Otonomy OTO-313 — Treatment of Tinnitus

[ajc]

Isn't the OTO-313 trial only for unilateral tinnitus? Why are so many of you thinking you can enroll? Unilateral tinnitus is very rare...

 

[Gb3]

Isn't the OTO-313 trial only for unilateral tinnitus? Why are so many of you thinking you can enroll? Unilateral tinnitus is very rare...

I'd be worried about @Piney and @Mentos.

I on the other hand have unilateral tinnitus.

 

[Ehren M]

How do they choose the parameters?

How do they decide what is the 'right/important' age/duration etc?

Genuine questions, open to anyone. I'm not familiar with scientific studies, so curious how parameters don't indicate who they think the drug will work for.

That's a great question.

What's necessary to include as a factor is more of a conversation piece rather than a set of rules. It's often a matter of incorporating knowledge gained from related studies, common sense, and good old fashioned sleuthing through the data at-hand (graphing and testing relationships between variables).

In short, it all depends on how hard the investigators look at the data.

Meaningful trends can be easily overlooked and/or disguised if experiments are not designed and analyzed meticulously, including valid parameterization (in this case, I mean how investigators account for variables that are likely to influence results, like age, duration of symptoms, etc.). Then add in the issue of trying to analyze data from humans reporting a rather imperfect measure of discomfort, and you can see why it's tough to find trends in the kind of clinical studies people talk about here on Tinnitus Talk. A botanist or chemist might be over-doing it with a sample size of 20, but the Phase II OTO-313 study seeks a sample size of closer to 70 because this data is going to be noisy due to the sheer fact that people's assessment of tinnitus improvement is hard to measure accurately.

 

[FGG]

That's a great question.

What's necessary to include as a factor is more of a conversation piece rather than a set of rules. It's often a matter of incorporating knowledge gained from related studies, common sense, and good old fashioned sleuthing through the data at-hand (graphing and testing relationships between variables).

In short, it all depends on how hard the investigators look at the data.

Meaningful trends can be easily overlooked and/or disguised if experiments are not designed and analyzed meticulously, including valid parameterization (in this case, I mean how investigators account for variables that are likely to influence results, like age, duration of symptoms, etc.). Then add in the issue of trying to analyze data from humans reporting a rather imperfect measure of discomfort, and you can see why it's tough to find trends in the kind of clinical studies people talk about here on Tinnitus Talk. A botanist or chemist might be over-doing it with a sample size of 20, but the Phase II OTO-313 study seeks a sample size of closer to 70 because this data is going to be noisy due to the sheer fact that people's assessment of tinnitus improvement is hard to measure accurately.

My speculation on the unilateral parameter is three fold:

1) They are measuring subjective tinnitus impression and quality of life. If you only do one ear it will be muddied by how bad your other ear is.

2) There may also be a physiologic reason. Unilateral tinnitus may have more of a local cochlear Glutamate/NMDA receptor mediated pathology. This effect is pretty universal acutely but the people who "stay unilateral" might have less of a central hyperexcitabilty (due to the auditory damage/"phantom cochlea" maladaptive neuroplasticity) and more of a local hyperexcitabilty that gets propagated centrally. The drug may work better acutely except in cases of unilateral tinnitus for reasons such as this.

3) There could be a safety concern for reasons I can't even begin to speculate on. Even though we don't know if @ChrisBoyMonkey got the placebo or not, his tinnitus worsened in his other ear after getting the drug during Phase 1. Is there a risk with bilateral tinnitus? Who knows.

 

[Gb3]

My speculation on the unilateral parameter is three fold:

1) They are measuring subjective tinnitus impression and quality of life. If you only do one ear it will be muddied by how bad your other ear is.

2) There may also be a physiologic reason. Unilateral tinnitus may have more of a local cochlear Glutamate/NMDA receptor mediated pathology. This effect is pretty universal acutely but the people who "stay unilateral" might have less of a central hyperexcitabilty (due to the auditory damage/"phantom cochlea" maladaptive neuroplasticity) and more of a local hyperexcitabilty that gets propagated centrally. The drug may work better acutely except in cases of unilateral tinnitus for reasons such as this.

3) There could be a safety concern for reasons I can't even begin to speculate on. Even though we don't know if @ChrisBoyMonkey got the placebo or not, his tinnitus worsened in his other ear after getting the drug during Phase 1. Is there a risk with bilateral tinnitus? Who knows.

