Otonomy OTO-313 — Treatment of Tinnitus

[FGG]

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?

Per Frequency Therapeutics, they said they have evidence this literally happened with their Phase 2a. It wasn't discovered until they went back and compared baseline measurements to long term medical records.

There are a lot of people who would stick almost anything in their ear for a shot at improvement. Obviously people without tinnitus wouldn't do this but you can have tinnitus without matching the trial criteria.

 

[Tezcatlipoca]

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

Yes, that's what they submitted to the FDA, there's no secret criteria. And not that it's any of your business but I have been in 2 clinical trials.

 

[Gb3]

Yes, that's what they submitted to the FDA, there's no secret criteria. And not that it's any of your business but I have been in 2 clinical trials.

Seriously @Piney, you are 100% wrong about everything you said.

 

[Jrblovsky]

Obviously people without tinnitus wouldn't do this but you can have tinnitus without matching the trial criteria.

People without tinnitus think this is a minor inconvenience and nothing to worry about; hence ENT doctors.

 

[FGG]

Not sure if these have been posted before but I came across the safety data.

It looks like all the moderate to severe tinnitus worsening were from placebo, so that's good news (but still odd):

Makes me wonder if these effects were eardrum or otherwise injection related.

 

[Tezcatlipoca]

Not sure if these have been posted before but I came across the safety data.

It looks like all the moderate to severe tinnitus worsening were from placebo, so that's good news (but still odd):

View attachment 44515

Makes me wonder if these effects were eardrum or otherwise injection related.

Probably the vehicle in my opinion, intratympanic injection don't usually worsen tinnitus.

Is this a confirmation that @ChrisBoyMonkey got placebo?

 

[FGG]

Probably the vehicle in my opinion, intratympanic injection don't usually worsen tinnitus.

Is this a confirmation that @ChrisBoyMonkey got placebo?

The vehicle should be the same for drug and placebo, though, right? But it may have needed to be colored a certain way to blind the study and a dye or other additive caused a problem? I really don't know.

I was referring to things like ear drum rupture or something really esoteric like systemic allergy. But who really knows.

From this, it looks like Chris did get placebo though.

 

[rei]

Does Otonomy have the funds to complete their trials? It would be a shame if they went under.

 

[FGG]

Does Otonomy have the funds to complete their trials? It would be a shame if they went under.

I would think so considering they are still talking about starting new trials.

 

[Tezcatlipoca]

The vehicle should be the same for drug and placebo, though, right? But it may have needed to be colored a certain way to blind the study and a dye or other additive caused a problem? I really don't know.

I was referring to things like ear drum rupture or something really esoteric like systemic allergy. But who really knows.

From this, it looks like Chris did get placebo though.

Whatever they are doing to it, it's causing problems. Poor Chris.

 

[kingsfan]

Hmmmm... Is driving to magical Fresno, CA worth it for this trial...

 

[asey20]

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...

It's not so rare. I have unilateral tinnitus. If one ear is much louder than the other, you can consider it unilateral in my book as well.

 

[Gb3]

If one ear is much louder than the other, you can consider it unilateral in my book as well.

Consider all you want, but it's not unilateral.

 

[apple core]

If one ear is much louder than the other, you can consider it unilateral in my book as well.

That's the thing... a person suffering from "mostly in the left" or "mostly in the right" tinnitus might be unsure if they actually qualify as unilateral. Much of the time I feel like it is only in my left and I have a hard time understanding how someone could be sure it is ONLY in one ear since so much of it is "head noise".

Question for people who identify their tinnitus as unilateral - Do you feel any effects around the other ear that sometimes have you questioning if you are actually truly bilateral?

Also, have you been clinically diagnosed as having unilateral tinnitus?

 

[RichieTheKid]

The vehicle should be the same for drug and placebo, though, right? But it may have needed to be colored a certain way to blind the study and a dye or other additive caused a problem? I really don't know.

I was referring to things like ear drum rupture or something really esoteric like systemic allergy. But who really knows.

From this, it looks like Chris did get placebo though.

This worries me. Something in a tinnitus treatment possibly making it worse. I'll have to hold out until the trials are over.

 

[kingsfan]

Is it possible to have both bilateral and unilateral tinnitus? Say... hissing in both ears, but a deafening tone in only one ear?

 

[apple core]

Is it possible to have both bilateral and unilateral tinnitus? Say... hissing in both ears, but a deafening tone in only one ear?

I think that is bilateral, no question.

 

[asey20]

Also, have you been clinically diagnosed as having unilateral tinnitus?

No. Going to the doctor's office was basically being told that it's all in my head and there is nothing he can do about it. There was no diagnosing at all.

However, I can only hear tinnitus in one ear.

 

[FGG]

Consider all you want, but it's not unilateral.

This thread...

 

[Gb3]

Unilateral means one.

 

[Jrblovsky]

It's not so rare. I have unilateral tinnitus. If one ear is much louder than the other, you can consider it unilateral in my book as well.

This makes zero sense. It's like being a virgin or not. You either are or not. You can't have it your way; it's not Burger King. I'm scratching my head right now.

