Date: 2014-07-17
Type of information: Results
phase: 4
Announcement: results
Company: Shire (UK-USA)
Product: 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: CNS diseases - Mental diseases
Country:
Trial
details: Study SPD489-405: The Phase 4, randomized, double-blind, multicenter, parallel-group, active-controlled, dose-optimization efficacy and safety study with a placebo reference arm was designed to evaluate the efficacy of Vyvanse® compared with Concerta® in adolescents (13-17 years of age) with ADHD based on DSM-IV-TR criteria (N=459 treated patients). The primary efficacy outcome was defined as the change from baseline at Week 8 (Visit 8) in the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) total score. Patients were randomized to Vyvanse®, Concert®a, or placebo, respectively, and treated for 8 weeks to evaluate safety and efficacy, followed by a 1-week safety follow-up period. At the end of the dose optimization period, 8.2%, 27.2%, and 52.2% of treated patients were receiving Vyvanse® doses of 30, 50, and 70mg, respectively. At the end of the dose optimization period, 5.4%, 18.5%, 22.3%, and 46.2% of treated patients were receiving Concerta® doses of 18, 36, 54, and 72mg, respectively. Baseline ADHD-RS-IV total scores were 36.6, 37.8, and 38.2 for Vyvans®e, Concerta®, and placebo, respectively. Study SPD489-406: The Phase 4, randomized, double-blind, multicenter, parallel-group, active-controlled, forced-dose titration efficacy and safety study with a placebo reference arm was designed to evaluate the efficacy of Vyvanse® compared with Concerta® in adolescents (13-17 years of age) with ADHD based on DSM-IV-TR criteria (N=547 treated patients). The primary efficacy outcome was defined as the change from baseline at Week 6 (Visit 6) in the ADHD-RS-IV total score. Patients were randomized to Vyvanse®, Concerta®, or placebo, respectively, and treated for 6 weeks to evaluate safety and efficacy, followed by a 1-week safety follow-up period. The doses evaluated in this study were Vyvanse® 70mg and Concerta® 72mg daily. Baseline ADHD-RS-IV total scores were 37.3, 37.0, and 36.1 for Vyvanse®, Concerta®, and placebo, respectively.
Latest
news: * On July 17, 2014, Shire announced top-line results from two Phase 4 efficacy and safety studies of Vyvanse® (lisdexamfetamine dimesylate) compared with Concerta® (methylphenidate HCl) with a placebo reference arm in adolescents aged 13-17 diagnosed with Attention-Deficit/Hyperactivity Disorder (ADHD). In SPD489-405, the dose optimization study, neither Vyvanse® nor Concerta® was found to be statistically superior to the other on the primary efficacy analysis (p = 0.0717), with a larger mean improvement found for Vyvanse® than Concerta® (mean reductions on the ADHD-RS-IV total score of 25.6 and 23.5 points, respectively). The primary efficacy endpoint for both studies was defined as the change from baseline in ADHD-RS-IV total score at Week 6 and Week 8, respectively. In both studies, the types of adverse events appear to be generally consistent with the known safety profile for Vyvanse® established in studies of adolescents with ADHD. At the end of the study [Week 8 (Visit 8)], patients treated with Vyvanse® experienced a mean 25.6 point reduction in ADHD-RS-IV total score compared with a 23.5 point reduction for Concerta®, and a 13.4 point reduction for placebo. While not statistically significant (p = 0.0717), Vyvanse® was found to have a larger mean reduction (improvement) of 2.1 points compared to Concerta on the primary efficacy analysis. Shire plans to submit the efficacy and safety data from the two studies for presentation at a future scientific congress.
In SPD489-406, the forced-dose titration study, Vyvanse® was found to be statistically superior to Concerta® on the primary efficacy analysis (p = 0.0013) with mean reductions on the ADHD RS-IV total score of 25.4 and 22.1 points, respectively. At the end of the study [Week 6 (Visit 6)], patients treated with Vyvanse® experienced a mean 25.4 point reduction in ADHD-RS-IV total score compared with a 22.1 point reduction for Concerta®, and a 17.0 point reduction for placebo. Vyvanse® was found to be statistically superior to Concerta® (p = 0.0013) on the primary efficacy analysis, with an improvement of 3.4 points compared to Concerta® on the ADHD-RS-IV total score. In this study, 1 patient treated with Vyvanse®, 1 patient treated with Concerta®, and 1 patient treated with placebo experienced serious adverse events (SAEs). Sixteen (16) patients on Vyvanse®, 15 patients on Concerta®, and 1 patient on placebo had TEAEs that led to study discontinuation. The most commonly reported (>=5% of patients) TEAEs in patients taking Vyvanse included decreased appetite, headache, weight decreased, insomnia, dry mouth, dizziness, irritability, nausea, and upper abdominal pain. The most commonly reported (>=5% of patients) TEAEs in patients taking Concerta included decreased appetite, headache, insomnia, irritability, weight decreased, dizziness, nausea, and nasopharyngitis. There were no deaths in this study.
Safety and tolerability evaluations of Vyvanse® and Concerta® included treatment-emergent adverse events (TEAEs), vital signs, and weight. Exclusion criteria included a known history of cardiovascular disease, clinically significant ECG, blood pressure exceeding the 90th percentile for age, sex and height, current psychiatric diagnosis and a history of substance abuse or dependence.
In this study, 1 patient treated with Vyvanse®, 1 patient treated with Concerta®, and no patients treated with placebo experienced serious adverse events (SAEs). Fourteen (14) patients on Vyvanse, 3 patients on Concerta, and 3 patients on placebo had TEAEs that led to study discontinuation. The most commonly reported (>=5% of patients) TEAEs in patients taking Vyvanse® included decreased appetite, weight decreased, irritability, headache, insomnia, initial insomnia, dry mouth, nausea, upper abdominal pain, dizziness, nasopharyngitis, somnolence, fatigue, anxiety, and upper respiratory tract infection. The most commonly reported (>=5% of patients) TEAEs in patients taking Concerta included decreased appetite, weight decreased, headache, insomnia, nausea, irritability, nasopharyngitis, initial insomnia, dry mouth, heart rate increased, and upper abdominal pain. There were no deaths in this study. Further evaluation of the efficacy and safety information is currently under way.
Further evaluation of the efficacy and safety information is currently under way.
