Clinical Trials Register

Summary
EudraCT Number:	2010-021533-31
Sponsor's Protocol Code Number:	CRIT124D2302
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2010-11-17
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

Belgium - FPS Health-DGM

A.2

EudraCT number

2010-021533-31

A.3

Full title of the trial

A randomized, double-blind, placebo-controlled, multicenter study of the efficacy and safety of Ritalin® LA in adult patients with childhood-onset ADHD

A.3.1

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

Efficacy and Safety Study of Methylphenidate Hydrochloride Modified Release in Adults With Childhood-onset Attention Deficit/Hyperactivity Disorder (ADHD)

A.4.1

Sponsor's protocol code number

CRIT124D2302

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	Novartis Pharma Services AG
B.1.3.4	Country	Switzerland
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Novartis Pharma Services A.G.
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novartis Pharma AG
B.5.2	Functional name of contact point	Clinical Trial Information Desk
B.5.3	Address:
B.5.3.1	Street Address	Forum 1, Novartis Campus
B.5.3.2	Town/ city	Basel
B.5.3.3	Post code	4056
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	+41613241111
B.5.5	Fax number	+41613248001
B.5.6	E-mail	clinicaltrial.enquiries@novartis.com

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	Rilatine Modified Release 30 mg
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Pharma N.V.
D.2.1.2	Country which granted the Marketing Authorisation	Belgium
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.3.4	Pharmaceutical form	Modified-release capsule, hard
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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 HYDROCHLORIDE
D.3.9.1	CAS number	298-59-9
D.3.9.2	Current sponsor code	304417_S21_M_967_1
D.3.9.3	Other descriptive name	none
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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	Rilatine Modified Release 20 mg
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Pharma N.V.
D.2.1.2	Country which granted the Marketing Authorisation	Belgium
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.3.4	Pharmaceutical form	Modified-release capsule, hard
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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 HYDROCHLORIDE
D.3.9.1	CAS number	298-59-9
D.3.9.2	Current sponsor code	304417_S21_M_967_1
D.3.9.3	Other descriptive name	none
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule, hard
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Adult patients with childhood-onset Attention Deficit Hyperactivity Disorder

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
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	10037175 - Psychiatric disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10003737
E.1.2	Term	Attention deficit/hyperactivity disorder NOS
E.1.2	System Organ Class	10037175 - Psychiatric disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10003736
E.1.2	Term	Attention deficit/hyperactivity disorder
E.1.2	System Organ Class	10037175 - Psychiatric disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

•To confirm the clinically effective dose range of Ritalin LA in adults with childhood onset ADHD as measured by the change from Baseline to the end of a 9-week, fixed-dose treatment period in DSM-IV Attention-Deficit/Hyperactive Disorder Rating Scale (DSM-IV ADHD RS) total score.
•To evaluate improvement in functional impairment will be measured by the change from baseline in total score on the Sheehan Disability (SDS) is a self-rating scale designed to assess the functional impairment of patients with ADHD at the end of a 9-week fixed-dose treatment period.
•To evaluate the maintenance of effect of Ritalin LA in adults with childhood onset ADHD as measured by the percentage of Ritalin LA vs. placebo treatment failures at the end of a 6-month treatment withdrawal period.
•To evaluate the safety of Ritalin LA in adults with childhood onset ADHD as measured by the frequency of AEs, the results of laboratory tests, and the measurement of vital signs and ECGs.

E.2.2

Secondary objectives of the trial

•The key secondary objective is to evaluate overall improvement as measured by the proportion of patients with clinical improvement on the Clinical Global Impression – Improvement Scale (CGI-I) at the end of a 9-week fixed-dose treatment period.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients eligible for inclusion in this study have to fulfill all of the following criteria:
1.Written informed consent must be obtained before any assessment is performed.
2.Patients must be capable of complying with study procedures.
3.Male or female adults from 18-60 years of age.
4.Diagnosis of Attention-Deficit /Hyperactivity Disorder (ADHD) all types with a confirmed childhood onset according to DSM-IV diagnostic criteria.
5.DSM-IV ADHD Rating Scale total score greater than or equal to 30 at Screening and Baseline.
6.Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use an effective method of contraception during dosing of study treatment.