 

[Tezcatlipoca]

It's not so rare. I have unilateral tinnitus. If one ear is much louder than the other, you can consider it unilateral in my book as well.

Yeah that's not how it works.

 

[VeryUnfortunate]

Does anyone know if Otonomy has released information on if the Phase 1 trial actually had a positive result on people's tinnitus?

I saw that @FGG posted the preliminary safety summary.

I'm now just wondering if there is any number of people that have actually had an improvement in their tinnitus after the injection.

 

[FGG]

Does anyone know if Otonomy has released information on if the Phase 1 trial actually had a positive result on people's tinnitus?

I saw that @FGG posted the preliminary safety summary.

I'm now just wondering if there is any number of people that have actually had an improvement in their tinnitus after the injection.

Here is the data on the responders:

 

[VeryUnfortunate]

So I have high hopes for OTO-313, as it is one of the few things in the pipeline that is originally indicated for tinnitus and not something speculated for.

I hope it will work for people with chronic tinnitus, but since I am in the acute stage with unilateral tinnitus I am thinking about reaching out to see if I can participate in the clinical trial.

@Sentinel, can I ask you what location you are working with?

 

[AfroSnowman]

So I haven't been following OTO-313 closely, but I am aware it is/was being tested exclusively on acute tinnitus.

Could anyone save me the trouble of reviewing the thread and explain whether and why there is any reason to believe that this could be effective in chronic tinnitus?

 

[FGG]

So I haven't been following OTO-313 closely, but I am aware it is/was being tested exclusively on acute tinnitus.

Could anyone save me the trouble of reviewing the thread and explain whether and why there is any reason to believe that this could be effective in chronic tinnitus?

I'm not sure anyone knows for sure who this works for and why but the data so far is pretty interesting. In the first trial, they tested up to 6 months and 43% of people treated got improvements in tinnitus and 29% (4 patients) got a greater than 20 point TFI improvement (scroll up to see charts).

Interestingly, those 4 patients all had severe tinnitus.

It does seem that local cochlear NMDA receptor hyperexcitability (which is what the drug acts on) happens very acutely to everyone with cochlear damage (and the excitability gets propagated up the auditory channels) but that seems to be more variable long term when the central plasticity/"phantom cochlea" hyperexcitability may become a bigger part. This may be why it doesn't work for everyone and less than half of the participants responded.

However, it may be that people with *severe* tinnitus retain the local cochlear NMDA stimulation component of neural hyperexcitabilty longer. And actually studies have shown that the stress of severe tinnitus in and of itself can be somewhat self perpetuating, too, because of dynorphin release (which sensitizes the NMDA receptor further):

Endogenous dynorphins, glutamate and N-methyl-d-aspartate (NMDA) receptors may participate in a stress-mediated Type-I auditory neural exacerbation of tinnitus

In other words, this may work better in chronic cases when the tinnitus is severe. Which would be good news for the worst cases. Phase 2 would answer that better, though, obviously with a bigger sample size.

 

[Tezcatlipoca]

In other words, this may work better in chronic cases when the tinnitus is severe. Which would be good news for the worst cases.

So the worse your tinnitus is, the better a responder you are? That's great.

 

[FGG]

So the worse your tinnitus is, the better a responder you are? That's great.

Maybe. I think very acutely most people should respond though.

Since stress mediated axonal dynorphin release contributes to NMDA hyperexcitabilty chronically, the more stressed you are about your tinnitus (people with severe tinnitus tend to be more stressed about it) the more chance you might benefit imo.

Phase 2 would give a much better idea of the responders vs non responders and then patterns may emerge. I would like to see the profiles of the Phase 1 non responders too but I can't find that info anywhere.

 

[AfroSnowman]

I'm not sure anyone knows for sure who this works for and why but the data so far is pretty interesting. In the first trial, they tested up to 6 months and 43% of people treated got improvements in tinnitus and 29% (4 patients) got a greater than 20 point TFI improvement (scroll up to see charts).

Interestingly, those 4 patients all had severe tinnitus.

It does seem that local cochlear NMDA receptor hyperexcitability (which is what the drug acts on) happens very acutely to everyone with cochlear damage (and the excitability gets propagated up the auditory channels) but that seems to be more variable long term when the central plasticity/"phantom cochlea" hyperexcitability may become a bigger part. This may be why it doesn't work for everyone and less than half of the participants responded.

However, it may be that people with *severe* tinnitus retain the local cochlear NMDA stimulation component of neural hyperexcitabilty longer. And actually studies have shown that the stress of severe tinnitus in and of itself can be somewhat self perpetuating, too, because of dynorphin release (which sensitizes the NMDA receptor further):

Endogenous dynorphins, glutamate and N-methyl-d-aspartate (NMDA) receptors may participate in a stress-mediated Type-I auditory neural exacerbation of tinnitus

In other words, this may work better in chronic cases when the tinnitus is severe. Which would be good news for the worst cases. Phase 2 would answer that better, though, obviously with a bigger sample size.

Thanks for the update.

When are we expecting Phase 2 results?