Efficacy, Safety, Tolerability of Neramexane in Patients With Subjective Tinnitus

A Randomized, Double-Blind, Placebo-Controlled, Clinical Evaluation of the Efficacy, Safety and Tolerability of Neramexane in Patients With Subjective Tinnitus

The purpose of this study is to investigate the safety and efficacy of neramexane mesylate in the treatment of subjective tinnitus in comparison to placebo.

Study Overview

• Status: Completed
• Conditions: Subjective Tinnitus
• Intervention / Treatment: Drug: Neramexane mesylate; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 455
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8020
    • Krankenhaus der Elisabethinen
  • Kufstein, Austria, 6330
    • Bezirkskrankenhaus Kufstein
  • Linz, Austria, 4010
    • A. ö. Krankenhaus der Elisabethinen Linz
  • Wien, Austria, 1090
    • Clin Pharm International GmbH, Zentrum Wien
• Brazil
  • Bello Horizonte, Brazil, 30150-270
    • Consultório Dr. Marcelo Rates
  • Rio Grande do Sul, Brazil, 90035-001
    • Hospital de Clínicas de Porto Alegre
  • Rio de Janeiro, Brazil
    • Instituto de Otorrinolaringologia Linhares
  • Santo André/SP, Brazil
    • Faculdade de Medicina do ABC
  • Sao Paulo/ SP, Brazil
    • Universidade Federal de São Paulo - UNIFESP
  • São Paulo/SP, Brazil, 05469-000
    • Instituto Ganz Sanchez
  • Valenca, Brazil
    • Clínica OTOSUL
• Germany
  • Berlin, Germany, 13125
    • Klin. Forschung Berlin Buch GmbH
  • Braunschweig, Germany, 38100
    • Praxis im Schlosscarree
  • Darmstadt, Germany, 64283
    • Dr. Klaus Peter Jayme
  • Dresden, Germany, 01277
    • Dr. Christian Dörr
  • Halle/ Saale, Germany, 06112
    • Dr. Elisabeth Kühne
  • Heiligenhaus, Germany, 42579
    • Dr. Werner Gieselmann
  • Iserlohn, Germany, 58642
    • Dr. Wolfgang Lotte
  • Leipzig, Germany, 04103
    • ClinPharm International GmbH
  • Lichtenfels, Germany, 96215
    • HNO Praxis, Bamberger Str. 7
  • Lorsch, Germany, 64653
    • Dr. Dannesberger
  • München, Germany, 81377
    • LMU München, Klinikum Großhadern
  • Nürnberg, Germany, 90443
    • Dr. Susanne Wiedemann
• Mexico
  • Aguascalientes, Mexico, CP 20127
    • Instituto Biomedico De Investigacion A.C.
  • Chihuahua, Mexico, C.P. 31000
    • Hospital General de Chihuahua
  • Chihuahua, Mexico, CP 3100
    • Hospital Christus Muguerza del Parque
  • Edo. de México, Mexico, CP 54055
    • Clinical Research Instutute S.C.
  • Guadalajara Jalisco, Mexico, CP 44280
    • Hospital Civil de Guadalajara "Fray Antonio Alcalde", Servicio de Otorrinolaringología; Hospital No. 278
  • Guadalajara Jalisco, Mexico, CP 44630
    • Grupo Médico Terranova
  • Jalisco, Mexico, 44150
    • Unidad de Investigación Clínica Cardiometábolica de Occidente S.C. (UNICAMO)
  • México D.F., Mexico, 06726
    • Hospital General de México S.S. O.D.; Servicio de Otorrinolaringología
  • Nuevo León, Mexico, CP 64000
    • Hospital OCA Monterrey International Research Center (MIRC)
  • Nuevo León, Mexico, CP 64400
    • Hospital Universitario
  • Nuevo León, Mexico, CP64240
    • Unidad de Tratamientos Avanzados (UTRAV) S.C.
  • San Luis Potosí, Mexico, 78240
    • Hospital Central "Dr. Ignacio Morones Prieto"; Servicio de Otorrinolaringología
  • San Luis Potosí, Mexico, C.P. 78269
    • Medicentro del Parque
  • Sinaloa, Mexico, 80000
    • Unidad Médica de Especialidades del Noroeste (UMEN)
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85295
      • Horizon Clinical Research Associates PLLC
    • Phoenix, Arizona, United States, 85015
