Clinical trial NCT00784654: Double-blind, Placebo-controlled, Randomised Withdrawal, Extension, Safety and Efficacy Study of LDX in Children and Adolescents Aged 6-17
Official title: A Phase III, Double-blind, Placebo-controlled, Randomised Withdrawal, Multicentre, Extension, Safety and Efficacy Study of Lisdexamfetamine Dimesylate (LDX) in Children and Adolescents Aged 6-17 With Attention- Deficit/Hyperactivity Disorder (ADHD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: ADHD
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2008-11-04
Enrollment: 276
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main aim of this study is to evaluate the long-term maintenance of efficacy of LDX after administered to children and adolescents aged 6-17 with ADHD for at least 6 months


Eligibility criteria: Inclusion Criteria:

1. Subject's parent or legally authorised representative(LAR) must provide signature of informed consent, and there must be documentation of assent (if applicable) by the subject indicating that the subject is aware of the investigational nature of the study and the required procedures and restrictions in accordance with the International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) Guideline E6 and applicable regulations before completing any study-related procedures.
2. Subject and parent/LAR are willing and able to comply with all the testing and requirements defined in this protocol, including oversight of morning dosing. Specifically, the parent/LAR must be available upon awakening, at approximately 7:00AM, to dispense the dose of test product for the duration of the study.
3. Subject is a male or female aged 6-17 years inclusive at the time of consent for the antecedent study (SPD489-325).
4. Subject satisfied all entry criteria for the antecedent study (SPD489-325), and completed a minimum of 4 weeks of double-blind treatment, reached Visit 4 and completed the 1-week post-treatment washout in the antecedent study (SPD489-325), without experiencing any clinically significant AEs that would preclude exposure to LDX.
5. Subject must have a satisfactory medical assessment with no clinically significant or relevant abnormalities as determined by medical history, physical examination findings and clinical laboratory test results.
6. Subject has blood pressure measurements within the 95th percentile for age, gender, and height.

Exclusion Criteria:

1. Subject was terminated from SPD489-325 for non-compliance and/or experienced an SAE or AE resulting in termination from the antecedent study.
2. Subject has a current, controlled (requiring a restricted medication) or uncontrolled, comorbid psychiatric diagnosis with significant symptoms such as any severe comorbid Axis II disorder or severe Axis I disorder (such as Post Traumatic Stress Disorder, psychosis, bipolar illness, pervasive developmental disorder, severe obsessive compulsive disorder, severe depressive or severe anxiety disorder) or other symptomatic manifestations, such as agitated states, marked anxiety, or tension that, in the opinion of the examining clinician, will contraindicate treatment with LDX or confound efficacy or safety assessments. Comorbid psychiatric diagnoses will be established at the Screening Visit (Visit -1)of the antecedent study (SPD489-325)with the Screening interview of the Kiddie-SADS-Present and Lifetime-Diagnostic Interview (K-SADS-PL)and additional modules if warranted by the results of the initial interview. Participation in behavioural therapy is permitted provided the subject was receiving the therapy for at least 1 month at the time of the Baseline Visit (Visit 0) of the antecedent study (SPD489-325).
3. Subject has a conduct disorder. Oppositional defiant disorder is not exclusionary.
4. Subject has any concurrent chronic or acute illness or unstable medical condition that could confound the results of safety assessments, increase risk to the subject or lead to difficulty complying with the protocol.
5. 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.
6. Subject is female and is pregnant or lactating.
7. Subject has glaucoma.
8. Subject has any clinically significant ECG at Visit 8 of the antecedent study (SPD489-325) or clinically significant laboratory abnormalities at Visit 7 of the antecedent study (SPD489-325).
9. Subject has a documented allergy, hypersensitivity, or intolerance to amphetamine.
10. Subject has a recent history (within the past 6 months) of suspected substance abuse or dependence disorder (excluding nicotine)in accordance with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition - Text Revision (DSM-IV-TR)criteria.
11. Subject has a history of seizures (other than infantile febrile seizures), a tic disorder, a current diagnosis and or a known family history of Tourette's Disorder.
12. Subject has a known history of symptomatic cardiovascular disease, advanced 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.
13. Subject has a known family history of sudden cardiac death or ventricular arrhythmia.
14. Subject is taking any medication that is excluded.
15. Subject is taking other medications that have central nervous system (CNS) effects, affect performance, such as sedating antihistamines and decongestant sympathomimetics, or are monoamine oxidase inhibitors (during or within 14 days of investigational medicinal product administration). Stable use of bronchodilator inhalers is not exclusionary.
16. Subject has a documented allergy, hypersensitivity, or intolerance to any excipients in the investigational medicinal product(s).

