E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Adult patients with childhood-onset Attention Deficit Hyperactivity Disorder |
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E.1.1.1 | Medical condition in easily understood language |
Attention-deficit/hyperactivity disorder |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Behavioral Disciplines and Activities [F04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003735 |
E.1.2 | Term | Attention deficit-hyperactivity disorder |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003737 |
E.1.2 | Term | Attention deficit/hyperactivity disorder NOS |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003736 |
E.1.2 | Term | Attention deficit/hyperactivity disorder |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
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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 |
•To confirm the clinically effective dose range of Ritalin LA in adults with childhood onset ADHD as measured by the change from Baseline to the end of a 9-week, fixed-dose treatment period in DSM-IV Attention-Deficit/Hyperactive Disorder Rating Scale (DSM-IV ADHD RS) total score.
•To evaluate improvement in functional impairment will be measured by the change from baseline in total score on the Sheehan Disability (SDS) is a self-rating scale designed to assess the functional impairment of patients with ADHD at the end of a 9-week fixed-dose treatment period.
•To evaluate the maintenance of effect of Ritalin LA in adults with childhood onset ADHD as measured by the percentage of Ritalin LA vs. placebo treatment failures at the end of a 6-month treatment withdrawal period.
•To evaluate the safety of Ritalin LA in adults with childhood onset ADHD as measured by the frequency of AEs, the results of laboratory tests, and the measurement of vital signs and ECGs.
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E.2.2 | Secondary objectives of the trial |
•The key secondary objective is to evaluate overall improvement as measured by the proportion of patients with clinical improvement on the Clinical Global Impression – Improvement Scale (CGI-I) at the end of a 9-week fixed-dose treatment period. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients eligible for inclusion in this study have to fulfill all of the following criteria:
1.Written informed consent must be obtained before any assessment is performed.
2.Patients must be capable of complying with study procedures.
3.Male or female adults from 18-60 years of age.
4.Diagnosis of Attention-Deficit /Hyperactivity Disorder (ADHD) all types with a confirmed childhood onset according to DSM-IV diagnostic criteria.
5.DSM-IV ADHD Rating Scale total score greater than or equal to 30 at Screening and Baseline.
6.Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use an effective method of contraception during dosing of study treatment. |
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E.4 | Principal exclusion criteria |
Patients fulfilling any of the following criteria are not eligible for inclusion in this study:
1.Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer.
2.History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes.
3.Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/mL).
4.Patients with a BMI < 18.5 kg/m2 or ≥ 35 kg/m2
5.Patients who demonstrate a 30% or greater improvement in the DSM-IV ADHD RS total score at Baseline relative to the score obtained at the Screening Visit.
6.History of alcohol or substance abuse or dependence within the last six months.
7.History of seizures or use of anticonvulsant medication for seizure control (except childhood febrile seizures).
8.Any psychiatric condition, including anxiety, tension, agitation, aggressive behavior, psychotic symptoms, suicidal tendency that requires treatment with medication or that, in the judgment of the investigator, may interfere with study participation and /or study assessments.
9. Pre-existing cardiovascular disorders including severe hypertension, angina, aterial occlusive disease; heart failure, hemodynamically significant congenital heart disease, cardiomyopathies, myocardial infarction, potentially life-threatening arrythmias and channelopathies (disorders caused by the dysfunction of ion channels).
10. Evidence upon physical examination or history of any clinically significant respiratory, hepatic, gastrointestinal, renal, hematological, or oncologic disorder requiring current medical intervention/therapy or likely to have a significant impact on the outcome of this study.
11.Diagnosis of glaucoma, hyperthyroidism, pheochromocytoma.
12.Diagnosis or family history of Tourette's syndrome.
13.Patients receiving any psychotropic medications. The minimum discontinuation period varies according to drug class follows:
•One week prior to the Screening Visit: stimulants including MPH, antidepressants other than fluoxetine, antipsychotics, anticonvulsants for non-epilepsy uses, mood-stabilizing medications such as lithium, and herbal preparations with psychotropic potential.
•Two weeks prior to the Screening Visit: benzodiazepines, barbiturates, all other sedatives or hypnotics, and monoamine oxidase inhibitors (MAOIs).
•Four weeks prior to the Screening Visit: Fluoxetine.
14.Patients receiving any psychological or behavioral therapies for the treatment of ADHD. Such therapies must be discontinued at least one month prior to the Screening Visit.
15.Patients who have initiated any psychological or behavioral therapies for reasons other than ADHD within three months prior to the Screening Visit. If it has been ongoing for at least three months with the same therapist, the patient may be eligible to enter the study provided that it is continued throughout the study.
16.Patients who, in the investigator’s judgment, have a history of poor response or intolerance to stimulants (e.g. methylphenidate, dexmethylphenidate, amphetamine salts, dextroamphetamine salts).
17.Pre-existing cerebrovascular disorders such as cerebral aneurysm, vascular abnormalities including vasculitis or stroke.
No additional exclusions may be applied by the investigator, in order to ensure that the study population will be representative of all eligible patients.
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E.5 End points |
E.5.1 | Primary end point(s) |
•Change from baseline to the end of the Period 1 treatment (week 9) in the total score of the DSM-IV ADHD RS (Primary 1) .This will be analyzed for the FAS P1 population.
•Change from baseline to end of Period 1 treatment (week 9) in the SDS total score (Primary 2). This will be analyzed for the FAS P1 population.
•Percentage of treatment failures, predefined as at least a 30% worsening on ADHD RS from Period 3 baseline (randomization 2) to the end of Period 3 (Primary 3). This will be analyzed for the FAS P3 population.
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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 | No |
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 | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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) | No |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 58 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Colombia |
Singapore |
South Africa |
United States |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |