Comparative Efficacy and Safety of Lisdexamfetamine Dimesylate ...

significantly lower in both MAS XR groups compared with
3.4 (1.00) in the placebo group (P≤.0027; Table 2). Effect sizes
for treatment with LDX and MAS XR as assessed by the global
improvement scales are presented in Table 2.
In the LDX trial, a post hoc analysis of dichotomized CGI-I
difference in improved (very much improved [CGI-I=1] and
much improved [CGI-I=2]) versus placebo was significant for
both doses of LDX, at all weeks and at endpoint (P≤.0005 for
each). The percentage of subjects for 50 and 70 mg/day LDX,
respectively, at week 1 was 24.7% and 27.9%; at week 2 was
32.5% and 34.2%; at week 3 was 35.1% and 38.9%; at week 4
was 32.9% and 33.3%; and at endpoint was 32.5% and 31.8%.
For the MAS XR trial, the analysis indicated that the categorical
CGI-I difference in improved versus placebo was not significant
for the 20 mg/day dose of MAS XR at all weeks and at endpoint.
With the 40 mg/day dose of MAS XR, the percentage of subjects
that had a difference in improved versus placebo was significant
only at weeks 2 and 4, and at endpoint (P≤.0210 for each). The
CGI-I difference for the 40 mg/day dose of MAS XR at week 2
was 27.3%; at week 4 was 29.2%; and at endpoint was 29.1%.
Safety
The harmonization of AE terminology resulted in the reclassification
of the verbatim item mapping to the COSTART
“anorexia” to the MedDRA “decreased appetite” or “anorexia.”
The verbatim terms mapping to the COSTART “insomnia” was
TABLE 3
Comparative Efficacy and Safety of LDX and MAS XR in Adults With ADHD
reclassified to the MedDRA “initial insomnia” or “insomnia.”
In the LDX clinical trial, 80.3% of subjects in the active treatment
groups experienced at least one TEAE compared with
58.1% of those receiving placebo (Table 3). The most common
(≥10%) TEAEs reported by subjects receiving LDX were dry
mouth (28%), decreased appetite (25.5%), headache (21.3%),
and insomnia (19.2%). In the MAS XR clinical trial, 80.7% of
subjects experienced at least one TEAE compared with 53.3%
of those receiving placebo. After harmonization, the most common
(≥10%) TEAEs reported by subjects receiving MAS XR
were dry mouth (33.7%), decreased appetite (26.5%), insomnia
(21.7%), headache (20.5%), and weight loss (14.5%; Table 4).
The difference in percent incidence of all active treatment doses
for either trial minus placebo TEAEs for both stimulants were
dry mouth, decreased appetite, and insomnia; MAS XR all doses
included headache and weight loss. In the LDX trial 22.2% of
subjects and in the MAS XR trial 27.4% of subjects experienced
at least one difference in percent incidence of all active treatment
doses minus placebo TEAEs. In both trials, most TEAEs
were mild or moderate in severity. Severe TEAEs were reported
by 4.2% (n=10) of subjects receiving LDX, with only severe
fatigue (n=2; 0.8%) and severe insomnia (n=6; 2.5%) reported
by more than one subject. Among subjects receiving MAS XR,
8.4% (n=7) experienced severe TEAEs, with only severe insomnia
reported by more than one subject (n=3; 3.6%).
Both stimulants were associated with small mean increases
from baseline in SBP at endpoint (Table 5). LDX-treated
TEAES REPORTED DURING LDX TRIAL BY ≥5% OF SUBJECTS IN EITHER LDX TREATMENT GROUP
Body System Preferred Term
(MedDRA 9.1)
LDX 50 mg/day
(n=117) n (%)
LDX 70 mg/day
(n=122) n (%)
All LDX Doses
(n=239) n (%)
Placebo
(n=62) n (%)
Difference in % Incidence of All LDX
Doses Minus Placebo (%)
Any TEAE 90 (76.9) 102 (83.6) 192 (80.3) 36 (58.1) 22.2
Anorexia 8 (6.8) 6 (4.9) 14 (5.9) 0 5.9
Anxiety 7 (6.0) 9 (7.4) 16 (6.7) 0 6.7
Decreased appetite 33 (28.2) 28 (23.0) 61 (25.5) 1 (1.6) 23.9
Diarrhea 12 (10.3) 4 (3.3) 16 (6.7) 0 6.7
Dry mouth 29 (24.8) 38 (31.1) 67 (28.0) 2 (3.2) 24.8
Feeling jittery 4 (3.4) 9 (7.4) 13 (5.4) 0 5.4
Headache 22 (18.8) 29 (23.8) 51 (21.3) 8 (12.9) 8.4
Initial insomnia 7 (6.0) 7 (5.7) 14 (5.9) 2 (3.2) 2.7
Insomnia 20 (17.1) 26 (21.3) 46 (19.2) 3 (4.8) 14.4
Irritability 6 (5.1) 7 (5.7) 13 (5.4) 4 (6.5) -1.1
Nausea 7 (6.0) 8 (6.6) 15 (6.3) 0 6.3
Upper abdominal pain 7 (6.0) 1 (0.8) 8 (3.3) 1 (1.6) 1.7
Upper respiratory tract infection 6 (5.1) 7 (5.7) 13 (5.4) 3 (4.8) 0.6
TEAEs=treatment-emergent adverse events; LDX=lisdexamfetamine dimesylate; MedDRA=Medical Dictionary for Regulatory Activities.
Lasser R, Dirks B, Adeyi B, Babcock T. Primary Psychiatry. Vol 17, No 9. 2010.
Primary Psychiatry 49
© MBL Communications Inc. September 2010