Efficacy, Safety and Tolerability of Neramexane in Patients with Subjective Tinnitus MedDRA version: 9.1 Level: LLT Classification code 10042398 Term: Subjective tinnitus
Conditions
Sponsors
Merz Pharmaceuticals GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Signed written informed consent obtained from the patient 2) Patients 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 tinnitus present for at least 3 months but not more than 12 months. In case of bilateral tinnitus this criterion applies to both ears. 3) Outpatients (male or female) between 18 and 75 years of age (inclusively) at screening 4) For females of childbearing potential (last menses less than one year prior to enrolment): negative pregnancy test at screening and at baseline (i.e. prior to entry in the double-blind treatment phase); not breast-feeding; either surgically sterile or agreement to use a medically accepted, highly effective contraception during the entire duration of the study A highly effective method of birth control is defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or vasectomised partner. 5) TBF-12 total score = 9 6) HADS depression subscore = 10 and HADS anxiety subscore = 10 7) Physical examination and laboratory evaluations from the screening visit must be normal, or abnormal findings must be judged either “not clinically relevant” or “clinically relevant but of no concern” by the Investigator 8) Patient must be willing and able to comply with the protocol and study procedures Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1) Clinical diagnosis of intermittent or pulsatile tinnitus 2) Patients who have tinnitus as a concomitant symptom of an otological/neurological disease (such as otitis media, Menière’s disease, otosclerosis, etc) 3) Hearing impairment related to disturbance of sound conduction (air conduction threshold more than 20 decibel (dB) worse than in bone conduction in at least two tested frequencies) Remark: It might become acceptable that the answer provided for the Exclusion Criterion number 3 (Hearing impairment related to disturbance of sound conduction) is based on the results of Rinne/Weber tests. This is acceptable only in cases where results of audiometry are not available or not completely available to allow justification of the answer provided to the exclusion criterion number 3. In these exceptional cases queries will be written for clarification if the evaluation of Exclusion Criterion 3 can be done based on Rinne/Weber test. 4) Patients with evidence of clinically relevant and active -Pulmonary -Cardiovascular (e.g. sinus bradycardia 300 msec, AV block Mobitz II, prolonged QTc if > 500 msec, WPW syndrome, ST elevation, abnormal U wave, cardiac insufficiency NYHA III-IV or a history of myocardial ischaemia/infarction within the last 6 months) -Renal -Hepatic -Gastrointestinal - Neurological (e.g. epileptic seizures, multiple sclerosis, serious head/cervical trauma with residual deficits) -Psychiatric (e.g. dementia, schizophrenia, current major depressive episode) -Infectious (e.g. HIV infection/AIDS, tuberculosis) - Endocrine disorder of concern or other severe or uncontrolled systemic diseases which might interfere with the trial (patients with controlled diabetes who are normoglycemic under treatment may be included). 5) A systolic blood pressure (while seated) greater than 180 mmHg or less than 90 mmHg or diastolic blood pressure (while seated) greater than 105 mmHg or less than 45 mmHg 6) Patients with an oncology diagnosis (hematology or solid tumor) who are undergoing treatment, who have completed treatment within the last six months, and/or who still have evidence of active disease. (Patients with localized, benign dermatologic lesions may be included) 7) Former treatment with memantine, neramexane, rimantadine, amantadine 8) Documented history of hypersensitivity or intolerance to NMDA antagonists 9) Known hypersensitivity to the study drug or one of the ingredients of the formulation 10) Current absence from work due to tinnitus or application for a pension/retirement pay or granted pension/retirement because of tinnitus 11) Concomitant drugs and supplements intended for tinnitus treatment as well as non-pharmacological tinnitus treatments, e.g. biofeedback, maskers, noisers, acupuncture, hyperbaric oxygen therapy, low-power laser therapy, autogenic training, behavioural or psychotherapy during the last 28 days, 12) Patients who are taking any non-authorised concomitant medication as defined in Appendix 6 of the study protocol 13) Patients who plan to undergo elective surgery under local or general anaesthesia during the trial 14) Known or suspected alcoholism or drug abuse within the last three years 15) Patients who have participated in an investigational drug study or who have received treatment with an investigational drug within 30 days (or 5 half-lifes, whichever is longe
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective of this study is to evaluate the efficacy, safety and tolerability of neramexane in comparison to placebo in patients with subjective tinnitus;Secondary Objective: ;Primary end point(s): The primary efficacy endpoint is the change in the TBF-12 score from baseline to Week 17/EOT. The confirmatory analysis will be performed using an ANCOVA model with treatment and country as factors and baseline TBF-12 as covariate to compare placebo and neramexane (a=0.05). The factor country is chosen to account for country-specific differences in awareness and treatment of the disease. A hierarchical test procedure will be applied and the primary efficacy endpoint will be tested confirmatory in female subjects in the first step. Subsequent tests will then analyse the total population and the male population separately. In the analyses of female and male subjects no factor gender will be applied whereas in the ANCOVA of the total population, gender will be added as a factor. For US FDA approval the analysis for the primary and the co-primary variable will be performed identical as the change in the TRS item tinnitus annoyance from baseline to EOT. | — |
Countries
Czech Republic, France, Netherlands
Outcome results
None listed