TinnitusPhase 3TACTT2NCT01803646

AM-101 in the Treatment of Acute Tinnitus 2

A Phase 3 study testing AM-101 in people with Tinnitus, run by Auris Medical, Inc. at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

The purpose of this research study is to test the safety and effectiveness of the study drug, AM-101. AM-101 is tested for the treatment of tinnitus that started as the result of an injury to the inner ear or due to middle ear inflammation (otitis media). Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Tinnitus
What is being tested?: AM-101
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 343 participants
Where: 1 siteUnited States
Study dates: Feb 2014to Jun 2016
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Persistent subjective peripheral tinnitus (unilateral or bilateral) following traumatic cochlear injury (acute acoustic trauma, blast trauma, middle ear surgery, inner ear barotrauma, tympanic membrane trauma) or otitis media with onset no longer than 3 months prior to randomization
Age ≥ 18 years and ≤ 75 years (≥ 14 years and ≤ 75 years at selected sites);
Negative pregnancy test (woman of childbearing potential);
Willing and able to use adequate hearing protection, respectively to refrain from engaging in activities or work involving loud noise exposure where sufficient hearing protection is not possible or ensured;
Willing and able to protect ear canal and middle ear from water exposure as long as tympanic membrane is not fully closed.
Other protocol-defined inclusion criteria may apply.

Who cannot join

Fluctuating tinnitus;
Intermittent tinnitus;
Tinnitus resulting from traumatic head or neck injury;
Presence of chronic tinnitus;
Meniere's Disease, history of endolymphatic hydrops, or history of fluctuating hearing loss;
History of repeated idiopathic sudden sensorineural hearing loss or history of acoustic neuroma;

Show all 13Show fewer

Ongoing acute or chronic otitis media or otitis externa;
Other treatment of tinnitus for the study duration;
Known hypersensitivity, allergy or intolerance to the study medication or any history of severe, abnormal drug reaction;
Women who are breast-feeding, pregnant or who are planning to become pregnant during the study;
Women of childbearing potential who are unwilling or unable to practice contraception, such as hormonal contraceptives, double barrier, sexual abstinence or intercourse with a partner who has been vasectomised for at least three months;
Concurrent participation in another clinical study or participation in another clinical study within 30 days prior to randomization.
Other protocol-defined exclusion criteria may apply.

Trial locations and contacts

1 site in 1 country.

United States1 site

Medpace
Cincinnati, Ohio, 45227

Other trials in United States

About this study

Official title: Efficacy and Safety of AM-101 in the Treatment of Acute Peripheral Tinnitus 2

Read the detailed description

This phase III study is assessing the drug's safety and is aiming to demonstrate efficacy of repeated intratymanic AM-101 injections in the treatment of acute peripheral tinnitus (up to 3 months from onset).

Conditions: Tinnitus
Being tested: AM-101, Placebo
Medical subject headings: Tinnitus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AM-101Drug
AM-101 gel for intratympanic injection
PlaceboDrug
Placebo gel for intratympanic injection

