Clinical Trials Register

Summary
EudraCT Number:	2015-000488-15
Sponsor's Protocol Code Number:	3.0
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-08-07
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2015-000488-15

A.3

Full title of the trial

Vigilance regulation as predictor of response to Psychostimulants in adult patients with ADHD

Vigilanzregulation als Prädiktor der Response auf Psychostimulanzien bei adulten Patienten mit ADHS

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Vigilance regulation as predictor of response to Psychostimulants in adult patients with ADHD

Vigilanzregulation als Prädiktor der Response auf Psychostimulanzien bei adulten Patienten mit ADHS

A.3.2

Name or abbreviated title of the trial where available

VIP-ADHS

A.4.1

Sponsor's protocol code number

3.0

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	University of Leipzig
B.1.3.4	Country	Germany
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	University of Leipzig, Department of Psychiatry
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Department of Psychiatry of University of Leipzig
B.5.2	Functional name of contact point	OA Dr. med. Maria Strauß
B.5.3	Address:
B.5.3.1	Street Address	Semmelweisstraße 10
B.5.3.2	Town/ city	Leipzig
B.5.3.3	Post code	04103
B.5.3.4	Country	Germany
B.5.4	Telephone number	+493419724304
B.5.5	Fax number	+493419724539
B.5.6	E-mail	Maria.Strauss@medizin.uni-leipzig.de

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Medikinet adult 10 mg Hartkapseln, retardiert
D.2.1.1.2	Name of the Marketing Authorisation holder	MEDICE Arzneimittel Pütter GmbH & Co. KG, Kuhloweg 37, 58638 Iserlohn/Germany
D.2.1.2	Country which granted the Marketing Authorisation	Germany
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Methylphenidate
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	METHYLPHENIDATE
D.3.9.1	CAS number	113-45-1
D.3.9.4	EV Substance Code	SUB08870MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Medikinet adult 20 mg Hartkapseln, retardiert
D.2.1.1.2	Name of the Marketing Authorisation holder	MEDICE Arzneimittel Pütter GmbH & Co KG, Kuhloweg 37, 58638 Iserlohn / Germany
D.2.1.2	Country which granted the Marketing Authorisation	Germany
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Methylphenidate
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	METHYLPHENIDATE
D.3.9.1	CAS number	113-45-1
D.3.9.4	EV Substance Code	SUB08870MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Medikinet adult 30 mg Hartkapseln, retardiert
D.2.1.1.2	Name of the Marketing Authorisation holder	MEDICE Arzneimittel Pütter GmbH & Co. KG, Kuhloweg 37; 56838 Iserlohn / Germany
D.2.1.2	Country which granted the Marketing Authorisation	Germany
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Methyplhenidate
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	METHYLPHENIDATE
D.3.9.1	CAS number	113-45-1
D.3.9.4	EV Substance Code	SUB08870MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	30
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 4
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Medikinet adult 40 mg Hartkapseln, retardiert
D.2.1.1.2	Name of the Marketing Authorisation holder	MEDICE Arzneimittel Pütter GmbH & Co. KG, Kuhloweg 37, 58638 Iserlohn / Germany
D.2.1.2	Country which granted the Marketing Authorisation	Germany
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Methylphenidate
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	METHYLPHENIDATE
D.3.9.1	CAS number	113-45-1
D.3.9.4	EV Substance Code	SUB08870MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	40
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Attention deficit-hyperactivity disorder

Aufmerksamkeitsdefizit-Hyperaktivitaetsstoerung

E.1.1.1

Medical condition in easily understood language

Attention deficit-hyperactivity disorder

Aufmerksamkeitsdefizit-Hyperaktivitaetsstoerung

E.1.1.2

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10003735
E.1.2	Term	Attention deficit-hyperactivity disorder
E.1.2	System Organ Class	100000004873

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Primary objective of the trial is the investigation, if an unstable vigilance regulation in the EEG prior to medication (measured on VIGALL classification) predicates the response of therapy with methylphenidate in ADHD. The therapeutic target is a >30%-reduction of CAARS (CAARS-S:L - Conners’ Adult ADHD Rating Scales-Self-Report: Long Version).

