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

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)

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.

Study Overview

• Status: Completed
• Conditions: ADHD
• Intervention / Treatment: Drug: Lisdexamfetamine Dimesylate (LDX); Drug: Methylphenidate Hydrochloride; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 336
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Afdeling Psychiatrie, UZ Herestraat 49, Bus 07003
  • Antwerp
    • Hoboken, Antwerp, Belgium, 2660
      • ZiekenhuisNetwerk Antwerpen, Commandant Weynsstraat 165, Campus Hoge Beuken
  • East Flanders
    • Ghent, East Flanders, Belgium, 9000
      • Universitair Ziekenhuis Gent, Kinder-en Jeugdpsychiatrie, De Pintelaan 185
• France
  • Bordeaux Cédex, France, 33076
    • Centre Hospitalier Charles Perrens, Bordeaux, Service de Psychiatrie de l'Enfant et de l'Adolescent
  • Montpellier Cedex 05, France, 34295
    • Hôpital Gui de Chauliac, 80, avenue Augustin Fliche
  • Cedex 03
    • Nice, Cedex 03, France, 6202
      • Hospital Archet 2
  • Ile-De-France
    • Paris, Ile-De-France, France, 75019
      • Hôpital Robert Debré, Service de Psychopathologie de l'Enfant et de l'Adolescent
• Germany
  • Berlin, Germany, 13353
    • Universitätsmedizin Berlin
  • Freiburg, Germany, 79104
    • Albert-Ludwigs-Universität Freiburg
  • Fulda, Germany, 36037
    • Praxis Dr. Walter Robert Otto
  • Hagen, Germany, 58093
    • Praxis Dr. Wolff
  • Hamburg, Germany, 22415
    • Praxis Dr. med. Friedrich Kaiser und Dr. med. Ingrid Marinesse
  • Hamburg, Germany, 22767
    • Praxis für Neuropädiatrie, Schomburgstrasse 120
  • Baden Wuttemburg
    • Mannheim, Baden Wuttemburg, Germany, 68159
      • Zentralinstitut für Seelische Gesundheit Mannheim, Klinik für Psychiatrie und Psychotherapie des Kindes-und Jug, J4/J5
  • Bayern
    • Bamberg, Bayern, Germany, 96047
      • Schwerpunktpraxis für Entwicklung und Lernen, Heinrichsdamm 6
    • Würzburg, Bayern, Germany, 97070
      • Medizinisches Studienzentrum Würzburg, Augustinerstrasse 10
    • Würzburg, Bayern, Germany, 97080
      • Universität Würzburg, Klinik und Poliklinik fuer Kinder-und Jugendpsychiatrie und Psychotherapie
  • Hessen
    • Marburg, Hessen, Germany, 35039
      • Universitatsklinikum Gießen und Marburg GmbH, Hans-Sachs-Strasse 4
  • Niedersachsen
    • Göttingen, Niedersachsen, Germany, 37075
      • Universität Göttingen
  • Rheinland-Pfalz
    • Mainz, Rheinland-Pfalz, Germany, 55131
      • Klinikum der Johannes Gutenberg-Universität Mainz, Klinik und Poliklinik für Kinder-und Jugendpsychiatrie und-psychotherapie,
• Hungary
  • Budapest, Hungary, 1021
    • Vadaskert Korhaz es Szakambulancia
  • Gyula, Hungary, 5700
    • Pandy Kalman Korhaz
  • Pécs, Hungary, 7632
    • Gyermek és Ifjúságpszichiátriai Szakrendelés és Gondozó
  • Szeged, Hungary, 6750
    • Szegedi Tudomanyegyetem
• Italy
  • Cagliari, Italy, 9124
    • Università degli Studi di Cagliari, Dipartimento di Neuroscienze
  • Messina, Italy, 98125
    • Azienda Ospedaliera Universitaria Policlinico G. Martino
  • Napoli, Italy, 80131
    • Azienda Ospedaliera della 2 Universita di Napoli
• Netherlands
  • Maastricht, Netherlands, 6229 HX
    • Academisch Ziekenhuis Maastricht
  • Nijmegen, Netherlands, 6525 GC
    • Universitair Medisch Centrum Sint Radboud, Reinier Postlaan 10
• Poland
  • Kujawsko-pomorskie
    • Bydgoszcz, Kujawsko-pomorskie, Poland, 85-094
      • Szpital Uniwersytecki im. Dr. Antoniego Jurasza w Bydgoszczy
    • Torun, Kujawsko-pomorskie, Poland, 87-100
      • Wojewódzki Osrodek Lecznictwa Psychiatrycznego
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland, 00-576
      • Samodzielny Publiczny Dzieciecy Szpital Kliniczny
  • Pomorskie
    • Gdansk, Pomorskie, Poland, 80-282
      • Gdanski Uniwersytet Medyczna w Gdansku
• Spain
  • Badajoz, Spain, 6010
    • Complejo Hospitalario Universitario de Badajoz
  • Barcelona, Spain, 8221
    • Mútua de Terrassa
  • Madrid, Spain, 28034
    • Hospital Ramón y Cajal, Servicio de psiquiatría
  • Barcelona
    • Esplugues de Llobregat, Barcelona, Spain, 08950
      • Hospital Sant Joan de Déu
  • Malaga
    • Torremolinos, Malaga, Spain, 29630
      • Hospital Marítimo, Unidad de Salud Mental Infanto-Juvenil (USMI-J), Carretera del Sanatorio s/n
  • Navarra
    • Pamplona, Navarra, Spain, 31080
      • Clínica Universitaria de Navarra, Unidad de Psiquiatría Infantil y Adolescente, Dept. de Psiquiatría y Psicología Médica
  • Santa Cruz De Tenerife
    • San Cristóbal de la Laguna, Santa Cruz De Tenerife, Spain, 38320
      • Hospital Universitario de Canarias C/Ofra
• Sweden
  • Goteborg, Sweden, 41119
    • Drottning Silvias barnsjukhus
  • Stockholm, Sweden, 171 76
    • Astrid Lindgren Children's Hospital, Karolinska University Hospital
  • Stockholm, Sweden, 435 30
    • Barn och Ungdomsmedicin klinik Mölnlycke, Ekdalavägen 2,Box 9
  • Vastergotland
    • Mariestad, Vastergotland, Sweden, 54224
      • Utvecklingsneurologiska Enheten (UNE), BUC, Lockerudsv 12
• United Kingdom
  • Essex
    • Basildon, Essex, United Kingdom, SS16 5NL
      • Basildon Hospital, Child Developement Centre, Nethermayne
    • Southend-on-Sea, Essex, United Kingdom, SS2 6XT
      • Lighthouse Child Development Centre, Snakes Lane
  • Fife, Scotland
    • Kirkcaldy, Fife, Scotland, United Kingdom, KY2 5AH
      • Victoria Hospital, Paediatric Unit, Hayfield Road
  • Scotland
    • Dundee, Scotland, United Kingdom, DD1 9SY
      • Tayside Childrens Hospital, Clinical Research Facility, Level 4
  • Yorkshire
    • Sheffield, Yorkshire, United Kingdom, S10 5DD
      • Ryegate Children's Centre, Tapton Crescent Road

