Date: 2011-01-12
Type of information: Results
phase:
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: Excessive Daytime Sleepiness
Therapeutic area: CNS diseases
Country:
Trial
details: In this study, healthy men aged 18 to 40 underwent one night of sleep deprivation following blinded randomization, medication administration, and performance of multiple alertness assessments. This study model is an accepted simulation of the clinical experience of EDS. Both objective (Maintenance of Wakefulness Test or MWT) and subjective (Karolinska Sleepiness Scale or KSS) measures were performed.
Eligible subjects (n=27 per group, 135 total) were equally randomized to Vyvanse 20 mg, 50 mg, or 70 mg, or armodafinil 250 mg (NUVIGIL®) or placebo. The primary study end point (an objective measure) was the first ‘unequivocal sleep latency’, or how long it takes subjects to fall asleep from the start of the session, as assessed by the MWT. In the MWT, subjects lay reclined in a dark, quiet room for 30 minutes and were told to stay awake as long as possible while the length of time until sleep onset occurred was recorded. ‘Unequivocal sleep latency’ was defined as the time to the first three consecutive periods of Stage 1 sleep or one period of Stage 2, 3, 4, or REM sleep.
Latest
news: Vyvanse® is a prescription medicine currently approved in the US, Canada and Brazil for the treatment of ADHD. An investigational study assessed its effect in a model for Excessive Daytime Sleepiness (EDS). The trial was a single dose, single-site, randomized, placebo- and active-controlled study, 135 subjects received Vyvanse® 20 mg, 50 mg, 70 mg, placebo or the active comparator (armodafinil 250 mg (Nuvigil®)). On the primary end point, all groups improved objective wakefulness as compared to placebo (p<0.0001). Additional pre-specified analyses showed that Vyvanse® 70 mg demonstrated statistically significant improvement in objective wakefulness compared to armodafinil. No significant difference was demonstrated between Vyvanse® 50 mg and armodafinil. Vyvanse® 20 mg was demonstrated as inferior to armodafinil. No conclusions of comparability between Vyvanse® and armodafinil can be drawn from this signal finding study. However, based on these findings Shire plans to review potential development pathways with health authorities for Vyvanse as a possible EDS treatment option. The MWT measurements used in the primary analysis were performed every 2 hours over an 8 hour period (from 24:00 on Day 1 to 08:00 on Day 2). MWT average unequivocal sleep latency by group (mean ± SD) included Vyvanse® 20 mg (23.3 ± 5.7 minutes), Vyvanse® 50 mg (27.9 ± 3.3minutes), Vyvanse® 70 mg (29.3 ± 2.3minutes), armodafinil 250 mg (27.6 ± 3.3 minutes) and placebo (15.3 ± 5.2 minutes). Secondary end points included subjects’ perception of sleepiness assessed by the Karolinska Sleepiness Scale (KSS), a nine-point scale where 1 = very alert and 9 = very sleepy. The KSS was collected hourly following medication administration. Also, subjects’ ability to sustain attention was measured by Psychomotor Vigilance Task (PVT), where subjects respond to a stimulus by pressing a button as quickly as possible. On the subjective KSS, Vyvanse® 50 mg and 70 mg statistically improved subjective wakefulness in comparison to the placebo group (p<0.001; LS mean of average KSS score). Statistical comparisons revealed Vyvanse® 50 mg and 70 mg provided a statistically significant improvement of subjective wakefulness as measured by KSS compared to armodafinil 250 mg (p=0.0297 and p=0.0004, respectively). Neither the Vyvanse® 20 mg group nor armodafinil 250 mg group showed a statistically significant difference from the placebo group or each other. On the PVT, all active treatment groups significantly improved median reaction time compared to placebo (p<0.0001) with no significant differences between Vyvanse® 20 mg, 50 mg, or 70 mg and armodafinil. Safety findings are limited since subjects were dosed only one time: no Treatment Emergent Adverse Events (TEAE) were reported as serious or resulted in study discontinuation. All active treatment groups had more subjects with adverse events compared to the placebo group (Vyvanse® overall, 21%, armodafinil 250 mg, 14.8% vs. placebo, 7.4%). When examined by dose group, 11.1% of subjects receiving Vyvanse 20 mg, 29.6% of subjects receiving Vyvanse 50 mg, and 18.5% of subjects receiving Vyvanse 70 mg experienced TEAEs. The only TEAE occurring in more than 5%.
On the primary analysis of MWT, all doses of Vyvanse® statistically improved wakefulness compared to placebo (p<0.0001) as measured by unequivocal sleep latency during the MWT. Additional pre-specified analyses demonstrated that armodafinil 250 mg provided statistically significant improvement in wakefulness versus placebo (p<0.0001). These analyses also showed statistically significant improvement in wakefulness with Vyvanse® 70 mg versus armodafinil 250 mg (p =0.0351) as measured by MWT, no significant difference between Vyvanse® 50 mg and armodafinil, and Vyvanse® 20 mg as inferior to armodafinil.
Shire plans to submit data on this signal finding study of the investigative use of Vyvanse® in Excessive Daytime Sleepiness for possible presentation at upcoming medical meetings.
