Sulthiame decreases breathing pauses during sleep, daytime sleepiness score in OSA
Click Here to Manage Email Alerts
Key takeaways:
- The 300 mg sulthiame group had a 39.9% decrease in apnea-hypopnea index 3a at week 15.
- Other factors that improved among those receiving sulthiame included sleep quality and Epworth sleepiness scale scores.
Among patients with obstructive sleep apnea, receipt of sulthiame for 15 weeks reduced breathing pauses during sleep and daytime sleepiness, according to an abstract presented at the European Respiratory Society International Congress.
“Sleep apnea may obviously be effectively treated not only with mechanical devices but also pharmacological therapy,” Jan A. Hedner, MD, PhD, professor in the department of sleep medicine, respiratory medicine and allergology at Sahlgrenska University Hospital and the University of Gothenburg in Sweden, told Healio. “After adjusting compliance with treatment quite similar net responses to therapy may be achieved.
“It is possible that future improved classification of patients with sleep apnea may help us to combine and personalize therapy in OSA,” Hedner said. “New drug development like in our study may turn out to provide a tool to reach that process.”
In a randomized, double-blind, placebo-controlled, multicenter, dose-finding trial, Hedner and colleagues assessed 298 patients (mean age, 56.1 years; 26.2% women; mean BMI, 29.1 kg/m2) with OSA who did not accept/tolerate CPAP or oral splints to determine how three different carbonic anhydrase inhibitor sulthiame doses impact AHI vs. placebo at week 15 via polysomnography.
The mean apnea-hypopnea index with a 3% or greater drop in oxygen levels or an arousal from sleep [AHI3a] in this study population was 29 events per hour.
As Healio previously reported, a phase 2b, randomized, placebo-controlled, parallel-group, dose-guiding trial found that 4-week sulthiame was safe in patients with moderate to severe OSA and improved outcomes in the short term.
Of the total cohort, 74 patients received 100 mg of sulthiame, 74 received 200 mg of sulthiame, 75 received 300 mg of sulthiame and 75 received placebo.
Researchers observed the greatest change in baseline AHI3a among those receiving the 300 mg dose of sulthiame, with a decrease of 39.9% at week 15 (P < .0001). Following the highest dose, patients in the 200 mg group had a 34.8% reduction (P < .0001) and patients in the 100 mg group had a 17.8% reduction (P < .05) in AHI3a between baseline and week 15.
At week 15, researchers also found a 47.1% placebo-adjusted dose-dependent decrease in AHI with a 4% or greater drop in oxygen levels.
Further, patients receiving the 200 mg sulthiame dose had a 0.95% significant increase in mean overnight oxygen saturation at the 15-week mark. Similarly, patients receiving the 300 mg dose showed a 0.87% significant increase in this measure at 15 weeks.
“We were particularly happy to see that we could repeat, and overtrump, the data from an earlier exploratory study in this much bigger material,” Hedner told Healio. “Among treated patients we find some with very strong responses and some other ones with less pronounced responses. We believe this might be explained by different subgroups of patients — different disease mechanisms. This question will be addressed in future trials.”
Other factors that improved among those receiving sulthiame included total arousal index, sleep quality and Epworth sleepiness scale scores in patients with scores suggesting excessive daytime sleepiness.
In terms of safety, researchers noted paresthesia, headache, fatigue and nausea as adverse events reported by the sulthiame groups. The severity level of these events was “mostly mild to moderate.”
“Future studies, if they are completed, are expected to be bigger and extend over longer time periods (up to 1 year) — so called phase 3 studies,” Hedner told Healio. “They are expected to involve several different countries.
“[Additionally,] we are running a series of experimental studies in order to create a better understanding of the detailed mechanisms of this drug in sleep apnea,” Hedner said. “These studies extend from basic molecular mechanisms to clinical trial on various therapy combinations.”
Reference:
- Drug treatment shows promise for dangerous snoring condition, obstructive sleep apnea. https://www.ersnet.org/news-and-features/news/drug-treatment-shows-promise-for-dangerous-snoring-condition-obstructive-sleep-apnoea/. Published Sept. 10, 2024. Accessed Sept. 10, 2024.