Diffculties to recruit anticipated study size, now analysis

This study determined to measure non-adherence assessed by the number of non-adherent days during the clinical trial of 100 days using the Medication Event Monitoring System (MEMS).

Study Design:

• prospective
• multi-centric
• open-label
• randomized
• active-controlled trial

The study is designed as a prospective, multi-centric, open-label, randomized, active-controlled trial. ADHD-children and adolescents of both sexes, 6-17 of age, effectively treated with stimulants are recruited in two centres. Over a naturalistic run-in phase of four weeks adherence to medication taken before randomisation is measured. In the subsequent controlled clinical trial 50% of the participants are randomized to extended release (ER) methylphenidate (Medikinet retard®) applied with breakfast, 50% are randomized to immediate release (IR) methylphenidate (Medikinet®) in the morning and 3-4 h later (clinical trial). To optimize ecological validity, no double-dummy technique is applied; the allocation to either study arm is non-blinded.

According to the power calculation 106 patients will be randomized. The total duration of the study is 18 months. Starting with a run-in visit, each eligible patient is observed in the naturalistic run-in phase for four weeks. Subsequently, patients participate 100 days in the clinical trial starting with a baseline visit, an in between-visit and a final visit. Medical care is provided in the routine program of both study centres. To record the adherence, medication events are counted by Medication Event Monitoring System (MEMS).

Inclusion Criteria:

• Written informed consent (separately for children aged 6-11 years and 12-17 years)
• Children and adolescents of both sexes aged 6 - 17 years
• Confirmed diagnosis of ADHD by semi structured-clinical interview K-SADS
• ADHDRS-IV-Parent Version (18-Item-Scale) raw score ≥ 1,5 SD above norm under non-medicated conditions (either drug holiday or prior to medication within the past 6 months)
• Effective treatment with a stable dose of methylphenidate for at least one month (max. 60 mg/day) proved by a 25% symptom reduction in ADHD-RS under medication, compared to retrospective ADHD-RS without medication within the past 6 months.
• Acceptance and capability to swallow capsules of product size, proved by an equally sized placebo provided by Medice®.
• Sufficient knowledge of the German language
• Adequate contraception in case of sexual activity

Exclusion Criteria:

• Contraindications against methylphenidate
• Previous stable methylphenidate intake more than twice daily
• All severe psychiatric disorders except oppositional defiant disorder (ODD) or conduct disorder. In order to reflect the usual co-morbid spectrum of ADHD, mild or moderate anxiety or depressive disorders are accepted in the study.
• All severe somatic diseases as assessed by the baseline examination or medical history (including life-time history of epileptic disorders)
• Pathological results for vital signs, blood pressure and pulse
• Reported pathological results for ECG during the last 12 months
• Reported pathological results for differential blood count and hepatic metabolism during the last 6 months
• Indication for hospitalization
• Suicidality (assessed by MADRS Item 10, Score ≥ 3)
• IQ < 70 (clinically assessed)
• Any psychotropic co-medication
• Detention in an institution on official or judicial ruling
• Unwillingness to transmit pseudonym data according to German regulations
• Simultaneous participation in another clinical trial according to German Drug Law (AMG)