Double-blind, Placebo-controlled, Randomised Withdrawal, Extension, Safety and Efficacy Study of LDX in Children and Adolescents Aged 6-17

NCT00784654 | Completed Phase 3 Results

• 2 other identifiers: SPD489-3262008-000720-10
• Study Type: interventional
• Target: 276
• Locations: 9 countries
• Sites: 51

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

Conditions

ADHD

Outcome Measures

Primary Outcomes (1)

• Percent of Participants With Treatment Failures at End of The Randomized Withdrawal Period

  Treatment failure defined as 50% increase (worsening) in Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS-IV) total score and \>= 2 point increase (worsening) in the Clinical Global Impression-Severity of Illness (CGI-S) score observed at any visit during the randomized withdrawal period compared to the respective scores at baseline of randomized withdrawal period. Subjects without an endpoint value were classed as treatment failures.

  Baseline of the randomized withdrawal period and its relevant endpoint (Up to 6 weeks)

Secondary Outcomes (13)

• 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

  Open-label baseline and Endpoint (Week-26)

• Change From Randomized Withdrawal Baseline in The ADHD-RS-IV Total Score at Endpoint of The Randomized Withdrawal Period

  Baseline of the randomized withdrawal period and its relevant endpoint (Up to 6 weeks)

• Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at Endpoint (Week-26) of The Open-label Period

  At Week 26

• Percent of Participants With CGI-S at Endpoint of The Randomized Withdrawal Period, Last Observation Carried Forward (LOCF)

  At endpoint of the randomized withdrawal period (Up to 6 weeks)

• Percent of Participants With Improvement on Clinical Global Impression - Improvement (CGI-I) at Endpoint (Week-26) of The Open-label Period

  At Week 26

Other Outcomes (4)

• Percent of Participants With CGI-S at Open-label Baseline

  Open-label baseline

• Percent of Participants With CGI-S at Randomized Withdrawal Baseline

  Randomized withdrawal baseline

• Columbia-Suicide Severity Rating Scale (C-SSRS) During The Open-label Period

  From open-label baseline to Week-26

Study Arms (2)

Lisdexamfetamine dimesylate (LDX)

EXPERIMENTAL

Open-label 30, 50, or 70mg

Drug: Lisdexamfetamine dimesylate (LDX)

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Lisdexamfetamine dimesylate (LDX) DRUG

LDX 30, 50, or 70mg capsule once per day (open-label and double-blind periods)

Also known as: Vyvanse, SPD489

Lisdexamfetamine dimesylate (LDX)

Placebo DRUG

Placebo capsule once per day (double-blind period)

Placebo

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.
• 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.
• Subject is a male or female aged 6-17 years inclusive at the time of consent for the antecedent study (SPD489-325).
• 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.
• 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.
• Subject has blood pressure measurements within the 95th percentile for age, gender, and height.

You may not qualify if:

• Subject was terminated from SPD489-325 for non-compliance and/or experienced an SAE or AE resulting in termination from the antecedent study.
• 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).
• 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.
• 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.
• Subject is female and is pregnant or lactating.
• Subject has glaucoma.
• 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).
• Subject has a documented allergy, hypersensitivity, or intolerance to amphetamine.
• 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.
• 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.
• 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.
• Subject has a known family history of sudden cardiac death or ventricular arrhythmia.
• Subject is taking any medication that is excluded.
• Subject has a documented allergy, hypersensitivity, or intolerance to any excipients in the investigational medicinal product(s).

Sponsors & Collaborators

• Shire: lead

Study Sites (51)

Peninsula Research Associates, Inc.

Rolling Hills Estates, California, 66212, United States

Location

Miami Research Associates

South Miami, Florida, 47802, United States

Location

Vince and Associates Clinical Research

Overland Park, Kansas, 23112, United States

Location

CNS Healthcare

Memphis, Tennessee, 38119, United States

Location

ZNA Antwerpen, Commandant Weynsstraat 165

Hoboken, Antwerpen, 2660, Belgium

Location

Afdeling Psychiatrie, UZ Herestraat 49

Leuven, Flemish Brabant, B-3000, Belgium

Location

Universitair Ziekenhuis Gent, Kinder - en Jeugdpsychiatrie

Ghent, Oost-vlaanderen, 9000, Belgium

Location

Hôpital Gui de Chauliac

Montpellier, 34295, France

Location

Hospital Archet 2

Nice, 06202, France

Location

Hôpital Robert Debré

Paris, Île-de-France Region, 75019, France

Location

Albert-Ludwigs-Universitat Freiburg

Freiburg im Breisgau, Baden-wuttemberg, 79104, Germany

Location

Zentralinstitut für Seelische Gesundheit Mannheim

Mannheim, Baden-wuttemberg, 68159, Germany

Location

Schwerpunktpraxis für Entwicklung und Lernen

Bamberg, Bavaria, 96047, Germany

Location

Medizinisches Studienzentrum Würzburg

Würzburg, Bavaria, 97070, Germany

Location

Universität Würzburg

Würzburg, Bavaria, 97080, Germany

Location

Institutsambulanz Bad Nauheim

Bad Nauheim, Hesse, 61231, Germany

Location

Universitat Göttingen

Göttingen, Lower Saxony, 37075, Germany

Location

Universität zu Köln, Klinik und Poliklinik für Psychiatrie und Psychotherapie des Kindes und Jugendalters

