Randomized, Double-blind Safety and Efficacy Study of Lisdexamfetamine Dimesylate (LDX) in Children and Adolescents Aged 6-17

ADHD Clinical Trial

Official title:

A Phase III, Randomised, Double-Blind, Multicentre, Parallel-Group, Placebo- and Active-Controlled, Dose-Optimisation Safety and Efficacy Study of Lisdexamfetamine Dimesylate (LDX) in Children and Adolescents Aged 6-17 With Attention-Deficit/Hyperactivity Disorder (ADHD)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00763971
• Other study ID #: SPD489-325
• Secondary ID: 2008-000679-90
• Status: Completed
• Phase: Phase 3
• Start date: November 17, 2008
• Est. completion date: March 16, 2011

Study information

• Verified date: June 2021
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main aim of this study is to see if giving LDX to children and adolescents aged 6-17 years with ADHD decreases symptoms of ADHD.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 336
• Est. completion date: March 16, 2011
• Est. primary completion date: March 16, 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 17 Years

Eligibility

Inclusion Criteria:

1. Subject is a male or female aged 6-17 years inclusive at the time of consent.

2. Subject must meet Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition - Text Revision (DSM-IV-TR) criteria for a primary diagnosis of ADHD based on a detailed psychiatric evaluation.

3. Subject must have a Baseline ADHD-RS-IV total score =28.

4. Subject has blood pressure measurements within the 95th percentile for age, gender, and height at Screening and Baseline.

5. Subject is able to swallow a capsule.

Exclusion Criteria:

1. Subject has failed to respond to more than one adequate course (dose and duration) of stimulant therapy. One course must have been a long-acting formulation.

2. Subject has a conduct disorder. Oppositional Defiant Disorder is not exclusionary.

3. Subject is currently considered a suicide risk, has previously made a suicide attempt or has a prior history of, or is currently, demonstrating active suicidal ideation.

4. Subject has glaucoma.

5. Subject weighs less than 22.7kg (50lbs).

6. Subject is significantly overweight based on Centre for Disease Control and Prevention Body Mass Index (BMI)-for-age gender specific charts at Screening. Significantly overweight is defined as a BMI >97th percentile for this study.

7. Subject has a documented allergy, hypersensitivity, or intolerance to amphetamine or methylphenidate.

8. Subject has a documented allergy, hypersensitivity, or intolerance to any excipients in the test or reference products.

9. Subject has a history of seizures (other than infantile febrile seizures), a tic disorder, or a current diagnosis and/or a known family history of Tourette's Disorder.

10. Subject has a known history of symptomatic cardiovascular disease, advance arteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems that may place them at increased vulnerability to the sympathomimetic effects of a stimulant drug.

11. Subject has a known family history of sudden cardiac death or ventricular arrhythmia.

12. Subject is well controlled on their current ADHD medication with acceptable tolerability.

13. Subject has a pre-existing severe gastrointestinal tract narrowing (pathologic or iatrogenic).

Related Conditions & MeSH terms

• ADHD

Intervention

Drug:
• Lisdexamfetamine Dimesylate (LDX)
30, 50 or 70mg capsule once per day (Overencapsulated)
• Methylphenidate Hydrochloride
18, 36, or 54mg tablet one per day (Overencapsulated)
• Placebo
Placebo capsule once per day (Overencapsulated)

