A Multi-Center, Open Label, Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With Attention Deficit Hyperactivity Disorder and Autism Spectrum Disorder

RES 16-002

The purpose of this study is to evaluate the effect and safety of Lisdexamfetamine dimesylate (Vyvanse®) in the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in children and adolescents with ADHD and comorbid Autism Spectrum Disorder (ASD). This would be a novel study as there is no known safety or efficacy data for amphetamine based medications in this population. In addition, although health related quality of life and executive function are known to improve with the treatment of lisdexamfetamine dimesylate in the ADHD population (Banaschewski 2013; Findling 2009; Turgay 2010), it has not been shown in the co-morbid ADHD and ASD population. ADHD is the most common pediatric neurobiological condition affecting approximately five percent of the pediatric population (Feldman 2009). ASD is being increasingly recognized as affecting a substantial amount of the pediatric population, with recent prevalence data showing 1 in 68 affected (Baio, 2014). Prior to the introduction of DSM-5 (APA, 2013), exclusion criteria precluded the diagnosis of ADHD when ASD was present. Studies have shown that 41%-71% of children with ASD also meet criteria for ADHD (Goldstein 2004, Sturm 2004,Yoshida 2004, Gadow 2006). This means that up to 1% of the population may have co-morbid ADHD and ASD. With the official recognition of this comorbidity, treatment of comorbid ADHD when ASD is also present has been increasingly recognized as an important strategy in improving executive functioning and quality of life in those affected. Studies have indicated that some of the medications commonly used to treat ADHD, are effective and safe when used in comorbid ADHD and ASD. At this time, there have been well designed studies demonstrating safety and efficacy for methylphenidate (Ghuman et al. 2009; Handen et al. 2000; Quintana et al. 1995; RUPP 2005), guanfacine XR (Posey 2004; Scahill 2015), and atomoxetine (Arnold 2006; Harfterkamp 2012).

2018-09-26

2023-03-31

2023-03-31

Completed

Early phase I

48

Inclusion Criteria: 1. Male or female subject aged 6-12 years at the time of consent/assent. 2. Subjects parent(s) or legally authorized representative (LAR) must provide signature of informed consent, and there must be documentation of assent (if applicable) by the subject in accordance with the International Council on Harmonisation (ICH) Good Clinical Practice (GCP) Guideline E6 (1996), any updates or revisions, and applicable regulations, before completing any study related procedures. 3. Subject and parent(s)/LAR are willing and able to comply with all of the requirements defined in the protocol. 4. Subject meets Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-V) criteria for a diagnosis of ADHD combined presentation, inattentive presentation or hyperactive/impulsive presentation based on history and a minimum ADHD-RS score of 32 and a minimum CGI-S of 4 at baseline. 5. Subject meets DSM-V criteria for a diagnosis of ASD-level 1 based on history and Autism Diagnostic Observation Scale (ADOS-2). 6. Subject has an SRS-2 total score of ≥ 70. 7. Subject has a Clinical Global Impressions - Severity of Illness (CGI-S) score ≥ 4 at the baseline visit (visit 2) 8. Subject has a blood pressure measurement within 95th percentile for age, and sex (Appendix 1,1.1,2 \& 2.2). Subject and parent/legally authorized representative (LAR) are willing, able and likely to comply with the study procedures and restrictions within the protocol. Exclusion Criteria: 1. Subject has any condition that, in the opinion of the investigator, represent an inappropriate risk to the subject or may confound the interpretation of the study. 2. Subject has a known history or presence of structural cardiac abnormalities, cardiovascular or cerebrovascular disease, serious heart rhythm abnormalities, syncope, tachycardia, cardiac conduction problems (such as clinically significant heart block or QT interval prolongation), exercise-related cardiac events including syncope and pre-syncope or clinically significant bradycardia. 3. Subject has a known history of symptomatic cardiovascular disease, unexplained syncope, exertional chest pain, advanced arteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease or other serious cardiac problems placing them at increased vulnerability to sympathomimetic effects of a stimulant drug. 4. Subject has a history of seizure disorder (other than a single childhood febrile seizure occurring before the age of 3 years). 5. Subject has glaucoma. 6. Subject is currently using prohibited medication. 7. Subject has a known or suspected allergy, hypersensitivity, or clinically significant intolerance to LDX. 8. Subject has taken another investigational product within 30 day prior to baseline. 9. Subject has initiated behavioural therapy within 1 month of the baseline visit (visit 0). Subject may not initiate behavioural therapy during the study. 10. Subject is female and is pregnant or currently lactating. 11. 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 suicide ideation. Subjects with intermittent passive suicidal ideation are not necessarily excluded based on the assessment of the investigator. 12. History of failure to respond to an adequate trial of an amphetamine based medication. 13. Subject is currently abusing an illicit substance or lives with someone known to currently abuse stimulants or cocaine.. 14. Subject has a known renal or hepatic insufficiency.

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2024-02-12