Otonomy Starting Phase 1 Trial in 2015 for Tinnitus

As far as I know there is no new news. The trial isn't listed on clinicaltrials.gov.
There is a recent company presentation with information on pages 13 and 14 though there isn't really any new information:
http://phx.corporate-ir.net/Externa...9NjM2MDMyfENoaWxkSUQ9MzQwMjM3fFR5cGU9MQ==&t=1

I don't think Otonomy has said anything explicitly about chronic vs acute, but the assumption is that it will be for acute. Auris belies that as they point out in a SEC filing last year that OTO-311 is likely to be a competitor to AM-101.
http://ir.aurismedical.com/phoenix....ERVNDPVNFQ1RJT05fUEFHRSZleHA9JnN1YnNpZD01Nw==

The filing warns that OTO-104 is a likely competitor for AM-111. They also state/imply that they have patents that Otonomy may be infringing.

 

I read the trial should start this year! Maybe it's postponed.

 

@Aussie Lea Sorry, I wasn't clear. The Phase 1 trial started in 2015 and should complete in the first half of 2016. If successful, they anticipate a Phase 2 trial in the second half of 2016. (http://www.otonomy.com/pipeline/oto-311/)

 

Ya like wtf maybe Am101 holds the patents to this procedure so oto311 is dead in the water.

 

I just received this communication back from Otonomy.

Thank you for your inquiry regarding Otonomy’s clinical trials for our tinnitus product candidate, OTO-311. The FDA has cleared the company's Investigational New Drug application (IND) for OTO-311. The IND clearance enables Otonomy to initiate a Phase 1 dose escalation clinical safety trial of OTO-311 in a small number of volunteers who do not have tinnitus. We anticipate initiating a Phase 2 clinical trial and enrolling patients who do have a diagnosis of tinnitus, only after successful completion of Phase 1 safety trial.

Regards,

Dean Hakanson MD
Chief Medical Officer

 

Is OTO 311 for chronic T ?

 

@Mithrandir OTO-311 is treatment for tinnitus no matter on acute or chronic.

"OTO-311 is a sustained-exposure formulation of the N-Methyl-D-Aspartate (NMDA) receptor antagonist gacyclidine in development for the treatment of tinnitus.

The goal of our OTO-311 program is to develop a sustained-exposure formulation of gacyclidine that will provide a full course of treatment from a single IT injection. In November 2015, we initiated a Phase 1 dose escalation clinical safety trial in normal healthy volunteers. OTO-311 will be given as a single unilateral intratympanic injection and subjects will be observed for four weeks following dosing. Several dose cohorts have been completed without concerns of patient tolerability. The Phase 1 trial will remain open into the second half of 2016 pending the potential evaluation of additional dose levels."

 

I don't think that they'll find a treatment that only addresses acute T, I know that's what they say in the trials because that is their criteria, but I think if they find a treatment for a certain type of acute T that treatment will also be effective in chronic T of that same variety.

 

If it's an NMDA antagonist it's most likely going to be aimed towards the acute stage just like AM-101. It's only during the acute stage that targeting NMDA receptors is going to do any good since it's during that narrow time frame that one can prevent death of hair cells caused by release of glutamate upon for example acoustic trauma.

In chronic sufferers the cells have already died a long time ago. So an NMDA antagonist isn't going to do you any good in that case. In that case it's only about regeneration of hair cells or treating the brain.

 

Sad but true. The big question is how long does the acute phase last? And is it the same for everyone? I doubt it would be the same for everyone.

Sadly I think we are a long ways off from being able to treat chronic tinnitus.

 

I would guess it's a matter of weeks, perhaps a few months. And I also imagine that the results decrease over time until they reach 0 at some point. In other words, the sooner the better.

 

Having tinnitus doesn't mean your cells have died, so I doubt your theory is correct ,Many studies show that some people have cronic tinnitus and their hair cells still not died.

 

I personally think that there are two major obstacles to be overcome when we want Tinnitus to be healed.

The first obstacle would be the neural one. Healing and/or regenerating the neural damage/cells (like SGN's). Various researches have pointed that SGN damage occurs at a far lower sound level than hair cell damage and still be able to cause T. This implies that there are more cases of neural damage + hair cell damage and cases of only neural damage that cause T, then there are cases of only hair cell damage that cause T. Efficiency-wise, this should be the first obstacle to tackle.

The second obstacle would then be healing/regenerating the specific hair cell damage/hair cells.

First remark: the research about the SGN's also pointed out that SGN die several months (sometimes even up to 8-10 months) after the exposure to loud sounds.

That brings me to my second remark: if acute tinnitus can be 'fixed' by healing the hair cells, because of the acuteness (several weeks), than it might be possible that the T would reappear after several months due to death of the SGN's. Furthermore, this might even be the reason that the improvement levels of these drugs aren't as high as we may hope (Rarely over 50% improvement). This may be hurdled by the fact that even if the hair cells are healed, the previous damaged SGN's still cause misfiring and thus T.

PS: As I said in another post, I will try to find these researches I used, but I have too little time to really find them among the vast amounts of research.

 

Well in that case Am101 is not for me. However we don't actually even know what causes tinnitus because we can't look inside the ear and brain in vivo and witness the play between neurons. That's because we need an MRI machine which images the inner ear and brain and lights up the nerves so scientist can witness what's going on. That's what I'm working on, the plans for a new machine which can image tinnitus. And you know what? Even then they won't have a cure all for T because it arises from many causes but through this machine they will be able to see what kind of tinnitus you have based on how the images manifest. The different types of tinnitus won't all have cures, some will, and some might in the future. The holy grail would be regenerating hair cells and the vestibucochlear nerve, but the next best thing would be the ability to change plasticity by modulating brain activity to turn T "off" which could be monitored with a new ear/brain MRI imager, and through these images we could monitor and attempt to treat each individual type of T.

