| 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 | Classification code | 10003731 |
|
| 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 double-blind phase of this study is to evaluate the efficacy and safety of 3 fixed dosages of Prolonged Release (PR) OROS methylphenidate (18, 36 and 72 mg/day) compared with placebo in adult subjects with attention deficit/hyperactivity disorder (ADHD). The efficacy response will be measured by the change in the sum of the inattention and hyperactivity/impulsivity subscale scores of the investigator-rated Conners' Adult ADHD Rating Scale (CAARS), from start of treatment to the end of the double-blind phase. |
|
| E.2.2 | Secondary objectives of the trial |
| Assessment of the following, associated with the use of PR OROS methylphenidate (Concerta) compared with placebo: The global improvement in severity of illness; subject's self report of reduction of ADHD symptoms; the benefits to work, family and social functioning; investigator's assessment of treatment effectiveness, dose-response relationship of Concerta; safety on the basis of AE reporting, vital signs and clinical laboratory tests. The objective of the open-label extension is to assess safety and tolerability of Concerta in a flexible dose regimen (18-90 mg/day) in adult subjects diagnosed with ADHD. The effect in the open-label extension is assessed using the same assessments as mentioned above (primary and secondary objective in the double-blind phase). |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
| 1.Subjects can be male or female.2.Age must be aged between 18 and 65 years, inclusive.3.Diagnosis of ADHD according to the Diagnostic and Statistical Manual of Mental Diseases, Fourth Edition (DSM-IV)1,50 and confirmed by the Conners' Adult ADHD Diagnostic Interview for DSM IV.4.Described chronic course of ADHD symptomatology from childhood to adulthood, with some symptoms present before age 7 years and continue to meet DSM-IV criteria at the time of assessment. ADHD is not diagnosed if the symptoms are better accounted for by another psychiatric disorder (e.g. mood disorder (especially bipolar disorder), anxiety disorder, psychotic disorder, personality disorder).5.CAARS score of >= 24 as determined by investigator at screening visit.6.Female subjects of child-bearing potential must agree to use an acceptable form of contraception (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, male partner sterilisation) before entry and throughout the study, and must have a negative urine pregnancy test at screening.7.Informed Consent Form signed by the subject.8.Subject agrees to take only the supplied study drug as treatment for ADHD during the study.9.Subject agrees not to initiate a new behavioural modification programme during the study or if currently using a behavioural modification programme and agrees not to change this programme during the study.10.Subject is able to comply with the study visit schedule and willing and able to complete the protocol-specified assessments.11.Healthy on the basis of a physical examination, medical history, anamnesis, and the results of blood biochemistry or haematology tests. If the results of the biochemistry or haematology tests are not within the laboratory's normal reference ranges, the subject may be included if the investigator considers the deviations are not clinically relevant. This should be clearly recorded in the subject's source documents and the Trial Manager informed. |
|
| E.4 | Principal exclusion criteria |
| 1.Known to be a non-responder to methylphenidate, or subject has a child known to be a non-responder to methylphenidate.2.Has been treated with any methylphenidate-containing medication within 3 months of screening visit. Three months is considered a reasonable time for patients treated with methylphenidate to return to a disease status baseline.3.Known allergy or hypersensitivity to methylphenidate, or components of PR OROS methylphenidate.4.Any clinically unstable psychiatric condition including the following: acute mood disorder, bipolar disorder, acute obsessive-compulsive disorder (OCD), anti-social personality disorder.5.Subjects with a family history of schizophrenia or family history of affective psychosis.6.Autism or Asperger's syndrome.7.Subjects with presence of motor tics, history of Tourette's syndrome or family history of Tourette's syndrome.8.A diagnosis of substance use disorder (abuse/dependence) according to DSM-IV criteria within 6 months prior to screening evaluation (nicotine and caffeine dependence are not exclusionary). Episodic abuse in the past is not an exclusion criterion.9.Current eating disorder (e.g. bulimia, anorexia nervosa) or history of an eating disorder.10.Known or suspected mental retardation.11.Hyperthyroidism, myocardial infarction or stroke in the 6 months prior to screening for this study.12.Subjects with history of seizures, glaucoma or uncontrolled hypertension.13.Subjects with angina pectoris or cardiac arrhythmias.14.Pregnant or breast-feeding females.15.Any co-existing medical condition or taking any concomitant medication that is likely to interfere with safe administration of methylphenidate including any herbal or homeopathic remedies; herbal and over-the-counter weight loss or diet preparations or drugs that contain stimulants.16.Use of monoamine oxidase inhibitors, except if tapering off, within 4 weeks of the baseline visit.17.Use of other anti-depressants (unless subject has been on a stable dosage for at least 3 months prior to screening, in which case treatment may continue so long as dosage remains unchanged for the duration of the study) or mood stabilisers (e.g. anti-epileptics, lithium), except if tapering off, within 2 weeks of the baseline visit (for fluoxetine within 4 weeks). Any medication likely to interfere with safe administration of methylphenidate.18.Use of clonidine or other alpha-2 adrenergic receptor agonists, antipsychotic medications, theophylline, coumarin anticoagulants, anticonvulsants.19.Subjects who have clinically significant gastrointestinal problems, including severe narrowing (pathologic or iatrogenic) of the gastrointestinal tract.20.Subjects who are unable to swallow the study medication whole with the aid of liquids (participants may not chew, divide, dissolve or crush the study medication).21.History of severe drug allergy or hypersensitivity.22.Any serious illnesses including, but not limited to liver or renal insuffiency, significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurological, psychiatric or metabolic disturbances. 23. Confirmed cancer or malignancy. 24. Participation in an investigational drug trial in the 30 days prior to selection. 25. Employee of the investigator or the institution who have direct involvement in the trial or other trials under the direction of the investigator or their members. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary end point in the double-blind treatment phase will be the change in the sum of the inattention and hyperactivity/impulsivity subscale scores of the investigator-rated CAARS from baseline to last post-randomisation assessment in the double-blind treatment period. |
|
| 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 | Information not present in EudraCT |
| 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) | 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 | Yes |
| E.8.1.7.1 | Other trial design description |
| Open label study extenstion after double-blind phase |
|
| 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.8.5 | The trial involves multiple Member States | Yes |
| 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 | Information not present in EudraCT |
| 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 | 1 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
Print