I have unilateral tinnitus in my ear that suffered sudden hearing loss.

My other ear is fine and no tinnitus.

I don't know why you would have it in the other ear if there was no hearing loss. Does this happen to people that only have hearing loss in one ear?

 

[FGG]

I have unilateral tinnitus in my ear that suffered sudden hearing loss.

My other ear is fine and no tinnitus.

I don't know why you would have it in the other ear if there was no hearing loss. Does this happen to people that only have hearing loss in one ear?

Good question. I have read over the years here that most people's tends to feel "centralized" after awhile. But maybe because the people who don't, don't talk about it?

 

[ajc]

 

[FGG]

View attachment 44474

I wonder if this ratio changes after a certain time period though...

 

[Piney]

I'd be worried about @Piney and @Mentos.

I on the other hand have unilateral tinnitus.

I have unilateral tinnitus.

@Mentos, it's your ears, your brain and your choice alone, don't let anybody on here dictate your decision.

These companies don't know everything. If they did, there would be a cure.

Who is to say a 12-month time period isn't a bad parameter on their part, maybe if the duration was unlimited they would learn something new or save someone in distress.

Pretty sure if someone had tinnitus and got the shot, they could tell you if it worked or not. If someone chose to lie, they could lie about anything, even if they were honest and were within the parameters. Trust has to enter the picture somewhere.

 

[Tezcatlipoca]

I have unilateral tinnitus.

@Mentos, it's your ears, your brain and your choice alone, don't let anybody on here dictate your decision.

These companies don't know everything. If they did, there would be a cure.

Who is to say a 12-month time period isn't a bad parameter on their part, maybe if the duration was unlimited they would learn something new or save someone in distress.

Pretty sure if someone had tinnitus and got the shot, they could tell you if it worked or not. If someone chose to lie, they could lie about anything, even if they were honest and were within the parameters. Trust has to enter the picture somewhere.

You don't get it at all, do you? I won't waste my time anymore trying to explain it, just know that if you do get in the trial you're screwing everyone here.

 

[Jrblovsky]

Unilateral tinnitus is very rare...

It really isn't.

 

[Markku]

Thanks for sending me a ping!

I wonder if this ratio changes after a certain time period though...

Our survey from 2016, with over 5,000 respondents, and our more recent Tinnitus & The Body survey, with over 8,000 respondents, might shed some light. I guess we could see the percentages of bilateral/unilateral in various groups of tinnitus duration.

Of course it requires analyzing the raw data to make the connections. And this data set wouldn't show how many started with unilateral tinnitus, but ended up with bilateral (I've seen this mentioned quite a number of times here on the forums). This kind of longitudinal data collection is something we have planned to launch later this year.

@Hazel, want to run some quick analysis on these question pairs?

 

[FGG]

Who is to say a 12-month time period isn't a bad parameter on their part, maybe if the duration was unlimited they would learn something new or save someone in distress.

I don't disagree they might learn something new but I don't think during a clinical trial where they are trying to get as homogeneous of a group as possible is the time to do that.

Causing inconsistent data hurts everyone and delays drug release (or can even halt it). Even if you were thinking of your own suffering, you could even get placebo and then be contributing to a longer wait to get actual drug.

AM-101 had the same mechanism of action as this drug and failed. Picking the right patient is a really important part of drug trials.

 

[Ehren M]

You don't get it at all, do you? I won't waste my time anymore trying to explain it, just know that if you do get in the trial you're screwing everyone here.

Also, if you ever get tinnitus again (or it worsens), being dishonest now in order to join a clinical trial could screw up your chances of having the drug available when you need it later.

 

[Piney]

You don't get it at all, do you? I won't waste my time anymore trying to explain it, just know that if you do get in the trial you're screwing everyone here.

No, you don't get it. It's hard to tell anything to someone who thinks they know everything. I've stood in the trial ENT building in Carolina. It took months for anyone to qualify for FX-322 and their parameters, that's why they were late but yet they have the power to approve or disapprove anyone. They choose who is accepted into the trial. It's on them. Don't complain about the participants putting up their ear at risk because that is a distorted view. People weren't flying overseas to get into their trial just to lie about it. The companies take donations, the companies make money, it's up to them to get proper results.

 

[Piney]

Also, if you ever get tinnitus again (or it worsens), being dishonest now in order to join a clinical trial could screw up your chances of having the drug available when you need it later.

