Efficacy and Safety of AUT00063 Versus Placebo in Age-Related Hearing Loss

Study Overview
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Brief Summary
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This study aims to demonstrate that the investigational drug AUT00063 is effective and safe in the treatment of age-related hearing loss.

Detailed Description
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Reduced activity at certain sites in the brain (called voltage-gated potassium channels) has been linked to hearing problems, like age-related loss of hearing or tinnitus (a 'ringing' or buzzing noise in the ears). AUT00063 is an experimental new medicine that enhances the action of these specific channels and so may treat the brain component of these hearing problems. The main purpose of this study is to try to demonstrate an improvement in a speech-in-noise deficit after 4 weeks of treatment with the study drug versus the placebo (dummy drug which does not contain the drug). Subjects will undergo a safety follow-up after the treatment period. Safety and efficacy will be determined by looking at a number of assessments (physical examinations, blood sampling, hearing assessments, questionnaires, etc.). The amount of drug in the blood will also be measured. It is expected that around 70 people (at least 35 in each arm) with age-related hearing loss may take part in the study. The study participants will be recruited at around 13 sites in the USA.

Official Title
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A Balanced, Randomized, Placebo-Controlled, Double-Blind Study of the Efficacy and Safety of AUT00063 Versus Placebo in Age-Related Hearing Loss [CLARITY-1 Study]

Conditions
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Age-Related Hearing Loss

Intervention / Treatment
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* Drug: AUT00063
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Be between ages 50-89 years old American-English speaking Have difficulty hearing speech in a noisy environment No recent history of middle ear disease No severe insomnia, major depressive disorders, severe anxiety or post-traumatic stress disorder Not a current or previous user of hearing aids. You are eligible if you were noncompliant and stopped wearing a hearing aid device >6 months earlier for intermittent use or >3 years if you were a full-time consistent user of hearing aid devices Not be dependent on alcohol or drugs Have not participated in another research study within 30-days If female, you must confirm to be non child bearing (post-menopausal for at least 12-months or surgically sterile) If male, you must confirm to use a barrier method (condom) Not be a professional musician No history of important cardiac, endocrine, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, immunologic, or other major disease deemed clinically significant by the study doctor While you are in the study, you must: Follow the instructions you are given Come to the study centre for all visits with the study doctor or study staff Answer the telephone at the scheduled date and time for the 2 telephone calls Tell the study doctor or study staff about any changes in your health or the way you feel Tell the study doctor or study staff if you want to stop being in the study at any time Bring your Diary to each visit Not eat or drink anything containing Grapefruit beginning 7-days before Baseline visit (Visit 3, Day 1) until the end of the study Use sun screen if you plan to sunbathe Not use headphones or headsets at high volume Not use hearing aids or devices at any time during the study

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 89 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: AUT00063 (600 mg capsules)<br>3 capsules of 200 mg of the investigational drug AUT00063, to take orally once daily with food for 4 weeks | Drug: AUT00063<br>* 600 mg, orally, once a day, for 4 weeks<br>* Other names: Experimental;|
| Placebo Comparator: (AUT00063 placebo capsules)<br>3 capsules of placebo, to take orally once daily with food for 4 weeks | Drug: Placebo<br>* orally, once a day, for 4 weeks<br>* Other names: Comparator;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Hearing Loss After 4 Weeks of Treatment | To compare the change in hearing using the QuickSIN test (speech in noise performance) from baseline (Day 1 to Day 28) between AUT00063 and placebo. The QuickSIN test measures the level of signal compared to the noise that is required to achieve 50% recognition. The test is administered in a sound booth at 70-dB HL binaurally via insert-ear phones. Three lists are administered to each individual subject and the threshold or 50% signal-to-noise ratio (SNR) is calculated as the mean of the three lists completed. Each list consists of six sentences with five key words to be scored per sentence. The sentences are presented in four-talker babble noise. The sentences are presented at pre-recorded signal-to-noise ratios which decrease in 5-dB steps from 25 (very easy) to 0 (extremely difficult). | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Analysis of Change From Baseline in Adaptive Test of Temporal Resolution (ATTR) on End-Point Visit Day 28 | Final Average GDT Across-Channel at Day 28: Change from Baseline; FAS Population | 28 days | 
| Analysis of Change From Baseline in Adaptive Test of Temporal Resolution (ATTR) on End-Point Visit Day 28 | Final Average GDT Within-Channel at Day 28: Change from Baseline; FAS Population | 28 days | 
| To Further Investigate the Safety and Tolerability Profile of Repeat Administration of AUT00063 by Assessing Vital Signs, Physical Examination, Laboratory Exams and ECG | Number of Subjects With At Least One Treatment Emergent Adverse Event | 42 Days | 
| Pharmacokinetic of AUT00063, Plasma Levels | Exposure of AUT00063 ng/ml, in plasma levels at Day 28 | 28 Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hearing loss, speech-in-noise