Lisdexamfetamine Dimesylate 2-year Safety Study in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder (ADHD)

NCT ID: NCT01328756

Last Updated: 2021-06-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 314 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-07-07
• Study Completion Date: 2014-09-30

Brief Summary

While the Lisdexamfetamine Dimesylate (SPD489) clinical program has studied the efficacy, safety, and tolerability of SPD489 in treating core symptoms of ADHD in children and adolescents aged 6-17 years and adults aged 18-55 years, the majority of these studies have been of short duration - up to 8 weeks.

A number of long-term studies have been undertaken (up to 1 year) and these have confirmed the safety and ongoing efficacy in this patient population.

In order to run a study with investigational medication within Poland the study changed to a Phase 3 rather than a Phase 4 study in that country. Please note that the study number remains as SPD489-404.

Study SPD489-404 has been designed to further evaluate the long-term effects of SPD489 in children and adolescents over a 2-year treatment period.

Conditions

Attention Deficit Hyperactivity Disorder (ADHD)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Lisdexamfetamine Dimesylate

Group Type: EXPERIMENTAL

Lisdexamfetamine dimesylate

Intervention Type: DRUG

Optimized dose of either 30, 50 or 70 mg capsule administered once daily for 2 years

Interventions

Lisdexamfetamine dimesylate

Optimized dose of either 30, 50 or 70 mg capsule administered once daily for 2 years

Intervention Type: DRUG

Other Intervention Names

Vyvanse, SPD489, LDX

Eligibility Criteria

Inclusion Criteria

For subjects who participated in another SPD489 study (SPD489-317, SPD489-325, or SPD489 326):

• Subject is a male or female aged 6-17 years.
• Subject participated in SPD489-317, completed 9 weeks of treatment, and completed the 1 week post-treatment safety follow-up visit.

For subjects who have not participated in another SPD489 study:

• Subject is a male or female aged 6-17 years.
• Subject must meet DSM-IV-TR criteria for a primary diagnosis of ADHD based on a detailed psychiatric evaluation.

For all subjects:

• Subject has a Baseline ADHD-RS-IV total score greater than or equal to 28.
• Subject, who is female of childbearing potential (FOCP), must have a negative serum beta Human Chorionic Gonadotropin (HCG) pregnancy test, and a negative urine pregnancy test at Baseline, be non-lactating and agree to comply with any applicable contraceptive requirements of the protocol.
• Subject and parent/LAR are willing and able to comply with all the testing and requirements defined, including oversight of morning dosing. Specifically, the parent/LAR must be available upon awakening, at approximately 7:00 AM, to dispense the dose of Investigational Product for the duration of the study.
• Subject aged greater than or equal to 18 years has a systolic blood pressure less than or equal to 139 mmHg and a diastolic blood pressure less than or equal to 89 mmHg.
• Subject is able to swallow a capsule.

Exclusion Criteria

For subjects who participated in another SPD489 study (SPD489-317, SPD489-325, or SPD489 326):

• Subject was terminated from a previous SPD489 study (SPD489-325 or SPD489 326) for protocol non-adherence and/or subject non-compliance and/or experienced a medication-related SAE or AE resulting in termination from the previous study.
• Subject experienced any clinically significant AEs in a prior SPD489 study (SPD489 317, SPD489-325, or SPD489-326) that, in the opinion of the Investigator, would preclude further exposure to SPD489.

For all subjects:

• Subject's symptoms are well-controlled on their currently prescribed ADHD medication with acceptable tolerability.
• Subject has a positive urine drug result at Screening.
• 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.
• Subject has taken another Investigational Product or taken part in a clinical study with the exception of a prior SPD489 study (SPD489-317, SPD489 325, or SPD489 326) within 30 days prior to Screening.
• Subject weighs less than 22.7 kg (50 lbs).
• Subject is significantly overweight.
• Subject has a conduct disorder. Oppositional defiant disorder is not exclusionary.
• Subject has a concurrent chronic or acute illness (such as severe allergic rhinitis or an infectious process requiring antibiotics), disability, or other condition that might confound the results of safety assessments conducted in the study or that might increase risk to the subject.
• Subject is currently considered a suicide risk in the opinion of the Investigator, has previously made a suicide attempt, or has a prior history of, or is currently demonstrating active suicidal ideation. Subjects with intermittent passive suicidal ideation are not necessarily excluded based on the assessment of the Investigator
• Subject has glaucoma.
• Subject has current abnormal thyroid function, defined as abnormal thyroid stimulating hormone (TSH) and thyroxine (T4). Treatment with a stable dose of thyroid medication for at least 3 months is permitted.
• Subject has any clinically significant ECG abnormality.
• Subject has any clinically significant laboratory abnormalities.
• Subject has a documented allergy, hypersensitivity, or intolerance to any active ingredient or excipients in SPD489.
• Subject has a recent history (within the past 6 months) of suspected substance abuse or dependence disorder (excluding nicotine) in accordance with DSM-IV-TR criteria.
• Subject has a history of seizures (other than infantile febrile seizures), a chronic or current tic disorder, a current diagnosis of Tourette's Disorder, or a known family history of Tourette's Disorder. Subject has a history of tics that is judged by the Investigator to be exclusionary.
• Subject has a known history of symptomatic cardiovascular or cerebrovascular 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 has a medical condition, other than ADHD, that requires treatment with medications that have central nervous system effects and/or affect performance. Stable use of anticholinergic or theophylline bronchodilators is not exclusionary.

