Otonomy OTO-313 — Treatment of Tinnitus

Discussion in 'Research News' started by Michael Larsen, Jan 9, 2018.

    1. FGG
      No Mood

      FGG Member Podcast Patron Benefactor Ambassador Hall of Fame Advocate

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Multi-factorial
      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.
       
      • Agree Agree x 2
    2. Tezcatlipoca
      Question it

      Tezcatlipoca Member

      Location:
      Mexico
      Tinnitus Since:
      June 2020
      Cause of Tinnitus:
      NIHL
      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.
       
      • Agree Agree x 1
    3. Gb3

      Gb3 Member

      Tinnitus Since:
      12/19
      Cause of Tinnitus:
      Sshl
      Seriously @Piney, you are 100% wrong about everything you said.
       
      • Agree Agree x 1
    4. Jrblovsky

      Jrblovsky Member

      Location:
      USA
      Tinnitus Since:
      Christmas 2019
      Cause of Tinnitus:
      NOISE/Menieres Who knows
      People without tinnitus think this is a minor inconvenience and nothing to worry about; hence ENT doctors.
       
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    5. FGG
      No Mood

      FGG Member Podcast Patron Benefactor Ambassador Hall of Fame Advocate

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Multi-factorial
      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):

      Capture+_2021-04-11-20-33-54_(1).png

      Makes me wonder if these effects were eardrum or otherwise injection related.
       
      • Good Question Good Question x 1
    6. Tezcatlipoca
      Question it

      Tezcatlipoca Member

      Location:
      Mexico
      Tinnitus Since:
      June 2020
      Cause of Tinnitus:
      NIHL
      Probably the vehicle in my opinion, intratympanic injection don't usually worsen tinnitus.

      Is this a confirmation that @ChrisBoyMonkey got placebo?
       
    7. FGG
      No Mood

      FGG Member Podcast Patron Benefactor Ambassador Hall of Fame Advocate

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Multi-factorial
      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.
       
    8. rei

      rei Member Benefactor

      Tinnitus Since:
      2006 but not a problem till 10/19
      Cause of Tinnitus:
      loud music spiked with lyme disease
      Does Otonomy have the funds to complete their trials? It would be a shame if they went under.
       
    9. FGG
      No Mood

      FGG Member Podcast Patron Benefactor Ambassador Hall of Fame Advocate

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Multi-factorial
      I would think so considering they are still talking about starting new trials.
       
    10. Tezcatlipoca
      Question it

      Tezcatlipoca Member

      Location:
      Mexico
      Tinnitus Since:
      June 2020
      Cause of Tinnitus:
      NIHL
      Whatever they are doing to it, it's causing problems. Poor Chris.
       
    11. kingsfan
      Mellow

      kingsfan Member

      Location:
      Southern California
      Tinnitus Since:
      Sep 17 '20 / Oct 20 '20 / Mar 31 '21
      Cause of Tinnitus:
      turning everything up to 11
      Hmmmm... Is driving to magical Fresno, CA worth it for this trial...
       
    12. asey20
      Buzzed

      asey20 Member Benefactor

      Location:
      Toronto
      Tinnitus Since:
      July 13, 2020
      Cause of Tinnitus:
      Not sure.
      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.
       
    13. Gb3

      Gb3 Member

      Tinnitus Since:
      12/19
      Cause of Tinnitus:
      Sshl
      Consider all you want, but it’s not unilateral.
       
    14. apple core

      apple core Member

      Location:
      Milwaukee, Wisconsin, USA
      Tinnitus Since:
      12/2020
      Cause of Tinnitus:
      headphones, syringing, or cervical vertebrae issue
      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?
       
      • Good Question Good Question x 2
    15. RichieTheKid
      Question it

      RichieTheKid Member

      Tinnitus Since:
      2011
      Cause of Tinnitus:
      Many Different things
      This worries me. Something in a tinnitus treatment possibly making it worse. I'll have to hold out until the trials are over.
       
    16. kingsfan
      Mellow

      kingsfan Member

      Location:
      Southern California
      Tinnitus Since:
      Sep 17 '20 / Oct 20 '20 / Mar 31 '21
      Cause of Tinnitus:
      turning everything up to 11
      Is it possible to have both bilateral and unilateral tinnitus? Say... hissing in both ears, but a deafening tone in only one ear?
       
    17. apple core

      apple core Member

      Location:
      Milwaukee, Wisconsin, USA
      Tinnitus Since:
      12/2020
      Cause of Tinnitus:
      headphones, syringing, or cervical vertebrae issue
      I think that is bilateral, no question.
       
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    18. asey20
      Buzzed

      asey20 Member Benefactor

      Location:
      Toronto
      Tinnitus Since:
      July 13, 2020
      Cause of Tinnitus:
      Not sure.
      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.
       
    19. FGG
      No Mood

      FGG Member Podcast Patron Benefactor Ambassador Hall of Fame Advocate

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Multi-factorial
      This thread...

      Capture+_2021-04-13-16-40-09_(2)~2.png
       
      • Funny Funny x 6
    20. Gb3

      Gb3 Member

      Tinnitus Since:
      12/19
      Cause of Tinnitus:
      Sshl
      Unilateral means one.
       
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    21. Jrblovsky

      Jrblovsky Member

      Location:
      USA
      Tinnitus Since:
      Christmas 2019
      Cause of Tinnitus:
      NOISE/Menieres Who knows
      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.
       
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    22. Tezcatlipoca
      Question it

      Tezcatlipoca Member

      Location:
      Mexico
      Tinnitus Since:
      June 2020
      Cause of Tinnitus:
      NIHL
      Yeah that's not how it works.
       
    23. VeryUnfortunate
      Stressed

      VeryUnfortunate Member Benefactor

      Tinnitus Since:
      January 2021
      Cause of Tinnitus:
      Acoustic Trauma
      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.
       
    24. FGG
      No Mood

      FGG Member Podcast Patron Benefactor Ambassador Hall of Fame Advocate

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Multi-factorial
      Here is the data on the responders:

      Capture+_2021-04-11-20-31-55_(1).png

      Capture+_2021-04-11-21-54-41_(1).png
       
      • Informative Informative x 4
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    25. VeryUnfortunate
      Stressed

      VeryUnfortunate Member Benefactor

      Tinnitus Since:
      January 2021
      Cause of Tinnitus:
      Acoustic Trauma
      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?
       
    26. AfroSnowman
      Balanced

      AfroSnowman Member Podcast Patron Benefactor

      Tinnitus Since:
      April 16 2019
      Cause of Tinnitus:
      Nonnatural energy source
      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?
       
      • Like Like x 1
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    27. FGG
      No Mood

      FGG Member Podcast Patron Benefactor Ambassador Hall of Fame Advocate

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Multi-factorial
      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.
       
      • Optimistic Optimistic x 3
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    28. Tezcatlipoca
      Question it

      Tezcatlipoca Member

      Location:
      Mexico
      Tinnitus Since:
      June 2020
      Cause of Tinnitus:
      NIHL
      So the worse your tinnitus is, the better a responder you are? That's great.
       
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    29. FGG
      No Mood

      FGG Member Podcast Patron Benefactor Ambassador Hall of Fame Advocate

      Tinnitus Since:
      01/2019
      Cause of Tinnitus:
      Multi-factorial
      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.
       
    30. AfroSnowman
      Balanced

      AfroSnowman Member Podcast Patron Benefactor

      Tinnitus Since:
      April 16 2019
      Cause of Tinnitus:
      Nonnatural energy source
      Thanks for the update.

      When are we expecting Phase 2 results?
       
      • Good Question Good Question x 2
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