Study groups in NCT01803646
Study group	Role	What they receive
AM-101 injection	Experimental	AM-101 Receives: Drug: AM-101
Placebo injection	Placebo comparator	Placebo Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Efficacy: Change in Patient-reported Tinnitus Loudness Questionnaire (TLQ) Improvement From Baseline to Follow up Visit 3 (FUV3)
Starting at the screening visit (SV), each subject recorded the following numerical rating scales (NRS) throughout the entire study duration:
- Tinnitus loudness "at its loudest" within the last 24 hours (Tinnitus Loudness Questionnaire [TLQ] NRSLoudest). Subjects were asked "On a scale from 0 to 10, where 0 represents no tinnitus and 10 represents extremely loud tinnitus, what one number best describes your tinnitus at its loudest in the last 24 hours (including right now)?" TLQ NRSLoudest was collected from SV (D-14) to the evening before FUV3 (D83). The ratings were to be recorded every day before going to sleep on an electronic device.
As Baseline the10 ratings of the screening period before the first treatment were averaged. For the FUV3 endpoint, the ratings of the 7 days before FUV3 were averaged.
Measured: Screening (D-14) versus final follow-up (D83)
Co-Primary Efficacy: Improvement in Tinnitus Functional Index (TFI) Total Score From Baseline to FUV3
The TFI was recorded on an electronic device (electronic patient reported outcome) at Treatment Visit 1 (TV1), before randomization, and at Follow up Visit 1 (FUV1), FUV2 and FUV3.
The TFI is a patient reported outcome questionnaire and contains 25 questions. It includes eight subscales: Intrusive, Sense of Control, Cognitive, Sleep, Auditory, Relaxation, Quality of Life, and Emotional. Each question is to be rated on a NRS between 0 and 10 (or 0 to 100%), with a recall period of "over the past week".
The TFI total score is considered as valid if there are evaluable answers for at least 19 of the 25 items (76% of items) (Meikle et al. 2012). The repondent's overall TFI score is within a 0-100 range. For the subscales the range is the same. A lower value represents an improvement for all scales.
Please refer to the following publicly available link for more information: http://download.lww.com/wolterskluwer_vitalstream_com/PermaLink/EANDH/A/EANDH_2011_09_27_HENRY_200593_SDC15.pdf
Measured: D0 (=TV1) versus Day 84 (=FUV3)
Safety: Frequency of Subjects With Deterioration of Hearing at Follow up Visit 2 (FUV2)
Occurence of deterioration of hearing (Air and Bone conduction) in the treated ear at FUV2.
Deterioration is defined as a deterioration of hearing threshold of at least 15 dB from Baseline at the average of 2 contiguous frequencies.
Measured: Day 35

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Feb 2014Jun 2016

First posted4 Mar 2013 (estimated)
Study startFeb 2014
Primary completionJun 2016
Study completionJun 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for TinnitusStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 343 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01803646
Sponsor's protocol ID: AM-101-CL-12-01
Acronym: TACTT2
Status last verified: May 2018
First submitted: 1 Mar 2013
Last updated: 29 May 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Staecker H, Morelock M, Kramer T, Chrbolka P, Ahn JH, Meyer T. Safety of Repeated-Dose Intratympanic Injections with AM-101 in Acute Inner Ear Tinnitus. Otolaryngol Head Neck Surg. 2017 Sep;157(3):478-487. doi: 10.1177/0194599817711378. Epub 2017 Jun 13.
PubMed 28608739

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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A Study of the Safety and Efficacy of TRTL-913 in Healthy Volunteers (Part A) and in Adults With Tinnitus (Part B)
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Effect of a Totally Implantable Cochlear Implant on Tinnitus Severity in Adults With Preoperative Tinnitus
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Enrolling by invitationObservational study
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All Tinnitus trials

Study at a glance

From the registry record, last updated by the sponsor on 29 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Efficacy and Safety of AM-101 in the Treatment of Acute Peripheral Tinnitus 2
ClinicalTrials.gov ID: NCT01803646
Acronym / sponsor ID: TACTT2 / AM-101-CL-12-01
Conditions: Tinnitus
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 343 participants (actual)
Lead sponsor: Auris Medical, Inc.Industry (pharma, biotech, devices)
Study start: Feb 2014
Primary completion: Jun 2016 (actual)
Study completion: Jun 2016 (actual)
First posted: 4 Mar 2013 (estimated)
Results: Posted 29 May 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
AM-101 injection	Experimental	Drug: AM-101AM-101
Placebo injection	Placebo comparator	Drug: PlaceboPlacebo

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

Persistent subjective peripheral tinnitus (unilateral or bilateral) following traumatic cochlear injury (acute acoustic trauma, blast trauma, middle ear surgery, inner ear barotrauma, tympanic membrane trauma) or otitis media with onset no longer than 3 months prior to randomization
Age ≥ 18 years and ≤ 75 years (≥ 14 years and ≤ 75 years at selected sites);
Negative pregnancy test (woman of childbearing potential);
Willing and able to use adequate hearing protection, respectively to refrain from engaging in activities or work involving loud noise exposure where sufficient hearing protection is not possible or ensured;
Willing and able to protect ear canal and middle ear from water exposure as long as tympanic membrane is not fully closed.

