RABE - Ritalin LA and Breakfast Effect

RABE - Ritalin LA and Breakfast Effect

In dieser NIS soll die Wirkdauer einer Therapie mit Ritalin LA unter Berücksichtigung des Frühstückverhaltens bzw. die nahrungsabhängigige Verträglichkeit und/oder Compliance bei Patienten mit ADHS untersucht werden.
Weitere Erhebungsparameter dieser NIS sind: Ermittlung von Inzidenz und Profil der unerwünschten Ereignisse, die unter der Behandlung mit Ritalin LA während der dauer der NIS beobachtet werden.

Ritalin LA

200

600

Müller, Alfons

Phase IV Manager NIS

Novartis Pharma GmbH

Roonstr. 25

90429 Nürnberg

Deutschland

alfons.mueller@novartis.com

Telefon: 0911/273-12897

Telefax: 0911/273-15897

Novartis Pharma GmbH

Roonstr. 25

90429 Nürnberg

Deutschland

10.08.2011

Studie bereits abgeschlossen

Study design:
At baseline the following data will be collected:
• Global clinical impression (ADHS-KGE) through the physician
• self assessment questionnaire for ADHD (SBB-HKS)
• questionnaire for the quality of life assessment for ADHD (ILK)
• parent questionnaire for measuring the waning point of the medication and the
profile of the ADHD symptoms over the day
After 1 Month and after 3 Months the same questionnaires will be filled out.

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Population:
Inclusion criteria:
1) Definite ADHD (DSM IV criteria)
2) Informed consent by parents and patients
3) Age: 11-18 years
4) Sufficient ability to read, write, communicate and understand the study procedures

Exclusion criteria:
1) Contraindications for methylphenidate

20 Monate

2.11. Target Parameters
• Efficacy and tolerability of a Therapy with Ritalin® LA
• Type and frequency of Adverse Events (AE) or Adverse Drug Reactions (ADR) observed
2.12. Secondary Variables to be Observed
• To evaluate the effect of Ritalin® LA on ADHD-symptoms in children assessed by
“ADHS – Klinische Gesamteinschätzung durch den Arzt” (ADHS-KGE)
[Clinical global assessment by the physician (ADHS-KGE)].
• To evaluate the effect of Ritalin® LA on ADHD-symptoms in children assessed by the “Selbstbeurteilungsbogen” (SBB)
[Self assessment form (SBB)].
• To evaluate the effect of Ritalin® LA on ADHD-symptoms in children assessed by the
“Inventar zur Erfassung der Lebensqualität” (ILK)
[Inventory to assess quality of life (ILK].
• To evaluate the effect of Ritalin® LA on ADHD-symptoms in children assessed
by a parent questionnaire to assess the effect-profile (daily time schedule)

• Type and frequency of Adverse Events (AE) or Adverse Drug Reactions (ADR) observed

2.13. Plausibility Criteria and Statistical Approach
An examination of the integrity of all target parameters in the input control of the documentation was carried out by the record management staff of SIMW GmbH. Obvious input mistakes or lack of information was noted and the original documentation was returned to the treating physician for correction / completion. Furthermore, qualified monitors from SIMW GmbH contacted selected centers randomly by telephone or onsite and, using an interview process, a comparison was made of the documented data with the patient file (source data verification; SDV). In the SDV, however, only those parameters that were normally noted in the patient records were queried.

All documents received were immediately archived by scanning and all data were entered into a database by electronic data capturing (EDC). The documentation forms used were designed for scanning systems. The EDC was supplemented by visual / manual controls, performed by skilled medical specialists. Additional plausibility checks were performed by software, to discover, on the one hand, any implausible or incomplete records in the physician’s report, and on the other hand, to prevent any mistakes resulting from the data capture process. Where it was clear that there was implausible or incomplete data in the documentation, the relevant documentation was returned to the treating physician for clarification (query management).

