Date: 2013-11-05
Type of information: Results
phase: 3
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: binge eating disorder
Therapeutic area: CNS diseases - Mental diseases
Country:
Trial
details: Each of the two identically designed pivotal Phase 3, multi-center, randomized, double-blind, parallel-group, placebo-controlled, dose-optimized studies was designed to assess the safety, efficacy, and tolerability of Vyvanse® in patients aged 18 to 55 who met DSM-IV-TR® criteria for a diagnosis of BED.
Study SPD489-343 randomized 383 patients and study SPD489-344 randomized 390 patients. Patients were randomized in a 1:1 ratio to Vyvanse® or placebo. The primary efficacy endpoint for these studies was defined as the change from baseline to Weeks 11 - 12 (Visit 8) in the number of binge days per week determined by clinical interview based on participant diary data.
The studies consisted of a minimum 2-week screening period, a 12-week treatment phase (4 weeks of dose-optimization and 8 weeks of maintenance), and a follow-up visit 1 week after the last on-treatment visit. During the screening period, eligible patients demonstrated BED of at least moderate severity, defined in the study protocol as at least three or more binge days per week, for each of the 2 weeks prior to baseline, per diary entries. Patients were randomized to Vyvanse® or placebo treatment groups. During the dose optimization period, all Vyvanse®-treated patients were initiated at the 30-mg dose, and then titrated in 20-mg increments to their optimal dose (either 50 or 70mg).
Latest
news: * On November 5, 2013, Shire has announced positive top-line results from two identically designed randomized placebo-controlled Phase 3 studies evaluating the efficacy and safety of Vyvanse® (lisdexamfetamine dimesylate) Capsules (CII) versus placebo in adults with binge eating disorder (BED). In both studies Vyvanse® was found to be statistically superior to placebo on the primary efficacy analysis (p-value <0.001) of the change from baseline at weeks 11 to 12 in terms of number of binge days per week. The safety for Vyvanse® in these two studies appears to be generally consistent with the known profile established in studies in adults with Attention-Deficit/Hyperactivity Disorder (ADHD). The Company is reporting the data sooner than originally anticipated because of faster than expected completion of both studies.
In addition to the positive top-line primary results, both studies showed statistically significant (p-value <0.001) and consistent treatment effects for Vyvanse® across the key secondary efficacy endpoints that have been analyzed thus far in the top-line data. These include the Clinical Global Impressions – Global Improvement (CGI-I), 4-week binge cessation, percent change from baseline in body weight, and change from baseline in the Yale-Brown Obsessive Compulsive Scale Modified for Binge Eating (Y-BOCS-BE). Additional analyses continue for other secondary endpoints. Shire anticipates presenting the efficacy and safety data from both studies at a major scientific meeting in 2014.
Each of the two identically designed pivotal Phase 3, multi-center, randomized, double-blind, parallel-group, placebo-controlled, dose-optimized studies was designed to assess the safety, efficacy, and tolerability of Vyvanse® in patients aged 18 to 55 who met DSM-IV-TR® criteria for a diagnosis of BED. The primary efficacy endpoint for these studies was defined as the change from baseline to Weeks 11 - 12 (Visit 8) in the number of binge days per week determined by clinical interview based on participant diary data. Vyvans®e was statistically superior to placebo on the primary efficacy analysis for both studies.
The key secondary endpoints analyzed to date included CGI-I, 4-week binge cessation, percent change from baseline in body weight, and change from baseline in Y-BOCS-BE. The CGI-I was dichotomized as improved (including categories of ‘very much improved’ and ‘much improved’) or not improved (other categories excluding ‘not assessed’). The endpoint 4-week cessation of binge eating is defined as no binge episodes for 28 consecutive days prior to the last study visit. The Y-BOCS-BE is a modified version of Yale-Brown Obsessive Compulsive Scale that measures the obsession of binge eating thoughts and compulsiveness of binge eating behaviors. Vyvanse® was statistically superior to placebo on the key secondary efficacy endpoints analyzed to date for both studies.
The company plans to file for FDA regulatory approval of Vyvanse® for the treatment of BED in adults (ages 18 to 55) by Q3 2014.
Vyvans®e was statistically superior to placebo on the primary efficacy analysis for both studies.
The key secondary endpoints analyzed to date included CGI-I, 4-week binge cessation, percent change from baseline in body weight, and change from baseline in Y-BOCS-BE. The CGI-I was dichotomized as improved (including categories of ‘very much improved’ and ‘much improved’) or not improved (other categories excluding ‘not assessed’). The endpoint 4-week cessation of binge eating is defined as no binge episodes for 28 consecutive days prior to the last study visit. The Y-BOCS-BE is a modified version of Yale-Brown Obsessive Compulsive Scale that measures the obsession of binge eating thoughts and compulsiveness of binge eating behaviors. Vyvanse was statistically superior to placebo on the key secondary efficacy endpoints analyzed to date for both studies.
In study SPD489-343 there were 3 patients treated with Vyvanse® who reported serious adverse events (SAEs); 2 patients treated with placebo reported SAEs. There were 12 patients on Vyvanse who reported treatment-emergent adverse events (TEAEs) that led to study discontinuation; 5 patients on placebo reported TEAEs that led to study discontinuation. The most commonly reported (>=5% of patients) TEAEs in patients taking Vyvanse included dry mouth, insomnia, headache, decreased appetite, nausea, irritability, heart rate increased, anxiety, feeling jittery, constipation, hyperhidrosis.
In study SPD489-344 there was 1 patient treated with Vyvanse® who reported a serious adverse event (SAE); 2 patients treated with placebo-reported SAEs. There were 7 patients on Vyvanse reported TEAEs that led to study discontinuation; 4 patients on placebo reported TEAEs that led to study discontinuation. The most commonly reported (>=5% of patients) TEAEs in patients taking Vyvanse included dry mouth, headache, insomnia, fatigue, nausea, diarrhoea, decreased appetite, constipation, feeling jittery, blood pressure increased, and irritability. There were no deaths in either of the studies.