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shire

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

ZNA Antwerpen, Commandant Weynsstraat 165 Campus Hoge Beuken

Hoboken, Antwerp, Belgium

Afdeling Psychiatrie

Leuven, , Belgium

Albert-Ludwigs-Universität Freiburg

Freiburg im Breisgau, Baden-Wurttemberg, Germany

Zentralinstitut für Seelische Gesundheit Mannheim

Mannheim, Baden-Wurttemberg, Germany

Schwerpunktpraxis für Entwicklung und Lernen

Bamberg, Bavaria, Germany

Medizinisches Studienzentrum Würzburg

Würzburg, Bavaria, Germany

Praxis Dr.Christian Wolff

Hagen, North Rhine-Westphalia, Germany

Universitätsmedizin Berlin

Berlin, , Germany

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

Hamburg, , Germany

Gyermek es Ifjusagpszichiatriai Szakrendeles es Gondozo Veress E. u. 2.

Pécs, Baranya, Hungary

Szegedi Tudomanyegyetem, Gyermek- es Ifjusagpszichiatriai Osztaly Boldogasszony sgt. 15

Szeged, Csongrád megye, Hungary

Vadaskert Korhaz es Szakambulancia, Gyermek es Ifjusagpszichiatria Huvosvolgyi ut 116

Budapest, , Hungary

Pandy Kalman Korhaz, Gyermekpszichiatria Semmelweis u.1.

Gyula, , Hungary

Azienda Ospedaliero-Universitaria di Cagliari

Cagliari, , Italy

Azienda Ospedaliera Universitaria Policlinico G. Martino

Messina, , Italy

Academisch Ziekenhuis Maastricht

Heerlen, Limburg, Netherlands

Szpital Uniwersytecki im. dr. Antoniego Jurasza w Bydgoszczy

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland

Wojewodzki Osrodek Lecznictwa Psychiatrycznego W Toruniu

Torun, Kuyavian-Pomeranian Voivodeship, Poland

Samodzielny Publiczny Dzieciecy Szpital Kliniczny

Warsaw, Masovian Voivodeship, Poland

Spitalul Clinic de Urgenta pentru Copii "Louis Turcanu"

Timișoara, Timiș County, Romania

Spitalul Clinic de Psihiatrie "Prof. Dr. Alexandru Obregia"

Bucharest, , Romania

Spitalul Clinic de Psihiatrie Socola

Iași, , Romania

Hospital Son Llàtzer

Palma de Mallorca, Balearic Islands, Spain

Hospital Sant Joan de Deu, Servicio de Psiquiatria Infantil Passeig Sant Joan de Deu, 2 Esplugues de Llobregat

Esplugues de Llobregat, Barcelona, Spain

Mutua de Terrassa, Centro de Salud Mental Cap Rambla Psiquiatria Infantil Placa Doctor Robert, 5

Terrassa, Barcelona, Spain

Hospital Maritimo de Torremolinos

Torremolinos, Malaga, Spain

Clinica Universitaria de Navarra, Unidad de Psiquiatría Infantil y Adolescente, Dept. de Psiquiatria y Psicologia Medica Avenida Pio XII 36 Apartado 4209 Pamplona

Pamplona, Navarre, Spain

Hospital Univeritario de Canarias, Consultas Externas de Psiquiatria Ofra l La Cuesta s/n San Cristobal de la Laguna Laguna Santa Cruz

San Cristóbal de La Laguna, Santa CRUZ DE Tenerife, Spain

Complejo Hospitalario Universitario de Badajoz

Badajoz, , Spain

Hospital Clinic I Provincial de Barcelona

Barcelona, , Spain

Child Neuropsychiatry Centre The Queen Silvia Children's Hospita Otterhallegatan 12A

Gothenburg, , Sweden

Barn och Ungdomsmedicin klinik Molnlycke Ekdalavagen 2 Box 9

Mölnlycke, , Sweden

Paediatric Neurology Children's Hospital in Huddinge

Stockholm, , Sweden

Thurrock Hospital

Grays, England, United Kingdom

University of Dundee, Centre for Child Health 19 Dudhope Terrace Scotland

Dundee, Scotland, United Kingdom

Countries

Belgium; Germany; Hungary; Italy; Netherlands; Poland; Romania; Spain; Sweden; United Kingdom

References

Banaschewski T, Johnson M, Nagy P, Otero IH, Soutullo CA, Yan B, Zuddas A, Coghill DR. Growth and Puberty in a 2-Year Open-Label Study of Lisdexamfetamine Dimesylate in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder. CNS Drugs. 2018 May;32(5):455-467. doi: 10.1007/s40263-018-0514-8.

Reference Type: DERIVED

PMID: 29790103 (View on PubMed)

Coghill DR, Banaschewski T, Bliss C, Robertson B, Zuddas A. Cognitive Function of Children and Adolescents with Attention-Deficit/Hyperactivity Disorder in a 2-Year Open-Label Study of Lisdexamfetamine Dimesylate. CNS Drugs. 2018 Jan;32(1):85-95. doi: 10.1007/s40263-017-0487-z.

Reference Type: DERIVED

PMID: 29383572 (View on PubMed)

Coghill DR, Banaschewski T, Nagy P, Otero IH, Soutullo C, Yan B, Caballero B, Zuddas A. Long-Term Safety and Efficacy of Lisdexamfetamine Dimesylate in Children and Adolescents with ADHD: A Phase IV, 2-Year, Open-Label Study in Europe. CNS Drugs. 2017 Jul;31(7):625-638. doi: 10.1007/s40263-017-0443-y.

Reference Type: DERIVED

PMID: 28667569 (View on PubMed)

Other Identifiers

2010-020951-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

SPD489-404

Identifier Type: -

Identifier Source: org_study_id

NCT01413165

Identifier Type: -

Identifier Source: nct_alias