| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Attention-Deficit/Hyperactivity Disorder (ADHD) |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10064104 |
| E.1.2 | Term | ADHD |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The primary objective of the study is to assess the effect of missed doses of atomoxetine and OROS methylphenidate in ADHD patients who are stable on pharmacotherapy based on the patient’s daily behavior as assessed by the Daily Parent Report of Evening and Morning Behavior - Revised (DPREMB-R) scale from the parent perspective. The evaluation of the primary objective will be performed by comparing the DPREMB-R total score between days without missing doses (on-days) and days with missing doses (off-days) in patients receiving atomoxetine and in patients receiving OROS methylphenidate. |
|
| E.2.2 | Secondary objectives of the trial |
1. To compare the behavior of patients between on-days and off-days as measured by the:
- DPREMB-R subscores (parent rated)
- GIPD-Pat: total score and individual items
- Conners’ Global Index - Teacher rating scale, total score
2. To compare the effects of off-days between atomoxetine and OROS methylphenidate, as measured by:
- DPREMB-R total score and subscores
- GIPD-Pat total score and individual items
- Conners’ Global Index – Teacher rating scale, total score
- GIPD-Inv, total score and individual items, at weekly visits
- ADHD-RS-IV Parent:Inv total score and subscores at weekly visits
- CGI-ADHD-S at weekly visits
- Patient outcomes questions
3. To compare between atomoxetine and OROS methylphenidate the emotional aspects of the patient’s behavior at baseline and endpoint of the study.
- EESC, total score (parent rated).
4. To describe the safety of the treatments during the study in patients with atomoxetine and OROS methylphenidate. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
[1] Patients must be male or female outpatients of at least 6 years of age, but must not have reached their 17th birthday at Visit 1.
[2] Patients must meet the DSM-IV-TR™ diagnostic criteria for ADHD. For the purposes of this study the diagnosis of ADHD will be confirmed at Visit 1 by administering the K-SADS-PL.
[3] Patients must have an ADHD-RS total score of less than or equal to 20 at Visits 1 and 2.
[4] Patients must have a CGI-ADHD-I score of 1 (“very much better”) or 2 (“much better”) at Visits 1 and 2, compared to symptoms before initiation of their current treatment.
[5] Patients must have been taking either atomoxetine or OROS methylphenidate for the treatment of ADHD for at least 3 months and a maximum of 15 months prior to Visit 1.
[6] Patients must have been receiving the same dose of atomoxetine (allowed stable doses: 25, 40, 60, or 80 mg/day) or OROS methylphenidate (allowed stable doses: 18, 36, or 54 mg/day) as monotherapy in a single daily dose during the 4 weeks prior to Visit 1.
[7] Patients must be able to swallow capsules.
[8] 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 intelligence quotient [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.
[9] Patients and parents must have an educational level and degree of understanding sufficient to communicate suitably with the investigator and study coordinator.
[10] Patients and parents must have been judged by the investigator to be reliable to keep appointments for clinic visits and all tests and examinations required by the protocol.
[11] For 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 ethical review board (ERB) and/or regulatory bodies have different requirements then these requirements take precedence.
[12] Parents of patients must have signed an informed consent document (ICD) and assent should have been obtained from the patient (when appropriate). |
|
| E.4 | Principal exclusion criteria |
[1] Patients who weigh less than 20 kg or more than 70 kg at study entry.
[2] Patients who have a documented history of bipolar disorder, any history of psychosis or pervasive development disorder (autistic spectrum disorder).
[3] 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.
[4] Patients at serious suicidal risk as assessed by the investigator.
[5] Patients with a history of severe allergies to more than one class of medications or have had multiple adverse drug reactions.
[6] Patients who have glaucoma.
[7] Patients with a history of alcohol or drug abuse within the past 3 months prior to Visit 1 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.
[8] Patients with acute or unstable medical conditions, including (but not limited to) inadequately controlled diabetes, hepatic insufficiency (specifically any degree of jaundice), uncorrected hypothyroidism or hyperthyroidism, acute systemic infection, renal insufficiency , gastroenterological, respiratory, endocrine, neurological, immune, or hematological disease should be excluded.
[9] Patients with cardiovascular disease or other conditions that could be aggravated by an increased heart rate or increased blood pressure.
[10] Patients who have a medical condition that would markedly increase sympathetic nervous system activity (for example, catecholamine-secreting neural tumor), or who are taking a medication on a daily basis (for example, albuterol, inhalation aerosols, pseudophedrine) having sympathomimetic activity are excluded. Such medications can be taken on an as-needed basis.
[11] Patients who at any time during the study are likely to need psychotropic medications apart from the drugs under study.
[12] Patients who have used a monoamine oxidase inhibitor during the 14 days prior to Visit 1.
[13] Patients with hypertension which is clinically significant in the opinion of the investigator or who are currently taking an antihypertensive agent for blood pressure control.
[14] Patients who are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an off-label use of an investigational drug or device (other than the study drug used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.
[15] Have previously withdrawn from this study or any other study investigating atomoxetine or OROS methylphenidate.
[16] Pregnant or breastfeeding females are excluded from the study.
[17] 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.
[18] Patients who at any time during the study are likely to begin a structured psychotherapy program aimed at ADHD symptoms are excluded. Structured psychotherapy initiated at least 4 weeks prior to Visit 1 is acceptable; however, after study participation started, only ad hoc supportive or educational therapy is permitted.
[19] Patients whose families anticipate a move outside the geographic range of the investigative site within the anticipated duration of the study.
[20] Patients who will have long-term school holidays (more than 14 days or affecting more than 2 calendar weeks [Monday to Sunday]) within the anticipated duration of the study or starting any anticipated holiday in the last week of the on/off period (Week 4).
[21] Patients not participating in an educational system, i.e. not having a teacher.
[22] Patients who are investigator site personnel directly affiliated with this study and/or their immediate families. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.
[23] Patients who are Lilly employees.
[24] Patients who are unwilling or unable to participate in recording responses to questionnaires using technology provided by the sponsor.
[25] Patients who have pre-existing identified growth or sexual maturation retardation. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary end point is the Daily Parent Report of Evening and Morning Behavior - Revised (DPREMB-R). |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 13 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 14 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 14 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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