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lisdexamfetamine Dimesylate (LDX); Overencapsulated LDX 30, 50, or 70mg	Drug: Lisdexamfetamine Dimesylate (LDX); 30, 50 or 70mg capsule once per day (Overencapsulated); Other Names: Vyvanse™
Active Comparator: Methylphenidate Hydrochloride; Overencapsulated Concerta 18, 36, or 54mg	Drug: Methylphenidate Hydrochloride; 18, 36, or 54mg tablet one per day (Overencapsulated); Other Names: Concerta®, OROS MPH
Placebo Comparator: Placebo; Overencapsulated Placebo	Drug: Placebo; Placebo capsule once per day (Overencapsulated)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Shire

Publications and helpful links

General Publications

• 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/hyperactivity disorder. Eur Neuropsychopharmacol. 2013 Oct;23(10):1208-18. doi: 10.1016/j.euroneuro.2012.11.012. Epub 2013 Jan 15.
• 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 from a randomized, controlled trial. Eur Child Adolesc Psychiatry. 2014 Feb;23(2):61-8. doi: 10.1007/s00787-013-0421-y. Epub 2013 May 25.
• 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 adolescents with attention deficit hyperactivity disorder. CNS Drugs. 2013 Oct;27(10):829-40. doi: 10.1007/s40263-013-0095-5.
• Setyawan J, Yang H, Cheng D, Cai X, Signorovitch J, Xie J, Erder MH. Developing a Risk Score to Guide Individualized Treatment Selection in Attention Deficit/Hyperactivity Disorder. Value Health. 2015 Sep;18(6):824-31. doi: 10.1016/j.jval.2015.06.005. Epub 2015 Aug 20.

Helpful Links

• FDA-approved Label
• FDA recal information

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2008
• Primary Completion (Actual): March 16, 2011
• Study Completion (Actual): March 16, 2011

Study Registration Dates

• First Submitted: September 30, 2008
• First Submitted That Met QC Criteria: September 30, 2008
• First Posted (Estimate): October 1, 2008

Study Record Updates

• Last Update Posted (Actual): June 14, 2021
• Last Update Submitted That Met QC Criteria: June 9, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Methylphenidate; Lisdexamfetamine Dimesylate
• Other Study ID Numbers: SPD489-325; 2008-000679-90 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No