E.4

Principal exclusion criteria

Patients fulfilling any of the following criteria are not eligible for inclusion in this study:
1.Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer.
2.History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes.
3.Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
4.Patients with a BMI < 18.5 kg/m2 or ≥ 30 kg/m2
5.Patients who demonstrate a 30% or greater improvement in the DSM-IV ADHD RS total score at Baseline relative to the score obtained at the Screening Visit.
6.History of alcohol or substance abuse or dependence within the last six months.
7.History of seizures or use of anticonvulsant medication for seizure control (except childhood febrile seizures).
8.Any psychiatric condition, including anxiety, tension, agitation, aggressive behavior, psychotic symptoms, suicidal tendency, that requires treatment with medication or that, in the judgment of the investigator, may interfere with study participation and /or study assessments.
9.Pre-existing cardiovascular disorders including severe hypertension, angina, arterial occlusive disease; heart failure, hemodynamically significant congenital heart disease, cardiomyopathies, myocardial infarction, potentially life-threatening arrhythmias and channelopathies (disorders caused by the dysfunction of ion channels).
10. Evidence upon physical examination or history of any clinically significant respiratory, hepatic, gastrointestinal, renal, hematological, or oncologic disorder requiring current medical intervention/therapy or likely to have a significant impact on the outcome of this study.
11. Diagnosis of glaucoma, hyperthyroidism, pheochromocytoma
12. Diagnosis or family history of Tourette's syndrome
13.Patients receiving any psychotropic medications. The minimum discontinuation period varies according to drug class follows:
•One week prior to the Screening Visit: stimulants including MPH, antidepressants other than fluoxetine, antipsychotics, anticonvulsants for non-epilepsy uses, mood-stabilizing medications such as lithium, and herbal preparations with psychotropic potential.
•Two weeks prior to the Screening Visit: benzodiazepines, barbiturates, all other sedatives or hypnotics, and monoamine oxidase inhibitors (MAOIs).
•Four weeks prior to the Screening Visit: Fluoxetine.
14.Patients receiving any psychological or behavioral therapies for the treatment of ADHD. Such therapies must be discontinued at least one month prior to the Screening Visit.
15.Patients who have initiated any psychological or behavioral therapies for reasons other than ADHD within three months prior to the Screening Visit. If it has been ongoing for at least three months with the same therapist, the patient may be eligible to enter the study provided that it is continued throughout the study.
16.Patients who, in the investigator’s judgment, have a history of poor response or intolerance to stimulants (e.g. methylphenidate, dexmethylphenidate, amphetamine salts, dextroamphetamine salts).
17. Pre-existing cerebrovascular disorders such as cerebral aneurysm, vascular abnormalities including vasculitis or stroke.
No additional exclusions may be applied by the investigator, in order to ensure that the study population will be representative of all eligible patients.

E.5 End points

E.5.1

Primary end point(s)

•Change from baseline to the end of the Period 1 treatment (week 9) in the total score of the DSM-IV ADHD RS (Primary 1) .This will be analyzed for the FAS P1 population.
•Change from baseline to end of Period 1 treatment (week 9) in the SDS total score (Primary 2). This will be analyzed for the FAS P1 population.
•Percentage of treatment failures, predefined as at least a 30% worsening on ADHD RS from Period 3 baseline (randomization 2) to the end of Period 3 (Primary 3). This will be analyzed for the FAS P3 population.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

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

Yes

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Colombia

Singapore

South Africa

United States

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

Last Patient Last Visit

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

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects
F.1 Age Range
F.1.1	Trial has subjects under 18	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.2.1	Number of subjects for this age range:	700
F.1.3	Elderly (>=65 years)	No
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	50
F.4.2	For a multinational trial
F.4.2.1	In the EEA	500
F.4.2.2	In the whole clinical trial	700

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

2010-11-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-01-19

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2012-08-07

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