Vestipitant Or Vestipitant/Paroxetine Combination In Subjects With Tinnitus And Hearing Loss.
Status:
Completed
Trial end date:
2009-08-01
Target enrollment:
Participant gender:
Summary
Tinnitus associated to hearing loss is a high prevalent audiologic disorder with important
unmet needs as far as therapy is concerned. The present study is exploring the possible
beneficial effects on tinnitus loudness or annoyance of a combination drug treatment aimed to
increase the local inhibitory activity of neural circuitries involved in sound perception and
generation. Modest effects have been reported after 8-12 weeks treatment with
antidepressants, including high dose paroxetine (up to 50 mg/day). Biologic data suggests
that the combination of increase of extracellular serotonin using an SSRI and of blockade of
NK1 receptors using a novel NK1 antagonist may lead to a reduced tinnitus and, possibly,
improved hearing acuity. To this aim, two 14 day treatment conditions, i.e., SSRI paroxetine
(20 mg/day) plus the NK1 antagonist vestipitant (25mg /day) or vestipitant alone (25 mg
/day), will be compared to placebo in patients suffering from tinnitus previously selected
for their capacity to reliably score the transient attenuation of tinnitus loudness produced
by lidocaine infusion. Effects on principal endpoints will be collected within 4 hrs from
last administration, when the plasma levels of vestipitant are calculated to be in the range
associated to pharmacodynamic effects on VAS anxiety and qEEG (>30 ng/ml). PK, safety and
tolerability of the paroxetine-vestipitant combination was addressed with preclinical and
Phase I studies, showing no relevant issue. The cross-over study will require approximately
24 patients. Audiometry and computer-based Automated Psychoacoustics will be performed as
instrumental endpoints to support subjective scores. A diary will be used at home to score
tinnitus severity at home during the study.