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

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Title: Sultiame once per day in obstructive sleep apnoea (FLOW): a multicentre, randomised, double-blind, placebo-controlled, dose-finding, phase 2 trial.
Authors: Randerath, Winfried (AUTHOR), Grote, Ludger (AUTHOR), Stenlöf, Kaj (AUTHOR), Fietze, Ingo (AUTHOR), Chevts, Julia (AUTHOR), Buntinx, Erik (AUTHOR), Albares, Javier (AUTHOR), Kuhn, Katrin (AUTHOR), Hansen, Corinna (AUTHOR), Völp, Andreas (AUTHOR), Hedner, Jan (AUTHOR)
Source: Lancet. Oct2025, Vol. 406 Issue 10514, p1983-1992. 10p.
Subjects: Sleep apnea syndromes, Carbonic anhydrase inhibitors, Sleep quality, Clinical trials, Safety, Drug dosage, Treatment effectiveness, Randomized controlled trials
Abstract: Obstructive sleep apnoea (OSA) is highly prevalent but approved pharmacological treatment options are missing. Sultiame improves the ventilatory response and upper airway muscle activity by inhibiting carbonic anhydrase. This study aimed to prospectively assess the efficacy and safety of three dosages of sultiame in OSA. This multicentre, randomised, parallel, double-blind, placebo-controlled, dose-finding, phase 2 trial was performed at 28 hospitals and community-based sites in five European countries. Adults (aged 18–75 years) with untreated, moderate to severe OSA and an Apnoea–Hypopnea Index (AHI) of ≥15 to ≤50 events per h were randomly assigned (1:1:1:1), using interactive response technology, to receive placebo or sultiame 100 mg, 200 mg, or 300 mg tablets of identical appearance once per day at bedtime for 15 weeks. Randomisation was stratified by baseline AHI3a. The primary outcome measure for efficacy was the relative change of AHI3a from baseline to week 15 (scheduled treatment end). All participants who were randomly assigned were included in the primary efficacy analysis using an estimands framework and in the safety analysis. This trial is registered with EudraCT (2021–002926–26) and ClinicalTrials.gov (NCT05236842) and is complete. Between Dec 2, 2021, and April 8, 2023, 535 patients were screened and 298 were randomly assigned to placebo (n=75), or sultiame 100 mg (n=74), 200 mg (n=74), or 300 mg (n=75). 240 patients completed 15 weeks of treatment. 220 (74%) of 298 participants were male and 78 (26%) were female. In the full analysis set, placebo-subtracted relative AHI3a adjusted means change at week 15 was –16·4% (95% CI –31·3 to –1·4; p=0·032), –30·2% (–45·4 to –15·1; p<0·0001), and 34·6% (–49·1 to –20·0; p<0·0001) for sultiame 100 mg, 200 mg, and 300 mg, respectively. The incidence of adverse events increased dose-dependently: 46 (61%) of 75 patients in the placebo group, 54 (73%) of 74 in the 100 mg group, 62 (84%) of 74 in the 200 mg group, and 68 (91%) of 75 in the 300 mg group. Events reported in more than 10% of patients in the placebo, 100 mg, 200 mg, or 300 mg groups were paraesthesia (seven [9%] of 75, 16 [22%] of 74, 32 [43%] of 74, 43 [57%] of 75), headache (six [8%], five [7%], 12 [16%], 11 [15%]), COVID-19 (three [4%], three [4%], six [8%], ten [13%]), and nasopharyngitis (nine [12%], three [4%], seven [9%], seven [9%]). Sultiame caused consistent, dose-dependent improvements of OSA, nocturnal hypoxia, sleep quality, and excessive daytime sleepiness. These findings offer perspectives for a pharmaceutical approach to treatment of patients with obstructive sleep apnoea. Desitin Arzneimittel. [ABSTRACT FROM AUTHOR]
Copyright of Lancet is the property of Lancet and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: Sultiame once per day in obstructive sleep apnoea (FLOW): a multicentre, randomised, double-blind, placebo-controlled, dose-finding, phase 2 trial.
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  Data: &lt;searchLink fieldCode=&quot;JN&quot; term=&quot;%22Lancet%22&quot;&gt;Lancet&lt;/searchLink&gt;. Oct2025, Vol. 406 Issue 10514, p1983-1992. 10p.
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  Data: Obstructive sleep apnoea (OSA) is highly prevalent but approved pharmacological treatment options are missing. Sultiame improves the ventilatory response and upper airway muscle activity by inhibiting carbonic anhydrase. This study aimed to prospectively assess the efficacy and safety of three dosages of sultiame in OSA. This multicentre, randomised, parallel, double-blind, placebo-controlled, dose-finding, phase 2 trial was performed at 28 hospitals and community-based sites in five European countries. Adults (aged 18–75 years) with untreated, moderate to severe OSA and an Apnoea–Hypopnea Index (AHI) of ≥15 to ≤50 events per h were randomly assigned (1:1:1:1), using interactive response technology, to receive placebo or sultiame 100 mg, 200 mg, or 300 mg tablets of identical appearance once per day at bedtime for 15 weeks. Randomisation was stratified by baseline AHI3a. The primary outcome measure for efficacy was the relative change of AHI3a from baseline to week 15 (scheduled treatment end). All participants who were randomly assigned were included in the primary efficacy analysis using an estimands framework and in the safety analysis. This trial is registered with EudraCT (2021–002926–26) and ClinicalTrials.gov (NCT05236842) and is complete. Between Dec 2, 2021, and April 8, 2023, 535 patients were screened and 298 were randomly assigned to placebo (n=75), or sultiame 100 mg (n=74), 200 mg (n=74), or 300 mg (n=75). 240 patients completed 15 weeks of treatment. 220 (74%) of 298 participants were male and 78 (26%) were female. In the full analysis set, placebo-subtracted relative AHI3a adjusted means change at week 15 was –16&#183;4% (95% CI –31&#183;3 to –1&#183;4; p=0&#183;032), –30&#183;2% (–45&#183;4 to –15&#183;1; p&lt;0&#183;0001), and 34&#183;6% (–49&#183;1 to –20&#183;0; p&lt;0&#183;0001) for sultiame 100 mg, 200 mg, and 300 mg, respectively. The incidence of adverse events increased dose-dependently: 46 (61%) of 75 patients in the placebo group, 54 (73%) of 74 in the 100 mg group, 62 (84%) of 74 in the 200 mg group, and 68 (91%) of 75 in the 300 mg group. Events reported in more than 10% of patients in the placebo, 100 mg, 200 mg, or 300 mg groups were paraesthesia (seven [9%] of 75, 16 [22%] of 74, 32 [43%] of 74, 43 [57%] of 75), headache (six [8%], five [7%], 12 [16%], 11 [15%]), COVID-19 (three [4%], three [4%], six [8%], ten [13%]), and nasopharyngitis (nine [12%], three [4%], seven [9%], seven [9%]). Sultiame caused consistent, dose-dependent improvements of OSA, nocturnal hypoxia, sleep quality, and excessive daytime sleepiness. These findings offer perspectives for a pharmaceutical approach to treatment of patients with obstructive sleep apnoea. Desitin Arzneimittel. [ABSTRACT FROM AUTHOR]
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  Data: &lt;i&gt;Copyright of Lancet is the property of Lancet and its content may not be copied or emailed to multiple sites without the copyright holder&#39;s express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.&lt;/i&gt; (Copyright applies to all Abstracts.)
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      – SubjectFull: Carbonic anhydrase inhibitors
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