— The effectiveness of STRATTERA in the treatment of ADHD was established in 4 randomized, double-blind, placebo-controlled studies of pediatric patients (ages 6 to 18). Approximately one-third of the patients met DSM-IV criteria for inattentive subtype and two-thirds met criteria for both inattentive and hyperactive/impulsive subtypes. Acute Studies

Signs and symptoms of ADHD were evaluated by a comparison of mean change from baseline to endpoint for STRATTERA- and placebo-treated patients using an intent-to-treat analysis of the primary outcome measure, the investigator administered and scored ADHD Rating Scale-IV-Parent Version (ADHDRS) total score including hyperactive/impulsive and inattentive subscales. Each item on the ADHDRS maps directly to one symptom criterion for ADHD in the DSM-IV.

In Study 1, an 8-week randomized, double-blind, placebo-controlled, dose-response, acute treatment study of children and adolescents aged 8 to 18 (N=297), patients received either a fixed dose of STRATTERA (0.5, 1.2, or 1.8 mg/kg/day) or placebo. STRATTERA was administered as a divided dose in the early morning and late afternoon/early evening. At the 2 higher doses, improvements in ADHD symptoms were statistically significantly superior in STRATTERA-treated patients compared with placebo-treated patients as measured on the ADHDRS scale. The 1.8 mg/kg/day STRATTERA dose did not provide any additional benefit over that observed with the 1.2 mg/kg/day dose. The 0.5 mg/kg/day STRATTERA dose was not superior to placebo.

In Study 2, a 6-week randomized, double-blind, placebo-controlled, acute treatment study of children and adolescents aged 6 to 16 (N=171), patients received either STRATTERA or placebo. STRATTERA was administered as a single dose in the early morning and titrated on a weight-adjusted basis according to clinical response, up to a maximum dose of 1.5 mg/kg/day. The mean final dose of STRATTERA was approximately 1.3 mg/kg/day. ADHD symptoms were statistically significantly improved on STRATTERA compared with placebo, as measured on the ADHDRS scale. This study shows that STRATTERA is effective when administered once daily in the morning.

In 2 identical, 9-week, acute, randomized, double-blind, placebo-controlled studies of children aged 7 to 13 (Study 3, N=147; Study 4, N=144), STRATTERA and methylphenidate were compared with placebo. STRATTERA was administered as a divided dose in the early morning and late afternoon (after school) and titrated on a weight-adjusted basis according to clinical response. The maximum recommended STRATTERA dose was 2.0 mg/kg/day. The mean final dose of STRATTERA for both studies was approximately 1.6 mg/kg/day. In both studies, ADHD symptoms statistically significantly improved more on STRATTERA than on placebo, as measured on the ADHDRS scale.

Examination of population subsets based on gender and age (<12 and 12 to 17) did not reveal any differential responsiveness on the basis of these subgroupings. There was not sufficient exposure of ethnic groups other than Caucasian to allow exploration of differences in these subgroups.

— The effectiveness of STRATTERA in the maintenance treatment of ADHD was established in an outpatient study of children and adolescents (ages 6-15 years). Patients meeting DSM-IV criteria for ADHD who showed continuous response for about 4 weeks during an initial 10 week open-label treatment phase with STRATTERA (1.2 to 1.8 mg/kg/day) were randomized to continuation of their current dose of STRATTERA (N=292) or to placebo (N=124) under double-blind treatment for observation of relapse. Response during the open-label phase was defined as CGI-ADHD-S score ≤2 and a reduction of at least 25% from baseline in ADHDRS-IV-Parent:Inv total score. Patients who were assigned to STRATTERA and showed continuous response for approximately 8 months during the first double-blind treatment phase were again randomized to continuation of their current dose of STRATTERA (N=81) or to placebo (N=82) under double-blind treatment for observation of relapse. Relapse during the double-blind phase was defined as CGI-ADHD-S score increases of at least 2 from the end of open-label phase and ADHDRS-IV-Parent:Inv total score returns to ≥90% of study entry score for 2 consecutive visits. In both double-blind phases, patients receiving continued STRATTERA treatment experienced significantly longer times to relapse than those receiving placebo. Maintenance Study