Clinical trial NCT02315508: Evaluating Possible Improvement in Tinnitus Severity After 28 Days Dosing of the Study Drug AUT00063 Compared to Placebo
Official title: A Balanced Randomised Placebo Controlled Double-blind Phase IIa Study to Investigate the Efficacy and Safety of AUT00063 Versus Placebo in Subjective Tinnitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Tinnitus, Subjective
Lead sponsor: Autifony Therapeutics Limited
Sponsor class: INDUSTRY
Collaborators: name: University of Nottingham
First posted: 2014-12-12
Enrollment: 91
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study aims to demonstrate that the new medicine AUT00063 is effective and safe in the treatment of tinnitus.

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 has been developed to improve the action of these specific channels and so treat the brain component of these hearing problems.

The main purpose of this study is to try to demonstrate an improvement in the severity of tinnitus after 4 weeks of treatment with the study medicine or the placebo (dummy drug which does not contain the medication). 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.) and in case of any serious medical event during the study. The amount of drug in the blood will also be measured.

It is expected that up to 152 people with tinnitus may take part in the study. The study participants will be recruited at around 16 Hospital sites in the UK.

Eligibility criteria: Inclusion Criteria:

* English-speaking, who are UK residents registered with a UK General Practitioner;
* Experiencing stable tinnitus (consistent from day to day)
* Tinnitus has existed for not less than 6 months, and not more than 18 months - Contraceptive methods must be used before and for at least 30 days after the stop of the study treatment.

Exclusion Criteria:

* Severe hearing impairment such that verbal communication is unreliable;
* History of important cardiac, endocrine, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, immunologic, or other major diseases deemed clinically significant at the time of the study by the Investigator and which might be jeopardised by entering the study;
* Moderate or severe depression or generalised anxiety
* Participation in any clinical research study evaluating another investigational drug or therapy within 30 days of starting the investigational treatment
* Participation in hearing study, involving an intervention, within 3 months from last study visit;
* Central nervous system pathologies e.g. Multiple Sclerosis, Parkinson's disease;
* Tinnitus as a concomitant symptom of a known otological condition (including but not limited to otitis externa, otitis media, otosclerosis, cholesteatoma, Ménière's disease or other vestibular problems, acoustic neuroma, or temporo-mandibular joint disorder);
* Pulsatile tinnitus (rhythmical sounds that often beat in time with the heartbeat);
* Intermittent tinnitus (comes and goes from one day to the next);
* Surgery or medical condition that might would be expected to significantly affect absorption of medicines;

Primary outcomes:
measure: Change in subjective Tinnitus after 4 weeks treatment
timeFrame: 28 days
Secondary outcomes:
measure: To further investigate the safety and tolerability profile of repeat administration of AUT00063 (assessing vital signs, physical examination, laboratory exams and ECG)
timeFrame: 42 days
measure: Change in Tinnitus Loudness matching after 4 weeks of treatment
timeFrame: 28 days
measure: Pharmacokinetic of AUT00063 (Exposure of AUT00063 ng/ml, measured as AUT00063 plasma levels)
timeFrame: at day 28
Other outcomes:
Locations:
city: Birmingham
country: United Kingdom
facility: Birmingham University Hospital
city: Bradford
country: United Kingdom
facility: Bradford Teaching Hospital
city: Bristol
country: United Kingdom
facility: Bristol Royal Infirmary
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Trust
city: Frimley
country: United Kingdom
facility: Frimley Health NHS Foundation Trust
city: London
country: United Kingdom
facility: University College London Hospital NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: The Pennine Acute Hospitals NHS Trust
city: Newcastle
country: United Kingdom
facility: Freeman Hospital
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospital Foundation Trust
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
city: Plymouth
country: United Kingdom
facility: Derriford Plymouth NHS Trust
city: Portsmouth
country: United Kingdom
facility: Portsmouth Hospitals NHS Trust
city: Salford
country: United Kingdom
facility: Salford Royal Hospital
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital, Sheffield
city: Stevenage
country: United Kingdom
facility: Lister Hospital
city: Stoke-on-Trent
country: United Kingdom
facility: University Hospital of North Staffordshire
city: Telford
country: United Kingdom
facility: Shrewsbury and Telford Hospital NHS Trust
city: Wigan
country: United Kingdom
facility: Wrightington Hospital
Study officials:
affiliation: Sheffield Teaching Hospitals NHS Foundation Trust
name: Jaydip Ray, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hall DA, Ray J, Watson J, Sharman A, Hutchison J, Harris P, Daniel M, Millar B, Large CH. A balanced randomised placebo controlled blinded phase IIa multi-centre study to investigate the efficacy and safety of AUT00063 versus placebo in subjective tinnitus: The QUIET-1 trial. Hear Res. 2019 Jun;377:153-166. doi: 10.1016/j.heares.2019.03.018. Epub 2019 Mar 27.