Date: 2012-04-26
Type of information: Results
phase: 2
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: This Phase 2, multi-center, randomized, double-blind, parallel-group, placebo-controlled, forced-dose titration study assessed the efficacy, safety and tolerability of Vyvanse® in 270 adults aged 18 to 55 who met DSM-IV-TR® criteria for a diagnosis of binge eating disorder. The study consisted of a two-week screening period, an 11-week double-blind treatment phase and a one-week follow-up phase.
During the two-week screening period, patients recorded their binge eating episodes in a diary for at least 14 days. Eligible patients who had binge eating disorder of at least moderate severity, defined as at least three or more binge days/week for two weeks prior to their baseline visit, entered the double-blind treatment phase which consisted of a three-week forced-dose titration period and an eight-week dose-maintenance period. Patients were randomized to one of four treatment groups: Vyvanse® 30, 50, or 70 mg/day or placebo. During the forced-dose titration period, all Vyvanse®-treated patients initiated the study at the 30 mg dosage, and those assigned to the 50 mg and 70 mg doses had their dose titrated in 20 mg increments over a one or two week period, respectively.
Patients were excluded from the study if they had concurrent symptoms of bulimia nervosa or anorexia nervosa, other current comorbid psychiatric disorders, Montgomery-Åsberg Depression Rating Scale (MADRS) total score of 18 or more at baseline visit, a lifetime history of amphetamine, cocaine, or other stimulant abuse and/or dependence. In addition, certain medical comorbidities were excluded (eg, cardiovascular risk, moderate to severe hypertension, diabetes mellitus, etc.).
Latest
news: Shire has announced positive top-line results from a Phase 2 study to evaluate the safety and efficacy of Vyvanse® (lisdexamfetamine dimesylate) Capsules, (CII) in adults with binge eating disorder. Following discussions with the FDA, Shire plans to conduct additional larger studies to confirm the validity of the findings.
The primary objective of the study was to evaluate the efficacy of 30, 50 or 70 mg of Vyvanse® compared to placebo in the treatment of binge eating disorder at Week 11 as measured by the number of binge days per week as assessed by clinical interview based on patient diary. A binge day was defined as a day during which at least one binge episode occurred.
The primary study end point was the change from baseline to Week 11 in log transformed (number of binge days per week + 1). Vyvanse® 50 mg and 70 mg were statistically superior to placebo on the primary end point. Vyvanse® 30 mg was not statistically superior to placebo on the primary end point, clarifying the dose range for future trials in this patient population.
The study also evaluated the safety and tolerability of Vyvanse® 30, 50 and 70 mg doses based on occurrence of treatment-emergent adverse events (TEAEs), vital signs, weight, clinical laboratory results, electrocardiogram (ECG) results, and the Columbia-Suicide Severity Rating Scale (C-SSRS).
The safety profile based on currently available data seen in this study was generally consistent with the known profile of studies of Vyvanse® in adults with ADHD. Most commonly (>5%) reported TEAEs in subjects taking Vyvanse® included dry mouth, decreased appetite, insomnia, headache, nausea, constipation, nasopharyngitis, decreased weight, and irritability. There were three serious adverse events (SAEs), including one with the outcome of death, in patients treated with Vyvanse®. None were judged by the investigator to be related to the study drug. No SAEs were reported in patients taking placebo. Seven patients on Vyvanse® had TEAEs that led to study discontinuation; none on placebo. No new safety trends were observed in regards to early discontinuation due to TEAEs. Shire is still evaluating the safety information related to discontinuation rates, vital signs, ECG and clinical laboratory results.