      • Phoenix Clinical
    • Tucson, Arizona, United States, 85705
      • Paradigm Clinical Research
  • California
    • Burbank, California, United States, 91505
      • Providence Clinical Research
    • Fresno, California, United States, 93720
      • Central California Clinical Research
    • Sacramento, California, United States, 95817
      • UC Davis Health System
  • Colorado
    • Colorado Springs, Colorado, United States, 80909
      • Colorado Otolaryngology Associates
    • Golden, Colorado, United States, 80401
      • New West Physicians
  • Florida
    • Boynton Beach,, Florida, United States, 33472
      • Visions Clinical Research
    • Clearwater, Florida, United States, 33761
      • Tampa Bay Medical Research
    • Tampa, Florida, United States, 33603
      • Clinical Research of West Florida, Inc.
  • Illinois
    • Gurnee, Illinois, United States, 60031
      • Deerpath Physicians Group
    • Peoria, Illinois, United States, 61614
      • Knight Center for Integrated Health
  • Indiana
    • Evansville, Indiana, United States, 47714
      • Medisphere Medical Research Center, Llc
    • Evansville, Indiana, United States, 47710
      • Deaconess Clinic, Inc.
    • Newburgh, Indiana, United States, 47630
      • Deaconess Clinic, Inc.
  • Iowa
    • Iowa City, Iowa, United States, 52242-1078
      • University of Iowa Hospitals & Clinics
  • Kansas
    • Kansas City, Kansas, United States, 66160-0001
      • University of Kansas; Department of Otolaryngology Head & Neck Surgery
    • Wichita, Kansas, United States, 67205
      • Heartland Research Associates, LLC.
    • Wichita, Kansas, United States, 67207
      • Heartland Research Associates, LLC.
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Commonwealth Ear, Nose & Throat
  • Montana
    • Kalispell, Montana, United States, 59901
      • Glacier Ear, Nose, and Throat, Head and Neck Surgery, P.C.
  • New Jersey
    • Bloomfield, New Jersey, United States, 07003
      • Immedicenter
    • Somerville, New Jersey, United States, 08876
      • David L. Bortniker
  • New York
    • Bronx, New York, United States, 10867
      • Montefiore Medical Center
    • Buffalo, New York, United States, 14221
      • Erie County Medical Center, Department of Rehabilitation Medicine; State University of New York at Buffalo
  • North Carolina
    • Cary, North Carolina, United States, 27518
      • Cary Medical Research
    • Raleigh, North Carolina, United States, 27612
      • Wake Research Associates, LLC
    • Wilmington, North Carolina, United States, 28401
      • Wilmington Medical Research
    • Winston-Salem, North Carolina, United States, 27103
      • Piedmont Medical Research
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carlolina, Otolaryngology
  • Texas
    • Austin, Texas, United States, 78756
      • Future Search Trials of Neurology
    • Austin, Texas, United States, 78705
      • Austin Ear, Nose and Throat Clinic
    • Dallas, Texas, United States, 75231
      • FutureSearch Trials of Dallas
    • Lake Jackson, Texas, United States, 77566
      • R/D Clinical Research, Inc.
    • Laredo, Texas, United States, 78041
      • South Texas Research Alliance LLC
    • Plano, Texas, United States, 75093
      • Research Across America
  • Utah
    • West Jordon, Utah, United States, 84088
      • Advanced Clinical Research
  • Virginia
    • Newport News, Virginia, United States, 23606
      • Health Research of Hampton Roads, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Main Inclusion Criteria:

