Efficacy and Safety of AUT00063 Versus Placebo in Age-Related Hearing Loss (CLARITY-1)

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]

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

Study Overview

• Status: Completed
• Conditions: Age-Related Hearing Loss
• Intervention / Treatment: Drug: Placebo; Drug: AUT00063

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95815
      • Sacramento ENT
  • Colorado
    • Colorado Springs, Colorado, United States, 80909
      • Colorado ENT and Allergy
  • Florida
    • Boca Raton, Florida, United States, 33487
      • ENT Associates of South Florida
    • Miami, Florida, United States, 33143
      • QPS MRA (Miami Research Associates)
    • Tampa, Florida, United States, 33620
      • University of South Florida
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville
  • Minnesota
    • Rochester, Minnesota, United States, 55095
      • Mayo Clinic
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • The University of Mississippi Medical Center
  • New York
    • New Hyde Park, New York, United States, 11042
      • Long Island Jewish Medical Center
  • North Carolina
    • Wilmington, North Carolina, United States, 28401
      • PMG Research Inc.
    • Winston-Salem, North Carolina, United States, 27103
      • Piedmont Ear, Nose, & Throat Associates
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Utah
    • Murray, Utah, United States, 84107
      • Jean Brown Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 89 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: AUT00063 (600 mg capsules); 3 capsules of 200 mg of the investigational drug AUT00063, to take orally once daily with food for 4 weeks	Drug: AUT00063; 600 mg, orally, once a day, for 4 weeks; Other Names: Experimental
PLACEBO_COMPARATOR: (AUT00063 placebo capsules); 3 capsules of placebo, to take orally once daily with food for 4 weeks	Drug: Placebo; orally, once a day, for 4 weeks; Other Names: Comparator

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Autifony Therapeutics Limited
• Investigators: Principal Investigator: Robert Frisina, PhD, Director Global Center for Hearing and Speech Research

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (ACTUAL): May 1, 2016
• Study Completion (ACTUAL): June 1, 2016

Study Registration Dates

• First Submitted: January 19, 2015
• First Submitted That Met QC Criteria: January 22, 2015
• First Posted (ESTIMATE): January 26, 2015

Study Record Updates

• Last Update Posted (ACTUAL): August 9, 2018
• Last Update Submitted That Met QC Criteria: August 8, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: hearing loss; speech-in-noise
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Otorhinolaryngologic Diseases; Ear Diseases; Sensation Disorders; Hearing Disorders; Hearing Loss, Sensorineural; Hearing Loss; Deafness; Presbycusis
• Other Study ID Numbers: AUT022063