A 7 week multicenter, double-blind, randomized, placebo-controlled cross-over evaluation of the efficacy and safety of a modified-release oral dosage form of methylphenidate-HCl, Ritalin LA® (20 mg, q.d.) compared to Medikinet® ret. (20mg, q.d.) in children with attention deficit hyperactivity disorder (ADHD) aged 6 - 14

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2005-003002-28-DE
• Date of registration: 22/05/2006
• Prospective Registration: No
• Primary sponsor: Novartis Pharma GmbH
• Public title: A 7 week multicenter, double-blind, randomized, placebo-controlled cross-over evaluation of the efficacy and safety of a modified-release oral dosage form of methylphenidate-HCl, Ritalin LA® (20 mg, q.d.) compared to Medikinet® ret. (20mg, q.d.) in children with attention deficit hyperactivity disorder (ADHD) aged 6 - 14
• Scientific title: A 7 week multicenter, double-blind, randomized, placebo-controlled cross-over evaluation of the efficacy and safety of a modified-release oral dosage form of methylphenidate-HCl, Ritalin LA® (20 mg, q.d.) compared to Medikinet® ret. (20mg, q.d.) in children with attention deficit hyperactivity disorder (ADHD) aged 6 - 14
• Date of first enrolment: 31/10/2005
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-003002-28
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: yes Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no

Countries of recruitment

Germany

Key inclusion & exclusion criteria

Inclusion criteria:
1.Male and female patients aged 6-14.
2.Patients having a diagnosis of ADHD of any type according to DSM-IV criteria, as established by history, psychiatric examination and a structured diagnostic interview (Kiddie-Sads-Present and Lifetime Version; see Appendix 3)
3.Patients, whose symptoms are adequately controlled by a stable and well-tolerated dose of a immediate release methylphenidate equivalent of 20mg for one month before screening.
4.Patients may only be included, if according to the opinion of the investigator, a discontinuation of medication is justified to assess the condition of the child.
5.Patients with parents or a legal guardian, who will give written informed consent for the child to participate in the study. Additionally, assent to participate must be obtained from all children entering the study if the child is able to judge the nature, the meaning and the significance of the clinical trial (according to §40 Abs. 4 No. 4 AMG). Assent will be documented by the child’s signature on the consent form.
6.Health status: Patients must have no clinically significant diseases or clinically significant abnormal laboratory values as assessed during medical history and physical exam.
7.Patients meeting minimum intelligence requirements: In the opinion of the investigator the patient must generally be functioning at age-appropriate levels academically, which should take into account any prior cognitive or academic testing(basic knowledge of reading, writing and calculating).
8.Female patients who have reach menarche must have a negative result on the urine pregnancy test and, if sexually active, must be using adequate and reliable contraception (e.g. triple-barrier method) throughout the course of the trial. Effective contraceptive measures are the following:
• A hormonal oral, transdermal, or injectable contraceptive agent with a double-barrier method
•An implantable contraceptive device for at least 3 months prior to screening
•A double barrier-method of contraception (condom, diaphragm and a spermicide);
9.Patients already receiving behavioral therapies for HKS/ADHD may continue to do so during the course of the trial.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
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:
1.Patients with comorbid psychiatric conditions with symptoms requiring current pharmacological treatment (e.g. major depression, psychosis).
2.Patients with comorbid psychiatric or somatic conditions that may contraindicate treatment or confound efficacy or safety assessments.
3.Patients who are taking any concomitant medications likely to interfere with the study drug or confound efficacy or safety assessments, e.g.
•Tricyclic antidepressants, buproprion, clonidine, buspirone 2 weeks before randomization.
•Atomoxetine 2 weeks before randomization.
•Fluoxetine or antipsychotics 1 month before randomization.
•Pemoline and amphetamines 1 week before randomization.
4.Patients with a known non-response to methylphenidate.
5.History of hypersensitivity to any of the study drugs or to drugs with similar chemical structures.
6.Patients who are judged by the investigator as likely to be non-compliant with study procedures, including those with a suspected history of substance abuse, or patients living with a person diagnosed with a substance abuse disorder.
7.Patients who are pregnant.
8.Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer
9.Patients with warnings, mentioned in the German Basic Prescribing Information of Ritalin LA (Fachinformation, November 2002): anorexia, severe depression, anxiety disorder, Gilles de la Tourette-Syndrome, other tic disorder, hypertension, occlusive arterial diseases, severe stenocardia, tachycardiac arrhythmia, stroke, hyperthyroidism, increased intra-ocular pressure, hypertrophy of the prostate, known hypersensitivity to sympathomimetics, MAO-inhibitors.
10.Patients with a history of seizure disorder.
11.History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin.


