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

• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Tracking Information

• First Submitted Date: October 27, 2006
• First Posted Date: October 31, 2006
• Last Update Posted Date: October 28, 2016
• Study Start Date: December 2006
• Actual Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: July 5, 2007): 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). ]
• Original Primary Outcome Measures (submitted: October 30, 2006): 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).
• Change History: Complete list of historical versions of study NCT00394056 on ClinicalTrials.gov Archive Site
• Current Secondary Outcome Measures (submitted: July 5, 2007): 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). ]
• Original Secondary Outcome Measures (submitted: October 30, 2006): VAS to measure tinnitus pitch, distress and anxiety. Pure Tone Audiometry & Psychoacoustic assessment. Sleep & Tinnitus questionnaires. Safety, tolerability and pharmacokinetics of drug.
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Vestipitant Or Vestipitant/Paroxetine Combination In Subjects With Tinnitus And Hearing Loss.
• 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Tinnitus

Intervention

• Drug: Vestipitant
  NK1 receptor antagonist
• Drug: Vestipitant + Paroxetine
  NK1 receptor antagonist and SSRI
  Other Name: Vestipitant
• Other: Placebo
  Placebo

Study Arms

• Period 1
  Interventions:

  • Drug: Vestipitant
  • Drug: Vestipitant + Paroxetine
  • Other: Placebo
• Period 2
  Interventions:

  • Drug: Vestipitant
  • Drug: Vestipitant + Paroxetine
  • Other: Placebo
• Period 3
  Intervention: Other: Placebo

• Publications *: Claire Roberts, Amir Inamdar, Annelize Koch, Pauline Kitchiner, Odile Dewit, Emilio Merlo-Pich, Paolo Fina, Don J. McFerran & David M. Baguley. A Randomised, Double-blind, Placebo Controlled, Cross-over Study Comparing the Effects of Both Single and Repeated Dosing of Vestipitant or Vestipitant & Paroxetine in Treating Subjects with Moderate to Severe Tinnitus. [Otol Neurotol]. 2011;32(5):721-727.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 18, 2010): 26
• Original Enrollment (submitted: October 30, 2006): 24
• Actual Study Completion Date: August 2009
• Actual Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)

Eligibility 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 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT00394056
• Other Study ID Numbers: NKP106254
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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.

• Responsible Party: GlaxoSmithKline
• Study Sponsor: GlaxoSmithKline
• Collaborators: Not Provided

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

• PRS Account: GlaxoSmithKline
• Verification Date: October 2016