Concerta

CLINICAL RESULTS OF ONCE-DAILY TREATMENT FOR ADD/ADHD ANNOUNCED BY ALZA AND CRESCENDO PHARMACEUTICALS

      Initial Efficacy Data of Concerta, OROS® Methylphenidate, Highlighted at AACAP Meeting
MOUNTAIN VIEW, CA -- (INTERNET WIRE) -- 10/26/99 -- ALZA Corporation (NYSE: AZA) and Crescendo Pharmaceuticals Corporation (Nasdaq: CNDO) today announced the first presentation of pivotal clinical results of OROS® methylphenidate, which ALZA has named Concerta™ (methylphenidate HCl) extended-release tablets.   The results, which were included in a New Drug Application submitted to the U.S. Food and Drug Administration earlier this year, provide initial data on the product's efficacy and safety in children with Attention Deficit Disorder and Attention Deficit Hyperactivity Disorder (ADD/ADHD).   The studies were presented this past weekend at the 46th annual meeting of the American Academy of Child and Adolescent Psychiatry (AACAP) in Chicago.

      Concerta, which is under development by ALZA for Crescendo as a once-daily treatment for ADD/ADHD, utilizes a novel application of ALZA's OROS® osmotic technology designed to deliver a unique pattern of methylphenidate throughout the day.

      In the double-blind crossover study presented at AACAP, 68 children between the ages of 6 and 12 with a clinical diagnosis of ADD/ADHD were given Concerta™ once daily, conventional (immediate-release) methylphenidate three times daily or placebo.  The children were evaluated by various assessors both in the regular classroom setting and on three consecutive Saturdays in a laboratory school, a specialized school used to monitor children with ADD/ADHD for treatment evaluation purposes.

      An assessment of children's behavior was recorded using the Inattention/Overactivity with Aggression (IOWA) Conners measurement scale, which ranked behavior on a scale of 0 to 15, with higher ratings reflecting higher degrees of inattention and overactivity.  Based on this measurement, a significant reduction in inattention and overactivity was shown for both Concerta™ and conventional methylphenidate when compared with placebo (p<0.001).  Analysis of teachers' ratings of children in the laboratory setting showed mean ratings of 2.59 (with standard deviation of 3.91), 2.75 (SD 3.73) and 5.01 (SD 4.48) for children taking Concerta™, conventional methylphenidate and placebo, respectively.

      Similar results also were demonstrated in the community school.  In this setting, an analysis of teachers' ratings of children showed mean inattention and overactivity ratings of 4.69 (SD 3.31), 5.00 (SD 3.69) and 10.41 (SD 4.21) for children taking Concerta™, conventional methylphenidate and placebo, respectively.

      "In this study, the effects achieved with Concerta lasted throughout a child's 12-hour day, including the homework period and during after-school activities.  This is important because children with ADHD often show impairment during these times, and medication may help improve a child's functioning," said William E. Pelham, Ph.D., professor of Psychology and director of Clinical Training at the State University of New York at Buffalo, who presented the data at the meeting.  "We believe a once-daily dosing regimen may afford an opportunity to increase compliance, as neither the child nor school staff needs to remember to administer additional doses during the day."

      Similar results were seen in a second study of similar design involving 61 children with a clinical diagnosis of ADD/ADHD.  In this study, an analysis of teachers' ratings of children in the laboratory setting showed mean ratings of 5.25 (SD 3.90), 4.82 (SD 3.39) and 8.77 (SD 4.11) for children taking Concerta™, conventional methylphenidate and placebo, respectively. In the community school setting, teachers' ratings showed mean inattention and overactivity ratings of 6.66 (SD 3.58), 7.11 (SD 4.18) and 11.60 (SD 3.86) and parents' assessments showed ratings of 5.32 (SD 2.99), 5.97 (SD 3.22) and 9.90 (SD 3.65) for children taking Concerta™, conventional methylphenidate and placebo, respectively.