PMID- 33637230
OWN - NLM
STAT- MEDLINE
DCOM- 20211117
LR  - 20211117
IS  - 1875-7855 (Electronic)
IS  - 0079-6123 (Linking)
VI  - 260
DP  - 2021
TI  - 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.
PG  - 423-440
LID - S0079-6123(20)30234-X [pii]
LID - 10.1016/bs.pbr.2020.12.004 [doi]
AB  - 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.
CI  - (c) 2021 Elsevier B.V. All rights reserved.
FAU - Kucher, Klaus
AU  - Kucher K
AD  - Novartis Pharma AG, Basel, Switzerland. Electronic address: 
      klaus.kucher@novartis.com.
FAU - Johns, Donald
AU  - Johns D
AD  - NodThera Inc, Lexington, MA, United States.
FAU - Wagner, Frank
AU  - Wagner F
AD  - Charite Research Organisation GmbH, Berlin, Germany.
FAU - Abd-Elaziz, Khalid
AU  - Abd-Elaziz K
AD  - QPS, Groningen, The Netherlands.
FAU - Derne, Caroline
AU  - Derne C
AD  - NodThera Inc, Lexington, MA, United States.
FAU - Sverdlov, Oleksandr
AU  - Sverdlov O
AD  - Novartis Pharmaceuticals Corporation, East Hanover, NJ, United States.
FAU - Pfister, Christian U
AU  - Pfister CU
AD  - Novartis Pharma AG, Basel, Switzerland.
FAU - Langguth, Berthold
AU  - Langguth B
AD  - Department of Psychiatry and Psychotherapy, Bezirksklinikum, University of 
      Regensburg, Regensburg, Germany.
LA  - eng
SI  - ClinicalTrials.gov/NCT01302873
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20210120
PL  - Netherlands
TA  - Prog Brain Res
JT  - Progress in brain research
JID - 0376441
RN  - 0 (Quinazolinones)
RN  - 7WG1MR7DAR (selurampanel)
SB  - IM
MH  - Cross-Over Studies
MH  - Double-Blind Method
MH  - Humans
MH  - Quinazolinones/*therapeutic use
MH  - *Tinnitus/drug therapy
OTO - NOTNLM
OT  - AMPA receptor antagonist
OT  - BGG492
OT  - Randomized trial
OT  - Selurampanel
OT  - Tinnitus
COIS- Conflict of interest K.K. is an employee and shareholder of Novartis Pharma AG. 
      D.J. was an employee of Novartis Pharma AG during the study, and is an employee 
      of NodThera Inc., Lexington, MA. F.W. has no conflict of interest. K.A.-E. is 
      employee of QPS-Netherlands B.V., which received funding for the study conduct 
      from Novartis Pharma AG, and various pharmaceutical companies for execution of 
      phase 1 and 2 clinical trials. C.D. was an employee of Novartis Pharma AG during 
      the study. O.S. is an employee and shareholder of Novartis Pharmaceuticals. 
      C.U.P. was an employee of Novartis Pharma AG during the study, now retired. B.L. 
      received a consultancy honorarium from Novartis for his contribution to the 
      study.
EDAT- 2021/02/28 06:00
MHDA- 2021/11/18 06:00
CRDT- 2021/02/27 05:29
PHST- 2021/02/27 05:29 [entrez]
PHST- 2021/02/28 06:00 [pubmed]
PHST- 2021/11/18 06:00 [medline]
AID - S0079-6123(20)30234-X [pii]
AID - 10.1016/bs.pbr.2020.12.004 [doi]
PST - ppublish
SO  - Prog Brain Res. 2021;260:423-440. doi: 10.1016/bs.pbr.2020.12.004. Epub 2021 Jan 
      20.