Date: 2014-02-06
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: major depressive disorder (MDD) in adults who inadequately responded to antidepressant monotherapy with a SSRI or SNRI
Therapeutic area: Mental diseases - CNS diseases
Country:
Trial
details: Each of the two identically designed Phase 3, multi-center, randomized, double-blind, parallel-group, placebo-controlled, dose-optimized studies was designed to assess the efficacy, safety, and tolerability of Vyvanse in patients aged 18 to 65 who met DSM-IV-TR® criteria for a diagnosis of MDD. The first study randomized (404 adults), and the second study randomized (426 adults). The 16-week studies consisted of an 8-week single blind lead-in phase with an antidepressant (selective serotonin reuptake inhibitors (SSRI) or serotonin and norepinephrine reuptake inhibitors (SNRI)), and an 8-week double-blind adjunctive treatment phase. Subjects who demonstrated an inadequate response to the antidepressant treatment at Week 8, defined in the study protocol as having a MADRS total score ? 18 and a <50% reduction in the MADRS total score from the lead-in baseline (Week 0), entered the adjunctive treatment phase and were randomized to Vyvanse or placebo treatment groups. During the double blind period, Vyvanse dosing was optimized over the range of 20 to 70 mg, based on clinical criteria.Subjects were excluded if they had inadequate response to a treatment regimen with two or more approved single antidepressant agents in their current episode of MDD, a lifetime history of treatment resistant depression, or were considered a suicide risk; certain medical comorbidities (cardiovascular risk, moderate to severe hypertension); a history of ADHD diagnosis, symptoms or treatment with ADHD medication; and/or a lifetime history of amphetamine, cocaine, or other stimulant abuse and/or dependence.
Latest
news: * On February 6, 2014, Shire has announced top-line results from two pivotal Phase 3 investigational studies evaluating the efficacy and safety of Vyvanse® (lisdexamfetamine dimesylate) Capsules (CII) versus placebo as an adjunctive treatment for major depressive disorder (MDD) in adults who inadequately responded to antidepressant monotherapy with a SSRI or SNRI. Vyvanse® did not meet the primary efficacy endpoint versus placebo for either study. In the first study, subjects experienced a mean reduction of 6.1 in MADRS total score for Vyvanse compared with 6.3 for placebo. Augmentation baseline MADRS scores for Vyvanse and placebo groups were 25.4 and 25.2 respectively. In the second study, subjects experienced a mean reduction of 7.3 in MADRS total score for Vyvanse compared with 6.8 for placebo. Augmentation baseline MADRS scores for Vyvanse and placebo groups were 26.0 and 25.7 respectively. The safety profile for Vyvanse® in these two studies appears to be generally consistent with the known profile established in studies in adults with ADHD. Based on these clinical trial results, Shire will no longer pursue this clinical development program.
“While this news in major depressive disorder is disappointing for patients and Shire, we will later in the year be filing with the FDA for a new indication for Vyvanse in Binge Eating Disorder in adults, and Vyvanse is an effective and leading treatment for ADHD,” said Flemming Ornskov, M.D., Shire’s Chief Executive Officer. Safety and tolerability of Vyvanse were evaluated based on treatment-emergent adverse events (TEAEs), vital signs, weight, clinical laboratory results, and electrocardiogram (ECG) results. In study SPD489-322, 3 patients treated with Vyvanse and 5 patients treated with placebo experienced serious adverse events (SAEs). Eight (8) patients on Vyvanse and 7 patients on placebo had TEAEs that led to study discontinuation. The most commonly reported (>5% of subjects) TEAEs in subjects taking Vyvanse included insomnia, dry mouth, decreased appetite, headache, nausea, nasopharyngitis, and dizziness.
In study SPD489-323 1 patient treated with Vyvanse and 1 patient treated with placebo experienced serious adverse events (SAE). Two (2) patients on Vyvanse and 1 patient on placebo had treatment-emergent adverse events (TEAEs) that led to study discontinuation. The most commonly reported (>5% of subjects) TEAEs in subjects taking Vyvanse included headache, dry mouth, nasopharyngitis, decreased appetite, insomnia, hyperhidrosis and restlessness.
Further evaluation of the safety information related to vital signs, ECG, and clinical laboratory results and other safety assessments is currently under way.