• Patients aged between 18 and 75 years with a clinical diagnosis of first onset, persistent (i.e., tinnitus should never be absent for > 24 hours in a row), subjective, uni- or bilateral subacute tinnitus

Main Exclusion Criteria:

• Clinical diagnosis of intermittent or pulsatile tinnitus
• Patients who have tinnitus as a concomitant symptom of an otological/neurological disease (such as otitis media, Menière's disease, otosclerosis, etc)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Neramexane mesylate; Double-blind treatment period of 29 weeks up to 75 mg Neramexane mesylate per day	Drug: Neramexane mesylate; Double-blind treatment period of 29 weeks up to 75 mg Neramexane mesylate per day
PLACEBO_COMPARATOR: Placebo; Placebo: identical placebo tablets	Drug: Placebo; Double-blind treatment period of 29 weeks placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Change in TBF-12 (Tinnitus Handicap Inventory-12) Total Score from Baseline.	The TBF-12 is an adapted German version of the original English THI (Tinnitus Handicap Inventory). It is a self-report questionnaire assessing 12 items from 2 dimensions: emotional-cognitive factors and functional-communicational factors. Each item is rated with 0-2 (2= "often"; 1= "sometimes"; 0= "never"). The maximum score is 24 indicating most severe tinnitus impairment. Hierarchical test procedure: Step 1: week 29 in subjects reporting acute hearing loss; step 2: week 17, ditto; step 3: week 29 in total population; step 4: week 17, ditto.	Baseline to week 17 and 29
Absolute Change in TSSw (Tinnitus Severity Scale - One Week Version) Total Score from Baseline.	The TSSw is a measure of tinnitus severity. It will be self-evaluated by the patient at various time points on an 11-point Likert-like scale asking for the past week. The scores range from 0 (indicating no tinnitus) to the maximum score of 10 (characterizing the most severe tinnitus considered). Hierarchical test procedure: Step 1: week 29 in subjects reporting acute hearing loss; step 2: week 17, ditto; step 3: week 29 in total population; step 4: week 17, ditto.	Baseline to week 17 and 29

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TBF-12 Total Score: Change from Baseline	See outcome measure #1.	Baseline to week 5, 17, 23, and 29
TBF-12 Factorial Scores: Change from Baseline	See outcome measure #1.	Baseline to week 5, 17, 23, and 29
TBF-12: Individual Responder Rate	See outcome measure #1. A subject is considered responder if TBF-12 decreases at least 4 score points between baseline and respective visit.	Week 5, 17, 23, and 29
Tinnitus Rating Scale (one week version): Change from Baseline	Tinnitus Rating Scale is a self-evaluated 11-point Likert scale assessing tinnitus loudness, annoyance, and impact on life. The scores range from 0 (no impact), to the maximum score of 10 (worst influence of the problem considered). Single scores and sum scores will be analysed.	Baseline to week 5, 17, 23, and 29
Tinnitus Severity Scale (one week version): Change from Baseline	See outcome measure #2.	Baseline to week 5, 17, 23, and 29
Attention and Performance Self-Assessment (ASPA) Questionnaire: Change from Baseline	The ASPA consists of 30 simple statements for which the patient can determine how regular this happens to him/her. The response options for each statement are "never", "seldom", "sometimes", "often" and "always".	Baseline to week 5, 17, 23, and 29
Quality of Life Questionnaire (SF-36™ Health Survey): Change from Baseline	The SF-36 is a multipurpose health survey with 36 questions. It is a generic measure commonly used in general and specific populations, comparing the relative burden of diseases, and in differentiating the health benefits produced by a wide range of different treatments.	Baseline to week 17 and 29
Hospital Anxiety and Depression Scale (HADS): Change from Baseline	The HADS is a self-assessment scale with 14 items which has been developed for non psychiatrists to detect states of depression and anxiety in a hospital outpatient population. Every item is rated with a scale (3= very often indeed; 2= quite often; 1= not very often; 0= not at all). Lower total scores indicate "normal", higher total scores "abnormal".	Baseline to week 17 and 29

Collaborators and Investigators

• Sponsor: Merz Pharmaceuticals GmbH

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (ACTUAL): May 1, 2011
• Study Completion (ACTUAL): June 1, 2011

Study Registration Dates

• First Submitted: August 6, 2009
• First Submitted That Met QC Criteria: August 7, 2009
• First Posted (ESTIMATE): August 10, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): November 28, 2012
• Last Update Submitted That Met QC Criteria: November 27, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: Subjective, Tinnitus
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Otorhinolaryngologic Diseases; Ear Diseases; Sensation Disorders; Hearing Disorders; Tinnitus
• Other Study ID Numbers: MRZ 92579/TI/3003; 2009-011246-25 (EUDRACT_NUMBER)