Date: 2012-05-23
Type of information: Results
phase: 3
Announcement: results
Company: Shire (UK-USA)
Product: lisdexamfetamine dimesylate
Action
mechanism: CNS stimulant. Lisdexamfetamine dimesylate is a chemically formulated long-acting, prodrug of dextroamphetamine, that belongs to the group of central nervous system stimulants. Amphetamines target the trace amine-associated receptor 1 (TAAR1). Amphetamine is also believed to exert its effects by binding to the monoamine transporters (the dopamine transporter or DAT) and increasing extracellular levels of the biogenic amines dopamine, norepinephrine (noradrenaline) and serotonin.
Disease: Attention-Deficit Hyperactivity Disorder (ADHD)
Therapeutic area: CNS diseases - Mental diseases
Country: Europe USA
Trial
details: The clinical trial was a phase 3, double-blind, placebo-controlled, randomised withdrawal, multicentre, extension study to evaluate the long-term maintenance of efficacy, as well as safety, of lisdexamfetamine dimesylate (LDX) in children and adolescents aged 6 to 17 diagnosed with moderately symptomatic Attention-Deficit/Hyperactivity Disorder (ADHD) (Study SPD489-326). Subjects satisfied all entry criteria to the European phase 3 study of the efficacy and safety of LDX (Study SPD489-325). The primary objective of this study was to evaluate the long-term maintenance of efficacy of LDX, using a composite endpoint based on the ADHD-RS-IV and Clinical Global Impressions – Severity of Illness (CGI-S) rating scale, via a randomised withdrawal design (RWD) in children and adolescents diagnosed with moderately symptomatic ADHD. Children and adolescents were treated with LDX (30, 50, or 70mg/day) for at least 26 weeks prior to entering a 6-week double-blind randomised (LDX at the subject’s open-label fixed dose, or placebo) withdrawal period.1Subjects’ response status must be confirmed in order to be eligible for enrolment into the RWD period. The secondary objectives of this study were to: Assess secondary efficacy outcomes, including the efficacy of LDX through the open-label maintenance period, using the clinician-administered ADHD-RS-IV and a global clinical measure of improvement, the CGI-I. Secondary endpoints of the study were:
The study took place in 37 sites across Europe, including Belgium, France, Germany, Hungary, Italy, Poland, Sweden and the UK; and 4 sites in the US.To ensure that the sample size necessary to assess the primary efficacy measure was met, US children and adolescents (n = 40) were evaluated for direct entry into the study.
Assess the impact of LDX on the perception of health state preferences, health-related quality of life (HRQoL), and the relationship between changes in the core symptoms of ADHD and changes in functional outcomes, using the Health Utilities Index – Mark 2 (HUI-2), the Child Health and Illness Profile, Child Edition: Parent Report Form (CHIP-CE:PRF), and the Weiss Functional Impairment Rating Scale – Parent (WFIRS-P), respectively.
Evaluate the long-term safety of LDX based on the occurrence of treatment-emergent adverse events (TEAEs), specific evaluation of blood pressure and pulse, electrocardiogram (ECG) results, clinical laboratory test results, and physical examination findings.
Monitor subject safety based on responses to the Brief Psychiatric Rating Scale for Children (BPRS-C) and the Columbia-Suicide Severity Rating Scale (C-SSRS).
The primary efficacy endpoint for each subject was treatment failure at the end of the randomised withdrawal period.
The change from baseline of the ADHD-RS-IV at each visit
The CGI-I at each applicable visit
The HUI-2, CHIP-CE:PRF, and WFIRS-P at each applicable visit
Latest
news: * On May 23, 2012, at the EUNETHYDIS 2nd International ADHD Conference, the specialty biopharmaceutical company Shire presented results of the phase 3 study which demonstrated the long-term maintenance of efficacy of lisdexamfetamine dimesylate (LDX) in children and adolescents aged 6 to 17 years with Attention-Deficit/Hyperactivity Disorder (ADHD) (Coghill D, Banaschewski T, Lecendreux M et al. Maintenance of efficacy of lisdexamfetamine dimesylate in children and adolescents with attention-deficit/hyperactivity disorder: randomized-withdrawal design. Poster presented at the EUNETHYDIS 2nd International ADHD conference 23 - 25 May 2012, Barcelona, Spain. 2012). Children and adolescents diagnosed with ADHD were treated with LDX (30, 50 or 70mg/day)1 during an open-label period (comprising dose optimisation, maintenance, and fixed dose periods) of at least 26 weeks before entering a 6-week1 double-blind randomised withdrawal period, where subjects received either LDX or placebo.1 Results showed maintenance of efficacy in children and adolescents who continued to receive LDX, as demonstrated by a significantly lower proportion of ADHD treatment failures (13.5%) in this group, compared with placebo (65.8%); and the majority of placebo-treated subjects who met protocol-defined ADHD symptom relapse criteria did so within 2 weeks following randomisation.1 The overall nature, pattern, and incidence of treatment-emergent adverse events (TEAEs) were also consistent with those reported in other LDX studies in ADHD. This study is a critical element of the European submission package. A European MAA (Marketing Authorisation Application) for LDX was accepted for review in January 2012.
