeks

Secondary outcomes (11)
  1. Global Impression of Perceived Difficulties (GIPD) Scale-Patient Version Total Score and Individual Items (On-Days Versus Off-Days) During the 4-Week Treatment Period

    Assesses attention-deficit/hyperactivity disorder (ADHD)-related difficulties (overall difficulties perceived in morning, during school, during homework, in evening, over entire day and night). Participant rates difficulties during past week on 7-point scale (1=normal, not difficult at all; 7=extremely difficult) for each of 5 items. Total score=sum of all subscores (items); range: 5 to 35. Higher scores=greater impairment. GIPD-Pat total score and item scores between days without missing doses (on-days) and days with missing doses (off-days) were not analyzed due to insufficient sample size.

    Measured: Baseline through 4 weeks

  2. Conners' Global Index-Teacher Rating Scale Total Score (On-Days Versus Off-Days) During the 4-Week Treatment Period

    The teacher version of Conners' Global Index consists of 10 items with each item being scored on a 4-point scale ranging from 0 (not true at all, or never/seldom) to 3 (very much true, or very often/very frequent). The total score ranges from 0 to 30. Higher scores indicate greater impairment. The Conner's Global Index-Teacher Rating Scale total score between days without missing doses (on-days) and days with missing doses (off-days) was not analyzed due to the insufficient sample size.

    Measured: Baseline through 4 weeks

  3. Global Impression of Perceived Difficulties Scale-Patient Version (GIPD-Pat) Scale Total Score and Individual Items During the 4-Week Treatment Period

    Assesses attention-deficit/hyperactivity disorder (ADHD)-related difficulties (overall difficulties perceived in morning, during school, during homework, in evening, over entire day and night). Difficulties during past week are rated by participant on a 7-point scale (1=normal, not difficult at all; 7=extremely difficult) for each of 5 items. Total score=sum of all subscores (items); range: 5 to 35. Higher scores=greater impairment. Mean GIPD-Pat total score and individual item scores for days with missing doses (off-days) between both groups were not analyzed due to insufficient sample size.

    Measured: Baseline through 4 weeks

  4. Attention-Deficit/Hyperactivity Disorder Rating Scale-Parent Version: Investigator Administered and Scored (ADHD-RS-IV Parent:Inv) Total Score and Subscores at Weeks 2, 3, and 4

    Assesses 18 Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR) ADHD diagnosis symptoms/severity in past week. Each item: 0 (none/never, rarely) to 3 (severe/very often). Total score ranges from 0 to 54. Higher total scores indicate greater illness severity. This outcome measure was not analyzed due to the insufficient sample size.

    Measured: Weeks 2, 3, and 4

  5. Clinical Global Impression-Attention Deficit/Hyperactivity Disorder-Severity Scale (CGI-ADHD-S) at Weeks 2, 3, and 4

    This instrument is a single-item expert rating of the severity of the participant's attention-deficit/hyperactivity disorder (ADHD) symptoms in relation to the assessor's total experience of participants with ADHD. Severity is rated on a 7-point scale (1=normal, not ill at all; 7=among the most extremely ill participants). Higher scores represent greater illness severity. This outcome measure was not analyzed due to the insufficient sample size.

    Measured: Weeks 2, 3, and 4

  6. Emotion Expression Scale for Children (EESC)-Parent Rated Total Score up to Week 5

    29-item parent-reported measure used to monitor effect of attention-deficit/hyperactivity disorder (ADHD) medication; examines 3 aspects of emotion expression: positive emotions, emotional flatness, and emotional lability. Each item rated on 5-point Likert scale (1="not at all true" to 5="very much true"). Positive emotional subscale items reversed scored (6-raw score). Total score=transformed positive emotion + emotional flatness+ emotional lability subscales. Total scores range: 29 to 145. Higher scores=emotional impairment. This outcome measure not analyzed due to insufficient sample size.

