The current dosing regimen for the standard of care, Xyrem (sodium oxybate), in the United States is two equal, divided doses: the first dose at bedtime and the second dose 2.5 to 4 hours later. However, maker Flamel Technologies has identified formulations that demonstrate the potential to eliminate the second nighttime dose via its first in man clinical study in healthy volunteers. The elimination of the second dose for narcolepsy patients would not only provide more convenience, but may improve the benefit sodium oxybate provides as there will be no disruption to nighttime sleep. The potential for additional benefits, including improved safety, will be studied, the manufacturer says.
The trial was designed as a 16-subject four-way crossover evaluating three different formulations of Micropump sodium oxybate and Xyrem at a nightly dose of 4.5 g (two doses of 2.25 g for Xyrem) with an extension phase at 6 g for successful Micropump formulations. Each subject consumed a standard meal 2 hours prior to dosing. Subjects were instructed to maintain a consistent meal time and dosing schedule throughout the study. When a subject took Xyrem, they were instructed to take the second dose 4 hours after the first dose. Two subjects dropped out of the study prior to the completion of the 4.5 g dosing portion for reasons unrelated to drug. The key data for the 14 evaluable subjects at 4.5 g are:
- Onset of action similar to Xyrem;
- Cmax lower than Xyrem;
- Mean blood concentration (ug/ml) at hours 7 and 8 similar to Xyrem.
For the extension phase of the study, two formulations were moved forward for dosing at 6 g. Thirteen subjects were evaluable as one subject dropped out for a reason unrelated to drug. The profiles for both formulations were consistent with expectations.
The current study will continue to treat subjects at higher doses.
Given these results, Flamel plans to begin a new clinical study before the end of 2014 in a larger number of subjects further evaluating its formulations as well as certain pharmacodynamic endpoints. This study is not expected to be a registration study. Flamel plans to meet with regulatory authorities prior to embarking upon registration studies, which are expected to begin prior to the end of 2015. Xyrem is sold in the United States by Jazz Pharmaceuticals plc, in Canada by Valeant Canada Limited (via license from Jazz), and in 22 EU countries and Mexico by UCB Pharma Limited (via license from Jazz).