Vestipitant Or Vestipitant/Paroxetine Combination In Subjects With Tinnitus And Hearing Loss.

Phase 2

Completed

• Conditions: Tinnitus
• Interventions: Drug: Vestipitant; Drug: Vestipitant + Paroxetine; Other: Placebo

• Registration Number: NCT00394056
• Lead Sponsor: GlaxoSmithKline

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2006-10-27
• Study First Submitted QC: 2006-10-30
• Study First Posted: 2006-10-31
• Study Start: 2006-12
• Primary Completion: 2009-08
• Study Completion: 2009-08
• Status Verified: 2016-10
• Last Update Submitted: 2016-10-27
• Last Update Posted: 2016-10-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 26

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Period 1	Vestipitant + Paroxetine	-
Period 2	Vestipitant + Paroxetine	-
Period 2	Vestipitant	-
Period 2	Placebo	-
Period 3	Placebo	-
Period 1	Placebo	-
Period 1	Vestipitant	-

Primary Outcome Measures

Name	Time	Method
Visual Analog Scales (VAS) to measure the change in tinnitus loudness as perceived at the moment of the measurement at 2 hrs after dosing (or at any other time point vs. pre-dose baseline).	2 hrs after dosing (or at any other time point vs. pre-dose baseline).

Secondary Outcome Measures

Name	Time	Method
VAS to measure tinnitus pitch, distress and anxiety. Pure Tone Audiometry & Psychoacoustic assessment. Sleep & Tinnitus questionnaires. Safety, tolerability and pharmacokinetics of drug.	perceived at the moment of the measurement at 2 hrs after dosing (or at any other time point vs. pre-dose baseline).

Trial Locations

Locations (1)

GSK Investigational Site; 🇬🇧 Cambridge, Cambridgeshire, United Kingdom