Vestipitant Or Vestipitant/Paroxetine Combination In Subjects With Tinnitus And Hearing Loss. - Full Text View

Sponsored by:	GlaxoSmithKline
Information provided by:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT00394056

Purpose

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.

Condition	Intervention	Phase
Tinnitus	Drug: Vestipitant Drug: Vestipitant + Paroxetine	Phase II

Genetics Home Reference related topics: nonsyndromic deafness

MedlinePlus related topics: Hearing Disorders and Deafness Tinnitus Toe Injuries and Disorders

Drug Information available for: Paroxetine Paroxetine hydrochloride Paroxetine Mesylate Vestipitant

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double-Blind, Placebo Control, Crossover Assignment, Efficacy Study
Official Title:	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

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:

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). ]

Secondary Outcome Measures:

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). ]

Estimated Enrollment:	24
Study Start Date:	November 2006

Eligibility

Ages Eligible for Study:	18 Years to 60 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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 disorder or condition that would preclude the administration of vestipitant or Paroxetine.
Existence of any surgical or medical condition which might interfere with the PK of the drug.
Subjects with hepatic impairment or a history of liver dysfunction.
Subjects with renal impairment.
Subjects positive for HIV, hepatitis C or hepatitis B.Subjects with abnormal laboratory, ECG or physical examination findings.
Subjects who are not euthyroid.
Subjects with a history of hepatic, cardiac, renal, neurologic, cerebrovascular, metabolic or pulmonary disease.
Subjects who have had a myocardial infarction.
Subjects with a history of seizure disorders.
Subjects with history of cancer.
Subjects with a history of drug or other allergy.
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.
Medication or foodstuff (e.g. grapefruit or grapefruit juice) which is known to interfere with liver enzymes.
The subject had a non-psychotropic medication with a serotonergic mechanism of action.
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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00394056

Locations

United Kingdom
GSK Clinical Trials Call Centre	Recruiting
Cambridge, United Kingdom, CB2 2GG
Contact: GSK Clinical Trials Call Centre 1-877-379-8718

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director:

GSK Clinical Trials, MD

GlaxoSmithKline

More Information

No publications provided

Study ID Numbers:	NKP106254
Study First Received:	October 27, 2006
Last Updated:	July 5, 2007
ClinicalTrials.gov Identifier:	NCT00394056 History of Changes
Health Authority:	United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by GlaxoSmithKline:

randomised
placebo
crossover
balanced
repeated dose
vestipitant (GW597599)

paroxetine
combination
Tinnitus
Hearing Loss
loudness
annoyance

Study placed in the following topic categories:

Sensation Disorders
Neurotransmitter Agents
Otorhinolaryngologic Diseases
Psychotropic Drugs
Tinnitus
Ear Diseases
Paroxetine
Serotonin Uptake Inhibitors

Serotonin
Signs and Symptoms
Deafness
Hearing Disorders
Neurologic Manifestations
Antidepressive Agents, Second-Generation
Hearing Loss
Antidepressive Agents

Additional relevant MeSH terms:

Sensation Disorders
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Otorhinolaryngologic Diseases
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Nervous System Diseases
Psychotropic Drugs
Tinnitus
Ear Diseases
Paroxetine
Serotonin Uptake Inhibitors

Pharmacologic Actions
Signs and Symptoms
Deafness
Hearing Disorders
Serotonin Agents
Therapeutic Uses
Neurologic Manifestations
Antidepressive Agents, Second-Generation
Hearing Loss
Central Nervous System Agents
Antidepressive Agents

ClinicalTrials.gov processed this record on May 07, 2009