Auris Medical reporting results of phase I/II clinical
trial with AM-101
Editor: The folks at Auris Medical are developing drugs to treat
ear-related conditions. Here's their notice on recent clinical trials of
their tinnitus drug.
~~~~~~~~~~~~~~~~~
August 2008
Auris Medical reported the results of the first clinical trial with
AM-101, its investigational drug for the treatment of inner ear tinnitus.
The double blind, randomised clinical trial with placebo control involved
four study sites in Germany and had the evaluation of AM-101's safety as
primary objective. As a secondary objective, the potential efficacy of
AM-101 was evaluated. The study results show that intratympanically
injected AM-101 was well tolerated by study participants, and provided
first indications of therapeutic efficacy.
The first clinical evaluation of AM-101, an investigational medicinal
product under development by Auris Medical for the treatment of inner ear
tinnitus, was conducted from March 2007 to March 2008 in a phase I/II
study in Germany. A total of 24 patients suffering from persisting
moderate to severe tinnitus following acute noise trauma or sudden
deafness were enrolled at 4 study centres (3 clinics of the German
Bundeswehr and 1 private ear, nose and throat practice). Their tinnitus
had been refractory to a first-line corticoid treatment prior to study
inclusion, and was not older than 3 months (i.e. still at an acute stage).
Study participants were randomized to receive either AM-101 or placebo in
a single dose intratympanic injection, whereby a total of 4 dose
concentrations were tested under a dose escalation scheme.
Follow-up visits were performed 7, 30 and 60 days after treatment
administration. The primary objective of the study was to evaluate the
safety of AM-101 delivered by intratympanic injection. Secondary
objectives were a preliminary evaluation of the potential therapeutic
benefit of AM-101 in the treatment of acute inner ear tinnitus as well as
the determination of the systemic exposure from local drug administration.
The study's lead investigator was Professor Heinz Maier, Head of the
Otorhinolaryngology and Head and Neck Surgery Department of the Bundeswehr
clinic of Ulm (Germany).
At baseline, i.e. before administration of AM-101, study participants
on average had had tinnitus for 62 days. In 19 cases, tinnitus had been
provoked by acute acoustic trauma, in 5 cases it had been related to
sudden deafness. A slight majority of patients suffered from bilateral
tinnitus (13 out 24), in which case only the worse affected ear was
treated. The average audiogram was downward sloping with a maximum hearing
loss at 6 kHz.
Overall, AM-101 was well tolerated by study participants, irrespective
of the administered dose. Adverse events occurred in only few patients and
were either unrelated or considered unlikely related to the
phar-maceutical treatment. AM-101 and its primary metabolite could be
found in plasma samples obtained in the first hours following treatment in
traces only, which confirmed the favourable safety profile of
intra-tympanic injection. This minimally invasive procedure allows for a
highly site specific treatment with low doses and only minimal systemic
exposure.
In terms of efficacy, the clinical trial provided first indications for
the potential efficacy of AM-101 in the treatment of inner ear tinnitus.
The clinical data suggest that AM-101 has a positive effect on the
perceived loudness of tinnitus as well as on its maskability; in addition,
a positive trend was observed in the overall
Auris Medical AG, Aeschenvorstadt 37, CH-4051 Basel,
www.aurismedical.com Laboratoires Auris SAS, CEEI Cap Alpha, Avenue de
l'Europe, FR-34940 Montpellier Cedex 09 Auris Medical Inc., 444 North
Michigan Avenue, Chicago, IL 60611, USA
tinnitus handicap as measured by the TBF-12 questionnaire. Further
details of the clinical trial and its out-comes shall be published later
in a scientific journal.
Thomas Meyer, Auris Medical's founder and Managing Director, commented:
"We are very pleased with the positive results from this first clinical
evaluation of AM-101. The trial not only confirmed the presumed good
safety profile following local application, but also provided encouraging
early indications of potential efficacy." He added that the successful
conclusion of the study represented an important milestone for Auris
Medical and the development of a treatment for inner ear tinnitus, an area
of great unmet medical need. In a next step, Auris Medical is planning to
test AM-101's efficacy in a phase IIb clinical trial with a substantially
larger number of participants.
About AM-101
AM-101 contains a small molecule that selectively blocks NMDA
receptors. Based on research conducted at the INSERM Institute for
Neurosciences of Montpellier, France, NMDA receptors in the cochlea can
provoke aberrant activity of the auditory nerve which is perceived as
tinnitus. NMDA receptors do not seem to be involved in fast excitatory
neurotransmission which is essential for hearing, but may be activated
following some excitotoxic incident such as noise trauma or sudden
deafness. It had been demonstrated in behav-ioural and
electrophysiological models that local administration of the NMDA
antagonist AM-101 to ani-mals suffering from tinnitus effectively
suppressed the perception of the "phantom sound". The develop-ment of
AM-101 was supported by Oséo ANVAR, the French agency for the financing
and support of small and mid-sized business enterprises.
About Auris Medical
Auris Medical is a Swiss-French biotechnology company developing
specific pharmaceutical compounds for the prevention or treatment of inner
ear disorders, an area of great unmet medical need. Around the world, many
million people are suffering permanently from severe hearing loss and / or
tinnitus, still lacking truly effective and safe treatments for their
disorders. Auris Medical is currently focusing on the development of
treatments for acute inner ear tinnitus (AM-101) and for acute
sensorineural hearing loss (AM-111).
