Efficacy of AM 101 in Patients With Acute Inner Ear Tinnitus

Efficacy of AM 101 in Patients With Acute Inner Ear Tinnitus: A Multi-Centre, Double-Blind, Randomised, Placebo-Controlled, Multiple Dose, Group Comparison Phase II Study

The purpose of the study is the evaluation of the therapeutic benefit of intratympanic AM 101 injections in comparison to placebo in the treatment of persistent acute inner ear tinnitus following acute sensorineural hearing loss.

Study Overview

• Status: Completed
• Conditions: Tinnitus
• Intervention / Treatment: Drug: AM-101

Detailed Description

Tinnitus may seriously impact the ability to sleep, relax, or to concentrate, or lead to tiredness, irritation, nervousness, despair, frustration, or depression, thus severely impacting the quality of life and health of the affected person. To date, there exists no pharmaceutical treatment for persisting tinnitus.

Non-clinical studies with AM-101 have shown that the inhibition of cochlear NMDA receptors is successful in suppressing tinnitus without affecting normal glutamate neurotransmission respectively hearing function. In particular, it could be demonstrated that local administration of AM-101 in a single dose resulted in a complete suppression of tinnitus induced by acute acoustic trauma without any relapse thereafter.

• Study Type: Interventional
• Enrollment (Actual): 248
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Ulm, Germany, 89081
    • Bundeswehrkrankenhaus Ulm

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Persistent tinnitus following acute acoustic trauma, sudden deafness, or acute otitis media with onset less than three months ago (i.e. acute tinnitus)
• Tinnitus provoking incident of acute acoustic trauma, sudden deafness or acute otitis media is documented by audiogram and medical report and at onset resulted in an inner ear hearing loss of at least 15 dB in two adjacent frequencies
• Minimum Masking Level (MML) of at least 5 dB SL
• Age ≥ 18 years and ≤ 65 years
• Negative pregnancy test for women of childbearing potential
• Willing and able to attend the on-study visits
• Must be able to read and understand the relevant study documents
• Written informed consent before participation in the study

Exclusion Criteria:

• Tinnitus that is not completely maskable
• Fluctuating tinnitus
• Intermittent tinnitus
• Meniere's Disease
• Acute or chronic otitis media or otitis externa
• Any ongoing therapy known as potentially tinnitus-inducing (e.g. aminoglycosides, cisplatin, loop diuretics, high doses of aspirin, quinine etc.)
• Any drug-based therapy for inner ear hearing loss that is ongoing or was performed in the past 2 weeks, e.g. prednisolone, dexamethasone, pentoxifylline, betahistine, diazepam, carbamazepine, sodium valproate and antidepressants
• Concomitant use of any other NMDA receptor antagonist (e.g. memantine, dextromethorphan, ifenprodil)
• Any ongoing or planned concomitant medication for the treatment of tinnitus until 90 days after study drug application
• History or presence of drug abuse or alcoholism
• Any clinically relevant respiratory, cardiovascular, neurological (except vertigo), or psychiatric disorder
• Known hypersensitivity, allergy or intolerance to the study medication or any history of severe abnormal drug reaction
• Women who are breast-feeding, pregnant or who plan a pregnancy during the trial
• Women of childbearing potential who declare being unwilling or unable to practice contraception such as hormonal contraceptives, sexual abstinence or intercourse with a vasectomised partner
• Concurrent participation in another clinical trial with an investigational drug or participation in another clinical trial with an investigational drug within 30 days prior to study entry
• Any drug-based therapy for otitis media that is ongoing or was performed in the past 2 weeks

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1 AM-101; low dose	Drug: AM-101; Triple intratympanic injection (one on each day 1, 2, and 3)
Experimental: 2 AM-101; high dose	Drug: AM-101; Triple intratympanic injection (one on each day 1, 2, and 3)
Placebo Comparator: 3 Placebo	Drug: AM-101; Triple intratympanic injection (one on each day 1, 2, and 3)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in the minimum masking level from Baseline to Day 90	Day 90

Secondary Outcome Measures

Outcome Measure	Time Frame
Standard audiological evaluations	D7, D30, D90
Questionaires evaluating the impact of tinnitus	D7, D30, D90

Collaborators and Investigators

• Sponsor: Auris Medical AG
• Investigators: Study Director: Heinz Maier, MD, Bundeswehrkrankenhaus Ulm

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): May 1, 2011
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: March 11, 2009
• First Submitted That Met QC Criteria: March 11, 2009
• First Posted (Estimate): March 12, 2009

Study Record Updates

• Last Update Posted (Estimate): February 13, 2013
• Last Update Submitted That Met QC Criteria: February 12, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Keywords: tinnitus
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Otorhinolaryngologic Diseases; Ear Diseases; Sensation Disorders; Hearing Disorders; Tinnitus
• Other Study ID Numbers: AM-101-CL-08-01; EudraCT number: 2008-005178-10