Otonomy OTO-413 — Treatment of Hidden Hearing Loss

[Sim-Lev]

Does anyone know why the clinical trial for OTO-413 doesn't appear on the clinicaltrials.gov website?

 

[Pero1234]

Does anyone know why the clinical trial for OTO-413 doesn't appear on the clinicaltrials.gov website?

You can't find it because it's for HIDDEN hearing loss...



I apologize, couldn't resist!

 

[SouthKorean]

Does anyone know why the clinical trial for OTO-413 doesn't appear on the clinicaltrials.gov website?

https://clinicaltrials.gov/ct2/show/NCT04129775

Is this a new clinical trial?

Can someone tell me if it's a phase 1 or phase 2?

And what's the difference between the phase 1 and phase 2?

 

[spingee]

A Randomized, Double-blind, Placebo-controlled Phase 1/2 Study of OTO-413 Given as a Single Intratympanic Injection in Subjects With Speech-in-noise Hearing Impairment

 

[JohnAdams]

Damn, a single dose? I have low confidence that one dose is going to really do much.

 

[ChrisBoyMonkey]

Damn, a single dose? I have low confidence that one dose is going to really do much.

Supposedly they've come up with this slow release kind of gel. OTO-313 is the same way.

 

[JohnAdams]

Supposedly they've come up with this slow release kind of gel. OTO-313 is the same way.

That will certainly help. They could also mix it with platelet rich plasma. That stuff can setup in your head for a day.

 

[Jurger]

Supposedly they've come up with this slow release kind of gel. OTO-313 is the same way.

FX-322 uses it as well. I doubt this single dose is all they will be testing. They'll probably test multiple injections in Phase 2.

 

[Chriscom]

FX-322 uses it as well. I doubt this single dose is all they will be testing. They'll probably test multiple injections in Phase 2.

If "they'll" refers to FX-322, correct. From Frequency Therapeutics' Oct. 10 press release:

The Phase 2a clinical trial is a multi-center, randomized, double-blind, placebo-controlled, single- and repeat-dose study of FX-322, expected to enroll approximately 96 adults aged 18 to 65 with stable SNHL at 12 sites in the U.S. Patients will be randomized to one of four groups, each of which will receive four injections, once per week, at weekly intervals starting at the initial visit. The key efficacy endpoints of this trial are word recognition (WR), words-in-noise (WIN), and standard pure tone audiometry. Exploratory efficacy endpoints are extended high frequency pure tone audiometry, the Tinnitus Functional Index (TFI), and the Hearing Handicap Inventory in Adults (HHIA).

https://investors.frequencytx.com/n...eutics-commences-dosing-its-phase-2a-study-fx

 

[Jim51042]

It sucks that tinnitus is an exclusion for their clinical trial.

 

[ChrisBoyMonkey]

It sucks that tinnitus is an exclusion for their clinical trial.

No it's not, they are officially testing the drug to see if it helps. They just want the main concern to be hearing loss.

 

[Rb86]

It sucks that tinnitus is an exclusion for their clinical trial.

Hold on, where did you read that?

 

[SouthKorean]

It sucks that tinnitus is an exclusion for their clinical trial.

Isn't OTO-313 a clinical trial for tinnitus?

 

[ChrisBoyMonkey]

It sucks that tinnitus is an exclusion for their clinical trial.

Oh wait, for OTO-413 this seems to be right. It is an exclusion.. which I think makes no sense. This should be something they should officially measure to see if it helps. To me it seems like it's only logical that it would help.

 

[JohnAdams]

It sucks that tinnitus is an exclusion for their clinical trial.

Oh wait, for OTO-413 this seems to be right. It is an exclusion.. which I think makes no sense. This should be something they should officially measure to see if it helps. To me it seems like it's only logical that it would help.

ABRACADABRA
Just don't tell them you have tinnitus.

 

[Jim51042]

Just don't tell them you have tinnitus.

It's not testing on me I'm worried about, it's all the other people who will be turned away and the resulting lack of data/information that will follow from their exclusion.

 

[JohnAdams]

It's not testing on me I'm worried about, it's all the other people who will be turned away and the resulting lack of data/information that will follow from their exclusion.

I have a *sneaking suspicion* that it helps with tinnitus.

 

[Chinmoku]

I have a *sneaking suspicion* that it helps with tinnitus.

But with all tinnitus patients out there why exclude tinnitus? From a business point of view it doesn't make sense, unless they fear concretely that the drug might aggravate tinnitus.

 

[JohnAdams]

But with all tinnitus patients out there why exclude tinnitus? From a business point of view it doesn't make sense, unless they fear concretely that the drug might aggravate tinnitus.

