The investigators observed no serious adverse events during the trial. The most common adverse events included headache, vomiting, nausea, irritability, anxiety, hyperactivity, decreased appetite, and infections. In all, 12 patients discontinued participation in the trial because of neurobehavioral adverse events.
The flexible-dose trial did not indicate a benefit for arbaclofen over placebo for any outcome. The highest dose group in the fixed-dose trial had significantly better outcome than those who received placebo on the ABC Fragile X Irritability subscale. The same group demonstrated a trend toward benefit on the ABC Fragile X Social Avoidance and Hyperactivity subscales.
“Data from secondary measures and the long-term treatment extension (improved Vineland Socialization [domain score]) suggest that some patients derive benefit, but these studies illustrate the challenges of translating targeted treatments from animal models to humans in fragile X syndrome,” said Dr. Berry-Kravis.
Everolimus Reduces SEGA Volume in Tuberous Sclerosis Complex
Everolimus, an mTOR inhibitor, significantly reduces the volume of subependymal giant cell astrocytoma (SEGA) in children with tuberous sclerosis complex, according to an extension analysis presented. In a phase III trial, the researchers did not find any new safety concerns to be associated with the drug.
David N. Franz, MD, Pediatric Neurologist at Cincinnati Children’s Hospital Medical Center, and colleagues enrolled 117 patients in a randomized, double-blind trial of everolimus. All patients had SEGA associated with tuberous sclerosis complex of at least 1 cm in diameter. Participants received either 4.5 mg/m2/day of oral everolimus or placebo. The primary end point was SEGA response rate, which the investigators defined as the proportion of patients with 50% or greater reduction in SEGA volume, compared with baseline.
Patients’ mean age was approximately 11, and mean SEGA volume was 2.6 cm³. Participants received treatment for a median of 41 months.
At the original cutoff of the trial, SEGA response rate was 34.6% for everolimus and 0.0% for placebo. At that point, patients on placebo were offered open-label everolimus in the extension phase of the trial. As of January 11, 2013, 111 patients had received at least one dose of everolimus and were included in the extension analysis. The overall SEGA response rate was 48.6%, and the SEGA response rate for everolimus increased steadily until week 96. The duration of SEGA response ranged from 2.1 to 31.1 months.
Adverse events were common, but their incidence decreased with time. Approximately 40% of patients had serious adverse events, and 19% were suspected to be associated with everolimus. The most frequent serious adverse events occurring in more than 3% of patients were pneumonia, pyrexia, gastroenteritis, and convulsion.
—Erik Greb