    Measured: Up to Week 5

  7. Daily Parent Report of Evening and Morning Behavior-Revised (DPREMB-R) Scale Subscores (On-Days Versus Off-Days) During the 4-Week Treatment Period

    Parent-completed 11-item questionnaire; measures difficulty level of 8 common evening behaviors (such as, sit through dinner) and 3 common morning behaviors (such as, get out of bed) from 0 (no difficulty) to 3 (a lot of difficulty). Evening behavior total score range is 0 to 24. Morning behavior total score range is 0 to 9. Higher scores indicate greater difficulty in evening and morning behavior. DPREMB-R subscores between days without missing doses (on-days) and days with missing doses (off-days) not analyzed due to insufficient sample size.

    Measured: Baseline through 4 weeks

  8. Patient Outcomes Questions (On-Days Versus Off-Days) During the 4-Week Treatment Period

    6-item questionnaire from attention-deficit/hyperactivity disorder (ADHD) advocacy group evaluates treatment outcomes ADHD participant's perspective. Parent completed on each day of on/off period. Each item ranged from 1 ("I totally agree") to 5 ("I totally disagree"). Items 1 and 2 pertain to sleeping and eating; high scores=better outcome. Items 3-6 pertain to behavior; high scores=worse outcome. The mean scores for analysis would have been created for each question across the days of each of the on and off phases; however, mean scores were not analyzed due to insufficient sample size.

    Measured: Baseline through 4 weeks

  9. Daily Parent Report of Evening and Morning Behavior-Revised (DPREMB-R) Scale Total Score and Subscores During the 4-Week Treatment Period

    Parent-completed 11-item questionnaire; measures difficulty level of 3 common morning behaviors (such as, get out of bed) and 8 common evening behaviors (such as, sit through dinner) from 0 (no difficulty) to 3 (a lot of difficulty). Evening behavior total score range is 0 to 24. Morning behavior total score range is 0 to 9. Total score (evening+morning) range is 0 to 33. Higher scores indicate greater difficulty in evening and morning behavior. Mean DPREMB-R total score and subscores for days with missing doses (off-days) between both groups were not analyzed due to insufficient sample size.

    Measured: Baseline through 4 weeks

  10. Conners' Global Index-Teacher Rating Scale Total Score During the 4-Week Treatment Period

    The teacher version of Conners' Global Index consists of 10 items with each item being scored on a 4-point scale ranging from 0 (not true at all, or never/seldom) to 3 (very much true, or very often/very frequent). The total score ranges from 0 to 30. Higher scores indicate greater impairment. The Conners' Global Index-Teacher Rating Scale total score for days with missing doses (off-days) between both groups were not analyzed due to insufficient sample size.

    Measured: Baseline through 4 weeks

  11. Global Impression of Perceived Difficulties Investigator Version (GIPD-Inv) Total Score and Subscores At Weeks 2, 3, and 4

    Assesses attention-deficit/hyperactivity disorder (ADHD)-related difficulties (overall difficulties perceived in morning, during school, during homework, in evening, and over entire day and night). Difficulties during past week are rated by investigator on a 7-point scale (1=normal, not difficult at all; 7=extremely difficult) for each of 5 items. Total score=sum of all subscores (items) and ranges from 5 to 35. Higher scores indicate greater impairment. This outcome measure was not analyzed due to the insufficient sample size.

    Measured: Weeks 2, 3, and 4

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 May 2010 (estimated)
  2. Study startJun 2010
  3. Primary completionMay 2011
  4. Study completionMay 2011

Why it stopped: Due to lack of availability of study participants to accommodate the study design

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
23 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01127646
Sponsor's protocol ID
13070
Other IDs
B4Z-EW-LYEN, 2009-011426-33, 2009
Acronym
EMD
Status last verified
Apr 2012
First submitted
19 May 2010
Last updated
28 Nov 2012
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Atomoxetine and Osmotic-release oral system methylphenidate in people with Attention Deficit Hyperactivity Disorder, run by Eli Lilly and Company at 14 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 28 Nov 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in Spain, Sweden, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Jun 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Daily Parent Report of Evening and Morning Behavior-Revised (DPREMB-R) Scale Mean Total Score (On-Days Versus Off-Days) During the 4-Week Treatment Period (time frame: Baseline through 4 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Nov 2012.

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