Shire plc, the global specialty biopharmaceutical company, said the Biological Psychiatry published the results of Vyvanse (lisdexamfetamine dimesylate), the first prodrug stimulant for the treatment of Attention Deficit Hyperactivity Disorder (ADHD), provided significant efficacy in children for up to 12 hours.
The published study also found that Vyvanse demonstrated low interpatient variability of measured pharmacokinetic parameters, as reported by the coefficient of variance (per cent CV).
The phase II randomised, double-blind, placebo- and active-controlled crossover analogue classroom study in children aged 6 to 12 examined the efficacy and safety of Vyvanse (30 mg, 50 mg or 70 mg) and Adderall XR (mixed amphetamine salts extended-release: 10 mg, 20 mg or 30 mg) compared with placebo.
"This newly published research shows that Vyvanse provided a consistent time to maximum plasma concentration from patient to patient," said Ann S. Childress, M.D., president, Center for Psychiatry and Behavioural Medicine, Inc. in Las Vegas. "This prodrug stimulant also demonstrated significant efficacy up to 12 hours after administration, which is something that my patients' parents are interested in as it may help to improve their family and homework time in the evening."
Vyvanse is a therapeutically inactive prodrug in which d-amphetamine is covalently bonded to l-lysine, and after oral ingestion it is converted to pharmacologically active d-amphetamine. Release of the active ingredient in Vyvanse does not rely on gastrointestinal factors such as gastrointestinal transit time and gastric pH.
Vyvanse demonstrated significant efficacy for treatment of ADHD for up to 12 hours post dosing, based on the study's primary efficacy measure, SKAMP-D. Investigators observed a significant difference in patient behaviour based upon the average of investigator ratings on the Swanson, Kotkin, Agler, M-Flynn and Pelham Rating Scale deportment (SKAMP-D) scores across eight classroom sessions held during a 12-hour treatment day between patients who received Vyvanse and patients who received Adderall XR, both compared to placebo. The SKAMP-D is a standardized, validated classroom assessment tool used for evaluating the behavioural symptoms of ADHD and higher SKAMP-D ratings reflect greater impairment.
Patients in the study taking Vyvanse also demonstrated significant improvement in math problems attempted as compared to placebo, as measured by the Permanent Product Measure of Performance (PERMP) Derived Measures. When patients were observed at the 12-hour time period, the LS mean change in PERMP math problems attempted from the first measurement was 49 for patients taking Vyvanse and 22 for patients taking Adderall XR, compared to -24 for placebo. PERMP is an age-adjusted collection of math problems that provides an objective measure of performance based on the number of attempted and completed math problems. This study was not designed as a comparative trial between active treatments.
The majority of adverse events reported in this study were mild to moderate in severity. The most frequently reported adverse events for Vyvanse were insomnia (8 per cent), decreased appetite (6 per cent), anorexia (4 per cent) and upper respiratory tract infection (2 per cent); for Adderall XR they were decreased appetite (4 per cent), upper abdominal pain (4 per cent), insomnia (2 per cent), upper respiratory tract infection (2 per cent) and vomiting (2 per cent).
Vyvanse is currently approved in the United States for the treatment of ADHD in children aged 6 to 12 years.
Approximately 7.8 percent of all school-age children, or about 4.4 million US children aged 4 to 17 years, have been diagnosed with ADHD at some point in their lives, according to the US Centers for Disease Control and Prevention (CDC). ADHD is one of the most common psychiatric disorders in children and adolescents. ADHD is a neurobiological disorder that manifests as a persistent pattern of inattention and/or hyperactivity-impulsivity that is more frequent and severe than is typically observed in individuals at a comparable level of development.
Although there is no cure for ADHD, there are accepted treatments that specifically target its symptoms. The most common standard treatments include educational approaches, psychological or behavioural modification, and medication.
Abuse of amphetamines may lead to dependence. Misuse of amphetamine may cause sudden death and serious cardiovascular adverse events. These events have also been reported rarely with amphetamine use.
Vyvanse was generally well tolerated in clinical studies. The most common side effects reported in studies of Vyvanse were decreased appetite, difficulty falling asleep, stomach-ache, and irritability. Aggression, new abnormal thoughts/behaviours, mania, growth suppression, worsening of motion or verbal tics, and Tourette's syndrome have been associated with use of drugs of this type.
Shire focuses its business on attention deficit and hyperactivity disorder (ADHD), human genetic therapies (HGT), gastrointestinal (GI) and renal diseases. The structure is sufficiently flexible to allow Shire to target new therapeutic areas to the extent opportunities arise through acquisitions.