Locations

Country	Name	City	State
Belgium	Universitair Ziekenhuis Gent, Kinder-en Jeugdpsychiatrie, De Pintelaan 185	Ghent	East Flanders
Belgium	ZiekenhuisNetwerk Antwerpen, Commandant Weynsstraat 165, Campus Hoge Beuken	Hoboken	Antwerp
Belgium	Afdeling Psychiatrie, UZ Herestraat 49, Bus 07003	Leuven
France	Centre Hospitalier Charles Perrens, Bordeaux, Service de Psychiatrie de l'Enfant et de l'Adolescent	Bordeaux Cédex
France	Hôpital Gui de Chauliac, 80, avenue Augustin Fliche	Montpellier Cedex 05
France	Hospital Archet 2	Nice	Cedex 03
France	Hôpital Robert Debré, Service de Psychopathologie de l'Enfant et de l'Adolescent	Paris	Ile-De-France
Germany	Schwerpunktpraxis für Entwicklung und Lernen, Heinrichsdamm 6	Bamberg	Bayern
Germany	Universitätsmedizin Berlin	Berlin
Germany	Albert-Ludwigs-Universitat Freiburg	Freiburg
Germany	Praxis Dr. Walter Robert Otto	Fulda
Germany	Universitat Gottingen	Göttingen	Niedersachsen
Germany	Praxis Dr. Wolff	Hagen
Germany	Praxis Dr. med. Friedrich Kaiser und Dr. med. Ingrid Marinesse	Hamburg
Germany	Praxis für Neuropädiatrie, Schomburgstrasse 120	Hamburg
Germany	Klinikum der Johannes Gutenberg-Universität Mainz, Klinik und Poliklinik für Kinder-und Jugendpsychiatrie und-psychotherapie,	Mainz	Rheinland-Pfalz
Germany	Zentralinstitut für Seelische Gesundheit Mannheim, Klinik für Psychiatrie und Psychotherapie des Kindes-und Jug, J4/J5	Mannheim	Baden Wuttemburg
Germany	Universitatsklinikum Gießen und Marburg GmbH, Hans-Sachs-Strasse 4	Marburg	Hessen
Germany	Medizinisches Studienzentrum Würzburg, Augustinerstrasse 10	Würzburg	Bayern
Germany	Universität Würzburg, Klinik und Poliklinik fuer Kinder-und Jugendpsychiatrie und Psychotherapie	Würzburg	Bayern
Hungary	Vadaskert Kórház és Szakambulancia	Budapest
Hungary	Pándy Kálmán Kórház	Gyula
Hungary	Gyermek és Ifjúságpszichiátriai Szakrendelés és Gondozó	Pécs
Hungary	Szegedi Tudományegyetem	Szeged
Italy	Università degli Studi di Cagliari, Dipartimento di Neuroscienze	Cagliari
Italy	Azienda Ospedaliera Universitaria Policlinico G. Martino	Messina
Italy	Azienda Ospedaliera della 2 Universita di Napoli	Napoli
Netherlands	Academisch Ziekenhuis Maastricht	Maastricht
Netherlands	Universitair Medisch Centrum Sint Radboud, Reinier Postlaan 10	Nijmegen
Poland	Szpital Uniwersytecki im. dr. Antoniego Jurasza w Bydgoszczy	Bydgoszcz	Kujawsko-pomorskie
Poland	Gdanski Uniwersytet Medyczna w Gdansku	Gdansk	Pomorskie
Poland	Wojewodzki Osrodek Lecznictwa Psychiatrycznego	Torun	Kujawsko-pomorskie
Poland	Samodzielny Publiczny Dzieciecy Szpital Kliniczny	Warszawa	Mazowieckie
Spain	Complejo Hospitalario Universitario de Badajoz	Badajoz
Spain	Mutua de Terrassa	Barcelona
Spain	Hospital Sant Joan de Dèu	Esplugues de Llobregat	Barcelona
Spain	Hospital Ramón y Cajal, Servicio de psiquiatría	Madrid
Spain	Clínica Universitaria de Navarra, Unidad de Psiquiatría Infantil y Adolescente, Dept. de Psiquiatría y Psicología Médica	Pamplona	Navarra
Spain	Hospital Universitario de Canarias C/Ofra	San Cristóbal de la Laguna	Santa Cruz De Tenerife
Spain	Hospital Marítimo, Unidad de Salud Mental Infanto-Juvenil (USMI-J), Carretera del Sanatorio s/n	Torremolinos	Malaga
Sweden	Drottning Silvias Barnsjukhus	Goteborg
Sweden	Utvecklingsneurologiska Enheten (UNE), BUC, Lockerudsv 12	Mariestad	Vastergotland
Sweden	Astrid Lindgren Children's Hospital, Karolinska University Hospital	Stockholm
Sweden	Barn och Ungdomsmedicin klinik Mölnlycke, Ekdalavägen 2,Box 9	Stockholm
United Kingdom	Basildon Hospital, Child Developement Centre, Nethermayne	Basildon	Essex
United Kingdom	Tayside Childrens Hospital, Clinical Research Facility, Level 4	Dundee	Scotland
United Kingdom	Victoria Hospital, Paediatric Unit, Hayfield Road	Kirkcaldy	Fife, Scotland
United Kingdom	Ryegate Children's Centre, Tapton Crescent Road	Sheffield	Yorkshire
United Kingdom	Lighthouse Child Development Centre, Snakes Lane	Southend-on-Sea	Essex

