otherapeutic group: Centrally Acting Sympathomimetics, ATC code: N06 BA12.
Mechanism of action
Elvanse Adult is a pharmacologically inactive prodrug. After oral administration, lisdexamfetamine is rapidly absorbed from the gastrointestinal tract and hydrolysed primarily by red blood cells to dexamfetamine, which is responsible for the drug's activity.
Amfetamines are non-catecholamine sympathomimetic amines with CNS stimulant activity. The mode of therapeutic action of amfetamine in ADHD is not fully established, however it is thought to be due to its ability to block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space. The prodrug, lisdexamfetamine, does not bind to the sites responsible for the reuptake of norepinephrine and dopamine in vitro.
Clinical efficacy and safety
The efficacy of Elvanse Adult in the treatment of ADHD has been demonstrated in four controlled trials in adults, three controlled studies in adolescents aged 13-17 years, three controlled trials in children and adolescents (6 to 17 years) and three controlled studies in children aged 6 to 12 years. The patients in all these studies met DSM-IV-TR criteria for ADHD.
In clinical studies conducted in children and adults, when Elvanse Adult was taken once daily in the morning efficacy was ongoing at 14 hours after dosing in adults and 13 hours in children.
Adult population
The efficacy of Elvanse Adult in the treatment of adults who met DSM-IV-TR criteria for ADHD has been demonstrated in four controlled trials in which 846 patients were enrolled.
Study 1 was a double-blind, randomised, placebo-controlled, parallel-group study conducted in adults (n=420). In this 4-week study, patients were randomised to fixed dose treatment groups receiving final doses of 30, 50, or 70 mg of Elvanse Adult or placebo. All subjects receiving Elvanse Adult were initiated on 30 mg for the first week of treatment. Subjects assigned to the 50 and 70 mg dose groups were titrated by 20 mg per week until they achieved their assigned dose. Significant improvements in ADHD symptoms, based upon investigator ratings on the ADHD Rating Scale with adult prompts total score (ADHD-RS), were observed at endpoint for all Elvanse Adult doses compared to placebo (see Table 1). Treatment with Elvanse Adult significantly reduced the degree of functional impairment as measured by improvement on the Clinical Global Impression-Improvement (CGI-I) rating scale compared to placebo.
Table 1: Change from Baseline to Endpoint in ADHD-RS with Adult Prompts Total Score at Endpoint1 (Full Analysis Set)
Placebo
30mg
50mg
70mg
Baseline Total Score
N
Mean (SD)
62
39.4 (6.42)
115
40.5 (6.21)
117
40.8 (7.30)
120
41.0 (6.02)
Change from baseline at Endpoint
N
LS Mean (SE)
62
-8.2 (1.43)
115
-16.2 (1.06)
117
-17.4 (1.05)
120
-18.6 (1.03)
Placebo-adjusted difference
LS Mean
(95% CI)
p-value
NA
-8.04
(-12.14, -3.95)
<0.0001
-9.16
(-13.25, -5.08)
<0.0001
-10.41
(-14.49, -6.33)
<0.0001
1 Endpoint is the last post-randomisation treatment week for which a valid ADHD-RS-IV Total Score is obtained.
Note: Dunnett's test was used for the construction of CIs and p-values; p-values are the adjusted p-values and should be compared to a critical alpha of 0.05.
LS=least squares; SD= standard deviation; SE=standard error.
Study 2 was a 10-week, double- |
