Shire plc , the global specialty biopharmaceutical company, reports positive phase II results in a prospective clinical study of Vyvanse (lisdexamfetamine dimesylate) capsules, (CII) as adjunctive therapy to primary antidepressant treatment in adults with partial or full remission of recurrent major depressive disorder (MDD) and significant, persistent cognitive impairments.
Lisdexamfetamine dimesylate is a prescription medicine currently approved in the US, Canada, and Brazil for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD). Vyvanse should only be used to treat ADHD.
Vyvanse is a stimulant medication and federally controlled substance (CII) because it can be abused or lead to dependence. Misuse of stimulants may cause sudden death and serious cardiovascular adverse events.
Shire is investigating the use of Vyvanse as adjunctive therapy for patients with MDD. Some patients with MDD may continue to have cognitive impairment despite resolution of depressive symptoms following antidepressant therapy, although the time course and prevalence of cognitive symptoms in patients with MDD has not been fully characterized. This study, which examined MDD patients with partially or fully remitted symptoms of depression, met its primary end point, which was, change from baseline to end point in the Global Executive Composite (GEC) T-score of the Behavioural Rating Inventory of Executive Function - Adult Version (BRIEF-A) self-report. The BRIEF-A (self-report) is a 75-item instrument that assesses behaviours associated with specific domains of executive functions in adults. This scale is used in a variety of conditions in addition to depression.
This exploratory, double-blind, placebo-controlled, parallel-group, multi-centre study consisted of a two-week screening period, a nine-week double-blind period and a two-week single-blind period. During the entire study, subjects continued taking established maintenance doses of antidepressant monotherapy. Subjects in this study had mild or less than mild depressive symptoms (total score of = 18 on the Montgomery-Åsberg Depression Rating Scale [MADRS] at screening and baseline). The screening was followed by 1:1 randomization to Vyvanse (n = 71) or placebo (n = 72) augmentation for 9 weeks. Double-blind Vyvanse (or placebo) was administered orally as adjunctive therapy (20 to 70 mg per day, titrated over the initial 6 weeks), with the optimal individual dose being continued during a 3-week dose maintenance period. A 2-week single-blind phase followed the double-blind phase wherein all subjects were administered placebo.
On the primary efficacy measure, GEC T-score of the BRIEF-A self-report, Vyvanse was superior to placebo. "These data are intriguing in that they remind us of the impairment in executive functioning that patients may continue to manifest with mild depressive symptoms," stated Dr. Jeffrey Jonas, senior vice president of Research and Development for Shire's Specialty Pharmaceuticals business. "We will explore with regulatory agencies how these new findings might support our development programme for Vyvanse as an adjunctive therapy in patients with MDD."
On a secondary end point, mean change in MADRS total score from baseline to end point, Vyvanse was superior to placebo. The MADRS is a validated scale which is commonly used by investigators to assess the severity of depressive illness. "The results of this secondary end point (MADRS) reinforce Shire's decision to investigate Vyvanse as adjunctive therapy in MDD. This trial reflects Shire's approach to patient-centric targeting to potentially optimize outcomes in otherwise heterogeneous disorders," added Dr. Jonas.
Over all periods of the study, 24 subjects (out of 143) discontinued (11 on Vyvanse and 13 on placebo) treatment. During the double-blind phase, 5 subjects withdrew due to an adverse event (4 on Vyvanse and 1 on placebo). The 4 events which led to discontinuation from Vyvanse were loss of consciousness, suicidal ideation, rash, and worsening of depression. In the placebo group, 1 subject discontinued due to headaches. During the double-blind phase, 5 serious adverse events (SAEs) were reported: 2 on Vyvanse (aforementioned loss of consciousness [related], suicidal ideation [not related]), and 3 on placebo (viral gastroenteritis, rhabdomyolysis, and salmonellosis). Treatment-emergent adverse events (TEAEs) (= 5% and at least two times placebo rate) occurring in the Vyvanse treatment arm were decreased appetite (22.5%), insomnia (14.1%), urinary tract infection (9.9%), hyperhidrosis (5.6%), and somnolence (5.6%). Mean changes in blood pressure and pulse were all consistent with the current product labeling in ADHD. There were no notable effects on ECG or clinical laboratory assessments.
Vyvanse is a prescription medicine for the treatment of ADHD in children ages 6 to 17 and adults. Vyvanse should be used as part of a total treatment program that may include counseling or other therapies.