Dishonest about what? What's the timeframe they're measuring exactly? I hear my tinnitus. I'll be honest and tell you if I don't hear it.

 

[Gb3]

Unilateral tinnitus is very rare...

It really isn't.

Ya, it's not at all rare.

 

[Gb3]

You don't get it at all, do you? I won't waste my time anymore trying to explain it, just know that if you do get in the trial you're screwing everyone here.

I agree. This is what worries me. You have some people who only care about themselves and choose not to follow the rules and will ruin it for everyone. There is a reason they post the exclusion criteria so you don't waste their time.
@Piney said:

You should absolutely enter this trial. Whether you've had tinnitus for 4 months or 40 years, if the drug works, it works.

 

[Piney]

I agree. This is what worries me. You have some people who only care about themselves and choose not to follow the rules and will ruin it for everyone. There is a reason they post the exclusion criteria so you don't waste their time.

It doesn't matter, you're not getting it.

Be honest and the location will let you know if they want to see you at an appointment.

But on the other hand, you can never stop people from being dishonest. That can happen even if they meet the inclusion criteria. This is why it makes no sense to have a time parameter on this drug, it's all subjective.

Hey guys, you're correct, do what you gotta do.

 

[Hazel]

I wonder if this ratio changes after a certain time period though...

@Hazel, want to run some quick analysis on these question pairs?

Your wish is my command

I ran a quick analysis on our 2020 survey results for the question: "Where do you perceive your tinnitus?". The summary of results is as follows (n=8,266):

I then proceeded — for the sake of simplicity — with only the categories "in both ears equally" and "only in the left ear" and "only in the right ear" (n=3,684) and cross-referenced with the question "How long have you had tinnitus?"

The results were very interesting:

I would argue that even without a regression analysis we can see a clear trend here from unilateral to bilateral tinnitus over time!

 

[GlennS]

Top line results here:

Otonomy Reports Positive Top-Line Results from Phase 1/2 Clinical Trial of OTO-313 in Patients with Tinnitus

 

[Ehren M]

Dishonest about what? What's the timeframe they're measuring exactly? I hear my tinnitus. I'll be honest and tell you if I don't hear it.

I'm not sure of the timeframe they plan to measure across, but I think it starts at 2 months after onset.

Also, I didn't mean to imply that anyone was being or planning to be dishonest. Sorry if my statement came across like I was pointing fingers. I meant to just address the overall difficulty of making sense of subjective data. Makes me glad I don't study humans.

 

[Gb3]

Since unilateral tinnitus was brought up yesterday, I posted this in my Sudden Sensorineural Hearing Loss group. It seems the majority of people with sudden loss tend to have it just in one ear.

 

[Piney]

Otonomy now has 8 sites on the ClinicalTrials.gov page.

 

[Sentinel]

I will say that after going through the induction process and getting all my stuff faxed and sent over to them AND doing a follow-up call just to make sure I fit the criteria, I get why these trials take so long.

 

[Gb3]

I will say that after going through the induction process and getting all my stuff faxed and sent over to them AND doing a follow-up call just to make sure I fit the criteria, I get why these trials take so long.

Right. That's why they show the inclusion/exclusion criteria because most people can read and not waste their time. But as you see here, some people just ignore the criteria!

 

[Piney]

I will say that after going through the induction process and getting all my stuff faxed and sent over to them AND doing a follow-up call just to make sure I fit the criteria, I get why these trials take so long.

Any details on the criteria? How many days did it take after the fax? Although I'm sure some locations have a different speed as well.

 

[Tezcatlipoca]

Right. That's why they show the inclusion/exclusion criteria because most people can read and not waste their time. But as you see here, some people just ignore the criteria!

I hope those people read this message and re-evaluate trying to sign up for the trial, especially when they clearly don't fit the criteria.

 

[apple core]

I fall under the "mostly in my left ear" category and am sometimes unsure if it's only in my left ear and there are secondary effects causing perception of noise in the right.

I think these secondary effects mean I am truly bilateral, but I can see how one would be unsure and think they are unilateral.

 

[Piney]

Right. That's why they show the inclusion/exclusion criteria because most people can read and not waste their time. But as you see here, some people just ignore the criteria!

Really, so all the criteria they list on the website are 100% accurate, they don't have any other criteria beyond what's written?

How many trials have you and @Tezcatlipoca been in?

Keep in mind people are entering the trial willingly, knowing they might just get a needle in their ear for nothing. Who's going do that to falsify reports?