Cologne, North Rhine-Westphalia, 50931, Germany

Location

Klinikum der Johannes Gutenberg-Universität Mainz

Mainz, Rhineland-Palatinate, 55131, Germany

Location

Universitätsmedizin Berlin

Berlin, 13353, Germany

Location

Praxis Dr. Walter Robert Otto

Fulda, 36037, Germany

Location

Praxis Dr. Wolff

Hagen, 58093, Germany

Location

Praxis für Neuropädiatrie

Hamburg, 22767, Germany

Location

Praxis Dr med. Friedrich Kaiser und Dr. med. Ingrid Marinesse

Hamburg, D-22415, Germany

Location

Universitätsklinikum Gießen und Marburg GmbH, Universitätsklinikum Gießen und Marburg GmbH, Hans-Sachs-Straße 4,

Marburg, 35039, Germany

Location

Vadaskert Kórház és Szakambulancia

Budapest, 1021, Hungary

Location

Pándy Kálmán Kórház

Gyula, 5700, Hungary

Location

Gyermek és Ifjúságpszichiátriai Szakrendelés és Gondozó

Pécs, 7632, Hungary

Location

Szegedi Tudományegyetem

Szeged, 6750, Hungary

Location

Azienda Ospedaliera Policlinico Consorziale

Bari, 70124, Italy

Location

Università degli Studi di Cagliari

Cagliari, 9124, Italy

Location

Azienda Ospedaliera Universitaria Policlinico G. Martino

Messina, 98125, Italy

Location

Azienda Ospedaliera della 2? Universita di Napoli

Napoli, 80131, Italy

Location

Specjalistyczna Praktyka Lekarska

Poznan, Greater Poland Voivodeship, 60-792, Poland

Location

Szpital Uniwersytecki im. dr. Antoniego Jurasza w Bydgoszczy

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-094, Poland

Location

Wojewódzki Osrodek Lecznictwa Psychiatrycznego

Torun, Kuyavian-Pomeranian Voivodeship, 87-100, Poland

Location

Samodzielny Publiczny Dzieciecy Szpital Kliniczny, Poradnia Psychiatryczna, ul. Marszalkowska 24,

Warsaw, Masovian Voivodeship, 00-576, Poland

Location

Gdanski Uniwersytet Medyczna w Gdansku

Gdansk, Pomeranian Voivodeship, 80-282, Poland

Location

Drottning Silvias Barnsjukhus, Otterhällegatan 12A

Gothenburg, 41119, Sweden

Location

Utvecklingsneurologiska Enheten (UNE)

Mariestad, 542 24, Sweden

Location

Astrid Lindgren Children's Hospital, Karolinska University Hospital

Stockholm, 171 76, Sweden

Location

Barn och Ungdomsmedicin klinik Mölnlycke

Stockholm, 435 30, Sweden

Location

Parkview Clinic

Birmingham, England, B13 8QE, United Kingdom

Location

East Kent NHS and Social Care Partnership Trust

Ramsgate, England, CT11 9DH, United Kingdom

Location

Lighthouse Child Development Centre

Southend-on-Sea, Essex, SS2 6XT, United Kingdom

Location

Victoria Hospital, Paediatric Unit

Kirkcaldy, FIFE, KY2 5AH, United Kingdom

Location

Tayside Children's Hospital

Dundee, Scotland, DD1 9SY, United Kingdom

Location

Ryegate Children's Centre

Sheffield, Yorkshire, S10 5DD, United Kingdom

Location

Basildon Hospital - Child Development Centre,

Basildon, SS16 5NL, United Kingdom

Location

Northampton Child and Adolescent Mental Health Services

Northampton, NN1 2BG, United Kingdom

Location

Child and Family Mental Health Services

Wigan, WN2 2JA, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 25139785 DERIVED

• 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.

  PMID: 24839883 DERIVED

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity

Interventions

Lisdexamfetamine Dimesylate

Condition Hierarchy (Ancestors)

Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Dextroamphetamine; Amphetamine; Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2008
• First Posted: November 4, 2008
• Study Start: January 27, 2009
• Primary Completion: October 26, 2011
• Study Completion: October 26, 2011
• Last Updated: June 9, 2021
• Results First Posted: October 2, 2012

Record last verified: 2021-05

Locations

BE (3); IT (4); SE (4); PL (5); GB (9); US (4); DE (15); HU (4); FR (3)