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A randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of neramexane in patients with moderate to severe subjective tinnitus
BACKGROUND: Neramexane is a new substance that exhibits antagonistic properties at α(9)α(10 )cholinergic nicotinic receptors and N-methyl-D-aspartate receptors, suggesting potential efficacy in the treatment of tinnitus. METHODS: A total of 431 outpatients with moderate to severe subjective tinnitus...
Autores principales: | , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031239/ https://www.ncbi.nlm.nih.gov/pubmed/21223542 http://dx.doi.org/10.1186/1472-6815-11-1 |
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author | Suckfüll, Markus Althaus, Michael Ellers-Lenz, Barbara Gebauer, Alexander Görtelmeyer, Roman Jastreboff, Pawel J Moebius, Hans J Rosenberg, Tanja Russ, Hermann Wirth, Yvonne Krueger, Hagen |
author_facet | Suckfüll, Markus Althaus, Michael Ellers-Lenz, Barbara Gebauer, Alexander Görtelmeyer, Roman Jastreboff, Pawel J Moebius, Hans J Rosenberg, Tanja Russ, Hermann Wirth, Yvonne Krueger, Hagen |
author_sort | Suckfüll, Markus |
collection | PubMed |
description | BACKGROUND: Neramexane is a new substance that exhibits antagonistic properties at α(9)α(10 )cholinergic nicotinic receptors and N-methyl-D-aspartate receptors, suggesting potential efficacy in the treatment of tinnitus. METHODS: A total of 431 outpatients with moderate to severe subjective tinnitus (onset 3-18 months before screening) were assigned randomly to receive either placebo or neramexane mesylate (25 mg/day, 50 mg/day and 75 mg/day) for 16 weeks, with assessment at 4-week intervals. The primary (intention-to-treat) efficacy analysis was based on the change from baseline in Week 16 in the total score of the adapted German short version of the validated Tinnitus Handicap Inventory questionnaire (THI-12). RESULTS: Compared with placebo, the largest improvement was achieved in the 50 mg/d neramexane group, followed by the 75 mg/d neramexane group. This treatment difference did not reach statistical significance at the pre-defined endpoint in Week 16 (p = 0.098 for 50 mg/d; p = 0.289 for 75 mg/d neramexane), but consistent numerical superiority of both neramexane groups compared with placebo was observed. Four weeks after the end of treatment, THI-12 scores in the 50 mg/d group were significantly better than those of the controls. Secondary efficacy variables supported this trend, with p values of < 0.05 for the 50 mg/d neramexane group associated with the functional-communicational subscores of the THI-12 and the assessments of tinnitus annoyance and tinnitus impact on life as measured on an 11-point Likert-like scale. No relevant changes were observed for puretone threshold, for tinnitus pitch and loudness match, or for minimum masking levels. The 25 mg/d neramexane group did not differ from placebo. Neramexane was generally well tolerated and had no relevant influence on laboratory values, electrocardiography and vital signs. Dizziness was the most common adverse event and showed a clear dose-dependence. CONCLUSIONS: This study demonstrated the safety and tolerability of neramexane treatment in patients with moderate to severe tinnitus. The primary efficacy variable showed a trend towards improvement of tinnitus suffering in the medium- and high-dose neramexane groups. This finding is in line with consistent beneficial effects observed in secondary assessment variables. These results allow appropriate dose selection for further studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT00405886 |
format | Text |
id | pubmed-3031239 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-30312392011-02-01 A randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of neramexane in patients with moderate to severe subjective tinnitus Suckfüll, Markus Althaus, Michael Ellers-Lenz, Barbara Gebauer, Alexander Görtelmeyer, Roman Jastreboff, Pawel J Moebius, Hans J Rosenberg, Tanja Russ, Hermann Wirth, Yvonne Krueger, Hagen BMC Ear Nose Throat Disord Research Article BACKGROUND: Neramexane is a new substance that exhibits antagonistic properties at α(9)α(10 )cholinergic nicotinic receptors and N-methyl-D-aspartate receptors, suggesting potential efficacy in the treatment of tinnitus. METHODS: A total of 431 outpatients with moderate to severe subjective tinnitus (onset 3-18 months before screening) were assigned randomly to receive either placebo or neramexane mesylate (25 mg/day, 50 mg/day and 75 mg/day) for 16 weeks, with assessment at 4-week intervals. The primary (intention-to-treat) efficacy analysis was based on the change from baseline in Week 16 in the total score of the adapted German short version of the validated Tinnitus Handicap Inventory questionnaire (THI-12). RESULTS: Compared with placebo, the largest improvement was achieved in the 50 mg/d neramexane group, followed by the 75 mg/d neramexane group. This treatment difference did not reach statistical significance at the pre-defined endpoint in Week 16 (p = 0.098 for 50 mg/d; p = 0.289 for 75 mg/d neramexane), but consistent numerical superiority of both neramexane groups compared with placebo was observed. Four weeks after the end of treatment, THI-12 scores in the 50 mg/d group were significantly better than those of the controls. Secondary efficacy variables supported this trend, with p values of < 0.05 for the 50 mg/d neramexane group associated with the functional-communicational subscores of the THI-12 and the assessments of tinnitus annoyance and tinnitus impact on life as measured on an 11-point Likert-like scale. No relevant changes were observed for puretone threshold, for tinnitus pitch and loudness match, or for minimum masking levels. The 25 mg/d neramexane group did not differ from placebo. Neramexane was generally well tolerated and had no relevant influence on laboratory values, electrocardiography and vital signs. Dizziness was the most common adverse event and showed a clear dose-dependence. CONCLUSIONS: This study demonstrated the safety and tolerability of neramexane treatment in patients with moderate to severe tinnitus. The primary efficacy variable showed a trend towards improvement of tinnitus suffering in the medium- and high-dose neramexane groups. This finding is in line with consistent beneficial effects observed in secondary assessment variables. These results allow appropriate dose selection for further studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT00405886 BioMed Central 2011-01-11 /pmc/articles/PMC3031239/ /pubmed/21223542 http://dx.doi.org/10.1186/1472-6815-11-1 Text en Copyright ©2011 Suckfüll et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Suckfüll, Markus Althaus, Michael Ellers-Lenz, Barbara Gebauer, Alexander Görtelmeyer, Roman Jastreboff, Pawel J Moebius, Hans J Rosenberg, Tanja Russ, Hermann Wirth, Yvonne Krueger, Hagen A randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of neramexane in patients with moderate to severe subjective tinnitus |
title | A randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of neramexane in patients with moderate to severe subjective tinnitus |
title_full | A randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of neramexane in patients with moderate to severe subjective tinnitus |
title_fullStr | A randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of neramexane in patients with moderate to severe subjective tinnitus |
title_full_unstemmed | A randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of neramexane in patients with moderate to severe subjective tinnitus |
title_short | A randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of neramexane in patients with moderate to severe subjective tinnitus |
title_sort | randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of neramexane in patients with moderate to severe subjective tinnitus |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031239/ https://www.ncbi.nlm.nih.gov/pubmed/21223542 http://dx.doi.org/10.1186/1472-6815-11-1 |
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