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

October 27, 2016 updated by: GlaxoSmithKline

Randomised, Double-blind, Placebo Controlled, Cross-over Study Comparing the Effects of Both Single Dose and Repeated Dosing Treatment for 14 Days of Vestipitant or Vestipitant / Paroxetine Combination in an Enriched Population of Subjects With Tinnitus & Hearing Loss

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

26

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • Cambridgeshire
      • Cambridge, Cambridgeshire, United Kingdom, CB2 2GG
        • GSK Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • Male or female subjects with a diagnosed tinnitus.
  • Subject with THI severity grade of 3 or 4.
  • Subjects willing to restrict alcohol intake.
  • The subject must have given written consent.
  • Women of childbearing potential who abstain from intercourse OR agree to birth control.
  • Women of non-childbearing potential.

Exclusion criteria:

  • Subject with THI severity grade = 5 or less than or equal to 2.
  • Subject with pathologic level of anxiety or depression.
  • Subject with no audiogram deficit and with normal hearing.
  • Subjects that do not respond to the lidocaine infusion test or show a large variability in pre-infusion values.
  • Subjects with any serious medical or surgical condition
  • Subjects positive for drug use and/or a history of substance abuse or dependence.
  • Subjects who have taken psychotropic drugs or antidepressants within specified time frames.
  • Subjects who have recently used an investigational drug or recently participated in a trial.
  • Subjects who have exhibited intolerance to NK1 antagonists or SSRIs.
  • Women who have a positive pregnancy test.
  • Female subjects who intend to get pregnant or male subjects who intend to father a child within the next 4 weeks following the last study drug administration in the study.
  • Subjects, who have donated a unit of blood or more within the previous month or who intend to donate blood within one month of completing the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Period 1
Other: Placebo
Placebo
Drug: Vestipitant
NK1 receptor antagonist
Drug: Vestipitant + Paroxetine
NK1 receptor antagonist and SSRI
Other Names:
  • Vestipitant
Other: Period 2
Other: Placebo
Placebo
Drug: Vestipitant
NK1 receptor antagonist
Drug: Vestipitant + Paroxetine
NK1 receptor antagonist and SSRI
Other Names:
  • Vestipitant
Other: Period 3
Other: Placebo
Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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).
Time Frame: 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

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

GlaxoSmithKline

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2006

Primary Completion (Actual)

August 1, 2009

Study Completion (Actual)

August 1, 2009

Study Registration Dates

First Submitted

October 27, 2006

First Submitted That Met QC Criteria

October 30, 2006

First Posted (Estimate)

October 31, 2006

Study Record Updates

Last Update Posted (Estimate)

October 28, 2016

Last Update Submitted That Met QC Criteria

October 27, 2016

Last Verified

October 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NKP106254

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

  1. Individual Participant Data Set
    Information identifier: NKP106254
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  2. Clinical Study Report
    Information identifier: NKP106254
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  3. Informed Consent Form
    Information identifier: NKP106254
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  4. Dataset Specification
    Information identifier: NKP106254
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  5. Statistical Analysis Plan
    Information identifier: NKP106254
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  6. Study Protocol
    Information identifier: NKP106254
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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