EFFICACY, safety, and tolerability of sulthiame (STM) was explored in a new study on the treatment of obstructive sleep apnea (OSA). This randomized, double-blind, placebo-controlled, dose-ranging study offers treatment options for patients with moderate-to-severe OSA who struggle with traditional therapies like CPAP or MAD. The findings were presented as a late-breaking abstract at ATS International Conference 2024 in San Diego, California, USA.
Obstructive sleep apnea is characterized by repeated episodes of partial or complete obstruction of the upper airway during sleep, leading to disrupted sleep and decreased oxygen levels. Despite the availability of effective treatments, many patients find existing options uncomfortable or intolerable. Enter sulthiame, which in a previous Phase 2b study, demonstrated a significant reduction in apneas and a favorable safety profile.
The study, involving 298 patients with moderate-to-severe OSA, aimed to assess the impact of three different doses of STM (100 mg, 200 mg, and 300 mg) compared to a placebo. The participants, with a mean age of 56.1 years and a mean BMI of 29.1, were randomized to receive a daily evening dose of either STM or placebo. The primary efficacy endpoint was the relative change from baseline to week 15 in the apnea-hypopnea index (AHI3a).
The results were promising and found a dose-dependent reduction in AHI3a: -17.8% for the 100 mg dose, -34.8% for the 200 mg dose, and -39.9% for the 300 mg dose. Additionally, a post-hoc analysis confirmed a 47.1% reduction in AHI4 for STM at week 15. STM also improved overnight oxygen saturation and sleep quality, as evidenced by a significant reduction in the Total Arousal Index, while maintaining neutral effects on sleep macrostructure.
For patients with excessive daytime sleepiness (ESS ≥ 11), STM significantly improved mean ESS scores compared to placebo. Although adverse events, such as intermittent paresthesia, headache, fatigue, and nausea, were more frequent at higher doses, they were mostly mild or moderate. Importantly, no cardiovascular safety issues were observed during the 15-week treatment period.
This study suggests that sulthiame is a promising candidate for drug therapy in moderate-to-severe OSA, offering a new avenue for patients who cannot tolerate current treatment options. The consistent reduction in sleep-disordered breathing, alongside improvements in sleep quality and daytime sleepiness, positions STM as a potential breakthrough in OSA management.
Reference:
Hedner et al. Efficacy, Safety, and Tolerability of Three Doses of Sulthiame in Patients With Obstructive Sleep Apnea. A Randomized, Double-blind, Placebo Controlled, Dose-ranging Study (STM-042/K). B14. American Thoracic Society Annual Meeting 2024.
