In the two short-term trials, the primary endpoint was a reduction in ADHD symptoms as measured by the ADHD Rating Scale (ADHD-RS-IV). ADHD-RS-IV is a standardized, validated test for assessing symptoms of ADHD in children and for assessing their response to treatment. This scale, which contains 18 items, is based on the ADHD diagnostic criteria as defined in the APA's Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision(R).
In the first trial, 301, investigators compared 2 mg, 3 mg or 4 mg GXR doses to placebo during an eight-week treatment period. The participants randomized to GXR all began at the 1 mg dose. At weekly visits, doses were titrated in 1 mg increments over the first four weeks to achieve the randomized dose. Then, doses were tapered down weekly so that all participants randomized to GXR received the 1 mg dose at week eight.
Participants achieved overall significant mean reductions from baseline in ADHD-RS-IV total scores by study end, -16.7 points vs. -8.9 for placebo (P <.0001). Investigators observed improvement in ADHD-RS-IV scores as early as two weeks after dosing began, with significant improvement in all GXR dose groups occurring at the third week.
Effect sizes, calculated using results from the ADHD-RS-IV scores and evaluated using weight-adjusted actual doses, were 0.44 (0.01 to 0.04 mg/kg), 0.58 (0.05 to 0.08 mg/kg), 1.19 (0.09 to 0.12 mg/kg), and 1.34 (0.13 to 0.17 mg/kg). In general, effect sizes are categorized as small (0.2), medium (0.5) and large (0.8).
In the second short-term trial, 304, investigators examined 1
mg, 2 mg, 3 mg and 4 mg doses and placebo during nine weeks of
treatment. During the first three weeks, patients started at 1 mg
with doses escalating in once- weekly 1 mg increments to achieve