I don't fear, concretely, that it will aggravate tinnitus. As a matter of fact I would not fear getting this stuff injected into my ears whatsoever.

 

[Jim51042]

But with all tinnitus patients out there why exclude tinnitus? From a business point of view it doesn't make sense, unless they fear concretely that the drug might aggravate tinnitus.

That's probably not what they fear. What they are likely worried about is the objectiveness of tinnitus patients. Since there is not yet a way to measure numerical tinnitus without talking to the patient it adds some uncertainty for the company. That being said since this drug likely will help with tinnitus more than it will help for hearing improvement from a corporate perspective it is an extremely unwise exclusion to implement. But corporate upper management can be extremely dumb.

 

[JohnAdams]

Since there is not yet a way to measure numerical tinnitus without talking to the patient it adds some uncertainty for the company.

It's like "So sorry, we can't measure a disease that you definitely have, therefore we can't cure you."

 

[Chinmoku]

I don't fear, concretely, that it will aggravate tinnitus. As a matter of fact I would not fear getting this stuff injected into my ears whatsoever.

That's because you are one of the bravest daredevils in this forum. When I read the number of intratympanic injections you had in South Korea I almost fainted. However, I don't understand Otonomy's point of view really. I know you would go for the injections, what I don't understand is why don't they open the trial to tinnitus sufferers and record the effects on tinnitus with little additional work? It would broaden the use of the drug and that can only be good for them. Perhaps as @Jim51042 says it's just dumb management.

 

[Chinmoku]

That's probably not what they fear. What they are likely worried about is the objectiveness of tinnitus patients. Since there is not yet a way to measure numerical tinnitus without talking to the patient it adds some uncertainty for the company. That being said since this drug likely will help with tinnitus more than it will help for hearing improvement from a corporate perspective it is an extremely unwise exclusion to implement. But corporate upper management can be extremely dumb.

But they could run a questionnaire or check minimum masking volume at the very least. Even if it does not give strong evidence, there is NOTHING that works for tinnitus at the moment, so even a medication that substantially lowers the tinnitus questionnaire score would be welcome and probably sell well. I can't believe the management is so dumb, I wonder what could be happening here.

 

[ChrisBoyMonkey]

But they could run a questionnaire or check minimum masking volume at the very least. Even if it does not give strong evidence, there is NOTHING that works for tinnitus at the moment, so even a medication that substantially lowers the tinnitus questionnaire score would be welcome and probably sell well. I can't believe the management is so dumb, I wonder what could be happening here.

I think they might not want it to cannibalize with their OTO-313. Which is still stupid, if this drug works to help with the tinnitus too then they could just brand the one that works better specifically for tinnitus as so.

If this one works and the other doesn't work at all, then scratch the other one and sell this one as such.

 

[Pero1234]

Perhaps 313 and 413 are 90% similar drugs.

They are doing two tests in parallel

Hoping that for at least one of their groups it becomes a success...

 

[JohnAdams]

Perhaps 313 and 413 are 90% similar drugs.

They are doing two tests in parallel

Hoping that for at least one of their groups it becomes a success...

They're not similar at all.

 

[Pero1234]

They're not similar at all.

Can we read more about them somewhere?

 

[JohnAdams]

Can we read more about them somewhere?

Affirmative.
OTO-313 is gacyclidine
OTO-413 is BDNF

 

[JohnAdams]

tinnitus patients have lower BDNF levels:
"Serum BDNF level was found lower in the tinnitus patients than controls"
https://www.ncbi.nlm.nih.gov/pubmed/28615544

curcumin increases BDNF levels:
curcumin at doses of 50 and 100 mg/kg (p.o.) increased BDNF protein levels by 78.0% and 95.1%, respectively, compared to the control group.
https://www.hindawi.com/journals/mi/2017/6280925/

This is more than likely why curcumin helps with tinnitus in some of us.

Either the BDNF receptors are fried or our nerves aren't making enough. I'm leaning towards the receptors being fried.

 

[FGG]

tinnitus patients have lower BDNF levels:
"Serum BDNF level was found lower in the tinnitus patients than controls"
https://www.ncbi.nlm.nih.gov/pubmed/28615544

curcumin increases BDNF levels:
curcumin at doses of 50 and 100 mg/kg (p.o.) increased BDNF protein levels by 78.0% and 95.1%, respectively, compared to the control group.
https://www.hindawi.com/journals/mi/2017/6280925/

This is more than likely why curcumin helps with tinnitus in some of us.

Either the BDNF receptors are fried or our nerves aren't making enough. I'm leaning towards the receptors being fried.

It's significantly easier to get BDNF elevations in the blood than in significant amounts in cochlear circulation. I remember reading more gets in the brain than cochlea (would have to look for reference).