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

Health Condition(s) or Problem(s) studied

attention deficit hyperactivity disorder
MedDRA version: M15 Level: LLT Classification code 10064104

Intervention(s)

Trade Name: Ritalin LA
Product Name: Ritalin LA
Pharmaceutical Form: Capsule*
INN or Proposed INN: Methylphenidathydrochloride
CAS Number: 298-59-9
Current Sponsor code: RIT124
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Trade Name: Medikinet retard 20mg
Product Name: Medikinet retard 20mg
Pharmaceutical Form: Capsule*
INN or Proposed INN: Methylphenidathydrochloride
CAS Number: 298-59-9
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): The two primary instruments to measure efficacy during the laboratory classroom sessions are the SKAMP scale and Math Tests.
The SKAMP (Swanson, Kotkin, Agler, M-Flynn, and Pelham Rating Scale) (Swanson, Agler et al., 1999) is a rating scale that specifically measures the classroom manifestations of Attention Deficit Hyperactivity Disorder. The ratings are based on both the frequency of behaviors and the quality of behaviors. Observer ratings on the 13-item SKAMP scale will be used to calculate scores for each patient at each interval. The score is derived from 20 minutes of direct observations of subject behavior by trained, blind raters, who will be sitting in the classroom during all sessions.
To maintain consistency throughout the study, the blinded observers will be responsible for observing the same group of children at each classroom setting at each center.
The paper and pencil 10-Minute Math Test (Swanson et al 1998) is an objective written test with minimal practice effects, consisting of several pages of 100 math problems each. The problems are presented in ascending order of difficulty (requiring addition, subtraction, multiplication and division computations respectively) during a 10-minute period. Test difficulty can be altered for subjects at different skill levels by adjusting the number of digits being manipulated per calculation. All children are expected to be able to compute all problems on the first two pages; the last two pages of problems are expected to challenge the most capable children. At the end of the 10-minute Math Test, papers are collected and scored; the number of problems attempted and the number of problems correctly answered are generated as objective measures related to “academic productivity”.

Secondary Objective: The secondary objectives are to explore in children with ADHD aged 6-14 in a laboratory classroom setting:
•The efficacy of Ritalin LA 20 mg relative to Medikinet ret. 20mg and placebo at the five individual ratings (performed at 10:30 am, 12:00 am, 1:30 pm, 3:00 pm and 4:30 pm) measured by SKAMP-Attention subscale, the SKAMP-Deportment subscale and the SKAMP Combined.
•The efficacy of Ritalin LA 20 mg over all five ratings measured by the SKAMP-Attention subscale, the SKAMP Deportment subscale and SKAMP combined.
•The efficacy of Ritalin LA mg over the first three individual ratings measured by SKAMP-Attention subscale and the SKAMP-Deportment subscale.
•The efficacy of Ritalin LA 20 mg over the last two ratings measured by the SKAMP-Attention subscale, the SKAMP Deportment subscale and SKAMP combined.
•The safety of Ritalin LA 20 mg.
•The efficacy of Ritalin LA 20 mg measured by the NCBRF-TIQ (performed on day 7, day 14 and day 21).

Main Objective: The primary objective of the study is to demonstrate the efficacy of Ritalin LA 20 mg in children with ADHD aged 6-14 by testing the hypothesis that Ritalin LA 20 mg is superior to placebo and is clinically not inferior to Medikinet ret. 20mg retard over three ratings of the SKAMP Combined rating performed at 10:30 am, at 12:00 am and at 1:30 pm in a laboratory classroom setting.

Secondary ID(s)

CRIT124DDE01