 

Seriously stupid to make an imaginary cut off between acute and chronic T, I get it because this is a new feild of research and they need to define their variables but it's impossible to tell if you are in the acute or chronic phase because as pointed out above T sometimes arises 10 months after the actual trauma so you're already chronic (and doomed, jk) Tinnitus is Tinnitus and it never gets better, the is no "imaginary window" of time where somehow Tinnitus is reversible, Once you hear it you've got it, it's not going to spontaneously get better just because you are in the "imaginary Acute Phase" which we decided (not the body) was 3 months long. Nobody's tinnitus ever got better, they habituated, there is no acute phase it's a man made concept. Like oops yesterday it was acute now it's chronic oh poor me chronic tinnitus chronic they said 3 months im doomed.

 

Interesting! Explain?

Technically turning off the T would be a cure for the T, but not for the cause of it (eg. hearing loss (sound/medicinal/... induced), muscle tensions, TM(J)D,...). That is because of the fact that T is a symptom rather than a cause.

Purely tinnitus-regarded, finding the off switch isn't second best, but best. The causes would then be treated in their own medical department.

 

If we could turn T off we would be able to do so much other stuff, like turning on/off parts of the brain and seeing what happens - a rocket scientist could get a treatment to turn on the mathematics parts of his brain, lol the technology might even become banned in the NFL and NBA as a performance enhancer. Yes turning off/on parts of the brain will reveloutionize human existence, why not now? Why not us? How cool that a horrible struggle like tinnitus might pave the way for technology to access and program the entire brain!

 

Speculation that it, and nobody knows.

 

please take your medication

 

I can't believe it! I'm doomed wait maybe I'm acute no I'm chronic
No acute. It's enough to make anyone crazy and for no reason, AM101 is a special drug that might help a limited amount of people but it's not going to work for most people and we will need something else. I love that they are working on T but research and treatment is obviously in its infancy.

 

We don't actually know that because the only way to see if a persons cells are dead or not is to cut out their cochleas and preform a biopsy on them. And I guess that hasn't really been done. I at least haven't heard of any people signing up for those kind of tests.

But even if that was the case. AM-101 and OTO-311 would not work for you then because the mechanism of action for those drugs is to prevent cell death after auditory insult.

After an acoustic trauma the inner ear responds by releasing large amounts of Glutamate. Glutamate binds to NMDA receptors in the hair cells and that leads to the cells dying. Probably through a mechanism called apoptosis. (apoptosis = cell suicide)

An NMDA antagonist such as AM-101 and OTO-311 binds to the NMDA receptors and by doing so inhibits binding of Glutamate to those receptors which makes the cells survive. This is why I wrote that the best results will be achieved if the drug is administered immediately after an acoustic trauma and then decrease over time. It doesn't really matter if it's days, weeks or perhaps months. Eventually the Glutamate onslaught of cells will be completed and the drug won't be able to help you any more. But it most certainly will not be a matter of years though.

The drugs will therefore probably not work for everyone. Only for those that have acute tinnitus that is being caused by the mechanism I described above. And in the case that you have chronic tinnitus and there is nothing wrong with your hair cells then those drugs are not going to help you because their mechanism of action is to prevent cell death in the inner ear.

 

I can believe how many doctors we have in this forum.

 

Mine is rare Tinnitus from Labrythitis aka inflammation inside the cochlea they don't know what causes it. My 8th cranial nerve (vestibucochlear) is damaged, hair cells are still firing. The noises are so much worse from the nerve damage than when I just had T from loud music, that was nothing compared to these fluctuating noises from nerve damage.

 

May be we have more knowledge about the mecanism of T than those doctors

 

Yeah probably.

 

But we need the cure no more speculation.

 

I hope Charles Liberman is involved, OTONOMY has his profile on their site:
http://www.otonomy.com/charles-liberman-ph-d/

I just mailed Liberman to ask if he was involved in OTO-311 and if this has a potential to adress tinnitus originating from cochlear synaptopathy. Hope he will answer to my question as he did several times in the past.

 

This is what I got from Liberman about his involvment with OTONOMY and OTO-311 potential:
"Actually, I severed my connections to Otonomy when I joined forces with Decibel, but that’s neither here nor there. The ideas behind the use of NMDA blockers applied to the inner ear to treat tinnitus are controversial, so I don’t think that success is assured by any means. Since it seems like a pretty safe treatment, it wouldn’t hurt to try!"

Hi seems quite sceptical about efficacy of OTO-311.

 

We don't know whether AM-101 will work for chronic Tinnitus or not, simply because so-called chronic people didn't participate in the clinical trials. The boring answer: It remains to be seen.

We are not certain whether there a meaningful difference between acute and chronic Tinnitus, because current research is inconclusive. And if there indeed is a difference, we don't know where to draw the line. Is Tinnitus chronic after 3 days or 11 years? It's anyone's guess at this point.

We don't whether Otonomy is for chronic or not, because the company hasn't said anything about it, and they haven't started recruiting yet.

But hey, don't mind these facts. Because if people stop pretending to be experts, this forum will go dead pretty quickly.

 

hahaha who knew Liberman would be a shady queen.
just kidding haha, well i cant wait to see his work for decibel.
still have some faith on Otonomy.