Two studies’ results presented yesterday suggest long-term efficacy (up to 12 months) in boys and girls for the ADHD patch (Daytrana), as well as additional information about Intuniv, a new attention-deficit disorder (ADHD) medication not yet on the market.
“The findings are significant because only a relatively modest amount of work has been done to examine the effects of ADHD treatments by gender,” said Robert Findling, M.D., investigator of the analysis from Case Western Reserve University. “This is an important consideration for parents because not only do they need to recognize that ADHD symptoms present differently in girls than in boys, but also because it is important to understand the role of treatment for both sexes.”
This analysis was conducted using data from an open-label, flexible dose, 12-month extension study in which 326 children received Daytrana, a once-a-day methylphenidate transdermal system. Children who enrolled in this study previously participated in other studies in which they received the ADHD patch, osmotic-release oral system (OROS) methylphenidate or placebo as part of the study design.
The primary objective of this study was to investigate the long term safety profile of ADHD treatment with Daytrana, and the secondary objective examined the efficacy of the medication between genders.
Adverse events were reported in a higher percentage of boys than girls in all dose groups; however, they were generally comparable between genders.
Adverse events were typically mild or moderate and consistent with stimulant treatment. The most common adverse events included decreased appetite, headache, upper respiratory tract infection, cough, fever and decreased weight.
In the study, the efficacy of Daytrana was measured using the ADHD Rating Scale (ADHD-RS-IV), the Clinical Global Impressions-Improvement (CGI-I) scale and the Parent Global Assessment (PGA) rating scale and measurement results were found to be statistically significant on all scales. In the analysis, boys had a 41 percent change on the ADHD-RS-IV (as calculated from a mean baseline score of 11.6, with a mean change from baseline to endpoint of -4.8) and girls had a 23 percent change on the scale (as calculated from a mean baseline score of 11.3, with a mean change from baseline to endpoint of -2.6). Lower scores on the ADHD-RS-IV reflect an improvement in symptom control.
On the CGI-I scale, clinicians rated 83 percent of boys and girls “improved” or “very much improved” at the end of the study compared to week one. Additionally, the PGA rating scale showed that 78 percent of boys and girls “improved” or “very much improved” at the end of the study compared to week one. The results in both the CGI-I and PGA scale were comparable between boys and girls.
Findling added, “These positive findings, along with previously presented research, reinforces that the ADHD patch is an important treatment option for children, especially those who may benefit from an ADHD medication that can accommodate their changing daily needs.”
While this study evaluated the safety and effectiveness of Daytrana for up to 12 months, the ADHD patch has not been studied versus placebo for longer than 7 weeks.
Intuniv (a non-stimulant selective alpha-2A-agonist) is a new ADHD once-daily medication not yet on the market. Research data presented yesterday showed significant efficacy in reducing attention deficit disorer (ADHD) symptoms for patients taking the medication when compared to patients taking placebo.
The U.S. Food and Drug Administration (FDA) issued an approvable letter for Intuniv on June 20, 2007. Shire, Intuniv’s maker, is conducting additional clinical work which is designed to enhance the label as requested by the FDA.
The pooled analysis evaluated results from these patients on a weight adjusted mg/kg basis from two similarly designed, randomized, double-blind, forced-dose titration, multicenter phase III trials. The primary efficacy measure for both studies was change in the ADHD Rating Scale (ADHD-RS-IV) total score from baseline to endpoint.
All patient groups treated with Intuniv showed significantly greater improvement in ADHD-RS-IV total score from baseline to endpoint than the placebo group (P < .001). The ADHD-RS-IV is a standardized, validated test for assessing symptoms of ADHD and for assessing their response to treatment.
The analysis also studied duration of effect using the Conners’ Parent Rating Scale-Revised Short Form (CPRS-R), which is a comprehensive scale that used observer and self-report ratings to help assess ADHD and evaluate behavioral issues in children and adolescents. The CPRS-R assessments were completed on specified days at approximately 6 PM (after school and before dinner), 8 PM (dinner through bedtime) and 6 AM (waking time/new dose administration time), which represented 12, 14 and 24 hours after the administration of the dose of INTUNIV, respectively.
The data demonstrated significant improvement of ADHD symptoms based on total endpoint CPRS-R scores for all weight adjusted dose groups treated with Intuniv when compared to placebo for all time periods (at 12 hours, P < = .001; at 14 hours, P < .001; and at 24 hours, P=.003).
A separate analysis of the same phase III studies evaluated the percentage of ADHD patients who responded to weight-adjusted treatment with Intuniv versus those participants receiving placebo. Using the change in the ADHD-RS-IV total score from baseline to endpoint as the primary efficacy measure, responders were defined as those with a 25 percent reduction in score from baseline to endpoint.
Findings from the analysis showed that all groups treated with Intuniv responded to the medication in a shorter time period than the placebo group (14 days versus 20 days, respectively, P = .001).
In the phase III studies, adverse events (AEs) were reported in 80.7 percent of patients treated with INTUNIV and 71.8 percent of patients treated with placebo. Overall, the AEs were mostly mild to moderate in severity. Adverse reactions that appeared to be dose-related in patients given INTUNIV included upper abdominal pain, constipation, dizziness, dry mouth, hypotension, sedation, and somnolence. Serious AEs reported in these analyses were uncommon and rates were similar between patients treated with INTUNIV and patients treated with placebo (0.6% of the INTUNIV group and 0.7% of placebo group, respectively).
Intuniv is a once-daily formulation of guanfacine that provides a controlled, steady delivery of drug throughout the day with a delivery system that is designed to minimize the fluctuations between peak and trough concentrations as seen with immediate-release guanfacine. Intuniv is not a controlled substance and does not appear to have a known mechanism for potential abuse or dependence.
Although other ADHD medications work indirectly in the prefrontal cortex, it has been shown that guanfacine works directly by binding selectively to alpha-2A adrenergic cell receptors located in the prefrontal cortex.
The prefrontal cortex is an area of the brain associated with executive functioning, ie, working memory, behavioral inhibition, regulation of attention, distractibility, impulsivity, and frustration tolerance. The selective alpha-2A agonist strengthens working memory and prefrontal cortex neuronal firing.
Safety data showed that adverse events reported by participants using Intuniv were generally mild to moderate in severity, with the most common side effects being sedative in nature. Sedation-related, treatment-emergent adverse events were among the most common but emerged in the first two weeks and were usually transient and mild or moderate in severity.
Treatment-related adverse events greater than 10 percent included drowsiness (32 percent), headache (26 percent), fatigue (18 percent), upper abdominal pain (14 percent) and sedation (13 percent). Small to modest changes in blood pressure, pulse rate, and ECG parameters were also observed.
The findings were presented at the annual meeting of the American Psychiatric Association.
Source: Compiled from press releases published by Shire PLC