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

NCT01328756 | Completed Phase 4 Results

• 2 other identifiers: SPD489-4042010-020951-30
• Study Type: interventional
• Target: 314
• Locations: 10 countries
• Sites: 35

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)

Keywords

ADHD

Outcome Measures

Primary Outcomes (11)

• Number of Participants With All Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs

  An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. It included both serious and non-serious adverse event. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs were defined as treatment-emergent if they started or worsened during the period between the day of a participant's first dose of investigational product in this study and the 3 days following cessation of treatment.

  Baseline up to 3 days after the last dose of study treatment (up to 2 years)

• Change From Baseline in Pulse Rate at Last On-treatment Assessment (LOTA)

  Baseline (Week 0), LOTA (Week 104)

• Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Last On-treatment Assessment (LOTA)

  Baseline (Week 0), LOTA (Week 104)

• Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Last On-treatment Assessment (LOTA)

  Baseline (Week 0), LOTA (Week 104)

• Change From Baseline in Body Weight at Last On-treatment Assessment (LOTA)

  Baseline (Week 0), LOTA (Week 104)

• Change From Baseline in Height at Last On-treatment Assessment (LOTA)

  Baseline (Week 0), LOTA (Week 104)

• Change From Baseline in Body Mass Index (BMI) at Last On-treatment Assessment (LOTA)

  BMI was calculated as (weight \[kilogram\] per height \[square meter\]).

  Baseline (Week 0), LOTA (Week 104)

• Change From Baseline in Heart Rate at Last On-treatment Assessment (LOTA)

  Baseline (Week 0), LOTA (Week 104)

• Change From Baseline in QT Interval at Last On-treatment Assessment (LOTA)

  Baseline (Week 0), LOTA (Week 104)

• Change From Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF) at Last On-treatment Assessment (LOTA)

  Baseline (Week 0), LOTA (Week 104)

• Change From Baseline in Brief Psychiatric Rating Scale for Children (BPRSC) Total Scores at Last On-treatment Assessment (LOTA)

  The BPRS-C that was designed to provide a characterization of the child and adolescent psychopathology, was used to monitor participant's safety. The BPRS-C assessed 7 independent factors (3 items each), for a total of 21 items that represented behavioural disorders, depression, thinking disturbance, psychomotor excitation, withdrawal retardation, anxiety, and organicity. Each item was rated using a 7-point scale including 0 (not present), 1 (very mild), 2 (mild), 3 (moderate), 4 (moderately severe), 5 (severe), and 6 (extremely severe). Total score is the sum of each item score; range from 0 to 126. Higher score indicated worse psychology.

  Baseline (Week 0), LOTA (Week 104)

Secondary Outcomes (3)

• Change From Baseline in the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) Total Score at Last On-treatment Assessment (LOTA)

  Baseline (Week 0), LOTA (Week 104)

• Number of Participants With Clinical Global Impression-Global Improvement (CGI-I) at Last On-treatment Assessment (LOTA)

  LOTA (Week 104)

• Number of Participants With Clinical Global Impression-Severity of Illness (CGI-S) at Last On-treatment Assessment (LOTA)

  LOTA (Week 104)

Study Arms (1)

Lisdexamfetamine Dimesylate

EXPERIMENTAL

Drug: Lisdexamfetamine dimesylate

Interventions

Lisdexamfetamine dimesylate DRUG

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

Also known as: Vyvanse, SPD489, LDX

Lisdexamfetamine Dimesylate

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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 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.

Sponsors & Collaborators

• Shire: lead

Study Sites (35)

ZNA Antwerpen, Commandant Weynsstraat 165 Campus Hoge Beuken

Hoboken, Antwerp, 2660, Belgium

Location

Afdeling Psychiatrie

Leuven, B-3000, Belgium

Location

Albert-Ludwigs-Universität Freiburg

Freiburg im Breisgau, Baden-Wurttemberg, 79104, Germany

Location

Zentralinstitut für Seelische Gesundheit Mannheim

Mannheim, Baden-Wurttemberg, 68159, Germany

Location

Schwerpunktpraxis für Entwicklung und Lernen

Bamberg, Bavaria, 96047, Germany

Location

Medizinisches Studienzentrum Würzburg

Würzburg, Bavaria, 97070, Germany

Location

Praxis Dr.Christian Wolff

Hagen, North Rhine-Westphalia, 58093, Germany

Location

Universitätsmedizin Berlin

Berlin, 13353, Germany

Location

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

Hamburg, 22415, Germany

Location

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

Pécs, Baranya, H-7633, Hungary

Location

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

Szeged, Csongrád megye, H-6720, Hungary

Location

Vadaskert Korhaz es Szakambulancia, Gyermek es Ifjusagpszichiatria Huvosvolgyi ut 116

Budapest, H-1021, Hungary

Location

Pandy Kalman Korhaz, Gyermekpszichiatria Semmelweis u.1.

Gyula, H-5700, Hungary

Location

Azienda Ospedaliero-Universitaria di Cagliari

Cagliari, 09124, Italy

Location

Azienda Ospedaliera Universitaria Policlinico G. Martino

Messina, 98125, Italy

Location

Academisch Ziekenhuis Maastricht

Heerlen, Limburg, 6419XZ, Netherlands

Location

Szpital Uniwersytecki im. dr. Antoniego Jurasza w Bydgoszczy

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

Location

Wojewodzki Osrodek Lecznictwa Psychiatrycznego W Toruniu

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

Location

Samodzielny Publiczny Dzieciecy Szpital Kliniczny

Warsaw, Masovian Voivodeship, 00-576, Poland

Location

Spitalul Clinic de Urgenta pentru Copii "Louis Turcanu"

Timișoara, Timiș County, 300011, Romania

Location

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

Bucharest, 41914, Romania

Location

Spitalul Clinic de Psihiatrie Socola

Iași, Romania

Location

Hospital Son Llàtzer

Palma de Mallorca, Balearic Islands, 07198, Spain

Location

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

Esplugues de Llobregat, Barcelona, 08950, Spain

Location

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

Terrassa, Barcelona, 08221, Spain

Location

Hospital Maritimo de Torremolinos

Torremolinos, Malaga, 29620, Spain

Location

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, 31008, Spain

Location

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, 38320, Spain

Location

Complejo Hospitalario Universitario de Badajoz

Badajoz, 06010, Spain

Location

Hospital Clinic I Provincial de Barcelona

Barcelona, 08036, Spain

Location

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

Gothenburg, 41118, Sweden

Location

Barn och Ungdomsmedicin klinik Molnlycke Ekdalavagen 2 Box 9

Mölnlycke, 43530, Sweden

Location

Paediatric Neurology Children's Hospital in Huddinge

Stockholm, 14186, Sweden

Location

Thurrock Hospital

Grays, England, RM16 2PX, United Kingdom

Location

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

Dundee, Scotland, DD3 6HH, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 29790103 DERIVED

• 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.

  PMID: 29383572 DERIVED

• 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.

  PMID: 28667569 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

Limitations and Caveats

Since this study is an open-label trial, results should be interpreted with caution.

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 4
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2011
• First Posted: April 5, 2011
• Study Start: July 7, 2011
• Primary Completion: September 30, 2014
• Study Completion: September 30, 2014
• Last Updated: June 10, 2021
• Results First Posted: August 6, 2015

Record last verified: 2021-05

Locations

GB (2); DE (7); HU (4); NL (1); PL (3); ES (8); SE (3); IT (2); RO (3); BE (2)