Primäres Ziel der Studie ist die Untersuchung, ob eine instabile Vigilanzregulation im EEG vor Medikation (bestimmt anhand der VIGALL-Klassifikation) den Erfolg einer Therapie von ADHS mit Methylphenidat prädiziert. Das Therapieziel ist eine >30%-Reduktion der CAARS (CAARS-S:L - Conners’ Adult ADHD Rating Scales-Self-Report: Long Version).

E.2.2

Secondary objectives of the trial

In the secondary objectives of clinical trial should be investigated, if
- the intensity of vigilance regulation is related to therapeutic effect

Furthermore will be examined within the final examination compared with baseline and depending on therapeutic effect, whether and how the therapy
- has an effect on the quality of life, measured by „Quality of life questionnaire“ (WHOQOL-BREF)
- has an effect on interpersonal problems, measured by “Inventar zur Erfassung interpersonaler Probleme”
- has an effect on ADHD symptoms, measured by ASRS-v1.1 (Adult ADHD Self-Report Scale)

In den sekundären Zielen der klinischen Prüfung soll untersucht werden, ob
- die Stärke der Vigilanzregulation mit dem Maß des Therapieerfolgs zusammenhängt.

Ferner soll im Rahmen der Abschlussvisite im Vergleich zu Baseline und abhängig vom Therapieerfolg untersucht werden, ob und wie die Therapie
- die Lebensqualität, gemessen anhand des „Quality of life questionnaire“ (WHOQOL-BREF) beeinflusst.
- interpersonale Probleme, gemessen anhand des „Inventar zur Erfassung interpersonaler Probleme“ beeinflusst.
- die ADHS-Symptomatik, gemessen anhand des ASRS-v1.1 (Adult ADHD Self-Report Scale) beeinflusst.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

concomitant scientific Projects according to the protocol:
- actimetry
- cognitive performance

im Protokoll beschriebene wissenschaftliche Begleitprojekte:
- Aktometrie
- kognitive Leistungsfähigkeit

E.3

Principal inclusion criteria

- diagnosis of ADHD and ASRS-v1.1 part A cut-off 4 of 6
- ADHD-symptoms existing since childhood (WURS-k >= 30)
- >= 18 years
- legal capacity
- written informed consent of the patient
- knowledge of german language
- Intelligence test (MWT-B): IQ >= 85
- willingness to breakfast and lunch

- Diagnose der ADHS und ASRS-v1.1 Teil A cut-off 4 von 6
- ADHS-Symptomatik liegt bereits seit Kindesalter vor (WURS-k ≥ 30)
- ≥ 18 Jahre
-Geschäftsfähigkeit
- schriftliche Einwilligung des Patienten
- Beherrschung der deutschen Sprache
- Intelligenztest (MWT-B): IQ ≥ 85
- Bereitschaft zu Frühstück und Mittagessen

E.4

Principal exclusion criteria

- previous therapy with psychostimulants during the last 52 weeks before screening
- diagnosis or anamnesis of psychiatric comorbidity and –symptoms:
a. severe depression (according to ICD F32.2/F32.3; F33.2; F33.3)
b. Anorexia nervosa / anorectic disorder (SKID-I)
c. suicidal tendencies
d. psychotic symptoms (SKID-I)
e. severe affective disorders (SKID-I)
f. mania (SKID-I)
g. schizophrenia (SKID-I)
h. psychopathological / Borderline-personality-disorders (SKID-II)
i. severe and episodic (Typ I) bipolar affective disorders (SKID-I) (which are not well controlled)
j. dependence on alcohol, medication or drug during the last 6 months or manifest drug abuse (SKID-I)
k. diagnosis of tic disorder
l. acute severe panic disorder or generalised anxiety disorder (SKID-I)

- contraindication for therapy or according to SmPC:
a. hypersensitivity to methylphenidate or other components of the IMP
b. glaucoma
c. pheochromocytoma
d. during the therapy or within 14 days after cessation of treatment with MAO-inhibitor
e. hyperthyroidism or thyrotoxicosis
f. clinically relevant cardiovascular diseases (severe hypertension; heart failure; arterial occlusive disease; angina pectoris; haemodynamic significant, congenital cardiac defect; cardiomyopathy; myocardial infarction; arrhythmia of life-threatening potential; channelopathies)
g. cerebrovascular disease (cerebral aneurysm; abnormal blood vessels including vasculitis or apoplex)
h. pronounced anacidity of stomach with pH>5.5; under therapy with H2 receptor inhibitor or therapy with antacids

