Date: 2011-10-21
Type of information: Results
phase: 3
Announcement: results
Company: Shire (UK-USA)
Product: Venvanse® (US brand name Vyvanse®) 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: Mental diseases - CNS diseases
Country: Belgium, France, Germany, Hungary, Italy, Netherlands, Poland, Spain, Sweden, UK
Trial
details: The clinical trial was a phase III, randomised, double-blind, multicentre, parallel-group, placebo- and active controlled, dose-optimisation, safety and efficacy study of lisdexamfetamine dimesylate in 336 children and adolescents aged 6 to17 with Attention-Deficit/Hyperactivity Disorder (ADHD). The study took place in 48 sites across Europe.Doses were 30, 50, and 70mg/day for LDX and 18, 36, and 54mg for OROS-MPH (54 mg being the highest strength available in Europe). Patients were randomised in a 1:1:1 ratio to a daily morning dose of LDX, OROS-MPH, or placebo.The primary outcome measure was efficacy as measured by the ADHD Rating Scale IV (ADHD-RS-IV). The secondary outcome measures included Clinical Global Impressions-Improvement scale (CGI-I); Conners’ Parent Rating Scale-Revised (CPRS-R); Child Health and Illness Profile, Child Edition: Parent Report Form (CHIP-CE:PRF); the Health Utilities Index-Mark2 (HUI-2); and the Weiss Functional Impairment Rating Scale- Parent (WFIRS-P). Safety assessments included adverse events, vital signs, electrocardiograms, clinical laboratory parameters, physician examination, Brief Psychiatric Rating Scale for Children (BPRS-C) and the Columbia-Suicide Severity Rating Scale (C-SSRS).
Latest
news: Shire plc has presented positive top line results of the first European phase III study of once-daily lisdexamfetamine dimesylate (LDX) in children and adolescents aged 6 to 17 years with Attention-Deficit/Hyperactivity Disorder (ADHD). The study, conducted at 48 sites across Europe, showed that LDX demonstrated efficacy on the primary and key secondary measures compared to placebo, and a safety profile consistent with the known effects of amfetamine treatment and previous LDX trials.In the study, 336 patients were randomised to receive LDX, osmotic-controlled extended-release methylphenidate (OROS-MPH**) or placebo, over a period of seven weeks. The OROS-MPH active reference treatment arm was included to provide data on a current standard therapy for ADHD in Europe. The primary measure was the change in total score of the ADHD-RS-IV of LDX vs. placebo. At baseline, the ADHD-RS-IV total score was 40.7, 41.0, and 40.5 for subjects receiving LDX, placebo, and OROS-MPH respectively. At endpoint, the ADHD-RS-IV total score was 16.0 for LDX, 34.8 for placebo, and 21.7 for OROS-MPH.1 The difference between both active agents and placebo in least-square mean† change from baseline in ADHD-RS-IV total score was statistically significant. (p<0.001). A key secondary efficacy measure was the improvement with LDX vs. placebo with OROS-MPH included as an active control on the Clinical Global Impressions – Global Improvement (CGI–I) scale. Results showed improvement of symptoms from 78% of patients in the LDX group, 14% in the placebo group, and 61% in the OROS-MPH group. Serious adverse events occurred across all treatment groups (LDX, 3; placebo, 3; OROS-MPH, 2); most of them were judged to be unrelated to the treatment. The most common (>10%) treatment-emergent adverse events (TEAEs) reported by patients receiving LDX were decreased appetite, headache, insomnia, weight decreased, nausea, and anorexia. The percentage of subjects who had TEAEs leading to discontinuation across all treatment groups were LDX, 5%; placebo, 4%; and OROS-MPH, 2%. The overall nature, pattern, and incidence of TEAEs were consistent with those reported in other LDX studies in ADHD. The study will support the clinical package for European marketing authorisation application filing. LDX is available as a prescription-only medicine in the USA (brand name VYVANSE® ; approved for the treatment of ADHD in children and adolescents aged 6 to 17 and adults), Canada (brand name VYVANSE® available for use in children and adolescents aged 6 to 17 and adults) and Brazil (VENVANSE™; approved for children aged 6-12 years).
