Clinical trial NCT01328756: Lisdexamfetamine Dimesylate 2-year Safety Study in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder (ADHD)
Official title: A Phase 4, Open-Label, Multicentre, Safety Study of Lisdexamfetamine Dimesylate in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder (ADHD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Attention Deficit Hyperactivity Disorder (ADHD)
Keywords: ADHD
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2011-04-05
Enrollment: 314
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.


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.

Primary outcomes:
measure: Number of Participants With All Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
timeFrame: Baseline up to 3 days after the last dose of study treatment (up to 2 years)
measure: Change From Baseline in Pulse Rate at Last On-treatment Assessment (LOTA)
timeFrame: Baseline (Week 0), LOTA (Week 104)
measure: Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Last On-treatment Assessment (LOTA)
timeFrame: Baseline (Week 0), LOTA (Week 104)
measure: Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Last On-treatment Assessment (LOTA)
timeFrame: Baseline (Week 0), LOTA (Week 104)
measure: Change From Baseline in Body Weight at Last On-treatment Assessment (LOTA)
timeFrame: Baseline (Week 0), LOTA (Week 104)
measure: Change From Baseline in Height at Last On-treatment Assessment (LOTA)
timeFrame: Baseline (Week 0), LOTA (Week 104)
measure: Change From Baseline in Body Mass Index (BMI) at Last On-treatment Assessment (LOTA)
timeFrame: Baseline (Week 0), LOTA (Week 104)
measure: Change From Baseline in Heart Rate at Last On-treatment Assessment (LOTA)
timeFrame: Baseline (Week 0), LOTA (Week 104)
measure: Change From Baseline in QT Interval at Last On-treatment Assessment (LOTA)
timeFrame: Baseline (Week 0), LOTA (Week 104)
measure: Change From Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF) at Last On-treatment Assessment (LOTA)
timeFrame: Baseline (Week 0), LOTA (Week 104)
measure: Change From Baseline in Brief Psychiatric Rating Scale for Children (BPRSC) Total Scores at Last On-treatment Assessment (LOTA)
timeFrame: Baseline (Week 0), LOTA (Week 104)
Secondary outcomes:
measure: Change From Baseline in the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) Total Score at Last On-treatment Assessment (LOTA)
timeFrame: Baseline (Week 0), LOTA (Week 104)
measure: Number of Participants With Clinical Global Impression-Global Improvement (CGI-I) at Last On-treatment Assessment (LOTA)
timeFrame: LOTA (Week 104)
measure: Number of Participants With Clinical Global Impression-Severity of Illness (CGI-S) at Last On-treatment Assessment (LOTA)
timeFrame: LOTA (Week 104)
Other outcomes:
Locations:
city: Hoboken
country: Belgium
facility: ZNA Antwerpen, Commandant Weynsstraat 165 Campus Hoge Beuken
state: Antwerp
city: Leuven
country: Belgium
facility: Afdeling Psychiatrie
city: Freiburg
country: Germany
facility: Albert-Ludwigs-Universität Freiburg
state: Baden-Wuerttemberg
city: Mannheim
country: Germany
facility: Zentralinstitut für Seelische Gesundheit Mannheim
state: Baden-wuerttemberg
city: Bamberg
country: Germany
facility: Schwerpunktpraxis für Entwicklung und Lernen
state: Bayern
city: Wurzburg
country: Germany
facility: Medizinisches Studienzentrum Würzburg
state: Bayern
city: Hagen
country: Germany
facility: Praxis Dr.Christian Wolff
state: Nordrhein-Westfalen
city: Berlin
country: Germany
facility: Universitätsmedizin Berlin
city: Hamburg
country: Germany
facility: Praxis Dr. med. Friedrich Kaiser und Dr. med. Ingrid Marinesse
city: Pecs
country: Hungary
facility: Gyermek es Ifjusagpszichiatriai Szakrendeles es Gondozo Veress E. u. 2.
state: Baranya
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem, Gyermek- es Ifjusagpszichiatriai Osztaly Boldogasszony sgt. 15
state: Csongrad
city: Budapest
country: Hungary
facility: Vadaskert Korhaz es Szakambulancia, Gyermek es Ifjusagpszichiatria Huvosvolgyi ut 116
city: Gyula
country: Hungary
facility: Pandy Kalman Korhaz, Gyermekpszichiatria Semmelweis u.1.
city: Cagliari
country: Italy
facility: Azienda Ospedaliero-Universitaria di Cagliari
city: Messina
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico G. Martino
city: Heerlen
country: Netherlands
facility: Academisch Ziekenhuis Maastricht
state: Limburg
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki im. dr. Antoniego Jurasza w Bydgoszczy
state: Kujawsko-pomorskie
city: Torun
country: Poland
facility: Wojewodzki Osrodek Lecznictwa Psychiatrycznego W Toruniu
state: Kujawsko-pomorskie
city: Warszawa
country: Poland
facility: Samodzielny Publiczny Dzieciecy Szpital Kliniczny
state: Mazowieckie
city: Timisoara
country: Romania
facility: Spitalul Clinic de Urgenta pentru Copii "Louis Turcanu"
state: Timis
city: Bucuresti
country: Romania
facility: Spitalul Clinic de Psihiatrie "Prof. Dr. Alexandru Obregia"
city: Iasi
country: Romania
facility: Spitalul Clinic de Psihiatrie Socola
city: Palma de Mallorca
country: Spain
facility: Hospital Son Llàtzer
state: Baleares
city: Esplugues de Llobregat
country: Spain
facility: Hospital Sant Joan de Deu, Servicio de Psiquiatria Infantil Passeig Sant Joan de Deu, 2 Esplugues de Llobregat
state: Barcelona
city: Terrassa
country: Spain
facility: Mutua de Terrassa, Centro de Salud Mental Cap Rambla Psiquiatria Infantil Placa Doctor Robert, 5
state: Barcelona
city: Torremolinos
country: Spain
facility: Hospital Maritimo de Torremolinos
state: Malaga
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra, Unidad de Psiquiatría Infantil y Adolescente, Dept. de Psiquiatria y Psicologia Medica Avenida Pio XII 36 Apartado 4209 Pamplona
state: Navarra
city: San Cristóbal de la Laguna
country: Spain
facility: Hospital Univeritario de Canarias, Consultas Externas de Psiquiatria Ofra l La Cuesta s/n San Cristobal de la Laguna Laguna Santa Cruz
state: Santa CRUZ DE Tenerife
city: Badajoz
country: Spain
facility: Complejo Hospitalario Universitario de Badajoz
city: Barcelona
country: Spain
facility: Hospital Clinic I Provincial de Barcelona
city: Goteburg
country: Sweden
facility: Child Neuropsychiatry Centre The Queen Silvia Children's Hospita Otterhallegatan 12A
city: Molnlycke
country: Sweden
facility: Barn och Ungdomsmedicin klinik Molnlycke Ekdalavagen 2 Box 9
city: Stockholm
country: Sweden
facility: Paediatric Neurology Children's Hospital in Huddinge
city: Grays
country: United Kingdom
facility: Thurrock Hospital
state: England
city: Dundee
country: United Kingdom
facility: University of Dundee, Centre for Child Health 19 Dudhope Terrace Scotland
state: Scotland
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.