Primary outcomes:
measure: Percent of Participants With Treatment Failures at End of The Randomized Withdrawal Period
timeFrame: Baseline of the randomized withdrawal period and its relevant endpoint (Up to 6 weeks)
Secondary outcomes:
measure: Change From Open-Label Baseline in The Attention Deficit Hyperactivity Disorder Rating Scale-Fourth Edition (ADHD-RS-IV) Total Score at Endpoint (Week-26) of The Open-label Period
timeFrame: Open-label baseline and Endpoint (Week-26)
measure: Change From Randomized Withdrawal Baseline in The ADHD-RS-IV Total Score at Endpoint of The Randomized Withdrawal Period
timeFrame: Baseline of the randomized withdrawal period and its relevant endpoint (Up to 6 weeks)
measure: Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at Endpoint (Week-26) of The Open-label Period
timeFrame: At Week 26
measure: Percent of Participants With CGI-S at Endpoint of The Randomized Withdrawal Period, Last Observation Carried Forward (LOCF)
timeFrame: At endpoint of the randomized withdrawal period (Up to 6 weeks)
measure: Percent of Participants With Improvement on Clinical Global Impression - Improvement (CGI-I) at Endpoint (Week-26) of The Open-label Period
timeFrame: At Week 26
measure: Change From Open-label Baseline in The Health Utilities Index-2 (HUI-2) Scores at Endpoint (Week-26) of The Open-label Period, LOCF
timeFrame: At open-label baseline and endpoint (Week-26) of the open-label period
measure: Change From Randomized Withdrawal Baseline in The HUI-2 Scores at Endpoint of The Randomized Withdrawal Period
timeFrame: Baseline of the randomized withdrawal period and its relevant endpoint (Up to 6 weeks)
measure: Change From Open-label Baseline in The Child Health and Illness Profile, Child Edition: Parent Report Form (CHIP-CE:PRF) Global T-score at Endpoint (Week-26) of The Open-label Period
timeFrame: At open-label baseline and endpoint (Week-26) of the open-label period
measure: Change From Randomized Withdrawal Baseline in The CHIP-CE:PRF Global T-score at Endpoint of The Randomized Withdrawal Period
timeFrame: Baseline of the randomized withdrawal period and its relevant endpoint (Up to 6 weeks)
measure: Change From Open-Label Baseline in The Weiss Functional Impairment Rating Scale - Parent Report (WFIRS-P) Global Score at Endpoint (Week-26) of The Open-label Period
timeFrame: At open-label baseline and endpoint (Week-26) of the open-label period
measure: Change From Randomized Withdrawal Baseline in The WFIRS-P Global Score at Endpoint of The Randomized Withdrawal Period
timeFrame: Baseline of the randomized withdrawal period and its relevant endpoint (Up to 6 weeks)
measure: Change From Open-Label Baseline in The Brief Psychiatric Rating Scale for Children (BPRS-C) Total Score at Endpoint (Week-26) of The Open-label Period
timeFrame: At open-label baseline and endpoint (Week-26) of the open-label period
measure: Change From Randomized Withdrawal Baseline in BPRS-C Total Score at Endpoint of The Randomized Withdrawal Period
timeFrame: Baseline of the randomized withdrawal period and its relevant endpoint (Up to 6 weeks)
Other outcomes:
measure: Percent of Participants With CGI-S at Open-label Baseline
timeFrame: Open-label baseline
measure: Percent of Participants With CGI-S at Randomized Withdrawal Baseline
timeFrame: Randomized withdrawal baseline
measure: Columbia-Suicide Severity Rating Scale (C-SSRS) During The Open-label Period
timeFrame: From open-label baseline to Week-26
measure: C-SSRS During the Randomized Withdrawal Period
timeFrame: Baseline of the randomized withdrawal period to end of the study (Up to 6 weeks)
Locations:
city: Rolling Hills Estates
country: United States
facility: Peninsula Research Associates, Inc.
state: California
city: South Miami
country: United States
facility: Miami Research Associates
state: Florida
city: Overland Park
country: United States
facility: Vince and Associates Clinical Research
state: Kansas
city: Memphis
country: United States
facility: CNS Healthcare
state: Tennessee
city: Hoboken
country: Belgium
facility: ZNA Antwerpen, Commandant Weynsstraat 165
state: Antwerpen
city: Leuven
country: Belgium
facility: Afdeling Psychiatrie, UZ Herestraat 49
state: Flemish Brabant
city: Ghent
country: Belgium
facility: Universitair Ziekenhuis Gent, Kinder - en Jeugdpsychiatrie
state: Oost-vlaanderen
city: Paris
country: France
facility: Hôpital Robert Debré
state: Ile-de-france
city: Montpellier Cedex 05
country: France
facility: Hôpital Gui de Chauliac
city: Nice Cedex 03
country: France
facility: Hospital Archet 2
city: Freiburg
country: Germany
facility: Albert-Ludwigs-Universitat Freiburg
state: Baden-wuttemberg
