Sultiame once per day in obstructive sleep apnoea (FLOW): a multicentre, randomised, double-blind, placebo-controlled, dose-finding, phase 2 trial.

Summary

Once-daily sultiame reduced AHI3a in a dose-dependent fashion at 15 weeks and improved sleep-related outcomes, with paraesthesia and headache being the most common adverse events. Benefits were observed across multiple nocturnal and daytime measures, supporting carbonic anhydrase inhibition as a pharmacologic strategy in OSA.

Key Findings

• Placebo-subtracted relative AHI3a change at 15 weeks: -16.4% (100 mg), -30.2% (200 mg), -34.6% (300 mg).
• Improvements extended to nocturnal hypoxia, sleep quality, and daytime sleepiness measures.
• Adverse events were dose-dependent; paresthesia occurred in 22% (100 mg), 43% (200 mg), and 57% (300 mg).

Clinical Implications

Sultiame may offer an adjunct or alternative for OSA patients who are intolerant of CPAP or seeking pharmacologic options. Clinicians should monitor dose-related paresthesia and consider patient selection while awaiting phase 3 outcomes.

Limitations

• Phase 2 duration (15 weeks) without long-term outcomes or head-to-head comparison with standard care (e.g., CPAP).
• Dose-related adverse events may limit tolerability at higher doses.

Future Directions

Confirm efficacy and safety in phase 3 trials, define optimal dosing and patient phenotypes responsive to carbonic anhydrase inhibition, and evaluate combination with CPAP or oral appliances.