Last updated: 11/04/2018 09:44:08
Vestipitant Or Vestipitant/Paroxetine Combination In Subjects With Tinnitus And Hearing Loss.
EudraCT ID
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
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
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Crossover Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
Visual Analog Scales (VAS) score as a measure of the change in tinnitus loudness (intensity) at 2 hours after dosing
Timeframe: 2 hours post dose on Day 1 and 14 of each treatment period
Secondary outcomes:
VAS to measure the level in tinnitus pitch (or frequency) and tinnitus distress as perceived at the moment of the measurement
Timeframe: 2 hours post dose on Day 1 and 14 of each treatment period
VAS arousal/anxiety score (tired-energetic, active-drowsy, tense-peaceful, and worried-relaxed)
Timeframe: Day 1 and Day 14 of each treatment period
Tinnitus Handicap Inventory (THI) total scores assessed as a measure of Self-report questionnaire
Timeframe: Day 1 and Day 14 of each treatment period
Quick Inventory of Depressive Symptomatology (QIDS-SR 16) total score assessed as a measure of Self-report questionnaire
Timeframe: Up to Day 14 of teach treatment period
Mean Annoyance of Tinnitus: clinician rated scale
Timeframe: Up to Day 14
Mean annoyance score of Hyperacusis at Day 1 and 14
Timeframe: Up to Day 14 of each treatment period
Annoyance of Hyperacusis distress score on the 0–7 scale
Timeframe: Up to Day 14 of each treatment period
Number of participants with adverse events and serious adverse events
Timeframe: Up to Day 84
Mean Systolic and Diastolic blood pressure (SBP and DBP) over period
Timeframe: Up to Day 14 of each treatment period.(Approximately up to Day 84)
Mean heart rate over period
Timeframe: Up to Day 14 of each treatment period (Approximately up to Day 84)
Number of participants with abnormal electrocardiogram (ECG) Findings over period
Timeframe: Up to Day 14 of each treatment period (Approximately up to Day 84)
Mean Hematology Values-Basophils, Eosinophils, Lymphocytes, Monocytes, WBCs, Neutrophils, platelet count over period
Timeframe: Up to Day 14 of each treatment period (Approximately up to Day 84)
Mean hematocrit values over period
Timeframe: Up to Day 14 of each treatment period (Approximately up to Day 84)
Summary of mean Hematology Values-Hemoglobin (Hb) and Mean Corpuscle Hemoglobin concentration (MCHC)
Timeframe: Up to Day 14 of each treatment period (Approximately up to Day 84)
Summary of mean Chemistry Laboratory Values-Calcium, Cholesterol, Glucose, Potassium, Sodium, Phosphorus, Triglycerides, Urea/BUN
Timeframe: Up to Day 14 of each treatment period (Approximately up to Day 84)
Summary of mean Chemistry Laboratory Values-Albumin, Globulin
Timeframe: Up to Day 14 of each treatment period (Approximately up to Day 84)
Summary of mean Chemistry Laboratory Values-Total Bilirubin, Creatinine, Uric acid
Timeframe: Up to Day 14 of each treatment period (Approximately up to Day 84)
Mean Chemistry Laboratory Values of Alkaline Phosphatase (ALP), Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT), Lactate Dehydrogenase over period
Timeframe: Up to Day 14 of each treatment period (Approximately up to Day 84)
Plasma Pharmacokinetic Concentration of Vestipitant
Timeframe: pre-dose and 2 to 5 hours post-dose on each Day 1 and Day 14
Plasma Pharmacokinetic Concentration of Paroxetine
Timeframe: pre-dose and 2 to 5 hours post-dose on each Day 1 and Day 14
Interventions:
Enrollment:
24
Primary completion date:
2009-06-08
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical 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.
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.
Medical condition
Tinnitus
Product
paroxetine, vestipitant
Collaborators
Not applicable
Study date(s)
December 2006 to August 2009
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
18 - 65 years
Accepts healthy volunteers
No
- Inclusion criteria:
- Male or female subjects with a diagnosed tinnitus.
Inclusion and exclusion criteria
Inclusion 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.
Trial location(s)
Location
GSK Investigational Site
Cambridge, Cambridgeshire, United Kingdom, CB2 2GG
Status
Will Be Recruiting
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Study complete
Actual primary completion date
2009-06-08
Actual study completion date
2009-06-08
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
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