While effective treatments for obstructive sleep apnoea (OSA) exist, approved pharmacological options are currently unavailable. A recent phase 2 trial has investigated the efficacy and safety of sultiame, a carbonic anhydrase inhibitor, for treating this condition. The FLOW trial results suggest a dose-dependent improvement in key OSA metrics.¹

Sultiame is a carbonic anhydrase inhibitor that is understood to improve ventilatory response and upper airway muscle activity, which are key physiological factors in the pathology of OSA.²

The FLOW trial was a multicentre, randomised, double-blind, placebo-controlled, dose-finding study conducted across 28 sites in five European countries. The trial enrolled 298 adults aged 18–75 years with untreated, moderate to severe OSA, defined as having an Apnoea–Hypopnea Index (AHI) between 15 and 50 events per hour.¹

Participants were randomly assigned in a 1:1:1:1 ratio to receive either placebo or one of three daily doses of sultiame (100 mg, 200 mg, or 300 mg) at bedtime for 15 weeks. The primary endpoint was the relative change in AHI from baseline to the end of the treatment period at week 15.

After 15 weeks, sultiame demonstrated a dose-dependent reduction in the primary endpoint. The placebo-subtracted relative mean change in AHI was –16.4% for the 100 mg group (95% CI –31.3 to –1.4; p=0.032), –30.2% for the 200 mg group (95% CI –45.4 to –15.1; p<0.0001), and –34.6% for the 300 mg group (95% CI –49.1 to –20.0; p<0.0001).¹

The incidence of adverse events also increased in a dose-dependent manner. Events were reported by 61% of patients in the placebo group, 73% in the 100 mg group, 84% in the 200 mg group, and 91% in the 300 mg group. The most common adverse event was paraesthesia, reported by 9% of the placebo group and 22%, 43%, and 57% of the 100 mg, 200 mg, and 300 mg sultiame groups, respectively. Other common events included headache, COVID-19, and nasopharyngitis.

The investigators concluded that, “Sultiame caused consistent, dose-dependent improvements of OSA, nocturnal hypoxia, sleep quality, and excessive daytime sleepiness.”¹ These findings highlight the potential for a pharmaceutical approach to managing OSA, offering an alternative or adjunctive therapy for patients.

This study was funded by Desitin Arzneimittel.

References

1. Randerath W, Grote L, Stenlöf K, et al. Sultiame once per day in obstructive sleep apnoea (FLOW): a multicentre, randomised, double-blind, placebo-controlled, dose-finding, phase 2 trial. Lancet 2025. https://doi.org/10.1016/S0140-6736(25)01196-1

2. Heinzer R, Vat S, Marques-Vidal P, et al. Prevalence of sleep-disordered breathing in the general population: the HypnoLaus study. Lancet Respir Med. 2015;3:310-318. https://doi.org/10.1016/S2213-2600(15)00043-0

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