ADHD
NRP104 significantly reduced symptoms of attention deficit hyperactivity disorder in children
By Shire plc and New River Pharmaceuticals Inc.
May 25, 2006 - 1:20:00 PM

Treatment with the investigational drug, lisdexamfetamine dimesylate (NRP104), demonstrated statistically significant reduction in the symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD) in children aged 6 to 12 years according to the results of a phase III trial presented today at the American Psychiatric Association (APA) annual meeting.

A phase II trial of lisdexamfetamine dimesylate (NRP104), also presented at APA today, demonstrated a statistically significant reduction in ADHD symptoms comparable to mixed amphetamine salts extended-release (MAS XR). Both products were studied versus placebo in children aged 6 to 12 years with ADHD.

These studies showed that NRP104 significantly reduced ADHD symptoms and was well-tolerated, said Joseph Biederman, M.D., professor of psychiatry at Harvard Medical School and director of Pediatric Psychopharmacology at Massachusetts General Hospital. Dr. Biederman led both of the NRP104 studies presented at the APA meeting.

New River Pharmaceuticals Inc. developed NRP104 and on January 31, 2005, signed a collaborative agreement with Shire to develop and commercialize the product. On December 6, 2005 New River filed a New Drug Application with U.S. Food and Drug Administration to evaluate NRP104 for the treatment of ADHD. This application is currently under review.

In the phase III study, 30-milligram (mg), 50 mg, and 70 mg QD doses of lisdexamfetamine dimesylate (NRP104) demonstrated significant improvements in average ADHD symptoms compared with placebo (P less than 0.0001) after four weeks of once-daily treatment, as measured by 230 children's scores on the ADHD Rating Scale (ADHD-RS). ADHD-RS is a standard test for diagnosing ADHD in children and adolescents and for assessing their response to treatment. The scale, which contains 18 items, is based on the ADHD diagnosis criteria as defined in the APA��s Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision.

Average reductions in ADHD-RS scores were 51 percent (21.8 points), 54 percent (23.4 points) and 59 percent (26.7 points) for the 30 mg, 50 mg, and 70 mg dosage strengths, respectively, compared to baseline. All three NRP104 doses produced significant average differences in the scores during the first week of treatment (P less than 0.0001 versus placebo for each dose). Of the participants, 36 percent had previously received treatment for ADHD.

Each of the three dosage strengths (30 mg, 50 mg and 70 mg per day) demonstrated efficacy in the morning (~10:00 am); afternoon (~2:00 pm); and into evening (~6:00 pm), compared to placebo, as demonstrated by the Conners ADHD Rating Scale V Parent (CPRS).

Most adverse events were mild to moderate and occurred in the first week. The most common adverse events were decreased appetite, insomnia, headache and upper abdominal pain.

In a phase II three-way double-blind cross-over analog classroom study, investigators optimized 50 children aged 6 to 12 years to their MAS XR dose during a three-week period. The researchers then randomized the participants to receive one week each of lisdexamfetamine dimesylate (NRP104) (approximate equivalent dose to the child's optimal MAS XR dose), MAS XR (subject's optimal dose) or a placebo for a total of three weeks.

The results demonstrated consistently improved behavior when receiving either NRP104 or MAS XR as measured by the Swanson, Kotkin, Agler, M-Flynn and Pelham (SKAMP) deportment rating scale, which is a standard, validated classroom assessment tool used for testing ADHD treatment. Both NRP104 and MAS XR treatments resulted in significant and equivalent improved deportment (0.8 for both), versus placebo (1.7) (P less than 0.0001, for both).

The results also demonstrated that children��s academic productivity significantly improved with both NRP104 and MAS XR treatments, compared to placebo, as measured by PERMP, an age-adjusted collection of math problems that provides an accurate measure of a child's ability to pay attention and stay on task correlated by an increase in number of successfully completed problems. Average scores on PERMP-attempted were NRP104, 133.3, and MAS XR, 133.6, compared to placebo, 88.2, (P less than 0.0001, for both) and on PERMP-correct, NRP104, 129.6, and MAS XR, 129.4, compared to placebo, 84.1 (P less than 0.0001).

Adverse events were mild to moderate. The most common adverse events for NRP104 were insomnia (8 percent), decreased appetite (6 percent) and anorexia (4 percent); for MAS XR were decreased appetite (4 percent), upper abdominal pain (4 percent), insomnia (2 percent), and vomiting (2 percent).

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