Key exclusion criteria (13 listed)

Fluctuating tinnitus;
Intermittent tinnitus;
Tinnitus resulting from traumatic head or neck injury;
Presence of chronic tinnitus;
Meniere's Disease, history of endolymphatic hydrops, or history of fluctuating hearing loss;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
AM-101AM-101 gel for intratympanic injection	Drug	AM-101 injection
PlaceboPlacebo gel for intratympanic injection	Drug	Placebo injection

Primary outcome

Efficacy: Change in Patient-reported Tinnitus Loudness Questionnaire (TLQ) Improvement From Baseline to Follow up Visit 3 (FUV3)
Time frame: Screening (D-14) versus final follow-up (D83)
Starting at the screening visit (SV), each subject recorded the following numerical rating scales (NRS) throughout the entire study duration: - Tinnitus loudness "at its loudest" within the last 24 hours (Tinnitus Loudness Questionnaire [TLQ] NRSLoudest). Subjects were asked "On a scale from 0 to 10, where 0 represents no tinnitus and 10 represents extremely loud tinnitus, what one number best describes your tinnitus at its loudest in the last 24 hours (including right now)?" TLQ NRSLoudest was collected from SV (D-14) to the evening before FUV3 (D83). The ratings were to be recorded every day before going to sleep on an electronic device. As Baseline the10 ratings of the screening period before the first treatment were averaged. For the FUV3 endpoint, the ratings of the 7 days before FUV3 were averaged.
Co-Primary Efficacy: Improvement in Tinnitus Functional Index (TFI) Total Score From Baseline to FUV3
Time frame: D0 (=TV1) versus Day 84 (=FUV3)
The TFI was recorded on an electronic device (electronic patient reported outcome) at Treatment Visit 1 (TV1), before randomization, and at Follow up Visit 1 (FUV1), FUV2 and FUV3. The TFI is a patient reported outcome questionnaire and contains 25 questions. It includes eight subscales: Intrusive, Sense of Control, Cognitive, Sleep, Auditory, Relaxation, Quality of Life, and Emotional. Each question is to be rated on a NRS between 0 and 10 (or 0 to 100%), with a recall period of "over the past week". The TFI total score is considered as valid if there are evaluable answers for at least 19 of the 25 items (76% of items) (Meikle et al. 2012). The repondent's overall TFI score is within a 0-100 range. For the subscales the range is the same. A lower value represents an improvement for all scales. Please refer to the following publicly available link for more information: http://download.lww.com/wolterskluwer_vitalstream_com/PermaLink/EANDH/A/EANDH_2011_09_27_HENRY_200593_SDC15.pdf
Safety: Frequency of Subjects With Deterioration of Hearing at Follow up Visit 2 (FUV2)
Time frame: Day 35
Occurence of deterioration of hearing (Air and Bone conduction) in the treated ear at FUV2. Deterioration is defined as a deterioration of hearing threshold of at least 15 dB from Baseline at the average of 2 contiguous frequencies.

Results and safety

Results posted to the registry on 29 May 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
AM-101 0.87 mg/mL Gel	204	187
Placebo Gel	139	129

Primary outcome: Efficacy: Change in Patient-reported Tinnitus Loudness Questionnaire (TLQ) Improvement From Baseline to Follow up Visit 3 (FUV3)

Time frame: Screening (D-14) versus final follow-up (D83). Least squares mean (95% Confidence Interval). Unit: units on a scale

Measure	AM-101 0.87 mg/mL Gel n = 195	Placebo Gel n = 129
Value	0.80 (0.51 to 1.08)	0.63 (0.38 to 0.87)

AM-101 0.87 mg/mL Gel vs Placebo Gel: Mean Difference (Net): -0.17 (95% CI -0.51 to 0.17), p = 0.32, Mixed Models Analysis

Population analysed: Valid for Efficacy dataset includes all subjects treated with at least one i.t. injection (AM-101 or placebo), a valid TLQ NRSLoudest or TFI rating at baseline and at least one valid post-baseline rating. Ten subjects had neither TLQ nor TFI baseline and 2 subjects had no valid rating for the TLQ resulting in 324 evaluable subjects.

