evant improvements were observed beginning at doses in the range 0.05-0.08 mg/kg/day. Doses up to 0.12 mg/kg/day were shown to provide additional benefit.
Controlled, monotherapy long-term efficacy studies (>9 weeks) have not been conducted.
In the monotherapy trials (Studies 1 and 2), subgroup analyses were performed to identify any differences in response based on gender or age (6-12 vs. 13-17). Analyses of the primary outcome did not suggest any differential responsiveness on the basis of gender. Analyses by age revealed a statistically significant treatment effect only in the 6-12 age subgroup. Due to the relatively small proportion of adolescent patients (ages 13-17) enrolled into these studies (approximately 25%), these data may not be sufficient to demonstrate efficacy in the adolescent patients. In these studies, patients were randomized to a fixed dose of INTUNIV rather than optimized by body weight. Therefore, some adolescent patients were randomized to a dose that might have resulted in relatively lower plasma guanfacine concentrations compared to the younger patients. Over half (55%) of the adolescent patients received doses of 0.01-0.04mg/kg. In studies in which systematic pharmacokinetic data were obtained, there was a strong inverse correlation between body weight and plasma guanfacine concentrations. ®
Table 6: Fixed dose Studies
Study
(Age Range)
Primary Efficacy Measure
Treatment Group
Placebo Intuniv® 1mg
Intuniv® 2mg
Intuniv® 3mg
Intuniv® 4mg
(6 – 17 years)
1
Mean Baseline (SD)
38.1 (9.34)
-- 36.1 (9.99) 36.8 (8.72) 38.4 (9.21)
LS Mean Change from Baseline (SE)
-8.5 (1.42)
-- -15.9 (1.37) -16.0 (1.38) -18.5 (1.39)
LS Mean Difference from Placebo (95% CI)
-- -- -7.4 (-11.3, -3.5) a
-7.5 (-11.4, -3.6) a
-10.0 (-13.9, -6.1) a
(6 – 17 years)
2
Mean Baseline (SD)
39.3 (8.85)
41.7 (7.81)
39.9 (8.74)
39.1 (9.22)
40.6 (8.57)
LS Mean Change from Baseline (SE)
-12.7 (1.60)
-19.4 (1.69) -18.1 (1.60)
-20.0 (1.64) -20.6 (1.60)
LS Mean Difference from Placebo (95% CI)
-- -6.8 (-11.3, -2.2) a
-5.4 (-9.9, -0.9) a
-7.3 (-11.8, -2.8) a
-7.9 (-12.3, -3.4) a
LS Mean: least-square mean; SD