- medication, which can lead to interaction in case of concomitant use:
a. drugs, which increase blood pressure
b. halogenated narcotics
c. centrally effective alpha-2-agonists
d. dopaminergic agents
e. H2-inhibitors
f. antacids / proton pump inhibitor

- seizures in medical history
- EEG findings suggest seizure
- clinically relevant renal dysfunction (dialysis-dependent kidney insufficiency)
- clinically relevant hepatic disease (SGOT and/or SGPT greater > 2x upper normal value)
- lack of compliance
- Pregnant or nursing women. Fertile women (within 2 years of their last menstruation) without appropriate contraceptive measures.
- participation in other interventional trials
- closure relationship to investigator / sponsor
- concomitant medication with psychotropic substance

- vorangegangene Therapie mit Psychostimulanzien in den letzten 52 Wochen vor dem Screening
- Diagnose oder Anamnese psychischer Begleiterkrankungen und –Symptome:
a. schwere Depression (gemäß ICD F32.2/F32.3; F33.2; F33.3)
b. Anorexia nervosa / anorektische Störungen (SKID-I)
c. Suizidneigung
d. psychotische Symptome (SKID-I)
e. schwere affektive Störungen (SKID-I)
f. Manie (SKID-I)
g. Schizophrenie (SKID-I)
h. psychopathologische / Borderline-Persönlichkeits-störungen (SKID-II)
i. schwere und episodische (Typ I) bipolare affektive Störungen (SKID-I) (die nicht gut kontrolliert sind)
j. Alkohol-, Medikamenten- oder Drogenabhängigkeit in den letzten 6 Monaten oder manifester Drogenmissbrauch (SKID-I)
k. Diagnose einer Ticstörung
l. Akute stark ausgeprägte Panikerkrankung und generalisierte Angsterkrankung (SKID-I)

- Kontraindikation für einzusetzende Therapie bzw. Gegenanzeigen gemäß Fachinformation
a. Überempfindlichkeit gegen Methylphenidat oder einen der sonstigen Bestandteile des Prüfprodukts
b. Glaukom
c. Phäochromozytom
d. während oder innerhalb von 14 Tagen nach Absetzen der Behandlung mit MAO-Hemmern
e. Hyperthyreose oder Thyreotoxikose
f. Klinisch relevante Herz-Kreislauferkrankungen (schwere Hypertonie, Herzinsuffizienz, arterielle Verschlusskrankheit, Angina pectoris, hämodynamisch signifikanter, angeborener Herzfehler, Kardiomyopathien, Myokardinfarkt, potenziell lebensbedrohliche Arrhythmien und Kanalopathien)
g. zerebrovaskuläre Erkrankung (zerebrale Aneurysmen, Gefäßabnormalitäten inklusive Vaskulitis oder Schlaganfall)
h. ausgeprägte Anazidität des Magens mit pH>5,5, bei H2-Rezeptorblocker oder Antazidatherapie

- Medikation, die bei gleichzeitiger Anwendung zu Wechselwirkungen führen kann:
a. Medikamente, die den Blutdruck erhöhen
b. halogenierte Narkotika
c. zentral wirksame alpha-2-Agonisten
d. dopaminerge Wirkstoffe
e. H2-Blocker
f. Antazida / Protonenpumpenhemmer

- Anfallsleiden in der Vergangenheit
- EEG-Befund, der auf ein Anfallsleiden hindeutet
- Klinisch relevante Nierenfunktionsstörungen (dialysepflichtige Niereninsuffizienz)
- Klinisch relevante Lebererkrankung (SGOT und/oder SGPT > 2-fach obere Normgrenze)
- mangelnde Kooperationsbereitschaft (Compliance)
- Frauen während der Schwangerschaft und Stillzeit. Fertile weibliche Patienten (<2 Jahre nach der letzten Menstruation) ohne angemessene kontrazeptive Maßnahmen
- Teilnahme an anderen interventionellen Therapiestudien
- Abhängigkeit vom Prüfer/Sponsor
- Begleitmedikation mit psychotropen Substanzen

E.5 End points

E.5.1

Primary end point(s)

The lability index is determined using the VIGALL-algorithm based on vigilance-EEGs. Individual vigilance cases are assigned to three prototypical types of vigilance regulation (stable and physiological vigilance regulation vs. unstable vigilance regulation). It will be determined, if there is a relationship between stable/unstable vigilance regulation and treatment success/failure. A therapy ist successful, if total score of CAARS-S:L decreased 4 weeks after the end of titration >30% by comparison to baseline.

