A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Dose-Response Study to Evaluate Efficacy and Safety of Prolonged Release (PR) OROS® methylphenidate (54 and 72 mg/day) in Adults with Attention Deficit/Hyperactivity Disorder. - Lamda 2

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2007-002111-82-DE
• Date of registration: 10/03/2008
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International N.V., Turnhoutseweg 30, 2340 Beerse, Belgium
• Public title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Dose-Response Study to Evaluate Efficacy and Safety of Prolonged Release (PR) OROS® methylphenidate (54 and 72 mg/day) in Adults with Attention Deficit/Hyperactivity Disorder. - Lamda 2
• Scientific title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Dose-Response Study to Evaluate Efficacy and Safety of Prolonged Release (PR) OROS® methylphenidate (54 and 72 mg/day) in Adults with Attention Deficit/Hyperactivity Disorder. - Lamda 2
• Date of first enrolment: 21/04/2008
• Target sample size: 300
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-002111-82
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Belgium, Denmark, Finland, France, Germany, Netherlands, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects must satisfy the following criteria to be enrolled in the study:

1. Subjects can be male or female.
2. Subjects 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)1,60 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. Woman must be postmenopausal (no spontaneous menses for at least 2 years), surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy), abstinent or, if sexually active, be practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, male partner sterilization) before entry, and continue to use the same method of contraception throughout the study and for 1 week after the completion of the study.
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 behavioral modification program during the study or if currently using a behavioral modification program and agrees not to change this program 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 the results of blood biochemistry or hematology tests. If the results of the biochemistry or hematology 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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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. Has been treated with any methylphenidate-containing medication within 1 month of screening visit. One month is considered a reasonable time for patients treated with methylphenidate to return to a disease status baseline.
3. Participation in and premature withdrawal from 42603ATT3002 or 42603ATT3004 study.
4. Known allergy or hypersensitivity to methylphenidate, or components of PR OROS methylphenidate.
5. Any clinically unstable psychiatric condition including, but not limited to the following: acute mood disorder, bipolar disorder, acute obsessive-compulsive disorder (OCD), anti-social personality disorder, borderline personality disorder.
6. Subjects with a family history of schizophrenia or family history of affective psychosis.
7. Autism or Asperger’s syndrome.
8. Subjects with presence of motor tics, history of Tourette’s syndrome or family history of Tourette’s syndrome.
9. 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.
10. Current eating disorder (e.g. bulimia, anorexia nervosa) or history of an eating disorder.
11. Known or suspected mental retardation.
12. Hyperthyroidism, myocardial infarction or stroke in the 6 months prior to screening for this study.
13. Subjects with history of seizures, glaucoma or uncontrolled hypertension. Uncontrolled hypertension defined as systolic blood pressure at screening or baseline = 140 mmHg or diastolic blood pressure at screening or baseline = 90 mmHg.
14. Subjects with angina pectoris or clinically significant cardiac arrhythmias according to medical judgment or tachycardia (heart rate of > 100 beats/min).
15. Pregnant or breast-feeding females.
16. 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.
17. Use of monoamine oxidase inhibitors, except if tapering off, within 4 weeks of the baseline visit.
18. 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 stabilizers (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.
19. Use of clonidine or other alpha-2 adrenergic receptor agonists, antipsychotic medications, theophylline, coumarin anticoagulants, anticonvulsants.
20. Subjects who have clinically significant gastrointestinal problems, including severe narrowing (pathologic or iatrogenic) of the gastrointestinal tract.
21. 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). 22. History of severe drug allergy or hypersensitivity.
23. Any serious illnesses including, but not limited to l

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Attention Deficit-Hyperactivity Disorder (ADHD)
MedDRA version: 9.1 Level: LLT Classification code 10003735 Term: Attention deficit-hyperactivity disorder

Intervention(s)

Trade Name: Concerta 18 mg Retardtabletten
Product Name: CONCERTA 18 mg
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: methylphenidate hydrochloride
CAS Number: 113-45-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 18-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: CONCERTA 36 mg Retardtabletten
Product Name: CONCERTA 36 mg
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: methylphenidate hydrochloride
CAS Number: 113-45-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 36-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: The primary objective of this study is to evaluate the efficacy of 2 fixed dosages of Prolonged Release (PR) OROS methylphenidate (54 and 72 mg/day) compared with placebo in adult subjects with attention deficit/hyperactivity disorder (ADHD).

Primary end point(s): The primary objective of this study is to evaluate the efficacy of 2 fixed dosages of PR OROS methylphenidate (54 and 72 mg/day) compared with placebo in adult subjects with attention deficit/hyperactivity disorder (ADHD). The primary criterion will be the change in the sum of the inattention and hyperactivity/impulsivity subscale scores of the investigator-rated CAARS, from start of treatment to the end of the double-blind treatment (end of 13 weeks or last post-baseline assessment).

Secondary Objective: Assessment of the global improvement in severity of illness associated with the use of PR OROS methylphenidate compared with placebo using a clinical global impression score (CGI).
Assessment of subject’s self report of reduction of ADHD symptoms associated with the use of PR OROS methylphenidate compared with placebo using the Conners’ Adult ADHD Rating Scale-Self Report Short Version (CAARS-S:S).
Assessment of the benefits to work, family and social functioning associated with the use of PR OROS methylphenidate compared with placebo using the Sheehan’s Disability Scale (SDS).
Assessment of investigator’s assessment of treatment effectiveness using the investigator-rated CAARS subscales.
Assessment of safety on the basis of AE reporting, vital signs, ECG and clinical laboratory tests.

For a complete overview see section 2 of the Protocol

Secondary ID(s)

2007-002111-82-FR

42603ATT3013