Sponsors (1)

Lead Sponsor	Collaborator
Shire

Countries where clinical trial is conducted

Belgium,  France,  Germany,  Hungary,  Italy,  Netherlands,  Poland,  Spain,  Sweden,  United Kingdom, 

References & Publications (3)

Banaschewski T, Soutullo C, Lecendreux M, Johnson M, Zuddas A, Hodgkins P, Adeyi B, Squires LA, Coghill D. Health-related quality of life and functional outcomes from a randomized, controlled study of lisdexamfetamine dimesylate in children and adolescent — View Citation

Coghill D, Banaschewski T, Lecendreux M, Soutullo C, Johnson M, Zuddas A, Anderson C, Civil R, Higgins N, Lyne A, Squires L. European, randomized, phase 3 study of lisdexamfetamine dimesylate in children and adolescents with attention-deficit/hyperactivit — View Citation

Coghill DR, Banaschewski T, Lecendreux M, Zuddas A, Dittmann RW, Otero IH, Civil R, Bloomfield R, Squires LA. Efficacy of lisdexamfetamine dimesylate throughout the day in children and adolescents with attention-deficit/hyperactivity disorder: results fro — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHD-RS-IV) Total Score at up to 7 Weeks	The ADHD-RS-IV consists of 18 items scored on a 4-point scale ranging from 0 (no symptoms) to 3 (severe symptoms) with total score ranging from 0 to 54. A decrease in score indicates an improvement in ADHD symptomology.	Baseline and up to 7 weeks
Secondary	Percentage of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores	Clinical Global Impression-Improvement (CGI-I) consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved) or 2 (much improved) on the scale.	Up to 7 weeks
Secondary	Change From Baseline in Conner's Parent Rating Scale - Revised (CPRS-R) Total Score at up to 7 Weeks	The Conner's Parent rating Scale-revised short version (CPRS-R) consists of 27 questions graded on a scale from 0 (not true at all) to 3 (very much true) with a total score ranging from 0 to 81. Higher scores are indicative of increased ADHD. This scale allows parents to respond on the basis of the child's behavior and help assess ADHD and evaluate problem behavior.	Baseline and up to 7 weeks
Secondary	Health Utilities Index-2 (HUI-2) Scores at up to 7 Weeks	HUI is used to describe health status and to obtain utility scores by collecting data using one or more questionnaires in formats selected to match the specific study design criteria. Scoring ranges from 0.00 (dead) to 1.00 (perfect health). Higher scores represent better health status.	Baseline and up to 7 weeks
Secondary	Change From Baseline in the Child Health and Illness Profile, Child Edition: Parent Report Form (CHIP-CE:PRF) Global T-score at up to 7 Weeks	The CHIP-CE:PRF evaluates health-related quality of life. It is composed of 5 domains (satisfaction, comfort, resilience, avoidance, and achievement) consisting of a total of 76 items. The global score is an average of the scores for the 5 domains. The majority of items assess frequency of events using a 5-point response format. There is no range for a total score. Raw scale scores are used to generate T-scores. Higher scores indicate better health.	Baseline and up to 7 weeks
Secondary	Change From Baseline in Weiss Functional Impairment Rating Scale - Parent Report (WFIRS-P) Global Score at up to 7 Weeks	The WFIRS-P is a 50-item scale with each item scored from 0 (never/not at all) to 3 (very often/very much). Mean scores range from 0 to 3. Higher scores indicate greater functional impairment.	Baseline and up to 7 weeks
Secondary	Change From Baseline in Brief Psychiatric Rating Scale for Children (BPRS-C) Total Score at up to 7 Weeks	The BPRS-C characterizes psychopathology. A total of 21 items are rated on a scale from 0 (not present) to 6 (extremely severe) with a total score ranging from 0 to 126. A decrease in score indicates a reduction in psychopathology.	Baseline and up to 7 weeks
Secondary	Columbia-Suicide Severity Rating Scale (C-SSRS)	C-SSRS is a 19-item semi-structured interview designed to capture suicide-related thoughts and behaviors.	Up to 7 weeks

External Links

•   FDA recal information
•   FDA-approved label