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Shire plc, the global specialty biopharmaceutical company, today 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)1. LDX is the first chemically formulated long-acting, prodrug of dexamfetamine for treatment of ADHD, and is currently licensed only in the US, Canada and Brazil. 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.1
“The results of this European study show that a once-daily morning dose of LDX was effective in children and adolescents with at least moderately symptomatic ADHD, and are consistent with those of previous studies conducted outside of Europe,” said Dr Jeffrey Jonas, Senior Vice President of Research and Development for Shire’s Specialty Pharmaceuticals business. “These results provide important clinical trial data in support of LDX and its potential role as a new option for the treatment of ADHD in children and adolescents in Europe. The study will support the clinical package for European MAA* filing.”
Moderately symptomatic ADHD is defined as having a baseline ADHD-RS-IV total score = 28. The ADHD-RS-IV is designed to reflect current symptomatology of ADHD based on criteria set in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Series (DSM-IV), with a total score ranging from 0 (reflecting no symptoms) to 54 (reflecting severe symptoms).1
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.1 The primary comparison is LDX vs placebo. Formal comparisons between LDX and OROS-MPH were not planned. Study exclusion criteria included, but were not limited to: significant symptoms resulting from comorbid psychiatric diagnosis; symptoms that may have contraindicated LDX and/or OROS-MPH treatment such as a history of drug abuse; history of serious cardiac abnormalities; and hypersensitivity or intolerance to amfetamine and/or methylphenidate.
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.1
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.
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Home > Investors > Investor News > Shire news
21 Oct 2011
EU study shows once-daily lisdexamfetamine dimesylate (LDX) effective for symptom control in children and adolescents with ADHD
Success of pivotal, phase III trial marks long-acting, prodrug stimulant LDX as potential new treatment option for ADHD in Europe
BASINGSTOKE, UK – October 21, 2011 – Shire plc (LSE: SHP, NASDAQ: SHPGY), the global specialty biopharmaceutical company, today 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)1. LDX is the first chemically formulated long-acting, prodrug of dexamfetamine for treatment of ADHD, and is currently licensed only in the US, Canada and Brazil.1
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.1
“The results of this European study show that a once-daily morning dose of LDX was effective in children and adolescents with at least moderately symptomatic ADHD, and are consistent with those of previous studies conducted outside of Europe,” said Dr Jeffrey Jonas, Senior Vice President of Research and Development for Shire’s Specialty Pharmaceuticals business. “These results provide important clinical trial data in support of LDX and its potential role as a new option for the treatment of ADHD in children and adolescents in Europe. The study will support the clinical package for European MAA* filing.”
Moderately symptomatic ADHD is defined as having a baseline ADHD-RS-IV total score = 28. The ADHD-RS-IV is designed to reflect current symptomatology of ADHD based on criteria set in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Series (DSM-IV), with a total score ranging from 0 (reflecting no symptoms) to 54 (reflecting severe symptoms).1
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.1 The primary comparison is LDX vs placebo. Formal comparisons between LDX and OROS-MPH were not planned. Study exclusion criteria included, but were not limited to: significant symptoms resulting from comorbid psychiatric diagnosis; symptoms that may have contraindicated LDX and/or OROS-MPH treatment such as a history of drug abuse; history of serious cardiac abnormalities; and hypersensitivity or intolerance to amfetamine and/or methylphenidate.
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.1
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.
Further results on the study will be published soon.
* Marketing Authorisation Application
** Marketed as CONCERTA® and CONCERTA®XL by Johnson & Johnson
† “Least square mean” is a statistical way of measuring differences between means.
About the clinical trial
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).
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 study took place in 48 sites across Europe, including Belgium, France, Germany, Hungary, Italy, Netherlands, Poland, Spain, Sweden and the UK. 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)