city: Mannheim
country: Germany
facility: Zentralinstitut für Seelische Gesundheit Mannheim
state: Baden-wuttemberg
city: Bamberg
country: Germany
facility: Schwerpunktpraxis für Entwicklung und Lernen
state: Bayern
city: Würzburg
country: Germany
facility: Medizinisches Studienzentrum Würzburg
state: Bayern
city: Würzburg
country: Germany
facility: Universität Würzburg
state: Bayern
city: Bad Nauheim
country: Germany
facility: Institutsambulanz Bad Nauheim
state: Hessen
city: Göttingen
country: Germany
facility: Universitat Göttingen
state: Niedersachsen
city: Köln
country: Germany
facility: Universität zu Köln, Klinik und Poliklinik für Psychiatrie und Psychotherapie des Kindes und Jugendalters
state: Nordrhein-westfalen
city: Mainz
country: Germany
facility: Klinikum der Johannes Gutenberg-Universität Mainz
state: Rheinland-pfalz
city: Berlin
country: Germany
facility: Universitätsmedizin Berlin
city: Fulda
country: Germany
facility: Praxis Dr. Walter Robert Otto
city: Hagen
country: Germany
facility: Praxis Dr. Wolff
city: Hamburg
country: Germany
facility: Praxis für Neuropädiatrie
city: Hamburg
country: Germany
facility: Praxis Dr med. Friedrich Kaiser und Dr. med. Ingrid Marinesse
city: Marburg
country: Germany
facility: Universitätsklinikum Gießen und Marburg GmbH, Universitätsklinikum Gießen und Marburg GmbH, Hans-Sachs-Straße 4,
city: Budapest
country: Hungary
facility: Vadaskert Kórház és Szakambulancia
city: Gyula
country: Hungary
facility: Pándy Kálmán Kórház
city: Pécs
country: Hungary
facility: Gyermek és Ifjúságpszichiátriai Szakrendelés és Gondozó
city: Szeged
country: Hungary
facility: Szegedi Tudományegyetem
city: Bari
country: Italy
facility: Azienda Ospedaliera Policlinico Consorziale
city: Cagliari
country: Italy
facility: Università degli Studi di Cagliari
city: Messina
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico G. Martino
city: Napoli
country: Italy
facility: Azienda Ospedaliera della 2? Universita di Napoli
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki im. dr. Antoniego Jurasza w Bydgoszczy
state: Kujawsko-pomorskie
city: Torun
country: Poland
facility: Wojewódzki Osrodek Lecznictwa Psychiatrycznego
state: Kujawsko-pomorskie
city: Warszawa
country: Poland
facility: Samodzielny Publiczny Dzieciecy Szpital Kliniczny, Poradnia Psychiatryczna, ul. Marszalkowska 24,
state: Mazowieckie
city: Gdansk
country: Poland
facility: Gdanski Uniwersytet Medyczna w Gdansku
state: Pomorskie
city: Poznan
country: Poland
facility: Specjalistyczna Praktyka Lekarska
state: Wielkopolskie
city: Goteborg
country: Sweden
facility: Drottning Silvias Barnsjukhus, Otterhällegatan 12A
city: Mariestad
country: Sweden
facility: Utvecklingsneurologiska Enheten (UNE)
city: Stockholm
country: Sweden
facility: Astrid Lindgren Children's Hospital, Karolinska University Hospital
city: Stockholm
country: Sweden
facility: Barn och Ungdomsmedicin klinik Mölnlycke
city: Birmingham
country: United Kingdom
facility: Parkview Clinic
state: England
city: Ramsgate
country: United Kingdom
facility: East Kent NHS and Social Care Partnership Trust
state: England
city: Southend-on-Sea
country: United Kingdom
facility: Lighthouse Child Development Centre
state: Essex
city: Kirkcaldy
country: United Kingdom
facility: Victoria Hospital, Paediatric Unit
state: Fife
city: Dundee
country: United Kingdom
facility: Tayside Children's Hospital
state: Scotland
city: Sheffield
country: United Kingdom
facility: Ryegate Children's Centre
state: Yorkshire
city: Basildon
country: United Kingdom
facility: Basildon Hospital - Child Development Centre,
city: Northampton
country: United Kingdom
facility: Northampton Child and Adolescent Mental Health Services
city: Wigan
country: United Kingdom
facility: Child and Family Mental Health Services
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Banaschewski T, Johnson M, Lecendreux M, Zuddas A, Adeyi B, Hodgkins P, Squires LA, Coghill DR. Health-related quality of life and functional outcomes from a randomized-withdrawal study of long-term lisdexamfetamine dimesylate treatment in children and adolescents with attention-deficit/hyperactivity disorder. CNS Drugs. 2014 Dec;28(12):1191-203. doi: 10.1007/s40263-014-0193-z.
citation: Coghill DR, Banaschewski T, Lecendreux M, Johnson M, Zuddas A, Anderson CS, Civil R, Dauphin M, Higgins N, Lyne A, Gasior M, Squires LA. Maintenance of efficacy of lisdexamfetamine dimesylate in children and adolescents with attention-deficit/hyperactivity disorder: randomized-withdrawal study design. J Am Acad Child Adolesc Psychiatry. 2014 Jun;53(6):647-657.e1. doi: 10.1016/j.jaac.2014.01.017. Epub 2014 Mar 4.