Shire plc (LSE: SHP, Nasdaq: SHPGY), the global specialty biopharmaceutical company, today presented research results of once-daily INTUNIV™ (guanfacine) Extended-Release Tablets, coadministered with stimulants in children and adolescents diagnosed with Attention Deficit Hyperactivity Disorder (ADHD) who had suboptimal response to treatment with a long-acting stimulant alone. At study end point, patients receiving INTUNIV coadministered with a stimulant had significantly reduced symptoms on the ADHD Rating Scale IV (ADHD-RS-IV) compared with those receiving placebo with a stimulant, regardless of morning or evening dosing. These data were presented in a poster session at a major national scientific meeting of psychiatry in New York, NY.
"This study looked at patients who were taking a stable dose of a long-acting stimulant medicine but who continued to experience ADHD symptoms," said Timothy Wilens, MD, Staff in the Pediatric Psychopharmacology Unit at Massachusetts General Hospital and Associate Professor of Psychiatry at Harvard Medical School, who led the study. "These findings provide greater insight into the use of INTUNIV when combined with a stimulant."
INTUNIV is a selective alpha-2A agonist approved for the treatment of ADHD in children and adolescents ages 6 to 17. Efficacy was based on two pivotal studies (8 and 9 weeks in duration) of INTUNIV administered as monotherapy. INTUNIV is indicated as an integral part of a total treatment program that may include counseling or other measures.
These data presented today were included as part of a supplemental New Drug Application (sNDA) submitted to the Food and Drug Administration (FDA) on April 28, 2010, seeking approval for INTUNIV as an ADHD treatment combined with stimulants in this same patient population. The application is currently under review. The target FDA action date is February 28, 2011.
In This Investigational Study, Coadministration of INTUNIV With a Stimulant Showed Significant ADHD Symptom Improvement Over Stimulant Alone When Dosed Either in the Morning or Evening
This multicenter, double-blind, randomized, placebo-controlled study took place over 9 weeks in 455 patients aged 6 to 17 years with ADHD who had suboptimal response to treatment with a stimulant.
Throughout this dose-optimized study, patients continued to take their prescribed dose of a stimulant, with the addition of a morning or evening dose of INTUNIV (1 mg, 2 mg, 3 mg, or 4 mg) or placebo. The primary efficacy measure for the study was the ADHD-RS-IV. ADHD-RS-IV is a standardized tool for evaluating symptoms of ADHD and assessing response to treatment, in which clinicians can rate patients within a scoring range of 0 to 54, depending on the severity of symptoms. At end point, a significantly greater percentage of patients in the morning and evening administration of INTUNIV and stimulant groups compared with those taking placebo with a stimulant met criteria for symptomatic remission (ADHD-RS-IV less than or equal to 18). Data from the primary efficacy analysis of the study were previously presented at a national meeting of psychiatry in May 2010.
Secondary efficacy measures were based on scores from the Conners' Global Index – Parent (CGI-P) morning and evening assessment, and the exploratory Before-School Functioning Questionnaire (BSFQ). On a weekly basis, parents completed 2 assessments of the CGI-P, each composed of 10 questions. The first assessment evaluated patient behaviors in the morning before school, and during the week before the study visit. The second assessment evaluated patient behaviors in the evening, before bedtime. The groups that received INTUNIV coadministered with a stimulant showed greater improvement compared with those taking placebo and a stimulant on the CGI-P at both morning and evening assessments. Additionally, at end point, patients receiving INTUNIV coadministered with a stimulant showed greater improvement on the BSFQ compared with subjects who received placebo and a stimulant.
In this investigational study, INTUNIV given in the morning or evening when coadministered with a stimulant resulted in significant improvement in ADHD symptoms overall and at morning and evening time points.
In this study, the most commonly reported treatment-emergent adverse events (TEAEs) among patients treated with INTUNIV and a stimulant (greater than or equal to 5 percent) were headache, somnolence, upper respiratory tract infection, fatigue, insomnia, upper abdominal pain, dizziness, decreased appetite, cough, irritability, and nausea. The most commonly reported TEAEs among patients in the placebo/stimulant group (greater than or equal to 5 percent) were headache, upper respiratory tract infection, and irritability. The majority of TEAEs were mild or moderate in severity. No unique TEAEs were observed with INTUNIV given with a stimulant compared with those reported historically for either treatment alone.
Serious adverse events (SAEs) were reported in 3 patients taking INTUNIV and 1 sibling of a study participant (including one event of syncope). All SAEs were considered unrelated to INTUNIV.
"We are currently awaiting FDA review of these data and our application for a change in the product labeling for INTUNIV to include coadministration with a stimulant for the treatment of ADHD," said Michael Yasick, Senior Vice President of Shire's ADHD Business Unit. "Shire is pleased with the results of this trial and will continue to research and develop new treatments for ADHD as part of our commitment to patients and their families."