E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Attention Deficit/Hyperactivity Disorder |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003733 |
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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 |
The primary objective of the open label study is to assess long term safety and tolerability of PR OROS methylphenidate in a flexible dose regimen (18-90 mg/day) in adult subjects diagnosed with ADHD.
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are: · Assessment of the long term efficacy of PR OROS methylphenidate expressed as a function of change in the sum of the inattention and hyperactivity/impulsivity subscales of the investigator-rated CAARS. · Assessment of the long term effect on ADHD symptoms by means of change in total ADHD subscales. · Assessment of the long term effect on overall functioning, work, family and social functioning, and quality of life parameters as measured by the Clinical Global Impression Scale - Severity (CGI-S) and Change (CGI-C), Sheehan Disability Scale (SDS), Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) and Global Assessment of Effectiveness (GAE), respectively.
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Subjects must satisfy the following criteria to be enrolled in the study: 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)1,32 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. Completion of the open label phase in the 42603ATT3002 trial according to protocol. 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 and anamnesis.
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E.4 | Principal exclusion criteria |
Potential subjects who meet any of the following criteria will be excluded from participating in the study: 1. Known to be a non-responder to methylphenidate, or subject has a child known to be a non-responder to methylphenidate. 2. Known allergy or hypersensitivity to methylphenidate, or components of PR OROS methylphenidate. 3. Has been treated with any methylphenidate-containing medication within 1 month of screening visit, except trial medication provided in 42603ATT3002 trial 4. Any clinically unstable psychiatric condition including but not limited to the following: acute mood disorder, bipolar disorder, acute obsessivecompulsive disorder (OCD), anti-social personality disorder, borderline 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. 17. Use of other anti-depressants (unless subject has been on a stable dosage during the 42603ATT3002 trial, 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. 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 insufficiency, significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurological, psychiatric or metabolic disturbances. 23. Confirmed cancer or malignancy. 24. 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
EFFICACY CRITERIA: The primary efficacy criterion will be the change in the sum of the inattention and hyperactivity/impulsivity subscale scores of the investigator-rated CAARS from baseline at the end of the open follow-up phase. Secondary end points will include changes from baseline to the end of the treatment in: · CGI · Conners’ Adult ADHD Self-Report Short Version (CAARS-S:S) · SDS · Q-LES-Q · GAE
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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 | No |
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 | 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 | 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 | No |
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 | No |
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 | 2 |
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 | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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 |
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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
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Please refer to page 37 item 16.8 of the protocol. |
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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 | |
E.8.9.1 | In the Member State concerned months | 14 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 14 |