Shire plc presented positive top-level results of their first European phase III study of lisdexamfetamine dimesylate (LDX), designed for children and adolescents aged 6 to 17 years with Attention-Deficit/Hyperactivity Disorder (ADHD). LDX is administered once daily and is the first chemically formulated long-acting, prodrug of dexamfetamine for treating ADHD. It is currently only licensed in the US, Brazil and Canada.
Results of the phase III study demonstrated LDXs efficacy on the primary and key secondary measures compared with placebo, as well as a consistent safety profile with the known effects of amphetamine treatment and previous LDX trials.
Dr Jeffrey Jonas, Senior Vice President of Research and Development for Shire’s Specialty Pharmaceuticals business stated:
“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. 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 Marketing Authorization Application filing.”
The clinical trial was a phase III, double blind, multi-center, parallel group, placebo- and active controlled, dose-optimisation, safety and efficacy study of lisdexamfetamine dimesylate that was carried out across 48 sites in Europe (Belgium, France, Germany, Hungary, Italy, Netherlands, Poland, Spain, Sweden and the UK).
In the randomized, seven-week long study, 336 patients with ADHD aged between 6 to 17 years, received either LDX, osmotic-controlled extended-release methylphenidate (OROS-MPH**) or placebo in a 1:1:1 ratio once per day in the morning. The dosage was 30, 50, and 70mg/day for LDX and 18, 36, and 54mg for OROS-MPH (54 mg being the highest strength available in Europe).
Researchers defined moderately symptomatic ADHD as having a baseline ADHD-RS-IV total score of ≥ 28. The ADHD-RS-IV reflects current symptomatology of ADHD based on criteria set in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Series (DSM-IV). Scores range from 0 (reflecting no symptoms) to 54 (reflecting severe symptoms).
In order to provide data on a current standard therapy for ADHD in Europe, researchers included the OROS-MPH active reference treatment arm. The primary comparison was LDX vs. placebo without planning on formal comparisons between LDX and OROS-MPH. The following exclusion criteria was included in the study, but not limited to: symptoms, which may have contraindicated LDX and/or OROS-MPH therapy like a history of drug abuse; substantial symptoms as a result of comorbid psychiatric diagnosis; history of serious cardiac abnormalities; and intolerance or hypersensitivity to amfetamine and/or methylphenidate.
The primary measure was determined as a change in the overall score of the ADHD-RS-IV of LDX compared with placebo.
At baseline, the ADHD-RS-IV total score was 40.7 for patients who received LDX, 41.0 for those on placebo, and 40.5 for participants taking OROS-MPH. At study endpoint, the total score was 16.0 for patients in the LDX group, 34.8 for the placebo group, and 21.7 for OROS-MPH group. The difference was statistically significant (p
Written by Petra Rattue