Der Labilitätsindex wird nach dem VIGALL-Algorithmus mittels des Vigilanz-EEGs bestimmt. Individuelle Vigilanzverläufe werden drei prototypischen Vigilanzregulationstypen zugeordnet (stabile Vigilanzregulation und physiologische Vigilanzregulation vs. labile Vigilanzregulation). Es wird untersucht, ob ein Zusammenhang zwischen stabiler/labiler Vigilanzregulation und Erfolg/Misserfolg bei der Therapie besteht. Eine erfolgreiche Therapie ist, wenn sich der Gesamtscore von CAARS-S:L 4 Wochen nach Ende der Titrationsphase sich um >30% im Vergleich zum Baselinewert verringert hat.

E.5.1.1

Timepoint(s) of evaluation of this end point

4 weeks after end of titration

4 Wochen nach Abschluss der Titrationsphase

E.5.2

Secondary end point(s)

- The predictive value of lability index for changes of CAARS-Score from baseline until last visit is determined. Sex, dose of methylphenidate and weight will are considered.
- Changes of quality of life, measured by „Quality of life questionnaire“, are determined depending on therapy success and other covariats.
- Changes of interpersonal problems, measured by „ Inventar zur Erfassung interpersonaler Probleme“, are determind depending on therapy success and other covariats.
- Changes of ADHD symptoms, measured by ASRS-v1.1 (Adult ADHD Self-Report Scale), are determind depending on therapy success and other covariats.
- Therapy success, measured by CGI, is determined after adjusting for covariats.
- Changes of depressive symptoms, measured by MADRAS, are determind depending on therapy success and other covariats.
- Control of possible covariats of vigilance regulation (sleep, depression, ADHD symptoms, substance use, daytime sleepiness, chronotype)

- Der prädiktive Wert des Labilitätsindexes für Änderungen im CAARS-Score vom Baseline bis zur Abschlussvisite soll untersucht werden. Es werden auch Geschlecht und Methyphenidatdosis/Gewicht berücksichtigt.
- Änderungen in der Lebensqualität, gemessen anhand des „Quality of life questionnaire“ werden in Abhängigkeit des Therapieerfolgs und anderer Kovariaten untersucht.
- Änderungen bei interpersonalen Problemen, gemessen anhand des „Inventar zur Erfassung interpersonaler Probleme“ werden in Abhängigkeit des Therapieerfolgs und anderer Kovariaten untersucht.
- Änderungen der ADHS-Symptomatik, gemessen anhand des ASRS-v1.1 (Adult ADHD Self-Report Scale) werden nach Adjustierung für Kovariaten untersucht.
- Therapieerfolg, gemessen anhand des CGI-Scores, wird nach Adjustierung für Kovariaten untersucht .
- Änderungen depressiver Beschwerden, gemessen anhand MADRAS werden in Abhängigkeit des Therapieerfolgs und anderer Kovariaten untersucht
- Kontrolle von möglichen Kovariaten auf die Vigilanzregulation (Schlaf, Depression, ADHS-Symptome, Substanzkonsum, Tagesschläfrigkeit, Chronotyp) werden untersucht.

E.5.2.1

Timepoint(s) of evaluation of this end point

4 weeks after end of titration

4 Wochen nach Abschluss der Titrationsphase

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

Yes

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

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

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

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

LVLS

letze Visite des zuletzt eingeschlossenen Patienten (LVLP)

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

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

115

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

120

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Patient receive the dose of the last titration for further treatment with methylphenidate after end of the trial according to current guidelines, which suggest the continuation of medication for a total duration up to 12 months. The indication has to be critically reviewed after this time according to SmPC. The medication could continued after 12 months if there is a further indication.

Die Weiterbehandlung mit Methylphenidat mit der in der letzten Titration erreichten Dosis erfolgt nach Abschluss der Studie gemäß den geltenden Leitlinien, die eine Fortführung der Medikation über eine Gesamtdauer von bis zu 12 Monaten vorsehen. Entsprechend der Fachinformation muss die Indikation nach diesem Zeitraum kritisch überprüft werden. Bei Fortbestehen der Indikation nach 12 Monaten, kann die Medikation fortgeführt werden.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2015-09-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-10-07

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2018-08-16

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