Efficacy and safety of single- and repeated-selurampanel dosing for 2 weeks in patients with chronic subjective tinnitus: Results of a randomized, double-blind, placebo-controlled, cross-over, proof-of-concept phase IIa study.

Abstract

To evaluate efficacy and safety of BGG492 (selurampanel; an orally active, competitive AMPA glutamate receptor antagonist) in patients with moderate-to-catastrophic chronic subjective tinnitus. Study (NCT01302873) enrolled patients with subjective tinnitus based on THI severity grade 3, 4 or 5 (moderate, severe or catastrophic), and those with chronic (>6 and <36 months) tinnitus. Primary endpoints were clinical status of tinnitus using TBF-12 and tinnitus loudness using VAS after multiple dose 2-week BGG492 treatment. Safety was assessed by recording all adverse events (AEs). After a single dose of BGG492 VAS scores for tinnitus loudness (P=0.012) and tinnitus annoyance (P=0.004) were significantly reduced vs placebo. After 2 weeks treatment a significantly greater proportion of patients showed improvement of ≥4 points from baseline in TBF-12 (stringent responder definition) with BGG492 vs placebo (26.7% [n=23] vs 14% [n=12], respectively; odds ratio [OR] (90% CI):2.30 (1.10, 4.83); P=0.064), fulfilling proof-of-concept achievement criteria. No notable difference in proportion of responders to BGG492 vs placebo was observed as assessed using VAS (26.7% [n=23] vs 27.6% [n=24], respectively; OR (90% CI):0.94 (0.52, 1.67); P=0.848). Dizziness was the most frequently reported AE in 50% [n=21] and 31.5% [n=17] patients on BGG492 100 and 50mg TID, respectively vs 9.6% [n=9] on placebo. In conclusion, BGG492 showed reduction of both tinnitus loudness and annoyance after a single dose and reduction of tinnitus handicap after 2 weeks of treatment in patients with chronic subjective tinnitus, thereby supporting further clinical investigation of AMPA receptor antagonists with an improved benefit/risk ratio. A dose of 100mg TID BGG492 showed higher efficacy but somewhat lower tolerability compared to 50mg TID.

• Authors: Klaus Kucher, Donald Johns, Frank Wagner, Khalid Abd-Elaziz, Caroline Derne, Oleksandr Sverdlov, Christian U Pfister, Berthold Langguth
• Journal: Progress in brain research (Prog Brain Res) Vol. 260 Pg. 423-440 ( 2021) ISSN: 1875-7855 [Electronic] Netherlands
• PMID: 33637230 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 Elsevier B.V. All rights reserved.

Chemical References

• Quinazolinones
• selurampanel

Topics

• Cross-Over Studies
• Double-Blind Method
• Humans
• Quinazolinones (therapeutic use)
• Tinnitus (drug therapy)