This final analysis was conducted in the form of an “intention-to-treat” analysis on all documentation submitted. Likewise, all efficacy relevant aspects in the total number of participating patients (829) were analyzed irrespective of any inconsistencies. The statistical characteristics for all interval scaled parameters (number, mean value, median, minimum, maximum, lower 5% percentile, upper 95% percentile, standard deviation) were partially separated for male and female patients. In the case of ordinal scaled parameters, the absolute frequencies of the different responses have been listed as a proportional percentage of the participating cohort i.e., the adjusted relative frequency according to the number of entries total. Medications, entered as full-text answers were coded in accordance with the relevant coding system (ATC-DDD). Other full-text answers were left “as reported”. A homologation of terms was carried out in accordance with SIMW SOPs (because this study was carried out in Germany, the texts reported by the doctors are presented in German language). All reports of side effects have been coded in accordance with MedDRA (V 13.0) and compiled into a line-listing (CIOMS II). All reports on SAE / AE / ADR have been notified to the pharmacovigilance departments of Novartis Pharma GmbH, Nürnberg and Leti Pharma GmbH, Witten within the approved time-lines.

General Note: Any differences to 100% in the frequency distributions are always conditional on a lack of detailed data in the documentation.

In contingency analyses of the ADHD-key-symptoms (baseline versus visit 3) a significant decrease in the conspicuousness of nearly all symptoms (inattentiveness, impulsivity, hyperactivity, learning problems, complex of ADHD problems total) could be shown (p < 0.01).
The effect of Ritalin® LA from effect-onset to its end was in median 19% longer compared to the previous MPH medication (6.33 hrs previous MPH / 7.50 hrs Ritalin® LA).

4. ADVERSE EVENTS
See Tables 43 to 49 and Appendix (Line-listing)
This non-interventional study was monitored throughout its entire duration for reports of adverse events (including suspected cases). All document records were checked on receipt for completeness and plausibility of "safety" areas. Where there was a lack of clarity and / or an omission in the answers, contact was made with the treating physician. In cases of serious adverse events (regardless of a possible causes), reports were submitted within 24 hours to the sponsor for medical evaluation, classification and registration. All documents have been subjected to an independent evaluation by SIMW regardless of the physician’s opinion. All reported adverse events were made in English and encoded with the corresponding numbers in accordance with MedDRA (LLT; HLT; SOC).
Upon completion of the project, a database comparison with the sponsor’s registrations shall be performed. The line-listing in the appendix shall be regarded as preliminary.
In accordance with SOPs, evaluation of all case documents, where the treating physician reported adverse drug reactions (and where applicable also adverse events and suspected cases), shows that out of a total of 36 patients (13.7%) at least one adverse event (AE) was registered. Overall, within this non-interventional study of Ritalin® LA 63 single adverse events were recorded.
In 3 patients (8.33% of patients with AE), the adverse event was considered "serious”. In all the other 33 patients with adverse events, these were considered "not serious" (tables 43; 44 and 45).
The number of AE per patient sums up to 4 adverse reactions in one patient throughout the whole treatment course. Tables 44 and 45 show an overview of the serious - (table 44) and non serious adverse events (table 45) sorted by frequency of occurrence (coded by MedDRA).
Table 46 shows the frequency of the respective organ classes (SOC) of all AE, sorted by frequency of occurrence.
The causal relationship between the AE and Ritalin® LA (causality) was assessed by the physicians (reporters). Following reporter’s assessment a causal relationship with Ritalin® LA was not excluded in 55 AE (87.3% of all AE: related / probable / possible / not assessable / not assessed). In 8 AE cases (12.7%) there was no relationship to Ritalin® LA (not likely, no causality). Table 48 shows an overview of all AE coded by SOC1(short), causality and seriousness.
4 patients have been hospitalized during study course, the AE were classified as “serious” AE.
In 1 case the child was hospitalized, but AE was classified by the sponsor as “non serious” (regist. no. S2010DE05526 AE).
(50.79% of all AE) the outcome was "resolved". In 20 AE-cases (31.75%) the outcome was “not yet resolved”. In1 patient the outcome of the AE was not known ("unknown").

In contingency analyses of the ADHD-key-symptoms (baseline versus visit 3) a significant decrease in the conspicuousness of nearly all symptoms (inattentiveness, impulsivity, hyperactivity, learning problems, complex of ADHD problems total) could be shown (p < 0.01).
The effect of Ritalin® LA from effect-onset to its end was in median 19% longer compared to the previous MPH medication (6.33 hrs previous MPH / 7.50 hrs Ritalin® LA).