Primary outcome: Co-Primary Efficacy: Improvement in Tinnitus Functional Index (TFI) Total Score From Baseline to FUV3

Time frame: D0 (=TV1) versus Day 84 (=FUV3). Least squares mean (95% Confidence Interval). Unit: units on a scale

Measure	AM-101 0.87 mg/mL Gel n = 180	Placebo Gel n = 121
Value	10.4 (6.5 to 14.3)	9.6 (5.9 to 13.3)

AM-101 0.87 mg/mL Gel vs Placebo Gel: Mean Difference (Net): -0.79 (95% CI -4 to 2.4), p = 0.63, Mixed Models Analysis

Population analysed: Valid for Efficacy dataset includes all subjects treated with at least one i.t. injection (AM-101 or placebo), a valid TLQ NRSLoudest or TFI rating at baseline and at least one valid post-baseline rating. Ten subjects had neither TLQ nor TFI baseline plus additional 25 subjects had no baseline for the TFI resulting in 301 evaluable subjects.

Primary outcome: Safety: Frequency of Subjects With Deterioration of Hearing at Follow up Visit 2 (FUV2)

Time frame: Day 35. Count of participants. Unit: Participants

Measure	AM-101 0.87 mg/mL Gel n = 193	Placebo Gel n = 130
Air conduction: Subjects with hearing deterioration	12	9
Air conduction: Subjects without hearing deterioration	181	121
Bone conduction: Subjects with hearing deterioration	3	4
Bone conduction: Subjects without hearing deterioration	190	126

AM-101 0.87 mg/mL Gel vs Placebo Gel: p = 0.821, Fisher Exact
AM-101 0.87 mg/mL Gel vs Placebo Gel: p = 1.0, Fisher Exact

Population analysed: Valid for Safety dataset was used. Of the 336 valid for safety subjects, 323 could be evaluated for this endpoint.

Adverse events

Time frame: Assessed by Investigator at all Visits from Screening Visit (SV, D-14) to end of treatment visit FUV3 (D84). Including at treatment visit 1 (TV1), TV2, TV3, FUV1 and FUV2. It was also assessed at Conditional Visits if they were required.. Other adverse events reported at 2% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
AM-101 0.87 mg/mL Gel	5 of 201 (2.5%)	63 of 201 (31.3%)	0 of 201
Placebo Gel	1 of 135 (0.7%)	38 of 135 (28.1%)	0 of 135

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 28608739Staecker H, Morelock M, Kramer T, Chrbolka P, Ahn JH, Meyer T. Safety of Repeated-Dose Intratympanic Injections with AM-101 in Acute Inner Ear Tinnitus. Otolaryngol Head Neck Surg. 2017 Sep;157(3):478-487. doi: 10.1177/0194599817711378. Epub 2017 Jun 13.

Related trials for Tinnitus

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Acute Nicotine Gum and Auditory Brain Responses in Adults With Chronic Tinnitus
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RecruitingPhase 2
A Study of the Safety and Efficacy of TRTL-913 in Healthy Volunteers (Part A) and in Adults With Tinnitus (Part B)
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing AM-101 in people with Tinnitus, run by Auris Medical, Inc. at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 May 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 May 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Efficacy: Change in Patient-reported Tinnitus Loudness Questionnaire (TLQ) Improvement From Baseline to Follow up Visit 3 (FUV3) (time frame: Screening (D-14) versus final follow-up (D83)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01803646, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 May 2018.