Date: 2015-07-22
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. In the US, Vyvanse® is a federally controlled substance (CII) because it can be abused or lead to dependence.
Disease: bing eating disorder
Therapeutic area: CNS diseases - Mental diseases
Country:
Trial
details: Study SPD489-346: This Phase 3, 39-week, multi-center, placebo-controlled, double-blind, dose-optimized, randomized-withdrawal design study evaluated the maintenance of efficacy between Vyvanse® and placebo based on the primary endpoint of time to relapse of binge eating symptoms in adults with moderate to severe B.E.D. (N= 418) based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition – Text Revision (DSM-IV-TR®) criteria. Study SPD489-345: This Phase 3, 53-week, multi-center, open-label extension, dose-optimized study was designed to assess the safety and tolerability of Vyvanse® in adults with moderate to severe B.E.D. based on DSM-IV-TR® criteria (N= 604). Subjects enrolled were from previously completed double-blind, placebo-controlled studies. The study consisted of a 4-week dose-optimization period, a 48-week maintenance period, and a follow-up visit 1 week after the last on-treatment visit.
The study consisted of a 4-week screening period, a 12-week open-label treatment phase (4 weeks of dose optimization and 8 weeks of maintenance), followed by a 26-week, double-blind, randomized-withdrawal phase and a follow-up visit one week after the last on-treatment visit. 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-mg or 70-mg). Patients who met “response” criteria (one or fewer binge days each week for four consecutive weeks prior to the last visit at the end of the 12-week open-label phase and had a Clinical Global Impression-Severity [CGI-S] score of two or less at the same visit) were randomized to Vyvanse® or placebo treatment groups. During this randomized-withdrawal phase, patients (N=275) received either ongoing treatment with the same optimized dose of Vyvanse® from the open-label phase (N=137) or placebo (N=138).
The primary endpoint was defined as the time to relapse of binge eating symptoms during the randomized phase. Relapse was defined as a two or more point increase (worsening) in the investigator’s assessment of CGI-S score from the randomization baseline and two or more binge eating days per week in each week for two consecutive weeks prior to the visit.
Safety and tolerability evaluations included TEAEs, response to the Columbia-Suicide Severity Rating Scale (C-SSRS), vital signs, weight and waist circumference, clinical laboratory evaluations, and electrocardiogram (ECG) results.
Latest
news: * On July 22, 2015, Shire reported positive top-line results from a 39-week, long-term maintenance of efficacy study of Vyvanse® (lisdexamfetamine dimesylate) Capsules (CII) in adults with moderate to severe Binge Eating Disorder (B.E.D.). The objective of the study was to evaluate the maintenance of efficacy between Vyvanse® and placebo, based on the primary endpoint of time to relapse of binge eating symptoms in adults (aged 18 to 55) with moderate to severe B.E.D. During the 26-week, double-blind, randomized-withdrawal phase of the study, Vyvanse® demonstrated superiority over placebo (p<0.001) on the primary efficacy endpoint of time to relapse. Additionally, at the conclusion of the study, the group continuing on Vyvanse® had a significantly lower proportion of relapse (5/136, 3.7%) as compared to the placebo group (42/131, 32.1%). Based on these results, as well as findings from a separate 12-month open-label safety extension study, the Company plans to submit a supplemental New Drug Application (sNDA) to the FDA by year end. The FDA will evaluate adding these data to the current labeling for Vyvanse®. In a separate, 12-month open-label safety extension study (SPD489-345) in adults with moderate to severe B.E.D., the safety profile for Vyvanse® was generally consistent with that currently outlined in the United States Prescribing Information (USPI). During the 52-week open-label treatment phase, 17 patients treated with Vyvanse® experienced serious adverse events (SAEs) and 54 patients on Vyvanse® had treatment-emergent adverse events (TEAEs) that led to study discontinuation. The most commonly reported TEAEs in patients taking Vyvanse (reported in 5% or more of patients) included dry mouth, headache, insomnia, upper respiratory tract infection, nasopharyngitis, constipation, nausea, decreased appetite, irritability, bruxism, sinusitis, anxiety and feeling jittery. Shire anticipates presenting the data from studies SPD489-346 and SPD489-345 at future scientific meetings.
Vyvanse® is approved in the U.S. for the treatment of moderate to severe B.E.D. in adults. Vyvanse is not for weight loss. It is not known if Vyvanse® is safe and effective for the treatment of obesity.
